15 minute read
the aRRival of PeRsonalized healthcaRe is inevitaBle
Article translated by Pamela Lipson
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THE QUESTION IS, ARE WE UP TO THE CHALLENGE?
The developments and discoveries in disciplines such as genomics, proteomics, imagery, Information Technology and Communications (ICT) and community health ensure that we can now expect to reach the goal set by Hippocrates to determine preventive and treatment approaches for the right person at the right time.
For many, personalized healthcare (PHC) represents a revolutionary approach that will fundamentally change the ways in which health, disease and the medical practice are managed.6
Personalized medicine – more specifically, PHC – constitutes a tailored response to the healthcare challenges of the 21st century and especially to chronic disease, which is the leading cause of morbidity and mortality in modern societies and generates the most demands on the healthcare system. PHC fuels the hope of improving individual and community health of individuals and of better controling the rising healthcare costs.
PHC tools more accurately stratify the different sub-types of illnesses, thereby ensuring that only the patients who will benefit from a therapy will be treated. For example, HerceptinTM (TrastuzumabTM) cannot be used to treat all patients suffering from breast cancer because only 20-30 per cent of them can benefit from treatment.7 However, there exists a PHC tool/diagnostic test to identify women whose tumours exhibit the protein HER2, the target of HerceptinTM, and which are therefore able to benefit from the HerceptinTM treatment. This diagnostic test, used in conjunction with the drug Herceptin,TM increases the response rate to close to 80 per cent.8 As a result, the use of PHC enables patients to not only avoid adverse side effects, but also helps optimize the therapeutic use and achieve substantial savings because, depending on the therapeutics, between 20 per cent and 70 per cent of patients fully benefit from the therapies that are implemented.
PHC has the potential to not only better target treatments and lower the proportion of patients who could suffer from side effects, but also helps to adjust the treatment dosage and identify the types of patients most at risk for developing an illness (targeting patients who could benefit from preventive treatment). By stratifying the healthcare services being offered, PHC therefore has the potential to radically change the practice of medicine and transform the role of the individual with respect to his own health and that of the organization of the healthcare system.
Nevertheless, the hope fueled by PHC should not give the impression that a quick change or highly short-term results are on the agenda. Rising to these challenges is more analogous to a marathon than to a sprint, but it’s a marathon in which Québec must enter because the arrival of PHC is inevitable.
The development of PHC involves issues and challenges that Québec cannot avoid: technological, socioeconomic, industrial, as well as those challenges related to research financing, regulatory approval, intellectual property, training of those involved and management of the healthcare system.
Major changes in the health sector and in industries in this sector are in fact necessary
Issues and Challenges to Fully Benefit From the Potential of Personalized Health Care (PHC)
to be able to fully benefit from the potential offered by this approach.
Optimizing a PHC industry business model
The development of PHC can not only be beneficial for individuals’ health and an efficient healthcare system, it can also create economic wealth and fuel research.
The development of PHC is based on a value-creating chain of activities for the organizations that drive it. The creation, marketing and use of PHC solutions stimulate several high value-added sectors (biotechnologies, pharmaceutics, health technologies, research centres, ICT, etc.). Internationally, PHC market growth was buoyed by the combined effects of several factors including the need to optimize the drug development process, the reduced cost of human genome sequencing, the emergence of other high-throughput analysis technologies, preliminary results that demonstrate the effectiveness (and safety) of therapeutic products stemming from PHC solutions, the launch of programs to foster the development of biomarkers/genetic tests by agencies such as the FDA , the high demand for more effective care solutions, and increased investment in the sector.
A very important component of the PHC market is the diagnostic industry. The global market of biomarkers in companion diagnostics (i.e., that accomany a specific therapeutic approach: such as the detection of HER2 and the treatment with HerceptinTM) and inherent therapeutic solutions was valued at $26 billion in 2010 (irrespective of the sales of other diagnostic and followup products and services).4 The market has experienced robust growth over the last five years and will continue to grow at an accelerated pace over the next five years (for example, the growth in the biomarker, companion diagnostics and targeted therapeutic solution market is expected to be close to 15 per cent per year). PHC is not only a scientific reality; it is also an economic one. More than 50 biomarkers and companion diagnostic tests are already available on the market while an even greater number are still undergoing preclinical or clinical testing or awaiting validation.
The profitability of this industry sector is certainly not optimal according to many and is greatly limited by the complexity of the marketing development process. For example, in Québec, following approval by Health Canada, the decision to implement the majority of PHC diagnostic tests is currently under the responsibility of healthcare institutions’ budgets. This decision-making process, which is complex for manufacturers, also potentially hinders the general availability of tests in the different regions of the province and, as a result, the healthcare services offered are not harmonized. Also, the approval process by federal regulatory authorities has not evolved at the same pace as the development of PHC. The process will therefore need to be modernized to align the requirements for approval of the new genomic diagnostic or companion diagnostic test with those for approval of a new drug intended to improve the profitability prospects of marketing PHