IMS REAL-WORLD EVIDENCE SOLUTIONS AND HEALTH ECONOMICS & OUTCOMES RESEARCH
VOLUME 4, ISSUE 8 MAY 2014
AccessPoint News, views and insights from leading experts in RWE and HEOR
Oncology Special Edition Innovation demands RWE evolution
Research data selection Accounting for disparities is key
New gateways to real-world data Scandinavia leads the way
Payment by use Finding a path to broader access
Oncology poised for evidence transformation
High-value targeted therapies Accessing emerging markets
“We are entering a time of greater insight – and hope – about the progress being made towards a cure for cancer.”
Welcome I hope you find our latest edition of AccessPoint informative and thought provoking. As always, we explore dynamics shaping the HEOR, safety and RWE landscape. Our decision to dedicate the entire issue to oncology reflects both its importance across healthcare stakeholders and the recent, rapid innovations. We are entering a time of greater insight – and hope – about the progress being made towards a cure for cancer. Our exploration has highlighted four themes
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AccessPoint is published twice yearly by the IMS Real-World Evidence (RWE) Solutions and Health Economics & Outcomes Research (HEOR) team. VOLUME 4, ISSUE 8. PUbLISHEd MAY 2014.
Recent innovations signal a need to evolve and tailor RWE. Oncology outcomes research is delivering a deeper understanding of cancer and demonstrable impact. But as drug development broadens in developed and emerging markets such as Asia, and the scrutiny of value intensifies, we explore the need for new measures and tailored approaches. Data access is expanding RWE but focused application is key. Robust, longitudinal, linked real-world data is helping to complete evidenced-based patient pathways. The potential of Scandinavia as a global platform, pan-European collaborative initiatives, and creation of data pools from US oncology practices, are optimizing resources for improved outcomes research in cancer. But our comparison of linked datasets reinforces the need for a discerning approach to data selection. Methodologies are uniquely evolving in oncology. Unique demands on evidence requirements in oncology are driving innovative methods for demonstrating economic impact. Examples include adaptive approaches to modeling cost-effectiveness and budget impact, and the development of disease-specific co-morbidity scales in blood borne cancers. Emerging potential for RWE can further extend its value. Despite recent advancements many areas of research remain underserved, positioning the market for significantly expanded use of RWE. It can support optimal drug utilization, inform efficacy on an ongoing basis, and broaden access to new cancer treatments by enabling innovative contracting based on differential patient value.
At IMS Health we are passionate about improving patient outcomes and advancing healthcare and hope our insights will help to accelerate further innovations in cancer.
IMS HEALTH 210 Pentonville Road, London N1 9JY, UK Tel: +44 (0) 20 3075 4800 • www.imshealth.com/rwe RWEinfo@imshealth.com
©2014 IMS Health Incorporated and its affiliates. All rights reserved. Trademarks are registered in the United States and in various other countries.
Jon Resnick Vice President and General Manager Real-World Evidence Solutions IMS Health Jresnick@imshealth.com
IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
AccessPoint News, views and insights from leading experts in RWE and HEOR
Recent innovations signal a need to evolve and tailor RWE Trends in cancer care and global implications Evidence-based insights in oncology High-value oncology targeted therapies in Asia Pacific
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RWE is expanding but focused application is key Transforming oncology outcomes research in Sweden Future access to innovative oncology drugs in the EU Research questions drive data selection
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Methodologies are uniquely evolving in oncology
Understanding treatment patterns in prostate cancer Economic modeling for hematological cancers in Latin America Developing disease-specific scales for leukemia
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Emerging potential for RWE can further extend its value
Payment by use: Achieving a new value paradigm for oncology Drug utilization in oncology Connecting advancements to strengthen decision making
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NEWS
PROJECT FOCUS
2 IMS INSTITUTE ANALYZES TRENDS
56 HEMATOLOGICAL CANCERS Demonstrating value in Latin America 59 CHRONIC LYMPHOCYTIC LEUkEMIA Understanding the burden of co-morbidities
3 ONCOLOGY HEADS R&D PIPELINE 4 POST-AUTHORIZATION EFFICACY 5 NEW INSIGHTS INTO PATIENT JOURNEY 7 STRENGTHENING DECISION MAkING
ACCESSPOINT • VOLUME 4 ISSUE 8
IMS RWES & HEOR OVERVIEW 62 ENABLING YOUR REAL-WORLD SUCCESS Solutions, locations and expertise
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NEWS | IMS INSTITUTE INSIGHTS IMS Institute for Healthcare Informatics brings oncology to the forefront of its latest research with unique insights into market trends
Cancer innovation heads new analyses on healthcare dynamics globally The IMS Institute for Healthcare Informatics has conducted and published a wide range of groundbreaking research derived from granular analysis of information. Addressing key issues in healthcare and the use of medicines, it continues to enlighten with unique insights.
“India accounts for nearly one-third of global cervical cancer deaths, despite the fact that it is one of the few carcinomas that are preventable and curable to a large extent. The IMS Institute India believes there is an urgent need to strengthen the existing health systems in order to improve accessibility to primary and secondary prevention and screening measures.”
SPOTLIGHT ON ONCOLOGY
HEALTHCARE SPENDING, TECHNOLOGY AND SOCIAL MEDIA
Global market The Institute’s latest report, “Innovation in cancer care and implications for health systems: Global oncology trend report” offers the most comprehensive review of current trends in the oncology market. Published in May, 2014, it considers the state of innovation in therapeutics, measures of the value of treating cancer, pricing dynamics and, in the US, changes that are impacting the delivery of medicines in this area. It also assesses the potential for biosimilars to reshape the oncology market. Among its key findings are:
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Moderation of global market growth for oncology spending More targeted innovation in cancer therapies Increased payer scrutiny of pricing and the value of treatments Growing impact of biosimilars and non-original biologics
“Oncology is bringing higher levels of uncertainty to health systems across the globe – both in terms of the nature and rate of innovative treatments, and levels of reimbursement for patient care. The reality is that countries struggle to bring together the right combination of preventive measures and clinical interventions, including vaccines, diagnostics and therapeutics.” Advancing oncology in India Complementing the broader cancer report, a recent study from the IMS Institute in India, “Defeating India’s silent killer: The fight to diagnose and treat cervical cancer”, brings a perspective on key aspects relating to disease burden, screening, diagnosis and treatment of this common but preventable cancer, sharing learnings from other countries and providing recommendations for effective control.
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Other recent topics covered by the Institute include:
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Medicine use and shifting costs of healthcare (April, 2014). The first view of total system spending on medicines in the US in 2013, with a focus on the utilization of key healthcare services, patient costs for medicines and shift in the types of employer-provided insurance. Riding the information technology wave in life sciences (March, 2014). An outlook on how the current technology wave – defined in terms of cloud-based storage, new applications, systems integration and embedded analytics – will be harnessed by life sciences companies in their commercialization activities and why this is necessary for them to succeed in bringing innovative diagnostic and treatment options to patients. Engaging patients through social media (January, 2014). A review of the impact of social media on the use of medicines, including the role that pharmaceutical manufacturers are playing in leveraging social media platforms as part of their business model.
Innovation in cancer care see our R&D report on page 3 and Insights feature on page 8 to discover more findings from the IMS Institute cancer trends report.
Copies of these reports and other insights are available from the IMS Institute website at www.theimsinstitute.org, together with further information on its extensive range of research activities.
IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
R&D TRENDS IN ONCOLOGY | NEWS New dynamics are changing the focus of drug development activities in cancer
Oncology dominates R&d pipeline but report uncovers key shifts After several years of significant innovation, oncology still represents the largest area of drug development according to a new report from the IMS Institute for Healthcare Informatics. There are nearly 2,000 products for cancer in the pipeline – four times the number of the next largest therapeutic class. However, despite the high level of pharma investment, fewer of these drugs are progressing to phase II and III, underscoring the challenges of achieving successful results in the clinic. The comprehensive evaluation of current market trends in oncology, “Innovation in cancer care and implications for health systems: Global oncology trend report”, notes that while 22 new molecular entities (NMEs) for cancer have been launched over the past two years, the high failure rate and increasing competition make it risky and expensive to bring new cancer therapies to patients. Among some of the report’s key findings in this area are: Increasingly targeted nature of innovation in cancer therapies. The research pipeline is overwhelmingly populated with targeted therapies which have dramatically increased their share of the oncology market in the past ten years. This reflects a clear shift away from biologics; the majority of NMEs approved in cancer over the last decade have been non biologics.
Immunology therapy has become a strong area of recent investment, based on current success in clinical trials and a promising outlook.
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Clustering of innovation around cancer types. Advances in underlying science have led to innovation clusters around certain cancer types as new molecular targets have been identified. This has been witnessed by the recent developments in therapies for metastatic melanoma, prostate cancer and lung cancer. An R&D focus on factors other than prevalence. Currently, much of the late-stage pipeline is centered on higher prevalence tumors, such as breast, lung and colorectal cancer (Figure 1). However, another key driver of innovation is unmet needs which are not always tied to prevalence; tumor types with lower prevalence, such as ovarian, leukemia, stomach and liver cancers also are being actively pursued. Growing number of accelerated approvals. After an innovation slowdown through 2008, the oncology pipeline has increased with more accelerated approvals; cancer products comprise 34% of Breakthrough Therapy Designations (BTDs), a fast-track process allowing investigational agents to receive FDA approval as early as 3 months ahead of schedule. Together with a new Uk Early Access to Medicines program, this could play a significant role in accelerating oncology drug development and approval in the future.
FIGURE 1: PHASE III TRIALS BY CANCER TYPE AND 5-YEAR DISEASE PREVALENCE
A copy of the full report, published May, 2014, is available to download at the Institute website www.theimsinstitute.org
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5-year Global Prevalence (Millions)
0
Breast
6 5 4
Prostate
CRC
3 2 1
Lung
Cervical Uterine Thyroid
Bladder NHL
Stomach Melanoma
Kidney Liver
0 0
5
10
15
Ovarian
Leukemia 20
Number of phase III trials
25
30
35
40
Innovation in cancer care See our insights feature on page 8 to discover more findings from the IMS Institute cancer trends report.
Source: IMS R&D Focus, Globocan
ACCESSPOINT • VOLUME 4 ISSUE 8
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NEWS | POST-AUTHORIZATION EFFICACY IMS Health/ENCePP collaboration informs and shapes policy debate to advance pharmacovigilance in Europe
Partnership initiatives accelerate move towards continuous monitoring of efficacy and safety Reinforcing a commitment to promoting excellence in pharmacoepidemiological and pharmacovigilance (PV) research, IMS Health has been working with leading scientific network, ENCePP,1 on initiatives to further strengthen Europe’s comprehensive legislation for drug safety monitoring. The company partners with ENCePP to develop and disseminate standards in this area and is a member of the ENCePP-HTA working group established in collaboration with EUnetHTA.2 Recommendations arising from this collaboration are helping to guide regional policy on post-authorization efficacy studies (PAES) and to facilitate their more efficient implementation. DELEGATED ACT Providing direction on PAES Europe’s well-established and highly respected regulatory framework for PV, reformalized by new laws and guidelines in 2010 and 2012, has been recently augmented by the adoption of a delegated act (Delegated Regulation (EU) No 357/2014). Effective from 30 April, 2014, this clarifies the circumstances in which postauthorization efficacy studies (PAES) may be required by regulatory authorities. PAES are studies conducted after a drug has been approved to gather additional information on efficacy. They can be requested when questions exist that can only be addressed once a product is in real-world use or when they arise post-authorization.3 Increased emphasis on PAES reflects growing recognition that while safety is the
principal focus of PV, any new information or signals detected could potentially affect a product’s overall benefit:risk balance.4 The enactment follows a period of extensive public consultation by the European Commission to gather stakeholder views, including those of industry associations, manufacturers, public institutions, and academia and healthcare professionals. Input provided by ENCePP, in response to the request for feedback, was led and coordinated by IMS Health as part of the ENCePP-HTA working group. Their recommendations and advice, which included accounting for the requirements of HTA bodies, establishing a common standard for PAES, and ensuring dissemination of study results, has helped to shape, and is reflected in, the final version of the Act. Identifying potential for efficiencies in post-authorization research The new legislation marks a key step forward in the continuous assessment of both efficacy and safety in everyday practice in Europe through the use of PAES and PASS (post-authorization safety studies) to ensure that any unintended harmful effects of a medicine do not offset its intended clinical benefits. Further supporting policy progress in this area, IMS Health, as a member of the ENePP-HTA working group, recently joined representatives from the European Medicines Agency (EMA), the French Haute Autorité de Santé (HAS) and the University of Bordeaux, to lead a workshop exploring the potential benefits of increased regulatory/HTA agency collaboration in post-authorization studies.5 This is increasingly valid given the overlap in their requirements for this research. Held during the ISPOR 16th Annual European Congress in Dublin in November, 2013, the workshop considered collaborative opportunities to avoid duplication of continued opposite
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European Network of Centres for Pharmacoepidemiology and Pharmacovigilance European network for Health Technology Assessment 3 Specifications for additional efficacy studies for medicines published in the Official Journal of the EU http://www.ema.europa.eu 4 http://ec.europa.eu/health/files/pharmacovigilance/2013_pc_paes/summary_public_consultation.pdf 5 Post-authorisation studies in Europe: Bridging the gap between regulatory and health technology assessment (HTA) stakeholder needs for additional evidence. ISPOR 16th Annual European Congress, Dublin, Ireland, 4 November, 2013 2
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IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
IMS HEALTH AND PYGARGUS | NEWS
continued from previous page research effort and stimulate more effective use of resources. These included the possibility of centering such initiatives on work packages being developed by EUnetHTA and ENCePP as a means of ensuring that the scope and design of additional studies are sufficient to meet the needs of both regulators and HTA bodies.
For further information on IMS Health capabilities in developing combined strategies for safety and HTA or for clarification on PAES, please email Massoud Toussi at Mtoussi@fr.imshealth.com Find out more Delegated Act http://www.ema.europa.eu
MOVING FORWARD The concepts discussed at this initial workshop are being carried forward for further exploration at a workshop to be held during the 30th Annual Meeting of ISPE later in 2014. This will consider examples of initiatives that are ongoing in the EU and Asia to bridge gaps between regulatory and HTA requirements, and the potential for global harmonization of methodological standards in postauthorization studies.
Public Consultation http://ec.europa.eu/health/files/pharmacovigilance/ 2013_pc_paes/summary_public_consultation.pdf ENCePP response http://ec.europa.eu/health/files/pharmacovigilance/ 2013_pc_paes/encepp.pdf ISPOR workshop W31 on post-authorization studies http://www.ispor.org/Events/EventInformation.aspx? eventid=42&p=127
Scandinavia opens gateway to understanding the entire treatment journey Marking a new milestone in helping healthcare decision makers identify, link and interpret real-world outcomes in near real time, IMS Health recently announced the acquisition of Pygargus AB, a leading independent Scandinavian life science consultancy specializing in RWE. The move provides researchers with customized access to uniquely robust and granular anonymous patient-level data. With a history of 20 years, this data enables a comprehensive understanding of the patient treatment pathway and empowers unique RWE insights when linked to national and disease-specific registries. Generated from Sweden and the broader Nordic region, it can also inform science and decision making globally with coverage across all disease areas, led by cancer. Traditionally, the disconnected nature of healthcare data across various sites of service delivery has limited the potential of outcomes research to deliver meaningful,
holistic insights. In oncology, this challenge has been magnified by the scarcity of credible, long-term data following-up patients and their treatment experience over time. In this respect, the Nordic region is exceptionally well-placed as a setting for real-world data, with several key advantages compared to other research environments: Well-structured public healthcare Long established high-quality EMRs National registry environment Mature regulatory research framework
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REAL-WORLD INSIGHTS The new offering combines IMS Health’s market-leading capabilities in RWE with proprietary technology developed by Pygargus for extracting and integrating patientanonymous information from such sources as EMR, health registries and claims databases (Figure 1, overleaf).
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NEWS | IMS HEALTH AND PYGARGUS Scandinavia opens gateway to understanding the entire treatment journey continued from previous page
COMPLETING THE CANCER PATIENT PATHWAY Specifically in oncology, the Nordics are a key source of qualitative patient-level health information on disease diagnosis and management. The region has a 10-year history of EMRs and long established National Cancer Registries. Sweden, for example, has more than 20 robust, tumorspecific registries available for oncology research in cancers such as breast, gynecological, hematological, lung and prostate. These include complementary health information around the time of diagnosis and during disease progression. Covering all diagnosed cases of cancer over more than 50 years, the data can be linked via unique patient identifiers from birth to death. By connecting patient attributes to therapies and outcomes, this high-quality linked dataset delivers the deepest granularity in oncology observed in any single European market, to inform global research in more innovative and streamlined ways. The complete pathway is enabled with information that includes: Co-morbidities Surgical procedures & other measures Socio-economic variables Metastasis development (or progression of cancer/tumor) Death (and underlying cause) Hospitalizations (length of stay, etc) Medical treatments Family disease history Patient histology
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Tumor characteristics (TNM, staging information) All laboratory test results Risk factors & performance status
REAL-WORLD IMPACT Pygargus has a history of developing and contributing to large-scale, scientifically credible epidemiology and outcomes studies which rely on a complete view of the patient journey, to meet specific needs in epidemiology, outcomes research and pharmacovigilance across a range of disease areas. Some of these have led to breakthrough research. Recent cohorts from executed studies have extracted anonymous patient-level health information related to 1.6 million patients with cardiovascular disease, approximately 90,000 patients with diabetes, and approximately 7,000 patients with prostate cancer. The acquisition adds to IMS Health’s deep outcomes research expertise and scalable RWE platform supporting a broad range of applications, from epidemiological studies and comparative effectiveness and safety research, to commercial analytics. For further information on the IMS Health/Pygargus RWE platform and opportunities to efficiently link and analyze complex datasets in oncology and other disease areas in Scandinavia, please email Patrik Sobocki at Psobocki@se.imshealth.com
FIGURE 1: TAILORED DATABASE USING CUSTOMIZED EXTRACTION PROGRAM
Socio-economic information
Electronic Medical Records data
Hospital discharge register
Cause of death register
Prescription register
Hospital outpatient care
Tailored study database
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IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
IMS HEALTH AT ISPOR | NEWS ISPOR congress explores stimulants of change in the adoption of new healthcare technologies
Connecting advancements in RWE to strengthen healthcare decision making Unprecedented developments in the magnitude, reach and availability of real-world data are creating new opportunities for HEOR to support faster, more efficient decision making. But alongside the potential there are significant challenges in deriving the maximum value. These and other advancements impacting technology assessments drove the topics of debate at the ISPOR 16th Annual European Congress in November, 2013. More than 3,800 participants gathered in Dublin to consider progress towards “Finding the Right Pieces for the Health Care Decision-Making Puzzle” and discover the latest research from more than 1,800 podium and poster presentations.
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INTERSECTION OF RWE AND HEALTH ECONOMICS Leading an extensive range of IMS Health activities at ISPOR was the IMS Health Symposium,“The intersection of health economics and real-world evidence: Validating healthcare decision making.” The panel included senior industry guest speakers Dr Melvin Olson, Global Head of HEOR for Neuroscience and Ophthalmology at Novartis; and Dr Patrik Sobocki, CEO at Pygargus AB; and IMS Health experts, Dr Jacco keja and Dr Mark Lamotte. The session offered insights into the importance of RWE and its potential to bring about a step change in traditional approaches to health economics. Referencing case study examples in cancer and cardiovascular disease, the presentations explored: Role of RWE in validating healthcare decision making Current gaps in RWE use from an industry perspective Power of high quality patient-level Nordic data Synergies between RWE and health economics Potential for improved economic modeling using RWE Among the key outputs from the discussion were: RWE has potential but perceptions must change. The goal of health economics is to present and project real-world effectiveness in an economic framework, allowing informed decision making for cost-effective resource allocation. Heath economic and outcomes researchers have for too long relied on internal validity and clinical trial data. RWE allows for better estimates of transition rates and probabilities, enabling a move
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ACCESSPOINT • VOLUME 4 ISSUE 8
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from effectiveness projection to effectiveness measurement. However, perceptions of observational research must change in ways that build the reputation and practical application of RWE. RWE boundaries must be expanded and standards established. Despite its growing importance, RWE is not being applied creatively or strategically; it is time to challenge just how it could and should be used. The RWE strategy of the future should be a comprehensive plan across the lifecycle using evidence from multiple sources with a focus on establishing partnerships, involving kOLs, and on improving internal awareness and communication as well as external awareness and education. RWE generation needs to start early and build over time. Evidence platforms (data marts) are a key enabler, allowing the creation of larger, more powerful datasets and more cost-effective access, based on housing and linking multiple data sources (eg, pharmacy and claims, hospital, EMRs, RCTs, observational research, PRO studies). RWE needs can be uniquely met in the Nordics. Scandinavia brings the opportunity to link real-time anonymous patient-level data for the creation of datasets to answer multiple research questions. The combination of data from EMRs with registries allows a complete picture of the patient in terms of clinical measures and demographics. Examples exist of its tangible impact on pre-launch activities and in informing economic models. RWE can drive true cost-effectiveness models. Health economic modelers need to become more aware of what RWE data is available and where it can be found, instead of relying solely on data from clinical trials or the literature more generally. This means breaking down silos and doing more than before to build a model that incorporates all available data. This will make it possible to move more and more away from a cost-efficacy model towards a real cost-effectiveness model. Proceedings of the symposium can be obtained from Angelika Boucsein at Aboucsein@de.imshealth.com
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INSIGHTS | RWE TRENDS
Cancer is a leading priority for health systems globally, and stakeholders continue to seek the right combination of measures to assess treatments and investments. A recent comprehensive study of trends, innovation and spend in oncology, from the IMS Institute for Healthcare Informatics, provides a step forward in that search.
The author Kjel Johnson, PHARM.D, BCPS, FCCP, FAMCP is Vice President Global Oncology, IMS Health Kjel.johnson@us.imhealth.com
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IMS REAL-WORLD HEALTH ECONOMICS AND OUTCOMES RESEARCH IMS EVIDENCE SOLUTIONS & HEOR
RWE TRENDS | INSIGHTS
Innovation in cancer care Implications for global healthcare systems The IMS Institute, in collaboration with an external advisory board, undertook a comprehensive evaluation of current market trends for cancer medicines. Leveraging IMS Health databases, analytics platforms and forecasting tools, as well as published literature, the study included a review of innovation in therapeutics, measures of the value of treating cancer and pricing dynamics globally. It also analyzed dynamics impacting the delivery of oncology medicines in the US specifically. This article highlights several of its key findings, including the changes in oncology spend occurring in parallel to evolving innovations in treatment. ONCOLOGY SPENDING Although oncology spending has increased consistently over the past few years, the trend has moderated. Cancer spend has increased over the past decade to reach $91bn in 2013. The advent of targeted therapies marked an initial upsurge in the early 2000s, followed by slowing growth rates. A series of successful launches in 2012 and 2013 created a more recent uptick, reflecting innovations in previously underserved tumor types, such as castration-resistant prostate cancer (CRPC) and metastatic melanoma (Figure 1). Nevertheless, current trends demonstrate a compound annual growth rate (CAGR) for the overall oncology class (including supportive care) of 5.4% worldwide. For Europe Oncology Market Dynamics in Key Markets specifically – where stringent regulatory processes may dampen approvals and utilization – it is less than 5%. In the US, despite less stringent reviews, it is only 3.5%. FIGURE 1: GLOBAL ONCOLOGY MARKET DYNAMICS 2003-2013
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OUTCOMES - Issue 1 ACCESSPOINT • VOLUME 4 ISSUE 8
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INSIGHTS | RWE TRENDS
To provide a truly comprehensive evaluation of oncology spend, both therapeutic oncology and supportive care agents were included in the analysis. It also included generic and branded utilization. As the report demonstrates, total spend reflects more than drug pricing alone, notably the distribution channel in the US. Specifically, the physician office is generally the most economical infusion setting in the US for all stakeholders involved, but administration in the hospital outpatient setting is increasing despite being more costly than all other channels. Furthermore, from a real-world perspective, oncology is not practiced in a vacuum and oncologics are seldom used under perfect conditions in realization of their estimated costs. Instead, a disparity between ideal utilization (>85% of the approved dose) and actual utilization is driven by factors such as dose intensity, patient tolerance and affordability to the patient. Inadequate relative dose intensity (RDI) can impact the cost of care by significantly diminishing an agent’s potential for improved outcomes.1,2 Represented by the amount of drug administered per unit of time, expressed as the fraction of that used in the standard regimen, an RDI of <85% in clinical practice essentially provides placebo-level effectiveness at nearly the same cost.1,2 This phenomenon exists independently of drug pricing and is unfortunately common in real-world scenarios.3
PIPELINE FRUITION Landmark discoveries have helped foster an abundant cancer pipeline but failure rates remain high. The R&D drug pipeline is overwhelmingly populated by oncology therapies, with nearly 30% of the 6,357 active products to date seeking a cancer-related indication. A record 11 NMEs were approved globally in oncology in 2012 followed by 10 approvals in 2013. However, only ~10% of investigational agents that continue on to late-stage development receive eventual approval (Figure 2). FIGURE 2: CHARACTERIZATION OF THE ONCOLOGY-SPECIFIC SHARE OF THE ACTIVE DRUG PIPELINE
These launches reflect the trend toward waves of therapies being introduced by cancer type, such as the clusters of approvals for renal cell carcinoma a few years ago and in metastatic melanoma and CRPC more recently. When a new pathway or molecular target for treating a particular tumor is identified, numerous manufacturers often choose to exploit the pathway in developing new therapeutics. Thus, following the approval and hugely successful launch of Yervoy (ipilimumab) for metastatic melanoma in 2011, it was not surprising to see a host of other agents with similar indications either approved (Zelboraf (vemurafenib); Mekinist (trametinib); Tafinlar (dabrafenib)) or nearing approval in late-stage clinical trials. 1
Bonadonna G, Zambetti M, Valagussa P, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: The results of 20 years of follow-up. N Engl J Med, 1995; 332:901–906 2 kwak LW, Halpern J, Olshen RA, Horning SJ. Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: Results of a tree-structured survival analysis. J Clin Oncol, 1990; 8:963–977 3 Johnson k. The most costly chemotherapy today. Managed Care Oncol, 2008; 3(4):5-6
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RWE TRENDS | INSIGHTS
LAUNCH SUCCESS Launch success is often influenced by payer perception of unmet need as much as by specific outcomes data and Pomalyst-2013 Xofigo-2013, Zelboraf-2011 Xalkori-2011, Zaltrap-2012, individual drug pricing. Stivarga-2012, Iclusig-2013, Jakafi-2011, Adcetris-2011 Oncology launches over the past four years have differed substantially in their success. While Avastin (bevacizumab), launched a decade ago, is largely considered to be the most successful cancer drug launch of all time, Zytiga (abiraterone) is following a similar trajectory. Yervoy (ipilimumab) is keeping pace with the successful launches of Glivec/Gleevec (imatinib) and Erbitux (cetuximab) some time ago. Conversely, several recent launches have been far smaller, having achieved ≤$10mn per month in global sales (Figure 3). FIGURE 3: SELECTED US ONCOLOGY LAUNCHES ON A 3-MONTH ROLLING AVERAGE IN FIRST 24 MONTHS SINCE LAUNCH US$MN
Interestingly, some of the products from this latter group offered significant improvements in overall survival (OS) or progression-free survival (PFS). A key factor driving the differential success of these launches is payer perception of therapeutic need. While it may seem counterintuitive for a new product treating a relatively limited available patient population (eg, multiple myeloma) to surpass those targeting a larger one (eg, colorectal cancer), perceived unmet need on the part of payers may trump a larger available patient population given the numerous therapeutic options already available.4
PAYER SCRUTINY Payers are increasingly looking for ways to define the value of meaningful clinical outcomes, with a trend toward increased management interventions for certain cancer therapies. The American Society of Clinical Oncology (ASCO) recently released a report compiling the input of experts on four tumors – pancreatic, lung, breast and colon – in defining the expected outcomes for deeming a particular therapy effective.5 For each of these tumors, a range of between 3 and 6 months improvement in overall survival (OS) was selected as the primary endpoint (Table 1, overleaf ). However, it was noted that this would not necessarily diminish the value of PFS and other surrogate endpoints in certain clinical situations.5
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Lux W, kontos N. Adapting to new market realities: Achieving launch excellence in oncology. IMS Health White Paper, 2011 Ellis LM, et al. American Society of Clinical Oncology perspective: Raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol, 2014; Mar 17:epub ahead of print 10.1200/JCO.2013.53.8009.
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INSIGHTS | RWE TRENDS
TABLE 1: ASCO-RECOMMENDED TARGETS FOR MEANINGFUL CLINICAL TRIAL OUTCOMES.5 Primary End Point i
Secondary End Point
Cancer type
Patient population
Current baseline median OS (months)
Improvement over current OS that would be clinically meaningful (months)
Target HRs
Improvement in 1 year survival rate(%)
Improvement in PFS (months)
Pancreatic Cancer
FOLFIRINOX-eligible patents
10 to 11
4 to 5
0.67 to 0.69
48 to 63
4 to 5
3 to 4
0.6 to 0.75
35 to 50
3 to 4
3.25 to 4
0.76 to 0.8
53 to 61
4
2.5 to 3
0.77 to 0.8
44 to 53
3
4.5 to 6
0.75 to 0.8
63 to 71
4
3 to 5
0.67 to 0.67
25 to 36
3 to 5
Pancreatic Cancer
Gemcitabine or gemcitabine/ hab-pac itaxel-eligible patients
8 to 9
Lung Cancer
Nonsquamous cell carcinoma
13
Lung Cancer
Squamous cell carcinoma
10 ,
Breast Cancer
Metastatic triple negative, previously untr ated for metastatic disease
18
Colon Cancer
Disease progression with all prior therapies (or not a candidate for standard second or third-line options)
4 to 6
Abbreviations: FOLFIRINOX, leucovori
,
uracil, irinotecan and oxaliplatin; HR , hazard ratio; OS, overall survival; PFS, progression-free survival
Source: i. Ellis LM, et al.J Clin Oncol. 2014; Mar 17:epub ahead of print 10.1200/JCO.2013.53.8009, ii. Conroy T, et al. N Engl J Med 2011;364:1817-1825. DD, et al. N Engl J Med. 2013;369: 1691-1703. v. Porter ME. N Engl J Med. iii. Kindler HL, et al. Lancet Oncol. 2011;12:256-262. iv. . 2010;363:2477-2481. vi. Rossi A, et al. J Clin Oncol. 2012;30:1692-1698. vii. O’Shaughnessy, et al. Oncologist. 2012;17:476-484. viii. Cortazar P, et al. J Clin Oncol. 2012; 30:1705-1711. ix. Grothey A, et al. Lancet. 2013;381:303-312.
With multiple treatment options for various cancer types, coupled with increasing financial pressures across all therapeutic classes, payers and physicians are likely to look hard at the relative value of new launches and ultimately could reference these or similar guidelines in making coverage and treatment decisions. Although agents with relatively slight improvements in OS and PFS may be approved for use on the basis of other criteria, such as improved quality of life, the signs point to a future of more rigorous evaluations in oncology. The rise of more restrictive coverage and utilization criteria would not be surprising given the cost of modern-day oncologics. In Europe, health technology assessments have already become more stringent. In the US, according to a recent benchmarking survey of pharmacy benefit trends, over 90% of healthcare plans with a medical formulary report the use of prior authorization for high-cost injectable drugs such as those to treat cancer.6
PATIENT OUT-OF-POCKET COSTS IN THE US Financial pressures on patients following recent legislation have the potential to impact cancer care in the US. The number of medical oncologists in the US continues to grow while the nature of medical practices is changing. There has been a 24% increase in the number of oncology practices acquired by a hospital and a 21% increase in the number of oncology practices that have closed; concurrently, the size of remaining oncology practices has grown as groups of providers aggregate7 to mitigate increasing financial constraints resulting in part from the Affordable Care Act (ACA). One particular change is the ACA’s expansion of 340B eligibility. By design, the 340B Drug Pricing Program is intended to enable healthcare organizations that care for underserved patients to purchase outpatient drugs at discounted prices (~51% of average wholesale price; AWP). However, while uncompensated care as a percentage of total hospital expenses has remained unchanged over the past decade, the percentage of hospital drug purchases through 340B pricing has increased dramatically to 25% in 2013. One factor may be the ACA’s expanded eligibility to participate in this program. This arrangement can encourage the referral of cancer drug infusions to the facility outpatient setting from the oncologist’s office, where the hospital can purchase the drug at a significant discount and yet charge a premium to payers for hospital-based administration. In fact, the average cost increase to payers for a patient to receive a cancer drug in the hospital versus the physician’s office was found to be 189% for a set of frequently used therapies (Figure 4). 6 7
Magellan Rx Management 2013 Medical Pharmacy Trend Report, May 2014. Available at: http://www.magellanrxinsights.com/ Community Oncology Alliance (COA) Practice Impact Report, 2012, 2013
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FIGURE 4: HOSPITAL OUTPATIENT COSTS COMPARED TO PHYSICIAN OFFICE COSTS
Patients pay a portion of these increased costs, with an average $134 increase in out-of-pocket cost per dose of chemotherapy. Considering that they frequently receive several infusions in one visit, even a seemingly minimal increased cost per dose may be immediately compounded depending on the number of therapies in a particular therapeutic regimen. This increased spend should inform patient affordability discussions given that the total out-ofpocket cost for a cancer patient today is approximately $9,000 annually. An implication of these cost increases to the patient is therapeutic adherence since literature shows that even modest increases in co-pay amounts can result in measurable reductions in adherence.8,9 Furthermore, as therapeutic adherence decreases, the cost of care may actually increase, with approximately $8,000 per year higher costs for nonadherent patients in a recent evaluation of early-stage ER+/PR+ breast cancer patients.10 In this manner, recent changes to the US healthcare system may ultimately have unintended consequences on the quality and cost of American care for cancer patients.
CONCLUSION Oncology innovation, outcomes and spend are all important elements to consider in developing appropriate measures to assess treatments and investments. This Institute report provides a uniquely comprehensive study in an emerging world of data and evidence developed to inform those decisions. This article is based on findings presented in “Innovation in cancer care and implications for health systems: Global oncology trend report” published by the IMS Institute for Healthcare Informatics in May, 2014. Further analyses and insights can be found in the full report which is available to download at www.theimsinstitute.org The IMS Institute for Healthcare Informatics leverages collaborative relationships in the public and private sectors to strengthen the vital role of information in advancing healthcare globally. Its mission is to provide key policy setters and decision makers in the global health sector with unique and transformational insights into healthcare dynamics derived from granular analysis of information. 8
Bach PB. Limits on Medicare's ability to control rising spending on cancer drugs. N Engl J Med, 2009; 360:626-633 Eaddy MT, Cook CL, O’Day k, Burch SP, Cantrell CR. How patient cost-sharing trends affect adherence and outcomes: A literature review. PT 2012, Jan; 37(1):45-55 10 Neugut AI, et al. Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer. J Clin Oncol, 2011; 29:2534-2542 9
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Oncology outcomes research, for many years limited to snapshots of patient experiences, is starting to deliver a much deeper understanding of cancer and its treatment based on insights into the entire patient pathway. As continued innovation in data access and linkage transforms the potential of real-world evidence in oncology, the market is set for significant growth in its use. Already, its expanding value is yielding impressive results globally but, as an industry perspective reveals, the full possibilities have yet to be realized.
The author Chirag Ghai, MBA is Director RWE Solutions & HEOR, IMS Health Cghai@us.imshealth.com
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Evidence-based insights in oncology The journey is only just beginning Historically, inadequate access to anonymous patient-level oncology data outside of randomized clinical trials has posed challenges in developing research and commercial insights. Although traditional oncology real-world databases were available, they existed in silos. In the absence of data management techniques there was no means of integrating these data sources and they were thus not a true learning healthcare system.1 They also lacked depth, missing elements that are critical to providing meaningful insights in oncology, such as mortality, tumor information and progression status. Thus, while researchers could develop snapshots of patient experiences, they were unable to illustrate a near real-time and comprehensive view of the patient journey. As a result, real-world evidence (RWE) in oncology has primarily been used as a tool for value and safety demonstration, with a host of broader applications remaining unaddressed.
RECENT INNOVATIONS ACCELERATING POTENTIAL OF ONCOLOGY RWE The advent of the HITECH act in 2006 dramatically accelerated oncology RWE. Health IT (HIT) changes have opened up access to broad and deep patient-level data assets2 and data management, making it possible to link real-world oncology patient-level data3 (Figure 1, overleaf ). This provides a capability to build longitudinal patient journeys to follow populations across different types of cancers. For example, the proliferation of EMRs through oncology practices makes clinically rich data available for linkage to gold-standard databases such as health plan claims, pharmacy and socio-demographics.3 Patient mortality information, when linked to medical and pharmacy claims and clinical attributes in oncology EMRs, provides insights on survival patterns of patients diagnosed at different cancer stages. Through access to integrated data, bio-pharma most commonly generates oncology RWE for disease burden, line of therapy, risk stratification and clinical profiling studies. But they are not alone – payers and providers are also using oncology RWE. Payers, for example, are establishing evidence-based oncology treatment pathways aimed at eliminating unnecessary medical interventions and promoting cost-effective treatments.4 Providers, meanwhile, are generating insights such as tracking of hospital treatment trends and patient care evaluation.5 Thus, by linking patient characteristics to treatment options and outcomes, a broad and deep real-world oncology database can enable answers to more complex questions at the product and disease level.
continued on next page 1
Institute of Medicine (IOM). Delivering High Quality Cancer Care: Charting a New Course for a System in Crisis. Washington DC: The National Academies Press, 2013 Health Plan and Medical Claims, Hospital CDM, Specialty pharmacy, oncology registers, tumor banks and socio-demographic information, Electronic Medical Records (EMRs) ASCO and the National Cancer Institute have been spearheading initiatives for oncology practices to implement EMRs to interconnect oncology practices 3 American Society of Clinical Oncology. Shaping the Future of Oncology: Envisioning Cancer Care in 2030. Outcomes of the ASCO Board of Directors Strategic Planning and Visioning Process, 2011-2012 4 NICE provides a useful specialists access to a host of cancer pathway recommendations. http://pathways.nice.org.uk/ 5 Banner Health’s Oncology Hospital, Fairbanks Memorial, maintains a Tumor Registry, under the medical direction of the Cancer Committee, comprising clinical data on all cancer patients seen at FMH 2
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FIGURE 1: UNIQUE POSSIBILITIES IN ONCOLOGY LINKED DATA
MARKET POISED FOR DRAMATIC EXPANSION OF RWE IN ONCOLOGY The increasing availability of RWE in oncology is moving stakeholders towards a data-driven approach in cancer research and commercial engagement. Supply-side On the supply side, several factors will enrich oncology with new real-world data. Aided by IT advances, the collection and sharing of biospecimens will support molecular-based cancer. The move away from a one-size-fits-most approach in oncology will result in oncology RWE initiatives integrating and mining genomic (sequencing), proteomic, clinical, imaging and financial data, thereby expanding interrogation and analytics to include dozens of variables.6 Patient-initiated data is likely to be another new source, with patient-friendly HIT interfaces positioning the patient as an active participant in the RWE exchange. For example, real-time connections with oncologists will allow patients to report their health status, side-effects and other experiences as they happen. Demand-side Even with such supply-side advances, demand for oncology RWE is likely to outpace supply (Figure 2) especially in cases where a deep understanding of the patient is lacking. For example, in blood-borne cancers it is difficult to perform analyses on lines of therapy or pre- versus post-relapse based on therapy sequences, since almost every (lymphoma, myeloma and leukemia) course involves administration of the same product. A very detailed combination of lab results is required to confirm whether patient cohorts are consistent with a particular clinical pathway. Consequently, data mining capabilities are required to tap into the clinical notes (or unstructured data within EMRs) to extract the insights required.7 6 7
http://www.upmc.com/media/NewsReleases/2013 IMS Health HEOR expertise: Vernon Schabert
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FIGURE 2: ONCOLOGY RWE DEMAND AND SUPPLY EVOLUTION
RWE demand is a function of two sources: the first is pull for RWE among stakeholders external to bio-pharma such as national and private payer systems, regulatory agencies and provider systems for decision making; the second is the evolving application and user-set expansion to commercial stakeholders within bio-pharma such as brand managers, market access experts, sales teams, market researchers and forecasters. Externally, RWE application for payers will move beyond monitoring appropriate product usage to meet needs around product pricing and access decisions. For example, payers will increasingly demand that data be used to match patients with specific treatments to improve outcomes in key populations and incentivize pathway prescribing. Payerdeveloped clinical guidelines have the potential of being transformed into living, evolving documents that are not reliant on clinical trials and expert analyses. In Europe, RWE may enable HTA dialogue to identify critical research questions that have not been adequately answered in the past, as well as address study variability due to quickly changing treatment options. Its ability to do so is in providing the types of patient sample sizes and follow-up times required to measure overall survival (OS) rates – HTAs choice of endpoint.8 Beyond payers, hospitals and care delivery settings will also actively participate in RWE exchange. In hospitals and new care delivery settings,9 decision makers such as administrators will ascertain product value by seeking insights from published evidence. Through the aggregation and analysis of data from patient experiences in real time, integrated oncology RWE systems will predict and identify trends and associations between hosts of variables and generate new hypotheses. Physicians and researchers will evaluate those hypotheses and determine which lead to improved care in real-world settings. RWE opportunities for new stakeholder engagement vehicles will also include value-added services such as embedding routinized quality measurement and improvements in oncologist practices and sites of care. continued on next page
8
Overcoming Incomplete Evidence Network and Heterogeneity Issues with Simulated Treatment Comparisons. Workshop at ISPOR 16th Annual European Congress, Dublin, Ireland, 2-6 November, 2013 9 Care process data includes high tech imaging guidelines, radiation therapy “pathways”, chemotherapy regimen compliance
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Internally, within bio-pharma, RWE in oncology has been under the purview of health economics and outcomes researchers and epidemiologists. Now, bio-pharma is expected to drive adoption of RWE capabilities to address a range of commercial applications. Those organizations that understand the breadth and depth of RWE uses (Figure 3) will expand adoption to a commercial audience and embrace new ways to engage with stakeholders on addressing more complex questions. RWE can improve a host of tactics such as physician targeting, detailing, promotional activities, rep visits. However, the real source of value will be in shaping launch strategies and targeted marketing campaigns, and understanding patient pathways and flows for commercial planning. Lessons learned from bio-pharma oncology commercial teams indicate that winners will lever RWE in areas such as key opinion leader and patient advocacy engagement, messaging (life extending versus symptom reducing), compendia diagnostics, and physician and patient segmentation. For example, projecting patient-level data nationally provides a far more granular and clinically-oriented perspective in market sizing and forecasting as compared to traditional methods. Going forward, as bio-pharma seeks deeper levels of oncology evidence, it will be critical for HEOR, epidemiology and commercial functions to collaborate as a collective, given the unique scientific and commercial insights that each area brings. FIGURE 3: TRENDS IN RWE APPLICATION
Note: Not an exhaustive list of oncology RWE applications
The increasing availability of RWE in oncology is moving stakeholders towards a data-driven approach in cancer research and commercial engagement.
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CASE STUDY Scaling RWE to reach main opportunity areas and bio-pharma functions10 Challenge: One company started its RWE journey by creating an integrated evidence platform in response to value and safety demonstration challenges. When the FDA questioned the appropriate use of a $1 bn oncology product, up to $500 mn of revenue was placed at risk due to potential label changes. Approach: The company realized that the FDA was basing its decisions on an incomplete picture of current treatments, with the potential for misperceptions that could affect the entire oncology franchise. Its response was to develop the broadest RWE platform at the time, enabling a variety of insights to inform discussions with a multitude of stakeholders. Impact: With the RWE platform in place, the company successfully defended the FDA challenge, justifying the initial investment. It was also able to counter misleading academic-led publications in high profile forums such as the New England Journal of Medicine. Moreover, it could rebut each one in as little as two weeks. Incremental benefits: Once the company saw the power of RWE insights, it continued to invest in the platform beyond value and safety demonstration. Commercial leaders acquainted with RWE capabilities started to systematically lever detailed patient pathways to understand product use, identify patterns of under-diagnosis and under-treatment and shape highly targeted marketing campaigns. These campaigns nearly doubled brand growth. Over time, RWE became the company’s currency and competitive advantage for engaging health systems, with granular forecasting and disease progression models levered by a series of medical center partners for their own service planning. For the first time in the industry, it effectively developed a closed-loop system to use insights to engage and improve patient pathways. Future outlook: For this company and its multi-year RWE investment, the opportunities continue to expand. For example, it recently added tissue sampling to its data platform to enable step changes across clinical development (eg, improving sample size for biomarkers and phase II development).
THE EXPANDING VALUE OF RWE IN ONCOLOGY – AN INDUSTRY PERSPECTIVE INTERVIEW WITH ALEX LIEDE, PHD Alex Liede is Director, Center for Observational Research at Amgen and heads the company’s industry-leading oncology evidence platform partnership for commercial and research insights. IMS Health has been working with Amgen on this evidence platform for over six years. Alex holds a PhD in Genetic Epidemiology from the University of Toronto and is currently in his 10th year at Amgen. Here he shares his perspective on the evolution and practical application of RWE in oncology and why its full potential has yet to be realized. Q: Why did Amgen build an RWE capability in oncology? AL: We realized that RWE would be a tremendous asset in oncology, especially as we engaged with scientific and regulatory stakeholders. The overall understanding of cancer patients in real-life settings used to be very limited because of isolated datasets, and claims databases did not provide a sufficient level of detail (eg, laboratory values). And we saw how incomplete pictures of that patient experience could lead to poor decisions. We therefore committed to building a better fact base about oncology by increasing not only the amount of real-world data but also data linkable to additional sources to build a more comprehensive picture. Amgen’s oncology evidence platform represents an oncology EMR database that is linkable to several additional data assets within IMS Health in a HIPAA-compliant manner. In 2014, we are building further collaborations with academic institutions and other third-party research partners to develop studies and glean additional insights. continued on next page
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Hughes B, kessler M. Breaking New Ground in RWE Value: How Some Pharmacos are Poised to Realize a $1 Billion Opportunity. IMS Health White Paper, 2014
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Q: How have you seen RWE evolve in oncology? AL: RWE is not a new concept and it has been in place since the early days of epidemiology in medicine. But we now benefit from the near real-time nature of RWE as compared to the past where insights relied on data sources that were not refreshed periodically. Consequently, the evidence generated was potentially outdated and not reflective of current patient care in oncology. Now there is very little lag time associated with the data that is mined, such as data from EMRs. Q: What does this evolution mean in terms of the use of RWE? AL: We have seen a strong ramp-up in the demand for these real-life insights now that the information is available to inform internal decisions as well as external interactions. Externally, RWE is becoming a more consistent baseline to inform decisions. Clinicians and payers are more willing to use it. We work with academic medical centers to jointly shape publications with experts and further validate real-world oncology data. This way, we can jointly develop evidence to address questions that customers and regulators may have after product launch. Internally, the applications are broad. In clinical development, we now better understand the patient experience in the clinical setting from how they are diagnosed to how they are treated. We know more about them, such as the age distribution of certain cancers. After launch, RWE helps us understand more about the patients as well as what happens to them during and after treatment. For us, it means thinking about market share in a more meaningful, patient-centric way. We also better understand persistence on therapy and some of the characteristics of non-persistent patients to help us identify ways to better deliver our value to patients and payers. Q: Can you provide a recent example of how RWE enabled a better outcome for Amgen? AL: We recently used RWE to build the case for orphan drug status for an oncology agent. The agent was being prepared for review with the FDA and we were seeking a new orphan drug indication (hypercalcemia of malignancy or HCM). To do this, we used RWE for understanding how many patients in a specific year experienced HCM. By examining EMR data linked with claims data we were able to estimate the proportion and prevalence for patients who experienced high calcium values after a cancer diagnosis â&#x20AC;&#x201C; we could never have estimated the population size so accurately without access to calcium laboratory data. The FDA granted the agent orphan drug designation for the regulatory filing. This was a big achievement in that we successfully demonstrated to the FDA that the oncology EMR data represents a robust evidence platform, representative of cancer care in the US. Q: Building on the success of linking EMRs and claims, what are some next generation data sources that would be valuable for oncology RWE? AL: There are two areas that come to mind: the first is bringing in biomarker and genetic data. As an example, determining and demonstrating how many patients have a genetic marker associated with improved response to a therapy would provide a viable path to bringing a product to market; the second area is patient-reported outcomes where it would be valuable to capture outcomes such as pain scores. Q: Would you say we are at the beginning of the journey for oncology RWE generation? AL: Yes. We now need a focused RWE approach since there are so many sources emanating oncology data. The full potential would include expansion to social media, consumer databases and non health-related behaviors. Even existing data sources such EMRs are generating new, ever expanding data as new measures are recorded from patient visits such as chemotherapy and follow-up. Much expertise is required to understand the privacy, regulatory and legal aspects.
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2. Understandin g of free text
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Transforming oncology outcomes research through data linkage in Sweden At a time of concentrated pressure on evidence demands in oncology, the Scandinavian region oďŹ&#x20AC;ers unique potential for RWE generation. With a population base of more than 25 million, a history of extensive data collection, and the ability to link data at the patient level, it enables unparalleled insights into the entire cancer treatment journey and outcomes related to the management of the disease.
The author Patrik Sobocki, PHD, MSC is Senior Principal RWE Solutions & HEOR, IMS Health Psobocki@se.imshealth.com
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Transforming oncology outcomes research through data linkage in Sweden A unique real-world lens on the entire patient journey Oncology presents one of the most complex and challenging disease areas for outcomes research, not least due to limited and heterogeneous data, significant gaps across relevant care settings, and lack of robust longitudinal information to allow an understanding over time. Yet, more than ever, it is reliant on RWE, reflecting increased product scrutiny by regulators and payers but also growing use by medical oncologists, a majority of whom have reported considering RWE in their recommendations for treatment.1 At the same time, oncology has one of the richest R&D pipelines, exploring new molecules and therapeutic approaches and extended indications for existing agents across a range of different cancers. These include breast, lung and prostate cancer (PC) as well as less common tumor types such as ovarian, stomach and liver,2 which bring their own challenges for understanding epidemiology and generating RWE. As these trends continue, and science drives further growth in innovative new oncologics, the ability to overcome data limitations and maximize the value of existing resources will be key to ensuring more effective, efficient and insightful outcomes research in support of optimal patient care.
NEW OPPORTUNITIES In the growing global search for credible real-world oncology data, the Scandinavian region is unrivalled in opportunities to generate RWE, reflecting the well-structured public healthcare of Sweden, Norway and Denmark, their long established high-quality EMRs, national and disease-specific registries, and a mature regulatory framework for clinical research. Rich, longitudinal EMR and registry data The combination of EMRs and National Cancer Registries, the oldest of which (Denmark) has been collecting data since 1942, makes Scandinavian data a source of qualitative, patient-level health information on oncology diagnosis and management in a system of high-quality care. Sweden in particular, rated as the most advanced country in implementing value-based healthcare,3 has a 20-year history of quality patient-centric EMR data entry, with 100% coverage providing integrated information on both primary and specialist care. This compares to around 50%-100% coverage in EU (varying by country) and around 50%+ in North America. Uniquely, it enables access to EMR data for more than 5 million lives in the region, including patient information, diagnosis, side-effects, physician visits, lab tests, prescriptions and mortality (Figure 1).
1
87% of oncologists consider â&#x20AC;&#x2DC;real-worldâ&#x20AC;&#x2122; evidence when recommending treatment. 13 April, 2013. Accessed 3 May 2014 at http://social.eyeforpharma.com/marketaccess/oncologists-consider-real-world-evidence-rwe-decision-making Innovation in cancer care and implications for health systems: Global oncology trend report. IMS Institute for Healthcare Informatics, May, 2014 3 Progress toward Value-Based Health Care: Lessons from 12 countries, BCG, June 2012. Available at: http://www.bcg.com/ 2
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FIGURE 1: LONGITUDINAL DATA FROM EMRS IN SCANDINAVIA
Sweden is also a pioneer in building national, quality health registries in various disease areas and now has more than 100, many with a history of over 15 years. Based on a system of mandatory reporting, the Swedish Cancer Registry, established in 1958, records every case of newly diagnosed cancer across the entire population, registering approximately 50,000 malignant cases of cancer each year. Containing patient, medical and follow-up data, it is noted for its high level of completeness.4 In addition, more than 20 robust, tumor-specific registries are also available for research. Covering leading tumor types such as breast, colorectal, lung and prostate, as well as a range of less common cancers (eg, acute lymphoblastic leukemia, chronic myeloid leukemia, multiple myeloma) these include additional complementary health information around the time of diagnosis and during disease progression. All the Nordic national cancer registries achieve almost 100% coverage, from sources that include physicians, hospitals, and patients.5 Increasingly recognized for their value in driving quality improvements in healthcare,6 the use of these disease registries has been linked both to enhanced health outcomes as well as reduced healthcare costs.7 Sweden has been shown to have among the best 5-year survival rates for cancer in Europe among countries studied.8,9 Unique opportunities for database linkage The exceptional potential of patient-level cancer data for RWE generation in Scandinavia lies in the unique opportunity for linking databases at individual patient level, permitted by regulations for research purposes and enabled by the existence of a unique personal identification (Social Security) number in each country (Figure 2, overleaf ). The integration of EMR data and information from national and disease-specific registries enables unparalleled access to real-time, longitudinal population-based data for more than 25 million people, delivering the deepest granularity in oncology seen in a single European market. continued on next page 4
Barlow L, Westergren k, Holmberg L, Talbäck M. The completeness of the Swedish Cancer Register: A sample survey for year 1998. Acta Oncol. 2009; 48(1):27-33. Accessed 4 May, 2014 at: http://www.ncbi.nlm.nih.gov/pubmed/18767000 5 Møller B, Fekjaer H, Hakulinen T, et al. Prediction of cancer incidence in the Nordic countries up to the year 2020. Eur J Cancer Prev, 2002 Jun; 11 Suppl 1:S1-96 6 Fine-Tuning Health Care – improved outcomes and cost efficiency using quality registries. Accessed 4 May, 2014 at: www.government.se/qualityregistries 7 Larsson S, Laywer P, Garellick G, Lindahl B, Lundström M. Use Of 13 Disease Registries In 5 Countries Demonstrates The Potential To Use Outcome Data To Improve Health Care’s Value. Health Affairs, 2012, Jan; 31(1):220-7. Accessed 4 May, 2014 at: http://content.healthaffairs.org/content/early/2011/12/06/hlthaff.2011.0762.full 8 Berrino F, Verdecchia A, Michel Lutz J, et al. Comparative cancer survival information in Europe. European Journal of Cancer, 2009, April; 45(6):901-8 9 De Angelis R, Sant M, Coleman MP, et al. Cancer survival in Europe 1999-2007 by country and age: Results of EUROCARE-5 – a population-based study. The Lancet, 2014, Jan; 15(1):23-34
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Using this data, oncology researchers can build a complete patient pathway with information that includes: Co-morbidities Surgical procedures & other measures Socio-economic variables Metastasis development (or progression of cancer/tumor) Death (and underlying cause) Hospitalizations (length of stay, etc) Medical treatments Family disease history Patient histology Tumor characteristics (TNM, staging information) All laboratory test results Risk factors & performance status
FIGURE 2: OPPORTUNITIES FOR DATABASE LINKAGE
• • • • • • • • • • • •
Robust, comprehensive databases The possibility to extract and integrate high-quality, anonymous patient-level data from EMRs and registries in Scandinavia enables the development of robust, comprehensive tailored databases to meet specific needs in epidemiology, outcomes research and pharmacovigilance. Leveraging a unique software program (Pygargus CXP) for extracting large volumes of data, this involves a detailed process of study design and approval, data collection and mapping, and linkage and management (Figure 3).
FIGURE 3: CUSTOMIZED DATABASE USING CUSTOMIZED EXTRACTION PROGRAM
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Through the linkage of patient characteristics to therapies and outcomes, the Scandinavian dataset offers a powerful platform for developing highly-powered, large-scale epidemiological and outcomes research studies. Databases built from this resource have supported global research with real-world insights addressing a range of questions around comparative effectiveness, pharmacovigilance, epidemiology and clinical outcomes. The following case study provides a practical application of the process and potential in PC.
CASE STUDY Measuring outcomes of prostate cancer patients to define high risk and inform optimal management Background: PC is the second most common cancer diagnosed in men and the sixth leading cause of cancer death in men.10 In Sweden, an observed increase in the incidence of the disease has been attributed to extensive use of serum prostate-specific antigen (PSA) testing, with most new cases diagnosed as non-metastatic. In a percentage of men treated with curative intent the disease will recur, as evidenced by an increase in serum PSA in the absence of metastases. Responses to the current standard of care for recurrence are typically not durable, with nearly all patients ultimately progressing to castration-resistant disease (CRPC). The purpose of this retrospective cohort study was to identify the clinical course of PC in Sweden with a view to characterizing patients at particular risk of CRPC and other metastases, given the significant and growing burden of the disease and the absence of existing documented evidence, especially on the impact of time-varying factors such as PSA values. Approach: The study was based on longitudinal EMR data from eight Swedish outpatient urology clinics (where PC patients are predominantly seen) linked to national registry data in the country, which enabled a study cohort of more than 7,000 patients. Data was extracted and linked using Pygargusâ&#x20AC;&#x2122; unique proprietary Customized eXtraction Program (CXP) on an anonymous basis through the use of a unique study id in place of personal id numbers. The value of EMR was demonstrated in the type of information needed, which was otherwise not available, for this type of study. Specifically, EMRs provided PSA laboratory data, treatment details, as well as information on patient characteristics. The Swedish National Patient Register enabled tracking of patients who transitioned from the urology clinics to hospital-based oncology clinics, and the retrieval of information on metastatic diagnoses, co-morbidities and orchiectomies. Finally, the linkage of EMR data to the National Register of Cause of Death allowed for estimates of overall survival and incidence of death. Benefits: Presented at ICPE 2013 (the International Congress on Pharmacoepidemiology, Montreal, Canada) and with a manuscript accepted for publication in a peer-reviewed medical journal (Cancer Epidemiology), this breakthrough study described the disease progress and key predictors of outcomes. Based on the longitudinal capture of medical and demographic data and patterns of treatment and diagnosis in real-world clinical practice, it enabled the first insights into the clinical course of PC in a focused patient population treated with androgendeprivation therapies. Its unique ability to examine PSA values over time was critical to understanding risk determinants such as PSA doubling time for developing metastases and informing optimal management of the disease.
CONCLUSION The Scandinavian region represents a strong and compelling environment for RWE research in cancer, based on a long history of collecting oncology-specific health information in EMRs and national population-based health registers. By combining population-based anonymous patient-level health information from EMRs with health register data, powerful research programs can be developed to inform research questions that are difficult to answer anywhere else.
10
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: Cancer J Clin, 2011; 61(2):69-90
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Continued innovation in oncology is driving higher-cost, multi-line drug regimes. The emergence of novel products, with multiple indications and significant budget impact, is placing the existing ‘one product, one price’ system under increasing pressure. A bold move towards differential pricing, reflecting the value of a drug in a specific setting, could play a key role in helping payers manage finite resources, while rewarding innovation, broadening access and creating opportunities for improved outcomes.
The authors Ashley Woolmore, D.CLIN.PSYCH is Senior Principal RWE Solutions, IMS Health Awoolmore@imscg.com
Daniel Simpson, M.BIOCHEM is Senior Principal RWE Solutions, IMS Health Dsimpson@imscg.com
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Payment by use Achieving a new value paradigm for oncology Built on years of price tolerance and high willingness to pay for even relatively marginal benefits, in line with national priorities for cancer and public support, the oncology sector has fostered and rewarded some of the most expensive specialty medicines available. In Europe, and signaled elsewhere, there is a perceived need to closely manage patient access and thereby the growing budget impact of new agents. Compounding affordability issues is the emergence of sequential or combination multi-drug regimes. Despite major breakthroughs in targeted therapy, these are seen to offer “the best route – and quite possibly the only way forward – to overcome the enormous problem of genetic complexity and heterogeneity of human cancer.”1 The situation will only intensify as more new treatments target multiple tumor types, leading to higher scrutiny of exactly how a drug is being used. Today, in Europe, 50% of leading oncologics are already licensed for more than one cancer; by 2019, over 80% are anticipated to have multiple indications (Figure 1).
FIGURE 1: IN EUROPE, MORE THAN 80% OF LEADING ONCOLOGICS WILL HAVE MULTIPLE INDICATIONS BY 2019
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OUTCOMES - Issue 1 ACCESSPOINT • VOLUME 4 ISSUE 8
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INSIGHTS | PAYMENT BY USE
GROWING DIVISION BETWEEN PRICE AND VALUE Currently, the architecture for setting prices in the pharmaceutical industry in a given country is product-centric: one price for one product (be that pack or ‘mg per vial’). There is a growing mismatch between offering a single price and the value delivered by increasingly complex oncologics in different usage situations. For example, a product launched initially in one indication may well be priced at a payer-acceptable level given its clinical value or cost-effectiveness for that use. However, when subsequently expanded into another tumor type, where its impact on overall survival could be lower, it may not. Maintaining the price of the first indication will prohibit access for the second; reducing it will diminish the revenue potential proportionate to its established cost-effectiveness or value. Failure to address these issues now will accelerate the move toward measures for managing affordability: draconian pricing restrictions; usage according to prioritized cohorts (sub-populations); consideration of cost-capping; and exploration of options for third-party payments (insurer solutions/co-pays), leaving patients struggling to access drugs that could potentially improve their survival.
LIMITED SUCCESS FROM CURRENT APPROACHES To date, attempts to tackle the rising price demands from pharma for oncology drugs have centered on guidelines and governance of use, including relegating innovative products to later lines of therapy. Usage agreements have typically involved either imposing financial limits on products by patient or volume (unit or revenue), or restricting reimbursement to sub-populations with specific characteristics associated with improved outcomes. Whilst pharma companies have attempted to put in place innovative contracting and pricing schemes to impact the net price paid by payers,2 they have tended to be point solutions from individual manufacturers for individual products. These measures have so far met with limited success – certainly no global or European standard has emerged as a clear solution that meets both the needs of payers and suppliers to healthcare.
PAYMENT BY USE One potential solution would be a move towards a differential pricing system that allows an effective price to be paid as a function of actual product use (eg, line of therapy, combination, tumor type). This permits a closer alignment of the value delivered with price. Payment by Use (PbyU) allows a more logical reflection of value, particularly in the case of high-price products where the conditions of use vary (see panel on page 31). Necessary but not sufficient Price setting in oncology is complex and beyond the scope of this paper. Critically, however, one of the key barriers to achieving a more elegant solution has been a failure to recognize the core capability required to underpin more innovative approaches: a real-time (or rather, regular and consistent) understanding of exactly how oncology products are being used in clinical practice, by line of therapy, tumor type and dosage. Only with both of these building blocks in place is the move towards a new form of performance or outcomes-based scheme realizable (Figure 2). As the necessary (but not sufficient) first step on the journey, PbyU would establish the foundational knowledge base on which to build more adapted pricing schemes. FIGURE 2: BUILDING BLOCKS UNDERPINNING INNOVATIVE CONTRACTING IN ONCOLOGY
+
Payment by use (PbyU) is the foundation for payment by performance (PbP). Accurate patient-level information is a fundamental requirement for both. 1
Pricing strategy (list and net)
2
Accurate patient-level use information
Enables Today 3a
Payment by use
Payment as a function of USE (eg, tumor type, line of therapy, mono/combo)
Incorporate OUTCOME data
Future 3b Payment by performance
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Payment as a function of OUTCOME (eg, survival, PFS, recurrence)
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Challenges Already, there has been some progress towards implementing PbyU by individual actors within the industry; the approach is actively being discussed or even piloted by a number of top ten manufacturers. However, PbyU represents a major change in paradigm. As such, several factors drive the need not for individual company initiatives but for a pan-industry approach: 1. Creating a ‘win-win’ with payers 2. Ensuring perceived fairness for all stakeholders 3. Financing the cost of gathering and managing the data 4. Enabling independent information governance Financial flows and incentives within the healthcare system are complex. Current payment systems are not built to cope with a PbyU type of price management scheme. A plethora of net-pricing mechanisms bring inconsistency between management of products, while comparative value across therapy areas is difficult to distinguish due to different pricing and market access stipulations. For example, in Italy, patients receiving Yondelis (trabectedin) are evaluated after two treatment cycles (six weeks) whereby the treatment cost for non-responders is refunded. Within the Uk, the cost of the drug is covered if used for more than five treatment cycles, limiting the cost to the NHS to £17,500 ($28,000) to £25,000 ($40,000) per patient. An effective PbyU infrastructure would have to be built with the system’s stakeholders, and a pan-industry initiative could represent an acceptable engagement approach. Program system requirements Challenges to establishing PbyU also exist in linking the necessary elements of a coordinated, trusted system. Practically, in the immediate to near term, this involves bringing together four key components: 1. Oncology dataset based on the systematic collection of healthcare and treatment information, ideally at a national level, covering essentially all treated cancer patients. This would likely comprise 40 fields of data for every patient tracked in every country involved in the scheme. 2. Trusted third-party aggregator to de-identify and manage the data in a consistent manner on a secure and reliable system. 3. Clear governance of the information and rules regarding the access rights of different user types (national and local payers; scientific and medical community; suppliers to healthcare) with the appropriate safeguards to ensure patient anonymity. 4. Practical application of the data based on distinct outputs for respective users to support: a. Scientific and medical community: An understanding of clinical processes and outcomes based on real-world practice b. Payers/suppliers: Financial transaction management based on actual use and agreed value Core to the success of PbyU will be the level of trust in the underlying data – recognition by suppliers to healthcare of their role in helping payers better understand their investments and make more informed choices. This will mean establishing systems to assure data accuracy, quality and validity. The most effective way of achieving this is through focused effort and a collaborative approach to creating a PbyU pricing infrastructure in Europe. Realistic ambition Powered by such a unified strategy, the development of a foundational capability linking highly robust clinical data with information on drug consumption (Figure 3, overleaf ) is an achievable goal. The recently implemented SACT (Systemic Anti-Cancer Therapy) database in the Uk3 is a practical example of how a national, comprehensive linked dataset of cancer patients and oncology products can be developed in order to understand real-world management of the condition from a clinical perspective (ie, 4a. above and not conceived for PbyU). Done right, PbyU enables a pricing mechanism and data collection capability that responds to the need for payers to show they have made the best use of scarce financial resources, while ensuring that innovation is rewarded and offering outcomes improvements to patients which would otherwise be unavailable due to poor cost-effectiveness. continued on next page
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INSIGHTS | PAYMENT BY USE
FIGURE 3: A PBYU SYSTEM WILL REQUIRE A DATA SOURCE, TRUSTED THIRD-PARTY AGGREGATOR AND APPROPRIATE GOVERNANCE
Transparently governed, aggregated data will underpin multiple useful outputs
Implications As a fundamental change to the way in which information is used to manage healthcare in partnership between pharma and payers, the establishment of a PbyU system will raise a number of important, practical issues. For the industry as a collaborative group, the ability to execute and deliver on its promise will require answers to some key questions in relation to: Identifying the necessary capabilities and assets, and agreeing which party will be responsible for their development Understanding the notion of risk in terms of the uncertain long-term implications of PbyU versus taking no action Determining the right starting point for the practical implementation of PbyU with regard to product and territory, and planning how to build on that in phases to deliver value over the next 2-5 years At a broader level, there are far reaching implications to address in terms of: incorporating all providers/payers in a market into a single system; determining the steps involved both within and across different countries; running new and old systems in parallel mid-term; and working with payers to demonstrate the accuracy and value. However, PbyU is the lynchpin on the path towards increased integrated industry and healthcare understanding.
• • •
CONCLUSION The assumption of high prices and high rewards in oncology is fast giving way to a world where money is a finite quantity, where budgets are fixed, and where there is growing moral outrage at ever higher prices. A world where achieving product use is based not on price maximization but on ensuring the financial offer for the right product, for the right indication at an economic value that expands drug availability to a broader number of patients. This implies an evolution away from the traditional pricing architecture to a model that is based on the value to the individual cancer patient. PbyU offers a platform for creating a more balanced delivery of value, based on commitment, collaboration and a new model of engagement between industry and payers, leveraging closer links with the healthcare system and a deeper understanding of product use and how patients can derive maximum benefit. Consistent with discussions around access to innovative medicines,4 and supported by a trusted third party, it will enable data on cancer patients and
“The principle of this scheme in essence is value-based pricing; you pay for the value or performance of a drug. A differential pricing strategy would still reward and encourage innovation from a pharmaceutical company Payer, UK perspective, whilst managing budgets.”
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treatment, collated at source and appropriately governed, to serve as a reliable and clinically valid foundation for pricing oncology drugs in a more flexible, evidence-based way. As a core capability that can only be built collectively, it is perhaps not of itself an element of competitive advantage but when integrated with unique products to create a relevant pricing strategy for the market it will serve as the platform for advantage through differentiation. PbyU is bold in its demand for a consortium approach but also in the fact that while the near-term benefits to all parties are clear, the implications downstream are less certain. However, within the context of the current unsustainable dynamics, building such a pan-European infrastructure should be a strategic priority for the healthcare industry of the region. Based on a definitive collection of anonymous patient-level information covering cancer and its treatment, it will serve as the gateway to establishing more sophisticated, outcomes-based pricing in the future. Acknowledgment This article is based on collaborative work. The authors gratefully acknowledge the contributions of Brittany Blackstone, Sarah Gardner and Craig Montgomery at IMS Health.
WHICH PRODUCT TYPES MAY BENEFIT FROM PBYU? PbyU has particular applicability for products with: 1. Differential value by indication/patient: Where the value of the drug is different in each indication, for example in terms of: survival, cure rates, length of course (affecting economic metrics), QALY scores depending on the sub-population. 2. Differential dosing strength or positioning by indication/patient: If the way in which the drug is taken varies between indications then the value may differ, for example, through different dosing (strength, frequency, duration). The drug may be listed as a different line of therapy for different indications, eg, first-line for breast cancer but second-line for lung cancer. 3. Usage in combination: The value of the drug may change depending on which other drugs it is combined with as this can affect outcomes, reflects choices available and will have varying effects on budgets. 4. High risk of off-label or experimental use: PbyU can help to manage this risk. 5. High-cost: These drugs come under the greatest payer scrutiny, have the highest budget impact and require innovative differentiation vs. competitors. Candidates are those where large sums of money are potentially being left on the table. Setting up and managing PbyU will prohibit use in $1-10/day products, at least initially.
1
Tackling cancer’s biggest challenge: Combination treatments offer hope to overcome drug resistance. Professor Workman, Deputy Chief Executive, Institute for Cancer Research. Accessed 9 Apr 2014 at: http://www.icr.ac.uk/press/recent_featured_articles/archive_featured_article/combination_treatments/index.shtm 2 Innovation in cancer care and implications for health systems: Global oncology trend report. IMS Institute for Healthcare Informatics, May, 2014. 3 http://www.ncin.org.uk/collecting_and_using_data/data collection/chemotherapy 4 Improving patient access to innovative medicines. EFPIA, March 2014. Accessed 11 May, 2014 at: http://www.efpia.eu
“Although challenging, this type of arrangement could be achievable. It is similar to web-based registries whereby the therapy reimbursement is linked directly to the registry. This method allows differential pricing, and the ability Payer, Italy to distinguish between indications.”
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INSIGHTS | THERAPY ACCESS IN EU
The breadth of applications for which regulators, payers and physicians use real-world evidence (RWE) in oncology continues to expand in their eďŹ&#x20AC;orts to provide cancer patients with rapid and ongoing access to innovative and life-prolonging therapies.1 Looking ahead, illustrated through examples, it is possible to see how RWE use could evolve in Europe and where opportunities exist for industry to play a more proactive role with these stakeholders without compromising their commercial interests.
The authors Amanda McDonell, MSC is Senior Consultant RWE Solutions & HEOR, IMS Health Amcdonell@uk.imshealth.com
Michael Opel, PHD is Senior Consultant RWE Solutions & HEOR, IMS Health Mopel@imscg.com
Karin Berger, MBA is Principal RWE Solutions & HEOR, IMS Health Kberger@de.imshealth.com
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Future access to innovative oncology drugs in the EU Evolution and proactive application of real-world evidence RWE provides a valuable complement to randomized controlled clinical trial (RCT) data, the gold standard of clinical evidence. RCT data is the only drug-specific evidence available prior to market authorization and hence serves as the primary driver behind initial pricing, reimbursement and market access decisions. This principle applies, with some variation, across countries and indications. For example, in Germany the IQWiG assesses the benefit of a new medication relative to the standard of care; in France the HAS assesses the relative and overall clinical benefit; and in England and Wales NICE distils its clinical assessment into the infamous quality-adjusted life year (QALY). However, stakeholders are also keenly aware that current RCTs do not provide the answers to all of their questions, often capturing surrogate rather than hard patient-relevant endpoints (eg, progression-free survival vs. overall survival).2 While this reflects practical trial design considerations, it leaves payers to base cost-effectiveness decisions on statistically-defined outcomes only.3 Even where trials are designed to measure outcomes, the ethical need for cross-over can make results less compelling.4,5
“We focus on the primary RCT endpoint when assessing novel drugs and will continue to do so.“ National Payer, UK, March 2014 REAL-WORLD EVIDENCE TODAY Evidence generated in the real world, if collected and analyzed correctly, can help to answer these and other stakeholder questions.6 Prior to market authorization, it can help to characterize disease epidemiology, treatment paradigm and associated resource utilization. Post-market authorization it can help assess a drug’s performance outside the artificial RCT setting and describe any shifts in the treatment paradigm. Today, we observe very different levels of RWE usage across these areas. Pre-market authorization, there is some RWE usage, commonly limited by the focus of the national healthcare system: in the Uk, for example, RWE describing the treatment paradigm is used to inform cost-effectiveness calculations. In one recent submission to the Scottish Medicines Consortium (SMC ) for a breast cancer medication, the use of industry-submitted RWE successfully changed the SMC’s perception of the standard of care. In France, while limited in use today at initial pricing and market access decisions, French payers have signaled some interest in using RWE to improve epidemiological assessment. While RWE is used more for post-market than pre-market authorization, payers are recognizing the importance of understanding a disease to enable more informed decisions. Use of drug-specific RWE is already extensive and still growing post launch: pharmacovigilance is a well established application. Given unmet medical need and premium drug pricing, payer interest in RWE has been particularly high in oncology as exemplified by Italy’s complete reliance on innovative agreements in this therapeutic area. In fact, innovative pricing and market access agreements are a growing consumer of RWE insights. continued on next page
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INSIGHTS | THERAPY ACCESS IN EU
FIGURE 1: TIME SAVING FROM USING ORAL RATHER THAN IV VINORELBINE BY STAkEHOLDER (MINUTES)8
Patient
Pharmacist
Nurse
Physician
+85
+35
+30
+2
RWE can also be used by regulators, payers and physicians to help products: in Germany, a real-world study for remifemin (see panel, right) indicated a reduction in breast cancer risk which led to the removal of a black box warning from the label and hence maintained access for patients.7 Across Europe, the oral formulation of vinorelbine was shown to produce substantial time savings (Figure 1).8 Such time savings have led to a marked shift in prescribing practice.9
AN EXPANDING ROLE Going forward, the use of drug-specific RWE in the post-market authorization setting is likely to intensify as countries follow the example of France and reassess drug efficacy on an ongoing basis. These frequent assessments place additional pressure on pharmaceutical companies to develop more evidence. The need for additional evidence to support ongoing access in oncology may be more muted than in other indications, given the ethical requirement for continuing drug availability. However, the complexity of drawing conclusions based on the diseases means that RWE must be developed carefully.
REMIFEMIN CASE EXAMPLE Situation: Standard hormone therapy is contra-indicated for women with a history of breast cancer; safety of the treatment alternative (remifemin) unclear for this patient cohort; black box warning on the label. Data & analysis: Observational retrospective cohort study using IMS Disease Analyzer. Result: No increase in breast cancer risk from remifemin treatment. Benefit: Black box removal and continued access for patients.
RWE is also likely to play a greater role within pharmaceutical companies to direct research efforts towards the areas of highest unmet need and demonstrating drug benefit for specific patient cohorts. RWE can help identify patients with particular characteristics for further research. It can also enable better definition of RCT populations, which in turn will enhance the primary endpoint signal and thus drive access potential. In fact, the future holds great commercial promise for RWE use to support oncologics. The mortality associated with oncologic indications commands rapid adoption post-market authorization. A recent adoption analysis of a breast cancer medication indicated a later use than indicated for 50% of patients (see panel, opposite). As such, real-world data can be used more extensively to monitor and drive adoption.
by leading the way in understanding cancer in real-life settings, the industry can ensure its relevance beyond specific products.
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THERAPY ACCESS IN EU | INSIGHTS
OPPORTUNITIES FOR INDUSTRY TO SUPPORT ACCESS It is clear that regulators and payers are requiring more RWE and that industry must respond to ensure ongoing compliance. However, there are also distinct opportunities for companies to generate RWE proactively to support their commercial interests: 1. Pre-market authorization Use epidemiology- and treatment paradigm-specific RWE to drive R&D • towards areas of highest unmet need • Inform RCT design and drive primary endpoint magnitude 2. Post-market authorization Monitor effectiveness, epidemiology, safety, changes in treatment • patterns and compliance to help all stakeholders ensure that evolving treatment insight is rapidly adopted into standard practice in an equitable manner While there are undoubtedly other opportunities for proactive use of RWE, these will allow pharmaceutical companies to better target research, improve pricing and market access potential, and drive product adoption.
BREAST CANCER TREATMENT PARADIGM CASE EXAMPLE Research question: Do patients receive a novel oncologic in the indicated line of therapy or later? Data: Robust panel of 800 physicians and >590 hospitals, with >57,000 patients/year reported in EU5. Result: Approximately 50% of patients receive the novel medication post the indicated line of therapy. Benefit: Monitoring and ensuring best practice.
RWE brings value in many ways for oncology stakeholders, both in understanding cancer as well as assessing potential treatments. Pharmaceutical companies should be active generators and consumers of RWE to engage effectively with other stakeholders and continue to provide more insights into the disease. By leading the way in understanding cancer in real-life settings, the industry can ensure its relevance beyond specific products.
1
McCabe, C. Market and patient access to new oncology products in Europe: A current, multidisciplinary perspective. Annals of Oncology, 2009; 20:403-412 Booth C, Eisenhauer E. Progression-free survival: Meaningful or simply measurable? Journal of Clinical Oncology, 2012; 30(10):1030-3 3 Fleming T, Rothmann M, Lu H. Issues in using progression-free survival when evaluating oncology products. Journal of Clinical Oncology, 2009; 27(17):2874-80 4 Trotta F, Apolone G, Garattini S, Tafuri G. Stopping a trial early in oncology: For patients or for industry? Annals of Oncology, 2008; 19:1347-53 5 Chabot I, LeLorier J, Blackstein M. The challenge of conducting pharmacoeconomic evaluations in oncology using crossover trials: The example of sunitinib for gastrointestinal stromal tumour. European Journal of Cancer, 2008; 44(7):972-7 6 Garrison L, Neumann P, Erickson P, Marshall D, Mullins C. Using real-world data for coverage and payment decisions: The ISPOR Real-World Data Task Force Report. Value in Health, 2007; 10(5):326-35 7 Zepelin, HH. Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. International Journal of Clinical Pharmacology and Therapeutics, 2007; 45 (3): 143-54 8 James, RD. Improving chemotherapy capacity by switching from intravenous to oral vinorelbine. European Journal of Oncology Pharmacy, 2010; 4(3):14-18 9 Jeynes-Ellis, A. The vision for real world data - Harnessing the opportunity in the Uk. ABPI White Paper, 2011 2
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INSIGHTS | UNDERSTANDING TREATMENT PATTERNS
The impact of new products in a therapeutic setting is highly dependent on prevailing practice and the preference of prescribing physicians. Identifying variance in patterns of treatment can thus aid understanding of potential parallels between markets sharing similar constraints on patient access. A comparison in metastatic castrate-resistant prostate cancer between the Uk and selected Asian markets reveals some important considerations for new therapeutic interventions.
The author Christopher King, MBA is Senior Manager Oncology, RWE Solutions & HEOR, Asia Pacific & China, IMS Health Cjking@sg.imshealth.com
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Understanding treatment in metastatic castrate-resistant prostate cancer Implications of variance between UK and Asia Since 2010, treatment options for patients with metastatic castrate-resistant prostate cancer (mCRPC) in Western Europe have increased with the EMA approval of agents such as Jevtana (cabazitaxel); Zytiga (abiraterone); Xtandi (enzalutamide); Xofigo (radium Ra 223 dichloride); and Provenge (sipuleucel-T). In the Uk, where product access is determined by NICE (England/Wales) and SMC (Scotland) based on demonstrated cost-effectiveness in conjunction with overall quality of life and efficacy, patients have two of the new treatment options available to them: Zytiga and the recently recommended (January, 2014), Xtandi. In Asia, there are similar concerns around ensuring cost-effective treatments for cancer. It is therefore helpful to determine how prescribing patterns for mCRPC have changed since the launch of Zytiga in the Uk, and to compare the current situation with the treatment of mCRPC in the selected Asian markets of korea, China and Japan. This is made possible through the use of anonymous patient-level data available in IMS Oncology Analyzer™ (OA).
COMPARING REAL-WORLD PRACTICE IN MCRPC Method OA is a patient database, collected through a quarterly physician panel survey, which reports information on patient case history related to treatment across all cancer types. For the purposes of this analysis, a comparison was made between the period before Zytiga’s launch (April 2011 to March 2012) and the most recent available data (January to December 2013) in korea, China, Japan and the Uk. Results From April 2011 to March 2012, 126 castrate-resistant prostate cancer patients were collected via OA in the Uk. A significant portion (43%) of these patients received a regimen containing docetaxel. From January 2013 to December 2013, 132 mCRPC patients were collected, of whom 34% were treated with a regimen containing docetaxel. Zytiga usage in 2013 was calculated to be 33% of all mCRPC patients (see Figure 1, page 38). By comparison, from January 2013 to December 2013:
• • •
Korea: OA collected 35 mCRPC patients, 57% of whom were treated with a regimen containing docetaxel. This usage of docetaxel had been consistent for a two-year period. China: OA collected 47 mCRPC patients, 66% of whom were treated with a regimen containing docetaxel. Japan: OA collected 31 mCRPC patients, 23% of whom were treated with a regimen containing docetaxel. Usage of docetaxel in mCRPC patients was found to have declined in the past year, from 42% (sample of 33 patients) during the period January to December 2012. This would appear to indicate that physicians are choosing to re-challenge with additional hormonal agents in favor of administering docetaxel.
continued on next page
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INSIGHTS | UNDERSTANDING TREATMENT PATTERNS
FIGURE 1: PROSTATE CANCER LANDSCAPE IN UK AND SELECTED ASIAN MARKETS
Total Prostrate Cancer Patients UK - 100% (1,053) korea - 100% (348) China - 100% (307) Japan - 100% (624)
Bone mets UK - 0% korea - 0% China - 0% Japan - 0%
Stage I-III UK - 52% (542) korea - 40% (138) China - 45% (132) Japan - 77% (480)
Stage IV UK - 44% (471) korea - 60% (207) China - 65% (175) Japan - 23% (144)
Bone mets UK - 87% korea - 68% China - 85% Japan - 75%
Castrate Resistant UK - 25% (132) korea - 17% (35) China - 28% (47) Japan - 22% (31)
N/S1 Uk - 5% (22) korea - 1% (2) China - 0% (0) Japan - 4% (5)
Unknown1 Uk - 11% (48) korea - 8% (16) China - 15% (27) Japan - 2% (3)
Hormone Sensitive Uk - 59% (269) korea - 74% (154) China - 57% (101) Japan - 73% (105)
UK mCRPC All lines of therapies
korea mCRPC All lines of therapies
China mCRPC All lines of therapies
Japan mCRPC All lines of therapies
TOP REGIMENS Zytiga - 16% Docetaxel/Goserelin - 10% Bicalutamide/Goserelin - 8% Zytiga/Goserelin - 8% Docetaxel - 6%
TOP REGIMENS Docetaxel - 54% Mitoxantrone - 14% Bicalutamide/Triptorelin - 9% Bicalutamide/Leuprorelin - 6% Cyproterone - 6%
TOP REGIMENS Docetaxel - 38% Flutamide - 9% Docetaxel/Flutamide - 4% Flutamide/Leuprorelin - 4% Mitoxantrone - 4%
TOP REGIMENS Goserelin - 10% Estramustine/Leuprorelin - 10% Bicalutamide - 6% Leuprorelin - 6% Docetaxel - 6%
Total Docetaxel 34%
Total Docetaxel 57%
Total Docetaxel 66%
Total Docetaxel 23%
Total Zytiga 33% N = Patients on a L01 and L02 regimen 140 patients are unstaged Source: IMS Oncology Analyzerâ&#x201E;˘, MAT Q4, 2013. Excluding trial patients
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UNDERSTANDING TREATMENT PATTERNS | INSIGHTS
Variable practices revealed Current treatment practices for patients with mCRPC vary by country. Physicians in korea and China have a higher preference for treating with a docetaxel-containing regimen than is the case in Japan, where there appears to be a preference to continue treating patients with hormonal therapies rather than chemotherapy agents. Furthermore, the data suggests that docetaxel-containing regimens are most often used in third-line treatment and later.
DISCUSSION Treatment patterns have changed significantly in the Uk since the availability of Zytiga and they are expected to continue evolving as new therapeutic options become available. Asian physicians would have a similarly positive attitude to new treatment options for mCRPC but currently are unable to prescribe newer therapies due to market access challenges. The way in which physicians in korea, China and Japan choose to treat their mCRPC patients in the future could follow a similar pattern to the Uk but ultimately this will be determined by the regulatory and reimbursement approval of new therapeutic agents. The relative size of mCRPC in the overall cancer population in Asia is fairly small in comparison to Western markets. There is an opportunity for new mCRPC treatments to be designated as orphan drugs due to the relatively small patient populations and clinical superiority to currently available therapeutic options. As orphan drug status influences regulatory and reimbursement decisions, this is a critical element of ensuring patient access to new treatments. As the regulatory authorities in Asia determine the usage parameters for new therapies, consideration of disease dynamics will also play a role. Incidence, prevalence and mortality in mCRPC vary greatly between Western and Asian populations, but also among different Asian populations. It is clear from the OA data that the difference in population distribution between early and metastatic disease can be substantial and this will have significant bearing on patient treatment options. Finding the optimal sequence of therapies will differ according to patient and disease characteristics and availability of treatments. Based on these dynamics, the most common treatment strategies will vary between countries and this should be accounted for in determining product positioning and messaging to physicians. FIGURE 2: STATUS OF EMA AND NICE RECOMMENDATIONS FOR RECENT MCRPC PRODUCTS
Product
EMA Recommendation
Nice Recommendation
Jevtana (cabazitaxel)
January, 2011
None issued
Zytiga (abiraterone)
July, 2011
June, 2012
Xtandi (enzalutamide)
April, 2013
January, 2014
Xofigo (radium 223)
September, 2013
None issued
Provenge (sipuleucel-T)
September, 2013
None issued
The most common treatment strategies will vary between countries and this should be accounted for in determining product positioning and messaging to physicians.
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INSIGHTS | RESEARCH DATA SELECTION IN NSCLC
The ability to link fragmented streams of data is enabling new levels of insight in cancer across the continuum of care. As more is demanded of available data sources, accounting for their respective strengths and limitations is essential to address specific questions eďŹ&#x192;ciently. A recent comparison of two linked datasets in the US for non-small cell lung cancer underscores the importance of this critical step in ensuring the best data selection for particular needs.
The authors Chi-Chang Chen, PHD, M.PHARM is Director RWE Solutions & HEOR, IMS Health Chi.Chen@us.imshealth.com
Shibani Pokras, MPH is Principal RWE Solutions & HEOR, IMS Health Spokras@us.imshealth.com
Rolin Wade, RPH, MS is Principal RWE Solutions & HEOR, IMS Health Rwade@us.imshealth.com
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IMS IMS HEALTH AND EVIDENCE OUTCOMES RESEARCH IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR HEORECONOMICS & REAL-WORLD SOLUTIONS
RESEARCH DATA SELECTION IN NSCLC | INSIGHTS
Research question-driven data selection A comparison of real-world insights in non-small cell lung cancer Lung cancer (LC) is the leading cause of cancer-related mortality globally.1 Often diagnosed at an advanced stage with poor prognosis, in the US alone it is responsible for around 159,000 deaths each year.2 Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all LC. Despite the existence of several large administrative claims and EMR databases in the US, the ability of any one of these individually to answer real-world research questions in NSCLC is limited. Increasingly, such questions require data elements that include histology and staging at diagnosis, longitudinal treatment patterns across multiple sites of care, as well as detailed utilization and cost data. Claims data contains information across various healthcare settings and includes detailed treatment and resource utilization. However, it lacks the clinical data that is critical to analyzing NSCLC populations, such as stage, morphology, laboratory results and performance status. EMRs from oncologist offices, on the other hand, do provide this type of detail but being sourced from a single site of care, such as an oncology practice or clinic, information on hospitalization or surgical care may be unavailable or incomplete. Thus, the fragmented data streams from individual databases have significant limitations in understanding the complete patient journey. One solution to this problem is the creation of a more comprehensive longitudinal patient record by linking data sources to one another at the individual patient level. With this in mind, IMS Health recently explored the generation of a NSCLC comprehensive disease record (CDR) linking the PharMetrics Plus™ health plan claims database to the IMS Oncology EMR database. A comparison of this linked dataset to the US National Cancer Institute SEER data (Surveillance, Epidemiology and End Results) for NSCLC, illustrates the importance of accounting for the strengths and limitations of available data sources to best address the particular needs of any given research question.
THE INDIVIDUAL DATABASES IMS Health linked the IMS PharMetrics Plus™ health plan claims database to the IMS Oncology EMR, as well as mortality data, to create the NSCLC Comprehensive Disease Record. This was compared to the SEER database. Summaries of each database are provided below. IMS PharMetrics Plus™ health plan claims database This longitudinal database comprises adjudicated claims for more than 150 million unique enrollees across the US, representing one of the largest claims databases in the US. Enrollees with both medical and pharmacy coverage represent more than 45 million unique lives annually. The database offers longitudinal information on outpatient diagnoses and procedures, prescription drug use, hospital admissions, patient demographic and payer details, costs and healthcare resource use.
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GLOBOCAN 2012, Estimated cancer incidence, prevalence and mortality worldwide in 2012. Accessed 9 May, 2014 at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. American Cancer Society, Cancer Facts and Figures, 2014. Accessed 9 May, 2014 at: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc042151.pdf
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INSIGHTS | RESEARCH DATA SELECTION IN NSCLC
IMS Oncology EMR With a history from 1997, this dataset encompasses over 500,000 cancer patients across 37 states and 550 treating oncologists. Approximately 60,000 patients are observed every month. Data elements include: cancer staging; TNM values; patient demographics; clinical lab results; injectables and oral medications prescribed or administered, with detailed dosing schedules and drug regimens; vitals; and radiation treatments, including sites radiated, and mortality.3 SEER database An authoritative source of cancer statistics, SEER collects and publishes cancer incidence and survival data in the US from population-based cancer registries covering approximately 28% of the population. Data elements include: patient demographics; primary tumor site; tumor morphology and stage at diagnosis; first course of treatment; and follow-up for vital status.4
DATABASE LINKAGE IMS Health linking technology uses a proprietary algorithm and deterministic matching method, executed through a trusted third-party leveraging a patented HIPAA-compliant de-identification process, to create a patient key. Patients with a matching encryption key in both datasets can be assembled into a third study cohort.
DATA EXTRACTION METHODOLOGY As shown in Figure 1, the NSCLC CDR linked dataset comprised three types of linked datasets based on the following inclusion criteria: 1. Core dataset The approximately 500 patients included in the Core dataset have an NSCLC diagnosis in both PharMetrics Plus health plan claims and oncology EMR. Information from both claims and oncology EMR is included for these patients. FIGURE 1: NSCLC CDR FEASIBILITY COUNTS Approximate patient counts (Jan 2006 â&#x20AC;&#x201C; March 2013)
Offering structure Core: Patients with at least 1 NSCLC diagnosis* in PharMetrics Plus health plan claims with medical and pharmacy coverage AND in oncology EMR Core with PharMetrics Plus: Patients with at least 1 NSCLC diagnosis* in PharMetrics Plus health plan claims with medical and pharmacy coverage PLUS all patients available in Core offering Comprehensive: Patients with at least 1 NSCLC diagnosis* in EITHER PharMetrics Plus health plan claims with medical and pharmacy coverage OR at least 1 NSCLC diagnosis* in EMR PLUS all patients available in Core offering
~500
~156,000
~182,000
* Counts include histologically confirmed NSCLC patients as well as patients proxied through either (1) lack of etoposide use, or (2) with pemetrexed use in history or follow-up
3
Mortality Data from Consumer (Cx) Database: Sourced from social security death index records. IMS Health receives approximately 50% of all deaths on average through linkage to this consumer data. 4 When linked to Medicare data, SEER can provide insight into healthcare resource use for patients covered by Medicare, and prescription treatment details for the subset that has Medicare Part D coverage. This linked data typically has a two-year time lag.
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RESEARCH DATA SELECTION IN NSCLC | INSIGHTS
2. Core with PharMetrics Plus dataset This includes approximately 156,000 patients with an NSCLC diagnosis available in PharMetrics Plus health plan claims and all their claims level detail. It also includes information from oncology EMR for the subset of approximately 500 patients who have an NSCLC diagnosis in oncology EMR and who are also diagnosed with NSCLC in PharMetrics Plus. 3. Comprehensive dataset This includes approximately 156,000 patients with an NSCLC diagnosis in PharMetrics Plus health plan claims and approximately 26,000 patients with an NSCLC diagnosis in oncology EMR. It also contains a subset of approximately 500 patients with an NSCLC diagnosis in both datasets. Available claims and EMR data for each of these populations varies by whether the patient is identified in PharMetrics Plus, oncology EMR, or both. In total, the comprehensive dataset provides information on approximately 182,000 NSCLC patients. The SEER NSCLC cohort contains pathology-confirmed NSCLC patients from 2006-2010 (152,000+ patients). As shown in Table 1, the respective databases differ, both in their source data as well as the collection methodology, and consequently have their own particular strengths and limitations. TABLE 1: COMPARISON OF NSCLC DATABASE ATTRIBUTES Attributes NSCLC Sample size
Core dataset
~500
Core with PharMetrics Plus
Comprehensive
SEER*
~156,000
~182,000
~152,000
Strengths
1. Comprehensive longitudinal claims and clinical data for all patients, beyond Medicare-eligible 2. Only 3-4 months data lag compared to 2+ years for SEER 3. Additional treatment details, such as clinical lab results and co-morbidities prior to diagnosis, enable expanded determination of risk profile 4. Allows segmentation by payer and product type 5. Availability of patient out-of-pocket payments
In addition to 1-5 strengths of Core and Core with PharMetrics Plus 1. Capable of building cohorts representative of both under and over 65 year population 2. Offers flexibility in cohort building /selection depending on research questions 3. Maximum longitudinal sample with clinical details
1. Generalizable to US population 2. Linked to NDI /Social security administration for mortality data 3. Complete race /ethnicity data
Limitations
1. Smaller sample size 2. May be underpowered for some research questions
1. Sample with stage/morphology data not as complete as SEER 2. Staging for blood cancers generally not available 3. Not a registry â&#x20AC;&#x201C; data fields are not always populated for all patients
1. No claims data for complete view of outpatient /inpatient /pharmacy utilization 2. Long data lag: 2+ years
1. Aged 65 and over NSCLC population under represented 2. Majority of patients do not have stage /morphology data
*Age at diagnosis for SEER is 20 and higher; Years used 2006 to 2010. ICD O codes used for SEER NSCLC include bronchioloalveolar (82503); large cell carcinoma (80123); adenosquamous carcinoma (85603); non-small cell carcinoma (80463)
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INSIGHTS | RESEARCH DATA SELECTION IN NSCLC
DATABASE ANALYSIS A breakdown of patient characteristics among the respective datasets is summarized in Table 2. It can be seen that gender distribution was broadly similar across all datasets, with an even split between male and female patients in the IMS Health datasets, and a slightly higher proportion of males than females in the SEER sample (56% vs. 44%). However, notable differences can be observed between the respective populations in relation to age at diagnosis and the stage of disease at diagnosis. TABLE 2: DATABASE PATIENT CHARACTERISTICS Core 2006-2013
Core with PharMetrics Plus 2006-2013
Comprehensive 2006-2013
SEER* 2006-2010
NSCLC sample size
~500
~156,000
~182,000
~152,000
Stage at diagnosis Stage IV/Metastatic Stage I to III or unknown
47% 53%
31% 69%
30% 70%
21% 79%
Age Group 18-34 years 35-44 years 45-54 years 55-64 years 65+ years
0% 2% 21% 53% 25%
1% 3% 15% 35% 45%
1% 3% 15% 34% 48%
0% 2% 10% 24% 64%
Gender Female Male
50% 50%
49% 51%
49% 51%
44% 56%
*Age at diagnosis for SEER is 20 years and over
Age at diagnosis Among the approximately 500 linked patients in the IMS Health Core dataset, 25% were aged 65 years and over at diagnosis compared to 64% in the SEER population (Table 1, Figure 2). In the two additional IMS Health datasets â&#x20AC;&#x201C; Core with PharMetrics Plus and Comprehensive â&#x20AC;&#x201C; the proportion of patients aged 65 years and over at diagnosis was higher than in the linked dataset (45% and 48%, respectively). The IMS Health datasets represent a younger population compared to the SEER sample, reflecting the source of data being a commercially-insured population. Stage at diagnosis Among the approximately 500 linked patients in the IMS Health Core dataset, 47% of patients were Stage IV/metastatic at diagnosis compared to 21% in the SEER population (Table 1, Figure 3). The two IMS Health datasets, Core with PharMetrics Plus and Comprehensive, have a more representative population of patients who were metastatic at diagnosis (31% and 30%, respectively) but have a larger portion of unknown stage.
CHOOSING THE RIGHT DATA OPTION The respective characteristics of the linked dataset and the SEER population reveal disparities that should be taken into account when choosing data to answer specific research questions. While the Core dataset is the smallest among the four comparison data options, it offers the most comprehensive data for all patients; the Core with PharMetrics Plus dataset provides the addition of longitudinal claims data for a much larger sample of NSCLC patients; the Comprehensive adds all NSCLC patients from the OEMR database; finally, the SEER NSCLC sample is nationally representative in terms of age and geography for patients with pathology-confirmed NSCLC and offers the most complete mortality status data.
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FIGURE 3: STAGE AT DIAGNOSIS
FIGURE 2: AGE GROUP AT DIAGNOSIS
100%
100% 90%
90%
25%
80%
80%
48%
45%
70%
53% 64%
69%
35%
40%
34%
30%
30%
24% 20%
20%
0%
79%
50%
53%
40%
10%
70%
60%
60% 50%
70%
15%
21%
15%
31% 10%
10% 0%
2%
3%
3%
2%
Core
Core with PharMetrics Plus
Comprehensive
SEER
18-34 years
35-44 years
45-54 years
55-64 years
47%
65+ years
30% 21%
Core
Core with PharMetrics Plus
Stage I to III or unknown
SEER
Comprehensive
Stage IV/Metastatic
Based on their respective profiles, Table 3 illustrates how the most robust and appropriate dataset may be chosen depending on the nature of the research enquiry. TABLE 3: SAMPLE OF RESEARCH QUESTIONS BY DATASET Core
Core with PharMetrics Plus
Comprehensive
SEER
Questions requiring a comprehensive examination of clinical, treatment and economic outcomes based on specific tumor characteristics and Research questions are adequately answered utilizing a small patient population A medical chart review is being considered to answer the research question
Questions requiring a comprehensive examination of clinical, treatment and economic outcomes based on specific tumor characteristics and What are the treatment patterns/healthcare resource utilization in the broad population? What are the differences in overall healthcare costs among patients being treated by treatment line? How do various patient co-morbidities and patient history affect treatment selection and outcomes? What types of supportive care, diagnostic testing and surgery are provided to patients with NSCLC? What are the utilization patterns of new treatment modalities to the market and in what types of patients and by line of therapy?
All questions for Core with PharMetrics Plus and How are clinical lab-confirmed treatment toxicities (eg, anemia, neutropenia) related to treatment exposure and patient characteristics? What is the distribution of first-line therapy based on tumor stage at diagnosis? How is performance status associated with hospitalization?
What are the trends in NSCLC over time such as incidence, prevalence and survival statistics? What is the breakdown by stage/morphology and by race/ethnicity at diagnosis? What is the impact of stage at diagnosis and morphology subtype on overall survival? What is the overall survival from the initiation of each line of therapy?
CONCLUSIONS Technology is now employed providing the ability to link diverse databases to one another and develop a longitudinal, clinically rich view of an NSCLC population. Comparisons between the IMS Health linked datasets and the SEER population highlight potential differences which should be considered when selecting data for specific research needs. Each database has its own unique set of strengths and limitations, and selection of the database should consider critical factors such as the target populations and specific study questions of interest to ensure the optimal choice for the purpose.
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INSIGHTS | TARGETED THERAPIES IN EMERGING MARkETS
Significant growth in the oncology sector as a leading area of healthcare expenditure reflects in part the rising contribution to sales of the emerging Asia Pacific markets. With their role set to expand even further, these countries are ripe with potential but also present significant challenges for pricing and market access. Innovative models and collaborative initiatives that are able to address aďŹ&#x20AC;ordability issues will be key to unlocking opportunities for high-value oncologics in the region.
The authors Amkidit Afable, MBA is Principal IMS Consulting Group, Asia Pacific, IMS Health Aafable@imscg.com
Joe Caputo, BSC is Regional Principal RWE Solutions & HEOR, Asia Pacific, IMS Health Jcaputo@sg.imshealth.com
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TARGETED THERAPIES IN EMERGING MARkETS | INSIGHTS
High-value oncology targeted therapies Opportunities and challenges in emerging Asia Pacific markets The global pharmaceutical market is set to increase to circa $1.2 trillion in the next few years, with pharmerging markets1 expected to contribute double-digit growth during the same period. This outlook is being driven by several therapeutic classes that provide attractive growth potential, including oncology, respiratory and diabetes. The Asia Pacific region is fast becoming a major contributor to global oncology sales. A recent report on innovation in cancer care by the IMS Institute for Healthcare Informatics confirms that pharmerging markets have made cancer their fourth largest healthcare spend area and are poised for further growth.2 Some are already ahead of the curve; in China, for instance, oncology now represents the second largest therapeutic class. These high growth rates (Figure 1) can be attributed to:
• • •
Greater numbers of people diagnosed with cancer, driving necessary demand for more advanced and affordable oncology products in the first instance Increasing income and patient affordability, resulting in rising spend on expensive oncology treatment Expanded coverage of oncology products under public health insurance schemes, eg, korea and Taiwan have extended coverage to include certain targeted cancer therapies such as Iressa (gefitinib)
FIGURE 1: SALES AND GROWTH OF TOP THERAPY AREAS IN ASIA-PACIFIC REGION
Source: IMS Health MIDAS, 2013; Top therapy areas comprise 80% of the Asia-Pacific market; MAT Q3/2008–MAT Q3/2013.
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Pharmerging countries are defined as those with >$1Bn absolute spending growth over 2013-17 and which have GDP per capita of less than $25,000 at purchasing power parity (PPP). Tier 1: China; Tier 2: Brazil, India, Russia; Tier 3: Mexico, Turkey, Venezuela, Poland, Argentina, Saudi Arabia, Indonesia, Colombia, Thailand, Ukraine, South Africa, Egypt, Romania, Algeria, Vietnam, Pakistan and Nigeria. 2 IMS Institute for Healthcare Informatics. Innovation in cancer care and implications for health systems: Global oncology trend report, May 2014
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INSIGHTS | TARGETED THERAPIES IN EMERGING MARkETS
CHALLENGES WITHIN GROWING MARKETS Although at face value there is a significant opportunity provided by the growth of emerging markets, pharma continues to face challenges, and multinational companies (MNCs) have lost ground both to local manufacturers and generic competition in terms of market share. Pricing, access and regulatory challenges continue to be pain points; pricing and market access is seen as the number one issue facing the industry in the next 3-5 years according to a survey of senior MNC executives. Specific challenges include affordability-constrained populations with limited access and low awareness:
• • • •
Around 3.8 bn people live in Asia, the vast majority on very low income levels (Figure 2) High out-of-pocket (OOP) spend on medicines (often >50%) Healthcare spend as a % of GDP (around 2% to 6%) lags developed-world averages Significant gap in healthcare delivery (eg, physicians per capita below half of OECD average)
FIGURE 2: POPULATION DISTRIBUTION ACROSS INCOME GROUPS IN REPRESENTATIVE EMERGING ASIAN COUNTRIES
Source: Based on data from: key indicators for Asia and the Pacific 2010. Asian Development Bank, August, 2010; p17
MULTINATIONAL RESPONSES MNCs are increasingly acknowledging the challenges of the emerging countries. Many are looking to innovate as an alternative to implementing traditional R&D pricing models in markets that cannot generally afford the price of global innovation. To address affordability barriers and expand access for oncology products in emerging Asia, evidence suggests that pharma has so far focused on applying discrete affordability-based levers, including:
•
Direct price cuts/simple discounts (blanket discount on price list) Sanofi price cuts in India. Despite the rarity of price cuts in India, Sanofi established a substantial presence within the vinca alkaloid (L1C) class of oncology drugs after reducing the price of both 20mg and 80mg Taxotere (docetaxel) by 60% in the country. Its share of volume increased significantly as a consequence across both dosage strengths.
•
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Roche discounts for Herceptin (trastuzumab) and Avastin (bevacizumab) in Thailand. With both of these • breast cancer products unreimbursed and patient affordability low, discounting helped Roche gain ground on non-targeted therapies such as Eloxatine (oxaliplatin) in terms of value share. After cutting the price of Avastin by 15% and Herceptin by 40% in 2007 the company achieved value growth of more than 25% annually, reflecting increased demand and affordability.
•
•
Volume-based patient discounts for each additional cycle or course Roche volume discounts for Tarceva (erlotinib) in Indonesia. With Tarceva unreimbursed for non-small cell lung cancer and patient affordability low, Roche offered patients volume-based discounts for the drug. As part of the scheme the company covered cycles 3 & 6 out of the total 6 cycles required for treatment, thereby increasing the likelihood of patients completing their course. This had the impact of reducing OOP costs and increasing loyalty to the brand.
•
Patient income-based discount (income-based tiered pricing) Patient access programs fall into this category where certain low-income segments of the population are given access to healthcare via partnerships and co-funding arrangements between pharma, government and the patients themselves. In China, for instance, Bayer’s Nexavar (sorafenib) is made available free to patients for their lifetime after they have purchased 3 months’ treatment.
•
Generally, such levers appear to have expanded the market and enabled MNCs to gain a competitive edge, resulting in overall value growth. In particular, MNCs have succeeded in expanding access to a broader population base by simply cutting prices to meet relatively lower affordability and income per capita levels in the developing world.
WAY FORWARD Pricing and access plays in oncology in Asia are ripe for innovation and change. One such example is in China, where Roche has created significant buzz by partnering with Swiss Re (see panel below). The government in particular has recently been encouraging a shift towards more pharma-private insurance partnerships to unlock access to high-cost treatments.
INNOVATIVE APPROACHES TO PRICING AND MARKET ACCESS Roche/Swiss Re partnership in China Background. In 2010, with a large percentage of its portfolio dedicated to high-cost oncology products and facing continued affordability issues in China, Roche partnered with global reinsurance company Swiss Re to accelerate access to innovative oncologics in the country. Key features. In a marked shift away from traditional patient access schemes, the partnership focused on supplementing basic government health insurance through provision of private insurance cover to China’s middle class. This included treatments for cancer which were mostly paid for OOP. Benefits. With 6 million enrollees by 2012 and substantial growth anticipated, this groundbreaking, market-shaping approach, supported by a novel funding mechanism, significantly expanded access to the country’s rising middle class with government backing for increased participation of private insurance in healthcare coverage. Source: Roche to boost cancer drug sales in China with Swiss Re health insurance partnership. IHS Global Insight. Accessed 9 May, 2014 at: http://www.ihs.com/zh/cn/products/global-insight/industry-economic-report.aspx?ID=1065973425
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INSIGHTS | TARGETED THERAPIES IN EMERGING MARkETS
Although such non-traditional partnerships are still in their infancy, a number of shifts could potentially occur as emerging Asia and the oncology space become an even more important battleground. These are expected to include:
• • • • •
Top-down, company-driven initiatives. Move towards more portfolio or company-wide driven brand-specific initiatives (eg, access, affordability or tiered pricing implementation across the entire portfolio) Innovative partnerships and funding mechanisms. Establishment of creative financing (eg, micro-financing schemes; partnerships with banks and other financial institutions; collective procurement; social media driven sponsorships, etc) and/or expanding partnerships and funding to non-traditional sources (eg, high net worth individuals; company CSRs; pseudo-government organizations; international NGOs; gaming and lottery corporations, etc). Broader stakeholder engagement through emerging channels. Expansion of stakeholder engagement to take into consideration an increasingly complex network of influencers (eg, patients, advocacy groups, NGOs, technology companies) as well as emerging channels of influence (eg, social media, tech apps, etc). Linkage and leverage of new sources of RWE and new technologies. This includes the ability to mine social media and will support more informed R&D, commercial strategies and outcomes (eg, use of RWE in reimbursement decisions in korea and Thailand; Merck, UCB and Novartis partnering with PatientsLikeMe, a patient organization, to gather patient views on psoriasis, epilepsy and organ transplant respectively to better inform outcomes, etc). Patient-centric business models. Shift from product to service and value-based offerings which provide a more holistic and personalized solution to patients, encompassing the whole patient journey as well as the pharmaceutical value chain in totality (eg, personalized medicine: individualized and customized approach to disease management; integration of patient needs throughout the value chain, etc).
KEY TAKEAWAYS MNCs increasingly have to adopt innovative pricing and access models to compete in high-value therapeutic classes, such as oncology. Reliance on the traditional R&D cost-based pricing model is no longer an option, particularly in emerging markets where affordability is a key issue. Whilst the inflection point for innovative pricing and access solutions may be more of a medium- to long-term game for most MNCs, there is nevertheless a willingness to support innovative access initiatives that include private funding mechanisms and collaborative partnerships. By taking calculated risks and positioning themselves as early movers, MNCs can potentially reap greater rewards over their peers and bridge the gap to expanded patient access to healthcare.
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IMS IMS HEALTH AND EVIDENCE OUTCOMES RESEARCH IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR HEORECONOMICS & REAL-WORLD SOLUTIONS
DRUG UTILIZATION | INSIGHTS
Drug utilization in oncology Real-world evidence has delivered great insights in oncology but many important research questions remain unanswered. As improvements in data capture, reach and access bring larger patient numbers and depth across settings of care, attention should focus on underserved areas of understanding in cancer, such as co-morbidities and thrombosis, to ensure optimal drug utilization and improved outcomes.
The authors Birgit Ehlken, MSC is Director RWE Solutions & HEOR, IMS Health Behlken@de.imshealth.com
Jacco Keja, PHD is Senior Principal RWE Solutions & HEOR, IMS Health Jkeja@nl.imshealth.com
Joel Kallich, PHD is Principal, Big Health Data Jkallich@bighealthdata.net
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INSIGHTS | DRUG UTILIZATION
Drug utilization in oncology Current topics and challenges Rising healthcare costs, particularly in cancer, together with continued concerns about safety, efficacy and quality have generated a call for more and better real-world evidence (RWE). The appropriate collection and interpretation of real-world data (RWD) is central to oncology research, treatment and coverage/reimbursement decisions. All stakeholders need to understand the vast amount of evidence being generated but, more importantly, be able to translate that evidence into decisions and processes that can benefit cancer care. Appropriate use of both drugs and information can lead to enhanced outcomes for patients, reduced healthcare costs, and increased value to all stakeholders.
CURRENT STATUS RWD sources vary in their richness, quality and timeliness, and hence in their value for pharmacovigilance. In recognition of the need for improvements, regulators have been developing tools to speed up the collection of data at the point of care, thereby enabling earlier detection of safety issues. The US Sentinel initiative is one example of a system designed to enable higher quality and faster information on a product’s use and adverse event profile in real-world (and sometimes real-time) clinical practice, and to use this knowledge more effectively. Epidemiological evaluations using population- or census-based approaches can help test hypotheses and define evolving safety problems quickly. However, this requires specially trained staff and significant resources. In addition, improved tools are required to aggregate health information electronically and then leverage other technology to access and analyze this quickly and reliably. Although the wider adoption of EMRs and other health information systems will help to harness these types of opportunities, more resources are needed for making more effective, frequent use of the practical clinical data culled from real-world settings.
UNMET RESEARCH NEEDS IN ONCOLOGY The ability to gain a deeper understanding of drug utilization is highly relevant in oncology, especially given that a broad range of new treatment options are emerging. An area where there is a particular requirement for more and better information is the way in which co-morbidities and other patient characteristics influence diagnosis, treatment and outcome. Impact of patient characteristics, including co-morbidities Survival patterns of cancer patients with co-morbid disease are well studied but often with compounded co-morbidity indexes. Cohort studies which dissect the interaction between disease and cancer are rare. A recent publication on a large cohort using data from medical and administrative registries found this interaction to be substantial in breast cancer, affecting mortality (Figure 1, overleaf ).1 Understanding this interaction and improved treatment of the co-morbid diseases and breast cancer should delay death caused by this interaction.
1
Ording AG, Garne JP, Nyström PM, Frøslev T, Sørensen HT, Lash TL. Comorbid diseases interact with breast cancer to affect mortality in the first year after diagnosis – a Danish nationwide matched cohort study. PLoS One, 2013; 8(10):e76013
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DRUG UTILIZATION | INSIGHTS
FIGURE 1: MORTALITY RATES PER 1,000 PERSON-YEARS FOR 0–1 YEAR OF FOLLOW-UP BY CHARLSON CO-MORBIDITY INDEX (CCI) SCORES AND INDIVIDUAL DISEASES IN THIS CO-MORBIDITY INDEX. 0-1 year of follow-up CCI score 1 CCI score 2-3 CCI score ≥ 4 Myocardial infarction Congestive heart failure Peripheral vascular disease Cerebrovascular disease Dementia Chronic pulmonary disease Connective tissue disease Ulcer disease Mild liver disease Diabetes I and II Hemiplegia Moderate to severe renal disease Diabetes with end organ damage Any tumor Leukemia Lymphoma Moderate to severe liver disease Metastatic solid tumor AIDS -80
20
120
220
320
420
520
Rate per 1000 person-years Baseline
Co-morbidity
Breast cancer
Interaction contrast
Source: Ording AG, Garne JP, Nyström PMW, Frøslev T, et al. (2013) Comorbid Diseases Interact with Breast Cancer to Affect Mortality in the First Year after Diagnosis – A Danish Nationwide Matched Cohort Study. PLoS ONE 8(10): e76013. doi:10.1371/journal.pone.0076013 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076013
•
•
Treatment patterns: Substantial co-morbid conditions also impact cancer treatment patterns. A retrospective cohort analysis of elderly chronic lymphocytic leukemia (CLL) patients, using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, found that ~60% of advanced stage CLL patients are not receiving treatment, possibly due to older age and/or a higher co-morbidity burden.2 Additional and better data on clinical and patient decision making is needed to determine the reasons for this finding. Similarly, understanding the interaction between disease progression and the side-effects of treatment and the way this impacts subsequent decision making, requires better and more complete data across the patient journey through the healthcare system. Long-term follow up: Recent studies have found that childhood cancer survivors are at-risk for many late effects of both treatments and the disease, potentially requiring additional therapies to improve their quality of life and outcomes. The results from a provincial health insurance registry and the Childhood Cancer Survivor Study indicate that survivors of childhood, adolescent and young adult cancer have an increased likelihood of using all categories of antidepressants compared to their peers. This may indirectly reflect increased underlying prevalence of mental health conditions among these individuals.3,4 H
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Satram-Hoang S, Reyes C, Hoang kQ, Faiyaz Momin F, Skettino S. The Unmet Need in Chronic Lymphocytic Leukemia: Impact of Comorbidity Burden on Treatment Patterns and Outcomes in Elderly Patients. Journal of Cancer Therapy, 2013; 4:1321-1329 3 Deyell RJ, Lorenzi M, Ma S, Rassekh SR, Collet JP, Spinelli JJ, McBride ML. Antidepressant use among survivors of childhood, adolescent and young adult cancer: A report of the Childhood, Adolescent and Young Adult Cancer Survivor (CAYACS) Research Program. Pediatr Blood Cancer, 2013; 60(5):816-22 4 Brinkman TM, Ullrich NJ, Zhang N, Green DM, Zeltzer Lk, Lommel kM, Brouwers P, Srivastava Dk, Jain N, Robison LL, krull kR. Prevalence and predictors of prescription psychoactive medication use in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. J Cancer Surviv, 2013; 7(1):104-14
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INSIGHTS | DRUG UTILIZATION
The findings of this study underscore the need for further research on the psychopharmacologic treatment of survivors of childhood cancer. Characterization of medication utilization, including indication for use, dose and polypharmacy, are important considerations for future studies. Understanding predictors of psychoactive medication use among this patient population has the potential to inform screening and intervention practices affecting many childhood cancer survivors. Research results from RWD of cancer patients with co-morbid conditions have triggered the development of clinical guidelines – steps towards the rapid learning healthcare system for oncology that the Institute of Medicine envisioned in 2009. These have included the release of guidance by ASCO in 2012 on appropriate chemotherapy dosing for obese cancer patients; real-world studies have demonstrated that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight, possibly affecting treatment effectiveness for these patients.5 Thrombosis The use of RWE in the past few years has enhanced understanding of cancer-associated thrombosis, a major cause of morbidity and mortality in cancer patients. By utilizing retrospective data, researchers have found high rates of clinical events; the most contemporary reports document rates as “unacceptably high”. With the increasing cancer prevalence and age of the population, enhanced detection of incidental thrombosis, and the greater thrombogenicity of multi-agent chemotherapeutic regimens, a steady increase in the incidence of cancer-associated thrombosis during the past two decades has been observed.6 In particular, cisplatin-based regimens are associated with a wide range of thromboembolic complications. A database analysis found that about 18% of patients receiving cisplatin-based chemotherapy experience a thromboembotic event.7 Venous manifestations of cancer-associated thrombosis include deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as visceral or splanchnic vein thrombosis, together described as venous thromboembolism (VTE). Cancer-associated thrombosis affects patient lives significantly. The consequences of VTE include: the need for longterm anticoagulation; a 12% annual risk of bleeding complications; up to 21% annual risk of recurrent events (even with anticoagulation); delay or discontinuation of chemotherapy; consumption of healthcare resources; and a potential impact on patient quality of life. Most importantly, thrombotic events are the second leading cause of death in cancer patients (after cancer itself ) and are associated with worsened short-term and long-term survival. The safety and efficacy of anticoagulant therapy prior to, during and post anticancer treatments has not been well studied. The use of EMRs in this respect has the potential to provide much information for clinicians. Further, the impact of co-morbidities, other demographic and clinical characteristics of patients, as well as other oral or intravenous medications, can be quickly and efficiently investigated by researchers with access to large numbers of these records.
DATABASE CHALLENGES IN ONCOLOGY Databases methods offer fast and efficient access to data. Approaches to linking datasets are now underway, further extending their application. These differ in the US and Europe but both lead to valuable sources and major initiatives are underway to open up data. However, datasets must be of high quality and sufficient size when dealing with oncology, especially given the lower incidence numbers and the need to create different cohorts of patients with different co-morbidities. US In the US, the usual claims data, promising volumes and particularly good access, falls short in this case due to lack of clinical detail. EMR data, which often has the clinical detail, does not have sufficient absolute numbers and is not linked across different treatment settings – making it challenging to capture real-world outcomes or track utilization patterns.
5
Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, Morrison VA, Pini TM, Runowicz CD, Rosner GL, Shayne M, Sparreboom A, Sucheston LE, Lyman GH; American Society of Clinical Oncology. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol, 2012; 30(13):1553-61 6 Lee AYY, Peterson EA. Treatment of cancer-associated thrombosis. Blood, 2013; 122:2310-2317 7 Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: A large retrospective analysis. J Clin Oncol, 2011; 29(25):3466–3473
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IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
DRUG UTILIZATION | INSIGHTS
Solutions therefore need to be built by creating integrated data platforms comprising comprehensive data acquisition, integration, warehousing and analytics to explore treatment patterns, drug utilization and clinical outcomes in the realworld setting – without compromising patient confidentiality. This has been accomplished successfully in the US through the creation of data pools from oncology practices and linking these to EMRs in other healthcare settings, as well as other databases such as healthcare claims. Europe In Europe, some of the strongest data for oncology exists in the Nordics with the possibility to link multiple different datasets including well-established public registries. This is often a public/private collaboration executed by third parties such as Pygargus (now part of IMS Health). More fundamental approaches are undertaken pan-European with strong support by the EU. One such example is the EurocanPlatform, an EC-funded project with 28 European cancer institutions and organizations working together in a unique collaboration. The centers share infrastructures and collaborate on projects to help advance cancer research and treatment.8 EurocanPlatform is building the necessary resources and know-how to improve cancer care from bench to bedside: basic research; early and late translational research; clinical research; epidemiological research; implementation in care; and population-based outcomes research.8 One further notable area of activity is the development of biobanks with comprehensive clinical data – a key advancement given the growth of personalized medicine and genomics in cancer. Issues around safety in oncology mainly concern appropriate and off-label use of (combinations of ) drugs in relation to the disease stage and subtypes of cancer. The recent Good Pharmacovigilance Practice (GVP)9 established a clear regulatory framework for drug safety monitoring and calls for the assessment of the effectiveness of risk minimization measures (RMMs). This should include the evaluation of their implementation and outcome. Drug utilization studies provide simple metrics for monitoring of appropriate drug use and thus the implementation of RMMs.
CONCLUSION This is an exciting time in oncologic care with RWD increasing in frequency, duration, detail, capture rate and linkage across disparate healthcare settings and administrative sources. As stakeholders come to better understand and leverage the data through the development of more flexible tools, its application across underserved areas of oncology outcomes research, such as co-morbidities and thrombosis, paves the way for real-world analyses that will help improve quality, safety and outcomes for cancer patients worldwide.
8 9
http://eurocanplatform.eu/ European Medicines Agency. Good pharmacovigilance practices, 2013. http://www.ema.europa.eu/
ACCESSPOINT • VOLUME 4 ISSUE 8
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PROJECT FOCUS | HEMATOLOGICAL CANCERS
Demonstrating cost-effectiveness and budget impact in hematological cancers in Colombia and Mexico Robust health economic evidence, specific to the local setting, is increasingly key to market access decision making in the Latin American region
Healthcare authorities across Latin America are generating new and growing demands for health economics and outcomes research to support the efficient allocation of resources and broader access to new technologies. Owing to the diversity in patient populations, local health practices and payer systems, economic models that are directly tailored to individual countries are vital to understand the total cost-effectiveness and budget impact of new therapies on the current market. In Latin America, different payers have different perspectives and needs: national formularies are typically focused on costeffectiveness analysis and adaptations while stakeholders at the local level are primarily concerned with the immediate financial implications of treatment through budget impact analyses. With more Latin American countries adopting a formal process for health technology assessment, the need for robust real-world evidence and health economic data has never been greater. For one bio-pharmaceutical manufacturer looking to launch in the region, the ability to demonstrate product cost-effectiveness within the context of the country setting was pivotal to market access decision making and local payer negotiations.
IDENTIFYING LONG-TERM VALUE
The authors Beth Wehler, MPH is Consultant RWE Solutions & HEOR, IMS Health Bwehler@us.imshealth.com David Bertwistle, PHD is Senior Consultant RWE Solutions & HEOR, IMS Health Dbertwistle@uk.imshealth.com Julie Munakata, MS is Principal RWE Solutions & HEOR, IMS Health Jmunakata@us.imshealth.com
PAGE 56
The company had recently attained the rights to a treatment for first-line chronic lymphocytic leukemia (CLL) and indolent nonHodgkinâ&#x20AC;&#x2122;s lymphoma (iNHL) in patients who had failed rituximab or a rituximab-containing regimen. The product was already approved in the US, and they now wished to launch it in Latin America. CLL is the most common adult leukemia in Western nations and patients with stage B or C disease have a life expectancy of between 2-7 years. Approximately 25-30% of NHL cases are indolent, characterized by slow growth and with survival of around 10 years. While CLL and iNHL may not represent a large patient population in the Latin American region, the extensive use of healthcare resources over the course of the disease can put a large strain on healthcare systems. To benefit patients, treatments for CLL and iNHL need to demonstrate improvements in overall survival (OS), progressionfree survival (PFS) and high complete response rates. Currently available treatments in Latin America are not shown to confer substantial clinical benefits in either condition. The product in question showed significant gains in OS and PFS, with a higher
IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
HEMATOLOGICAL CANCERS | PROJECT FOCUS
complete response rate, versus its immediate comparator in both CLL and iNHL. Longer PFS and higher response rates were expected to translate into quality of life gains, resulting in a favorable incremental cost-effectiveness ratio (ICER). The company was keen to demonstrate the clinical benefits of the product alongside the economic implications of its use in CLL and iNHL in Latin America, particularly in terms of long-term cost and patient outcomes. This information would be vital for reimbursement submissions in the region. However, differences in the healthcare systems of the two focus countries required extensive knowledge of system requirements. In IMS Health they found a partner with a coordinated, global team of experts who had extensive health economic modeling experience. This allowed them to adapt a CLL and iNHL model in two different countries, supported by a strong network of IMS Health affiliates with specialized local expertise.
DEVELOPING LOCAL MODELS The goal of the models was to show the productâ&#x20AC;&#x2122;s costeffectiveness in first-line CLL and iNHL in patients previously treated with rituximab or a rituximabcontaining regimen in Colombia and Mexico. The core model was developed for Colombia for each indication and was then adapted to Mexico. Leveraging recently reported clinical trial data and a recently published CLL meta-analysis, IMS Health designed partitioned survival models to capture the clinical effects, costs and quality of life outcomes for patients with CLL and iNHL. The models for both indications considered three health states: progressionfree, progressive disease, and death. Country-specific information included discount rates, willingness-to-pay, type and frequency of resource use and unit costs. Unit cost data for each country was collected by the local IMS Health affiliate in each market, with micro-costing allowing for reasonable cost estimates for health states and adverse events.
FIGURE 1: SURVIVAL OUTPUTS FROM THE COHORT MODEL WARNING: W AR NING: Con Con and and Ben B en arms arms should should be be set set to to the the same same parametric parametric model model when when using using the the KM/Single K M/ Single Parametric Parametric model model option option
1 .0 1.0
SSURVIVAL URV IV AL MODEL M ODEL OPTIONS OPTIONS 0 .9 0.9
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ACCESSPOINT â&#x20AC;˘ VOLUME 4 ISSUE 8
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PROJECT FOCUS | HEMATOLOGICAL CANCERS
Interviews with key opinion leaders were conducted in Colombia and Mexico for each indication in order to elicit information about local practice for type and frequency of resource use. Interviews were conducted in the local language. Outcomes were measured over a 25-year time horizon for CLL and a 35-year time horizon for iNHL, corresponding to lifetime horizons for each indication. key outcomes included ICERs for cost per life year (LY), per qualityadjusted life year (QALY) and per progression-free life year (PFLY). Extensive sensitivity analyses were conducted on all key parameters of the models. Additional model validation was conducted to test model assumptions using cross-validation by leveraging two different software programs (Excel and TreeAge Pro). A budget impact model was included for each model.
SIGNIFICANT BENEFITS REVEALED The IMS Health analyses showed that despite the higher drug acquisition cost the new product offered good value for money for both indications in both countries. The quality of life benefit due to better response rates and longer PFS with the new product contributed to favorable ICERs below the willingness-to-pay in each country. Sensitivity analyses showed that the models were most sensitive to estimates for OS and PFS, comparator drug prices and treatment duration (Figure 1, page 57).
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The cross-validation exercise indicated that the assumptions made with the Excel model produced more conservative, but still favorable, results versus the alternative implementation method of the TreeAge Pro platform. The most influential variables (in terms of the cost-effectiveness results) remained similar between the two implementation methods.
PRACTICAL TOOL FOR DECISION MAKING Through its work with IMS Health, the company gained a deep understanding of the value of its new product in the context of Latin America, based on robust health economic models, cross-validated for increased rigor and confidence in the results. These models are vital to inform market access decision making and serve as a field tool for their Latin American counterparts. They are currently being used in negotiations with different payers in Latin American countries and seven model-related conference abstracts have been presented at international conferences, enabling the broad dissemination of the study findings. The importance of collecting country-specific information for adaptations was demonstrated in this project by the substantially different results produced by the Mexican and Colombian models for CLL. The sensitivity analysis results from the models indicate that local resource use and cost inputs are critical to understanding the economic impact of a new product in these two countries.
IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
CHRONIC LYMPHOCYTIC LEUkEMIA | PROJECT FOCUS
Enabling understanding of co-morbidity burden in chronic lymphocytic leukemia Disease-specific scales, developed with a standardized methodology, can enhance clinical practice with a true appreciation of real-world patient experience
In the controlled setting of a clinical trial, the use of specific eligibility criteria, while essential for a study’s internal validity, can leave certain patient groups under-represented in research and development activities. This is especially true in oncology, where the particular strictness of inclusion criteria means that “only the very fittest cancer patients are enrolled.” 1 In these cases, tools that can aid understanding of real-world patient experience have a valid role to play in promoting improved disease management.
CHRONIC LYMPHOCYTIC LEUKEMIA Most cases of chronic lymphocytic leukemia (CLL) are diagnosed in patients aged over 50 years, increasing the likelihood of associated co-morbid conditions. Potentially life threatening when combined with the leukemia and its aggressive treatment, these can not only decrease quality of life but also life expectancy. Despite this, clinical trials in CLL have excluded patients with co-morbidities given the high risk of chemotherapy toxicity. Thus, the majority of CLL patients are poorly represented in this setting and hence not considered for new drug development. Traditionally, the burden of co-morbidities has been measured by the Cumulative Index Illness Rating Scale (CIRS)2, the kaplan-Feinstein index (kFI)3 and the Charlson Co-morbidity Index (CCI)4. Although widely used to assess the presence and frequency of co-morbidities in oncologic patients5,6 and patients with hematologic disorders7,8, they are unspecific for CLL and other oncologic diseases. A specific scale to assess the burden of co-morbidities in CLL would be more efficient, enabling focus on characteristics specific to this patient population.
The authors Montse Pedros, MD is Senior Consultant RWE Solutions & HEOR, IMS Health Montse.Pedros@es.imshealth.com Núria Perulero, BSC is Director RWE Solutions & HEOR, IMS Health Nperulero@es.imshealth.com Núria Lara, MD, MSC is Senior Principal RWE Solutions & HEOR, IMS Health Nlara@es.imshealth.com
ACCESSPOINT • VOLUME 4 ISSUE 8
DEVELOPING A DISEASE-SPECIFIC SCALE Against this background, IMS Health set out to develop a disease-specific scale to assess the burden of co-morbidities in patients with cancer and, more particularly, in patients with CLL. This was not intended for use as a decision tool but as a tool to measure the impact of the co-morbidities, considering not only their number but also their severity, to help treating physicians to understand their significance for a given patient.
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PROJECT FOCUS | CHRONIC LYMPHOCYTIC LEUkEMIA FIGURE 1: APPROACH TO DEVELOPING A NEW CO-MORBIDITY SCALE FOR CLL
1
Phase I Literature review
To identify existing scales used in studies with patients with the given cancer
To discuss the literature review To set the content of the draft scale To agree on a format for the draft scale
Phase II 2 Meeting with experts
3
Phase III Pilot study
To assess the feasibility of the draft scale to be used in patients with the given cancer under real-world conditions
4
Phase IV Qualitative analysis
To analyze the pilot study results To select the items to be included in the scale
5
Phase V Scale validation
To assess the psychometric properties of the scale
Methodology IMS Health proposed a phased approach, as shown in Figure 1 and outlined below. 1. Phase I: Literature review The first phase involved a standardized literature review to identify any pre-existing scales for measuring co-morbidities in CLL. Using the MedLine database and predefined search strategy, this focused on studies published in English or Spanish during the 10 years from 1999 to 2009. All identified articles were reviewed and those assessing co-morbidities selected for further evaluation. Six final papers were analyzed in depth by two independent reviewers and the data of interest abstracted in a standardized form (ie, presence, assessment and/or impact of co-morbidities). 2. Phase II: Securing expert consensus During the second phase, results from the literature review were discussed with an expert panel to determine the content of the scale. Five physicians with recognized expertise in managing CLL were invited to participate in a consensus meeting and agreement was reached on 19 patient characteristics and co-morbidities to be included in the scale. Some of the variables were stratified by tools commonly used in clinical settings where these cancer patients are managed, ie, the ECOG scale was split into five categories (0 to 4); and the WHO Body Mass Index (BMI) calculation was used to measure obesity.
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The relative weight for each category of co-morbidity was defined by its impact on the patient and management of the disease, ranging from 3: very important to 1: less important. The format was also agreed with a focus on ease of use. Elements included: electronic application; pull-down menus for response categories; and summary of the results with score. This process enabled a first draft of the scale in paper which was refined to implement a ‘traffic-light’ alert system for each item, making it easier to identify those with a higher score quickly (Table 1). At the end of this phase, the second draft of the paper scale was available and the corresponding electronic version ready for use. 3. Phase III: Pilot study The third phase involved assessing tool feasibility and usability by physicians treating CLL, in collaboration with the expert panel. Data was included from 10 patients across five participant sites. Physicians were asked to use the tool with data from the clinical chart of two patients, whose identity was not revealed, noting any problems and/or suggestions regarding the format and/or content of the scale, as well as the electronic application. This pilot confirmed the scale’s feasibility but also highlighted the need for certain changes, allowing development of the definitive version.
IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
CHRONIC LYMPHOCYTIC LEUkEMIA | PROJECT FOCUS 4. Phase IV: Qualitative analysis Next, in order to analyze the pilot study results and select the items to be included in the scale, a meeting was held to share all physician comments and suggestions. These included modifications to the classification of co-morbidities and corresponding scores, as well as to the response categories in some of the items, enabling the higher accuracy of the scale. Following this process, the final version was available for use as an electronic application. Among the parameters included were:
• •
• •
Creatinine clearance Heart disease Symptomatic cardiomyopathy of any cause or affecting ejection fraction Coronary or ischemic heart disease Atrial fibrillation/Arrhythmia Valve disease Hypertension Bronchial disease/COPD Smoking Cancer (past or present) Diabetes Liver disease Hepatitis (B/C)
• • • • • • • • • • •
Obesity (BMI) Mental disorders (in treatment)
Scoring system The electronic tool includes three sections: 1. Vital and functional scale capturing age, ECOG status, degree of dependency (for enhanced understanding only) 2. Co-morbidity scale containing 10 potential co-morbidities pertaining to CLL 3. CLL alerts, including drugs that interact with treatment Each co-morbidity is weighted (from 0-2) depending on its relevance or impact on therapeutic decisions. Response options are also weighted, with the absence of the co-morbidity scoring 0 points, a mild/moderate
TABLE 1: EXAMPLE OF THE CONTENT AND ASSESSMENT PARAMETERS OF THE CLL CO-MORBIDITY SCALE AFTER FIRST CONSENSUS MEETING Co-morbidity
Assessment parameters
Weighting factor
Kidney failure
60-89 – Mild 30-59 – Moderate 15-29 – Advanced <15 – On dialysis or with kidney failure
+2
Hypertension
Controlled Controlled but with damage to target organs Uncontrolled
+1
Bronchial disease/COPD
None Mild Moderate Severe, requiring oxygen
Smoking
Non-smoker 1-5 cigarettes/day 6-20 cigarettes/day >20 cigarettes/day
+1
≤25 normal weight 26-≤30 overweight 30-<35 obese ≥35 morbid obesity
0
Obesity (based on calculation of BMI)
+2
co-morbidity scoring 1 point, and a severe co-morbidity, 2 points. The score, automatically calculated by the electronic scale, ranges from 0 to 57 points according to the level of severity.
NEW UNDERSTANDING OF CO-MORBIDITY IMPACT Presented at ISPOR9, the new co-morbidity scale is currently being used in a prospective non-interventional multi-centric study to assess its psychometric properties in terms of internal and external validity in the Spanish version (Phase V, Figure 1). The stepwise approach to its development and validation with real-world patients will ensure and enhance its value within day-to-day clinical practice in CLL. It will help physicians understand the impact of co-morbidities, support their decision making process when managing CLL patients and facilitate appropriate treatment.
1
Chustecka Z. One in 5 Clinical Trials in Adult Cancer Not Completed. 29 Jan 2014. Quoting Matthew Galsky, MD, Associate Professor of Medicine, Icahn School of Medicine, Mount Sinai, New York. Accessed 2 May, 2014 at http://www.medscape.com 2 Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, et al. Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale. Psychiatry Res, 1992; 41:237-248 3 kaplan MH, Feinstein AR. The importance of classifying initial co-morbidity in evaluation the outcome of diabetes mellitus. J Chronic Dis, 1974; 27:387-404 4 Charlson ME, Pompei P, Ales kL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis, 1987; 40:373-383 5 Groome PA, Rohland SL, Siemens DR, Brundage MD, Heaton J, Mackillop WJ. Assessing the impact of comorbid illnesses on death within 10 years in prostate cancer treatment candidates. Cancer, 2011 Sep 1; 117(17):3943-52 6 Castro MA, Dedivitis RA, Ribeiro kC. Comorbidity measurement in patients with laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec, 2007; 69(3):146-52 7 kleber M, Ihorst G, Terhorst M, koch B, Deschler B, Wäsch R, Engelhardt M. Comorbidity as a prognostic variable in multiple myeloma: Comparative evaluation of common comorbidity scores and use of a novel MM-comorbidity score. Blood Cancer J, 2011 Sep; 1(9):e35 8 Timilshina N, Breunis H, Brandwein JM, Minden MD, Gupta V, O'Neill S, et al. Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML? Ann Oncol, 2014 Apr; 25(4):883-8 9 Carbonell F, De La Serna J, Giraldo P, Lopez A, Rios E, Perulero N, Castro-Gomez A. Development of a co-morbidity scale in patients with Chronic Lymphocytic Leukaemia (CoLLeCT). Value in Health, 2010; 13(7):A459
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IMS RWE SOLUTIONS & HEOR | OVERVIEW
Enabling your real-world success IMS Health has a globally unique and powerful RWE approach to understand patient outcomes and support successful market access. It is built off a long history in HEOR, scientific methodologies, anonymous patient-level information and cross-stakeholder collaborations. Our approach is designed to enable your success.
• Largest multi-disciplinary team of RWE and HEOR experts, as well as leading scientists in epidemiology, drug safety and risk management, based in 18 countries worldwide
• Credible scientific voice and deep therapy area knowledge, captured in over 2,500 publications • Market leadership in developing and adapting robust economic models • Most advanced capabilities in RWE management and analysis, leveraging relevant IMS Health proprietary and other key external, third-party patient-level data assets
• Proven expertise in generating and communicating RWE to advance stakeholder engagement at all levels
• Cutting-edge technology to power scientific and commercial insights Leadership and innovation across the RWE and HEOR spectrum
Anonymou Infor s Pat ma ie tio
TM
IMS LifeLink – the largest collection of scientifically validated, anonymous patient-level data assets • Health plan claims • PharMetrics Plus • Longitudinal Rx • Electronic medical records • Hospital disease • Custom data sourcing TM
Services and Engagement Generating scientifically and commercially relevant insights using novel patient-centric metrics
Strategic Support • Corporate, franchise and product RWE strategy development • Evidence plans aligned with commercial priorities • dynamic marketing plans and outcomes-based commercialization • Stakeholder engagement • RWE training/organizational readiness
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Tec hn o A
IMS REAL REAL-WORLD -WORLD E EVIDENCE VIDENCE SOL SOLUTIONS UTIONS & HEOR
abled -En gy ics lo alyt n
l eve L nt n
Anonymous Patient-Level Information
Technology-Enabled Analytics Analytic tools that leverage powerful technologies to deliver scientific and commercial insights efficiently • data integration & linking • Platform development • data warehouse/data marts • User interface & sophisticated analytics library • IMS Evidence 360
a n d S e r v i ce s e nt Engage m
Outcomes Research, Epidemiology & drug Safety
Health Economic Modeling & Market Access
• • • • • • •
• Health economic evaluations • Core models & local adaptations • budget impact • Indirect comparisons • Value dossiers • HTA readiness • Value communication
Evidence generation PRO, QoL studies Late-phase studies Mixed methods database studies, CER drug utilization studies Comparative safety & outcomes studies
Market-Level Engagement • Patient journeys, market landscapes and forecasts • Incentive compensation approaches • Performance management approaches • Targeted media and patient (where allowed) engagement models
IMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
LOCATIONS | IMS RWE SOLUTIONS & HEOR
Global scope, local expertise IMS RWE Solutions & HEOR experts are located in 18 countries worldwide and they have published on projects completed in more than 50 countries on all continents. Your primary contacts Jon Resnick, Vice President and General Manager One IMS drive, Plymouth Meeting, PA 19462, USA • Tel: +1 610 834 0800 • Jresnick@imshealth.com Dr. Michael Nelson, Senior Principal 8280 Willow Oaks, Corporate drive, Suite 775, Fairfax, Virginia 22031, USA • Tel: +1 703 837 5150 • Mnelson@us.imshealth.com Dr. Jacco Keja, Senior Principal 210 Pentonville Road, London N1 9JY, UK • Tel: +31 (0) 631 693 939 • Jkeja@nl.imshealth.com Patrik Sobocki, Senior Principal Sveavägen 155, SE-113 46 Stockholm, Sweden • Tel: +46 (0) 8 508 99 995 • Psobocki@se.imshealth.com
IMS RWE Solutions & HEOR office locations NORTH AMERICA REGIONAL HEADQUARTERS 11 Waterview boulevard Parsippany, NJ 07054 USA Tel: +1 973 316 4000
EUROPE REGIONAL HEADQUARTERS 210 Pentonville Road London N1 9JY United Kingdom Tel: +44 (0) 20 3075 4800
UNITED STATES 8280 Willow Oaks Corporate drive, Suite 775 Fairfax, Virginia 22031 USA Tel: +1 703 837 5150
BELGIUM Medialaan 38 1800 Vilvoorde belgium Tel: +32 2 627 3211
One IMS drive Plymouth Meeting PA 19462 USA Tel: +1 610 834 0800 CANADA 16720 Route Transcanadienne Kirkland, Québec H9H 5M3 Canada Tel: +1 514 428 6000 LATIN AMERICA REGIONAL HEADQUARTERS Insurgentes Sur # 2375 5th Floor, Col. Tizapan México City d.F. - C.P. 01090 México Tel: +52 (55) 5062 5239
FRANCE 29ème Etage Tour Ariane 5-7 Place de la Pyramide 92088 La défense Cedex France Tel: +33 1 41 35 1000 GERMANY Erika-Mann-Str. 5 80636 München Germany Tel: +49 89 457912 6400 ITALY Viale Certosa 2 20155 Milano Italy Tel: +39 02 69 78 6721
SPAIN dr Ferran, 25-27 08034 barcelona Spain Tel: +34 93 749 63 00 SWEDEN Sveavägen 155/Plan9 11346 Stockholm Sweden Tel: +46 8 508 842 00 SWITZERLAND Theaterstr. 4 4051 basle Switzerland Tel: +41 61 204 5071 UNITED KINGDOM 210 Pentonville Road London N1 9JY United Kingdom Tel: +44 (0) 20 3075 4800 ASIA PACIFIC REGIONAL HEADQUARTERS 8 Cross Street #21-01/02/03 Singapore 048424 Tel: +65 6412 7365
AUSTRALIA Level 5, Charter Grove 29-57 Christie Street St Leonards, NSW 2065 Australia Telephone: +61 2 9805 6800 CHINA 7/F Central Tower China Overseas Plaza Jianguomenwai Avenue, Chaoyang district beijing 100001 China Tel: +86 10 8567 4255 SOUTH KOREA 9F Handok building 735 Yeoksam1-dong Kangnam-ku Seoul 135-755 S. Korea Tel: +82 2 3459 7307 TAIWAN 8th Floor No 2, Tun Hwa South Road Section 1 Taipei 10506 Taiwan ROC Tel: +886 2 2721 5337
For further information, email RWEinfo@imshealth.com or visit www.imshealth.com/rwe
ACCESSPOINT • VOLUME 4 ISSUE 8
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IMS RWE SOLUTIONS & HEOR | EXPERTISE
Expertise in depth The IMS Health RWE Solutions & HEOR team brings unrivalled experience and specialist knowledge from industry, consulting, government and academia globally, and includes leading scientists in epidemiology, drug safety and risk management. With proven expertise in all key therapy areas, we have a track record of helping clients meet the growing demands of an increasingly complex pharmaceutical landscape. Our senior team Jean-Marc Aubert, M.ENG, MSC • Jean-Marc Aubert is a Senior Principal, supporting healthcare providers, health authorities and payers. • Jean-Marc has extensive pharmaceutical experience ranging from real-world effectiveness and the regulatory process to sales force, marketing effectiveness and brand performance. His background includes roles as a partner heading business development in the healthcare sector at Jalma, as deputy director at CNAMTS (French National Health Insurance Fund for Salaried Workers) and as Chief of Staff of the State Secretary for Health Insurance. • An expert in the French healthcare system, market access, commercial effectiveness, RWE and HEOR, Jean-Marc holds a Master’s degree in Engineering and a Master of Science degree, both from École Polytechnique, France; a Specialist Postgraduate diploma in Statistics and Economics from École Nationale de la Statistique et de l'Administration Économique (ENSAE); and a Specialist Postgraduate diploma in Economics (dEA) from École des Hautes Études en Sciences Sociales (EHESS), France.
Yumiko Asukai, MSC • Yumi Asukai is a Principal, specializing in the development of economic models across the product lifecycle and the interpretation of model outputs for strategic market access and value demonstration. Her expertise in this field spans from early strategic modeling through to global core cost-utility models. • Yumi’s background includes roles at Fourth Hurdle Consulting and in healthcare and business consulting in San Francisco and Tokyo, where she focused on comparative studies of health policies between Japan and the US complemented by analyses of primary data. Yumi has worked extensively in the cardiovascular, oncology and respiratory disease areas and she is part of a global modeling taskforce for COPd composed of academic and industry members. • Yumi holds a Master's degree in Health Policy, Planning and Financing from the London School of Hygiene & Tropical Medicine and the London School of Economics, and a bachelor's degree in Political Science from Stanford University.
Karin Berger, MBA • Karin berger is a Principal, with a focus on RWE, PROs and cost-effectiveness evaluation analyses at a national and international level. • Formerly Managing director of MERG (Medical Economics Research Group), an independent German organization providing health economics services to the pharmaceutical industry, university hospitals and European Commission, Karin has more than 15 years experience in the health economics arena. She lectures at several universities, has published extensively in peer-reviewed journals, and regularly presents at economic and medical conferences around the world. • Karin graduated as diplom-Kaufmann (German MbA equivalent) from the bayreuth University, Germany, with a special focus on health economics.
Nevzeta Bosnic, BA • Nevzeta bosnic is a Principal, focused on managing projects to meet the broad spectrum of client needs in the Canadian pharmaceutical market. • Formerly director of Economic Consulting at brogan Inc, Nev has led many strategic consulting, policy and data analyses for pharmaceutical clients, government bodies and academic institutions in Canada. She has extensive knowledge of public and private drug plans across the country and in-depth expertise and experience on the drug reimbursement process. • Nev holds a bachelor’s degree in business Economics from the School of Economics and business at the University of Sarajevo, bosnia-Herzegovina.
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EXPERTISE | IMS RWE SOLUTIONS & HEOR Joe Caputo, BSC • Joe Caputo is Regional Principal, Asia Pacific, leveraging more than 20 years experience in the pharmaceutical sector to help clients address the challenges of global reimbursement and market access throughout the drug development program. He has led numerous projects involving payer research, value dossiers, local market access models and HTA submissions. • Joe's background includes industry roles in drug development, sales and marketing, and UK and global health outcomes, as well as consulting in health economics. He has wide-ranging knowledge of the drug development process at both local and international level and a unique understanding of evidence gaps in light of reimbursement and market access requirements. • Joe holds a bachelor's degree in Applied Statistics and Operational Research from Sheffield Hallam University, UK. Adam Collier, MSC • Adam Collier is a Principal, with responsibility for consulting and data related to IMS Health patient-level data assets in the UK. He has 18 years commercial experience in the UK and European healthcare industry. • Adam’s background spans pharmaceuticals, consulting and healthcare provision, allowing an unusually broad view of the challenges inherent across the healthcare arena. He spent nine years at GlaxoSmithKline in roles within customer and trading strategy, commercial analysis and European marketing, and two years at Accenture, where he also completed a secondment to the Medicines & Healthcare Products Regulatory Agency (MHRA) to work on their patient data asset GPRd (now CPRd). Prior to joining IMS Health, he spent several years with a private healthcare provider. • Adam holds a Master’s degree in Chemistry from the University of Oxford.
Neil Corner • Neil Corner is a Leader, RWE Solutions, supporting government, academics and the pharmaceutical industry in understanding and delivering health outcomes data, with a focus on mHealth, integrated patient data and EMRs, including the creation of interactive electronic patient registries. • Neil has 27 years experience in the pharmaceutical industry in the UK, US, EMEA and Canada, 16 of which were spent at Janssen Pharmaceuticals, including the post of Global Commercial Leader. Prior to joining IMS Health, where his roles have included international franchise lead for patient and medical data, Neil led Helix Healthcare, a division of Quintiles. • Neil is the author of several publications on EMR data validation, RWE in the Canadian market and Customer Relationship Management. His research and development activities currently focus on the innovative design and construction of integrated health data ecosystems to create outcomes in the world of big data.
Mitch DeKoven, MHSA • Mitch deKoven is a Principal, leading teams in a variety of projects, including value development plans, retrospective database studies and observational surveys. • Prior to joining IMS Health, Mitch was an Associate director of Reimbursement and Market Access at ValueMedics Research LLC. His previous roles include Manager of Reimbursement Services at United bioSource Corporation’s Center for Pricing & Reimbursement, Consultant with CHPS Consulting, and Program Manager of the Center for Cancer and blood disorders Children’s National Medical Center in Washington, dC, a position he held after completing an administrative fellowship with the Johns Hopkins Health System. • A past president of the board of directors of the Lupus Foundation of America Greater Washington Chapter, Mitch serves on six editorial advisory boards and is a peer reviewer for a number of international healthcare journals. He has also authored several articles. Mitch holds an MHSA from the University of Michigan School of Public Health and a bachelor’s degree in Spanish from Washington University in St. Louis. Frank-Ulrich Fricke, PHD, MSC • dr. Frank-Ulrich Fricke is a Principal at IMS Health and Professor for Health Economics, Georg-Simon-Ohm University of Applied Sciences, Nuremberg in Germany, with a focus on health economic evaluations, market access strategies and health policy. • Formerly a Managing director of Fricke & Pirk GmbH, and previously Head of Health Economics at Novartis Pharmaceuticals, Frank-Ulrich has conducted health economic evaluations across a wide range of therapeutic areas, developing a wealth of experience in pricing, health affairs and health policy. As a co-founder of the NIG 21 association, he has forged strong relationships with health economists, physicians and related researchers working in the German healthcare system. • Frank-Ulrich holds a Phd in Economics from the bayreuth University, and an MbA equivalent from the Christian-AlbrechtsUniversity, Kiel.
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IMS RWE SOLUTIONS & HEOR | EXPERTISE David Grant, MBA • david Grant is a Senior Principal, specializing in reimbursement and market access, environmental analysis, prospective and retrospective data collection and communications for product support. • A co-founder and former director of Fourth Hurdle, david’s experience spans more than 10 years in health economics and outcomes research consulting, and 15 years in the pharmaceutical industry, including roles in clinical research, new product marketing and health economics in the UK and Japan. • david holds an MbA from the London business School and a degree in Microbiology.
Joshua Hiller, MBA • Joshua Hiller is a Senior Principal, supporting the strategic planning and development of IMS Health capabilities for data sourcing, integration, analytics and studies. He is also currently serving as Alliance director in the company’s collaboration with AstraZeneca for the advancement of RWE. • during a career that includes roles in market analytics, government and healthcare consulting in both the US and UK, Joshua has led a wide range of projects for clients in the pharmaceutical and biotech sector as well as industry associations. He has extensive experience in pharmaceutical pricing, contracting, market landscape development, supply management, cross border trade, lifecycle management, competitive defense, generics market drivers and account management, with expertise across US and European markets. • Joshua holds an MbA (beta Gamma Sigma) from Columbia business School, New York, and a bachelor of Science degree in Mathematics from James Madison University, Virginia. Benjamin Hughes, PHD, MBA, MRES, MSC • dr. ben Hughes is a Senior Principal, leading the development of the RWE service offering. He has helped many clients in the pharmaceutical industry to articulate and implement their RWE strategies, through definition of RWE vision, business cases for RWE investments, capability roadmaps, partnerships, brand evidence reviews, HEOR function design, RWE training programs and related clinical IT strategies. • Previously head of the European RWE service line at McKinsey & Co, ben has extensive experience advising healthcare stakeholders on health informatics and RWE-related topics. This includes work on France’s electronic health record strategy, EMR adoption strategy for governments across Europe and Asia, data releases to support the UK’s transparency agenda, and the development of payer health analytics and RWE capabilities across countries in Europe. • A widely published author on health informatics, ben holds a Phd in Medical Informatics from ESAdE barcelona, an MbA from HEC Paris, and Masters’ degrees in Research from ESAdE barcelona and in Physics from University College, London. Kjel A. Johnson, PHARM.D, BCPS, FCCP, FAMCP • dr. Kjel Johnson is a Vice President, focused on developing the company’s oncology data, analytics and informatics business across key geographies. • Kjel was previously Senior Vice President of Strategy and business development at Magellan Pharmacy Services/ICORE Healthcare, developing comprehensive specialty management strategies and services for payers. A co-founder of ICORE, he has significant expertise in outsourcing and turn-around strategies, outcomes measures and cost reduction strategies gained during a career that includes senior roles at deloitte Consulting, UPMC HealthPlan and Coventry Healthcare. • Principle investigator on more than 40 clinical trials, Kjel has authored over 50 papers and founded Managed Care Oncology. He lectures at the University of North Carolina and is a Fellow of the Academy of Managed Care Pharmacists and the American College of Clinical Pharmacy. Kjel holds degrees from the University of Minnesota and he completed a post-doctoral fellowship at St. Paul Ramsey Medical Center, Minnesota. He is board Certified in Pharmacotherapy.
Jacco Keja, PHD • dr. Jacco Keja is a Senior Principal, drawing on deep expertise in global market access, operational and strategic pricing, and health economics and outcomes research. • Jacco’s background includes four years as global head of pricing, reimbursement, health outcomes and market access consulting services at a large clinical research organization and more than 13 years experience in the pharmaceutical industry, including senior-level international and global roles in strategic marketing, pricing and reimbursement and health economics. • Jacco holds a Phd in biology (Neurophysiology) from Vrije Universiteit in Amsterdam, a Master's degree in Medical biology, and an undergraduate degree in biology, both from Utrecht. He is also visiting Professor at the Institute of Health Policy & Management at Erasmus University, Rotterdam.
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EXPERTISE | IMS RWE SOLUTIONS & HEOR Tim Kelly, MSC, BS • Tim Kelly is a Vice President, with responsibility for the company’s RWE data assets and data architecture backbone, and for overseeing platform delivery infrastructure and engagements to ensure at-scale, high-quality data mart deployment. He also leads the client services team supporting data and technology applications. • Tim’s background includes two decades of life-science experience managing large-scale data warehousing, technology, and analytic applications and engagements. He has worked with many clients in the pharmaceutical and biotech sectors, leveraging deep expertise in information management and modeling, commercial operations and analytics, advanced analytics, business intelligence, data warehousing and longitudinal analytics. • Tim holds a Master’s degree in Management Science from Temple University, Philadelphia and a bachelor’s degree in Quantitative business Analysis from Penn State University. Marla Kessler, MBA • Marla Kessler is a Vice President, also heads overall marketing efforts for IMS Health RWE Solutions; and is an active leader of global RWE projects. She helps clients develop commercial strategies for products and portfolios, define evidence plans to support them, and coordinate implementation to ensure successful execution. • Marla has 15 years strategic and business line experience gained through previous leadership roles at McKinsey & Company and Pfizer. during her career at IMS Health she has designed and led RWE boot camps to help clients build capabilities in this area across the broader organization, and also developed thought leadership in RWE. This includes coauthoring a major IMS Health benchmarking study exploring variations in RWE supply and demand across the pharmaceutical industry’s top markets. • Marla holds an MbA from duke University’s Fuqua School of business in durham, North Carolina. Joseph Kim, PHD, MPH • dr. Joe Kim is a Senior Principal, providing scientific direction in the design and analysis of observational studies across a wide range of projects. • A trained epidemiologist and statistician, Joe has over 20 years experience in population-based research in the US and Europe. He was previously Senior director in benefit-Risk Management at Quintiles assisting in the development of pharmacovigilance systems, risk management plans and benefit-risk evaluation reports, and in the design of post-authorization safety studies. Prior to this, worked in epidemiology at Roche and Amgen. • For the last 10 years, Joe has taught pharmacoepidemiology and pharmacovigilance at the London School of Hygiene & Tropical Medicine, and more recently on the MPH program at the French School of Public Health in Paris. He holds a Phd in Epidemiology from the University of Minnesota, and an MPH from the Graduate School of Public Health, San diego. Rob Kotchie, M.CHEM, MSC • Rob Kotchie is a Vice President, with a focus on bringing innovative solutions to clients through strategic alliances, collaborations and the deployment of novel technology. • Previously with ZS Associates, Rob has more than 10 years consulting experience, specializing in the synthesis and application of RWE to facilitate market access, drug uptake and the responsible use of medicines. In his former role as Chief of Staff at IMS Health, he supported all operational and management activities related to execution of the company’s strategy, and played an integral role in its 2013 dividend recapitalizations and initial public offering in 2014. • Rob has particular expertise in the areas of oncology, respiratory, cardiovascular and CNS and has published more than 30 peer-reviewed journal articles and poster presentations. He holds a first class honors degree in Chemistry from the University of Oxford and an MSC in International Health Policy from the London School of Economics. Mark Lamotte, MD • dr. Mark Lamotte is a Senior Principal, responsible for project management and quality assurance within his team, and for leadership of health economic modeling. • A medical doctor specialized in cardiology, Mark spent six years in clinical practice before joining Rhône-Poulenc Rorer as Cardiovascular Medical Advisor and later becoming Project Manager and Scientific director at the belgian research organization, HEdM. He has worked on over 300 cardiovascular, pulmonary, diabetes, urology and oncology projects, incorporating expert interviews, patient record review, modeling and report writing. Many of these projects have resulted in peer-reviewed publications. • Mark holds an Md from the Free University of brussels (Vrije Univeristeit brussel, belgium) and is fluent in dutch, French, English and Spanish. Claude Le Pen, PHD • dr. Claude Le Pen is a member of the strategic committee of IMS Health and Professor of Health Economics at Paris-dauphine University, providing expert economic advisory services to the consulting practice. • A renowned economist, leading academic and respected public commentator, Claude has served as an appointed senior member of several state commissions in the French Ministry of Health and is an expert for a number of parliamentary bodies, bringing a unique perspective and unparalleled insights into the economic evaluation of pharmaceutical technologies at the highest level. • Claude studied business Administration in HEC business School in Paris and holds a Phd in Economics from Panthéon-Sorbonne University.
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IMS RWE SOLUTIONS & HEOR | EXPERTISE Bo Lidman, MSC • bo Lidman is a Principal, with more than 30 years experience in the life sciences industry. • bo’s background spans roles in marketing, sales and business development in both start-up companies and pharmaceutical organizations, including Upjohn Ab and Merck Sharpe & dohme Ab. He served as the General Manager of Profdoc Ab, CPC Ab and Peritide Ab before co-founding the Nordic-based consultancy and research organization, Pygargus Ab, specializing in real-world evidence. He was most recently responsible for developing the company’s IT platform and EMR extraction methodology. • bo holds a Pol. Mag. (Master’s equivalent) and bachelor’s degree in business and Economics from the Institute of Philosophy in Marketing and Economics, Uppsala University, Sweden. Ragnar Linder, MSC • Ragnar Linder is a Principal, with more than 25 years experience in pharmaceutical marketing, sales and business development. • Co-founder of the Nordic-based consultancy and research organization, Pygargus Ab, Ragnar has worked in various senior level industry roles. These include General Manager of Amgen Nordic Ab, director of International Marketing at Aventis/Hoechst Marion Roussel, and Head of Sales & Marketing at Hoechst Pharmaceuticals Ab. He has also served on the board of directors for several CRO and biotech companies. • Ragnar holds a Master of Science degree in Chemical Engineering from the Royal Institute of Technology in Sweden.
Adam Lloyd, M.PHIL, BA • Adam Lloyd is a Senior Principal, with a focus on economic modeling and the global application of economic tools to support the needs of local markets. • A co-founder and former director of Fourth Hurdle, and previously Senior Manager of Global Health Outcomes at GlaxoWellcome, Adam has extensive experience leading economic evaluations of pre-launched and marketed products, developing submissions to NICE and the SMC, decision-analytic and Markov modeling, and in the use of health economics in reimbursement and marketing in continental Europe. • Adam holds a Master's degree in Economics and a bachelor's degree (Hons) in Philosophy, Politics and Economics from the University of Oxford. Charles Makin, MS, MBA, MM, BS • Charles Makin is a Principal, leading value strategy development, economic evaluations and health outcomes research studies and observational research. He has served as principal investigator on numerous US-based and global database analyses, adherence interventions, systematic literature reviews, and PRO research. • Charles has deep insight into best practices in global research and market access. He was previously Global Head of Research design and Proposal development at UnitedHealth Group. He also worked as Research Operations Manager at WellPoint, leading project teams to execute HEOR projects. • A widely published author, Charles holds a Master’s degree in Pharmacy Administration from Purdue University, Indiana, an MbA (summa cum laude) in Marketing Management and a Master’s degree in Management (summa cum laude), both from Goldey beacom College, delaware, and a bachelor’s degree in Pharmacy from the University of Pune, India. Ed Malka, PHD, MPH • dr. Ed Malka is a Principal, with a broad array of expertise in many disease states from basic science to population research. An experienced epidemiologist, biostatistician and chemist, he is skilled in the design and analysis of complex and novel studies to answer questions of CER and RWE studies. • Previously Associate director, Epidemiology and Health Outcomes at PPd, Ed has held various senior research positions at Rutgers University, and served as Associate Scientist at Ortho diagnostic Systems, Inc. and Assistant Professor of Epidemiology and biostatistics at SUNY downstate Medical Center. • Ed has a particular research interest in hypertension and wide ranging methodological expertise, from techniques associated with pharmacoepidemiology to those used in analyzing complex sampling designs with weighted sampling issues. He holds a Phd in Epidemiology (biostatistics specialization) and a Master of Public Health degree, both from the State University of New Jersey-New brunswick at Rutgers, and a bachelor’s degree in Chemistry from Columbia University. Frédérique Maurel, MS, MPH • Frédérique Maurel is a Principal, with a focus on observational research and health economics studies. • A skilled consultant and project manager, Frédérique has extensive experience in the economic evaluation of medical technologies gained in roles at ANdEM, Medicoeconomie, and AREMIS Consultants. • Frédérique holds a Master’s degree in Economics – equivalent to an MS – and completed a post-graduate degree equivalent to an MPH with a specialization in Health Economics at the University of Paris-dauphine (Paris IX) as well as a degree in Industrial Strategies at the Pantheon-Sorbonne University (Paris I).
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EXPERTISE | IMS RWE SOLUTIONS & HEOR Joan McCormick, MBA • Joan McCormick is a Principal, leading a team providing strategic advice to companies with new products coming to market and ongoing consultation on the rules for existing drugs post launch. • Formerly Head of Price Regulation Consulting at brogan Inc, Joan has supported many major pharmaceutical companies with the preparation of pricing submissions to the Patented Medicine Prices Review board (PMPRb), gaining extensive insights into the operation of the Canadian pharmaceutical market. • Joan holds an MbA from the University of Ottawa, Canada and a bachelor’s degree in Life Sciences from Queen’s University in Kingston, Canada. Carl de Moor, PHD • dr. Carl de Moor is a Senior Principal, with 25 years experience in epidemiology, biostatistics and health outcomes research in retrospective and prospective studies, clinical and patient-reported outcomes studies, economic analysis and design of registries. • Previously VP Epidemiology North America at MAPI, Carl has also held roles as Executive director, Epidemiology & Health Outcomes at PPd, and VP Health Outcomes and Pharmacoeconomics at Supportive Oncology Services, Inc. Prior to joining the industry, he was Associate Professor, department of Psychiatry at Harvard Medical School and Associate Professor, department of biostatistics at Md Anderson Cancer Center. • Carl has authored more than 100 peer-reviewed publications, served as co-investigator or co-principal investigator on over 40 NIH funded grants and contracts, performed editorial reviews for 12 industry publications, and served as thesis and dissertation advisor to numerous graduate students. He holds a Phd in biostatistics from the University of Washington with an emphasis on epidemiologic methods, and a bachelor’s degree in biology from San diego State University. Lisa Stockwell Morris, PHD, RPH • dr. Lisa Morris is a Vice President, with global responsibility for LifeLink, the company’s suite of patient-centered insights, and for developing patient-centered information capabilities within the US, EMEA, and Asia Pacific. • Lisa has many years experience in applying market research tools to answer a wide range of business questions, delivering customized solutions using LRx, medical and pharmacy claims data, EMRs and other clinically-rich secondary information sources. Previously Associate director for Health Outcomes Assessment at Wyeth-Ayerst Research, where she incorporated health outcomes and economic information into drug development plans, Lisa has also held roles as a senior manager in the Outcomes Research group at diversified Pharmaceutical Services (dPS) and United Healthcare Corporation (UHC), managing all aspects of customized health services research projects. • A registered pharmacist, Lisa holds a doctorate in Pharmacoeconomics with an emphasis on Marketing from the University of South Carolina, where she also received a bachelor’s degree in Pharmacy. Julie Munakata, MS • Julie Munakata is a Principal, with a focus on global economic modeling, value development planning, and survey data analysis. • An accomplished researcher and author of more than 25 original articles, Julie has extensive experience in managing clinical trials, health economic studies and decision analytic modeling work, gained in senior roles at ValueMedics Research LLC, the VA Health Economics Resource Center and Stanford Center for Primary Care & Outcomes Research, and Wyeth Pharmaceuticals. • Julie holds an a Master's degree in Health Policy and Management from the Harvard School of Public Health and a bachelor’s degree in Psychobiology from the University of California, Los Angeles. Michael Nelson, PHARM.D • dr. Michael Nelson is a Senior Principal, with particular expertise in retrospective database research, prospective observational research, health program evaluation, and cost-effectiveness analysis. • during a career that includes leadership roles in HEOR at PharmaNet, i3 Innovus, SmithKline beecham, and dPS/UnitedHealth Group, Mike has gained extensive experience in health information-based product development, formulary design, drug use evaluation, and disease management program design and implementation. • A thought leader in health economics for more than 20 years, Mike holds a doctorate in Pharmacy and a bachelor of Science degree, both from the University of Minnesota College of Pharmacy. He also served as an adjunct clinical faculty member at the University of Minnesota whilst in clinical pharmacy practice. Stefan Plantör, PHD, MBA, MSC • dr. Stefan Plantör is a Principal, with a focus on AMNOG-related projects, including benefit dossiers, as well as reference price management, health economic evaluations and health policy analyses. • Stefan’s background includes roles as a researcher and five years experience in the pharmaceutical industry. He has also served as a board member of ProGenerika, the German pharmaceutical association. Over the course of his career, Stefan has broadened his expertise to include data analyses and decision analytic modeling, authored a number of publications in international journals and presented his research at major congresses. • Stefan holds a Phd in biology from the University of Tübingen, an MbA in International Marketing from the European business School, Reutlingen and an a Master's degree in Microbiology from the Eberhardt-Karls-University (Tübingen).
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IMS RWE SOLUTIONS & HEOR | EXPERTISE Shibani Pokras, MPH • Shibani Pokras is a Principal, applying her outcomes research skill set in developing and marketing new data products for commercial, academic and government researchers. • An award-winning outcomes researcher, Shibani has worked with clients in the life science industry to design analyses for multiple research databases and convert these into novel interactive payer-ready applications. She has extensive experience in developing product-specific health economic value strategy informed by close interactions with managed care payers, clinicians and scientific research. • Shibani’s background includes roles at ValueMedics Research LLC, and a fellowship award through Novartis Pharmaceuticals and the duke University Center for Clinical and Genetic Economics. Shibani holds an MPH from the Yale School of Public Health and Yale School of Management, and a bachelor of Science degree (Hons) in Life Sciences and biochemistry from St. Xavier’s College in Mumbai, India. Jon Resnick, MBA • Jon Resnick is a Vice President and General Manager, leading the company’s global RWE & HEOR business, including the development of RWE strategy, offerings, collaborations and foundational technologies to meet the RWE needs of healthcare stakeholders. • A former Legislative Research Assistant in Washington dC and member of the Professional Health and Social Security staff for the US Senate Committee on Finance, Jon has 10 years consulting experience at IMS. He was most recently responsible for leading the European management consulting team and global HEOR business teams of 300 colleagues, advising clients on a wide range of strategic, pricing and market access issues. • Jon holds an MbA from the Kellogg School of Management, Northwestern University, with majors in Management and Strategy, Finance, Health Industry Management, and biotechnology. Daniel Simpson, M.BIOCHEM • daniel Simpson is a Senior Principal, with responsibility for diabetes portfolios and involvement in the UK CObIC initiative, focused on moving healthcare commissioning towards patient-based outcome measures. He also takes a leadership position on commercial analytics. • daniel has more than 18 years experience in healthcare and pharmaceutical markets. Over the course of his career he has worked for all the top 10 pharmaceutical companies and healthcare systems in major markets, delivering insights from patient-level data to support improved decision making on resource allocation. He previously worked in the healthcare/pharmaceutical strategy divisions for both Accenture and the Monitor Group. • Published in a series of conference posters and papers, dan holds a Master’s degree in biochemistry from St Anne’s College, University of Oxford. Patrik Sobocki, PHD, MSC • dr. Patrik Sobocki is a Senior Principal, with more than 14 years experience in RWE, HEOR and market access. • Patrik’s background spans academia, consulting and the life-science industry within RWE and HEOR, including international management responsibilities in various senior roles. He was most recently a partner at the Nordic-based consultancy and research organization, Pygargus Ab, where he worked with the company’s unique methodology for generating population-based RWE based on anonymous patient-level data from EMR and health registers. • Patrik has conducted numerous health economics projects, outcomes research and epidemiology studies and published more than 40 articles in international peer-reviewed journals. He holds a Phd in Health Economics from the Karolinska Institutet, a Master’s degree in Economics and business Administration from the Stockholm School of Economics, and an Associate Professorship at the Karolinska Institutet. Núria Lara Surinach, MD, MSC • dr. Núria Lara is a Senior Principal, with a focus on the design and coordination of local and international observational and patient-reported outcomes studies. • A former practicing GP and clinical researcher, Núria’s experience spans roles in outcomes research at the Institute of Public Health in barcelona and in Catalan Health Authorities, and consulting positions within the pharmaceutical and medical device industries focusing on medical regulatory and pricing affairs, pharmacoeconomics and market access strategies. • Núria holds an Md (specializing in Family and Community Medicine in barcelona), and a Master’s degree in Public Health from the London School of Hygiene and Tropical Medicine and London School of Economics. Patrick Svarvar, PHD • dr. Patrick Svarvar is a Principal, with more than 15 years pharmaceutical industry experience in HEOR and related functional areas. • Patrick’s background includes Swedish/Nordic affiliate roles in HEOR and pricing at Pfizer and Schering-Plough as well as global HEOR roles at AstraZeneca, Pfizer and Merck. Most recently, he was Executive director and Franchise Leader, Global Health Outcomes at Merck. Prior to moving into the industry, he worked for a number of years in health economics and health services research at the Swedish Institute for Health Economics (IHE). • Patrick has been involved in a wide range of HEOR study types across multiple therapeutic categories. He is also experienced in market access, health technology assessment, clinical development strategies & processes, strategic pricing & reimbursement, marketing, and payer market research. He holds a Phd in business Administration/Economics from Lund University.
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HEALTH ECONOMICS & OUTCOMES RESEARCH IMSIMS REAL-WORLD EVIDENCE SOLUTIONS & HEOR
EXPERTISE | IMS RWE SOLUTIONS & HEOR Marc Tapies, MBA • Marc Tapies is a Principal, with a focus on market access, health economics and outcomes research. • Prior to his current role at IMS Health, Marc worked within the company’s wholesaler data business in Spain where he was responsible for wholesaler panel management, design and quality control of data production and the development of new offerings based on wholesaler data. As Engagement Manager in the IMS Consulting team in Spain, he led projects in the areas of commercial effectiveness, market analysis and portfolio management in the pharmaceutical industry. Marc previously worked for 5 years in the areas of supply chain management and information technologies. • Marc holds an MbA from IESE business School and a degree in Industrial Engineering from Universitat Politècnica de Catalunya, Spain.
Massoud Toussi, MD, PHD, MSC, MBA • dr. Massoud Toussi is a Principal and Medical director, applying his expertise to assure the quality of outcomes research and pharmacovigilance. He is also the representative of IMS Health in ENCePP. • Previously head of Global Clinical Research Operations at Cegedim, Massoud has also worked with the French High Authority for Health (HAS) and various CROs as Project Lead, Scientific Manager and Operations director. His experience includes drug safety reporting, natural language processing, database linkage and drug utilization studies. • Massoud holds an Md from Mashad University in Iran, a Master's degree in Medical Informatics and Communication Technology from Paris VI, a Phd in Medical Informatics from Paris XIII University, and an executive MbA from a joint program of Universities of Paris-dauphine and Quebec à Montreal. Arnaud Troubat, PHARM.D, MBA, MHEM • dr. Arnaud Troubat is a Principal, with extensive consulting experience and special expertise in the development of registration dossiers and market access strategies across a large number of therapeutic areas. • A pharmacist by training, Arnaud began his career at the French pharmaceutical industry association (LEEM). He then spent a number of years in the pharmaceutical affairs department at ICI, leading regulatory work on registration submissions and reimbursement strategies, before subsequently moving into consulting. Most recently he was director at Carré-Castan Consultants, managing a research team. • Arnaud holds a doctor of Pharmacy degree and an MbA from IAE Paris and a Master’s degree in Health Economics and Management from Paris-dauphine University. Rolin Wade, RPH, MS • Ron Wade is a Principal and a recognized expert in the applications and limitations of using large retrospective datasets and late-phase datasets for health economics and outcomes research. • Prior to joining IMS Health, Ron served as a Healthcare Executive and Principal Investigator with Cerner Research and as a Research director at HealthCore. He also has experience generating evidence to support value messages to managed care, government payers and public health associations, gained in leadership roles within the pharmaceutical industry. • A widely published author with expertise in many therapy areas, Ron lectures at colleges of pharmacy and he has had leadership roles with the American College of Clinical Pharmacy and the Academy of Managed Care Pharmacy. He is a licensed pharmacist and holds a Master's degree in Pharmaceutical Sciences from the University of the Pacific, California and a bachelor of Science degree in Pharmacy. Jovan Willford, MBA • Jovan Willford is a Senior Principal, supporting growth strategy, offering development and commercialization of RWE solutions in the Asia-Pacific region. • Jovan’s background includes more than 10 years strategic advisory experience across payers, providers, life science organizations and technology companies, including several cross-industry collaborations to advance quality and value of care delivery. • Jovan holds an MbA from the Kellogg School of Management, Northwestern University, with majors in Management and Strategy, Managerial Economics and International business, and an undergraduate degree from the University of Notre dame with majors in Marketing and Philosophy. Ashley Woolmore, D.CLIN PSYCH, MBA • dr. Ashley Woolmore is a Senior Principal, with a focus on developing innovative approaches to help clients reinforce differentiation through the integration of real-world data into strategic decision making. He has 20 years experience in the life sciences and healthcare sector. • Ashley leverages a uniquely diverse background in clinical, healthcare system management and life sciences strategy consulting in senior advisory roles to support clients across developed and emerging markets on a wide set of healthcare system issues. His expertise includes strategy development, healthcare analytics, RWE for strategic insight, population health management applications, and differentiated market access approaches. • A thought leader with a particular interest in opportunities arising from convergence between the life sciences industry and broader healthcare system, Ashley holds a doctorate in Clinical Psychology from the University of Oxford, an MbA in Strategy from HEC in Paris, and a bachelor of Science (Hons) degree in Natural Sciences and Psychology.
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IMS REAL-WORLD EVIDENCE SOLUTIONS AND HEALTH ECONOMICS & OUTCOMES RESEARCH is based in 18 countries worldwide with regional headquarters in: THE AMERICAS 8280 Willow Oaks Corporate Drive Suite 775 Fairfax, Virginia 22031 USA Tel: +1 (703) 837 5150
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RWEinfo@imshealth.com www.imshealth.com/rwe
About IMS Health IMS Health is a leading global information and technology services company providing clients in the healthcare industry with comprehensive solutions to measure and improve their performance. By applying sophisticated analytics and proprietary application suites hosted on the IMS One intelligent cloud, the company connects more than 10 petabytes of complex healthcare data on diseases, treatments, costs and outcomes to help its clients run their operations more efficiently. Drawing on information from 100,000 suppliers, and on insights from more than 45 billion healthcare transactions processed annually, IMS Health’s approximately 9,500 employees drive results for healthcare clients globally. Customers include pharmaceutical, consumer health and medical device manufacturers and distributors, providers, payers, government agencies, policymakers, researchers and the financial community. Additional information is available at www.imshealth.com.
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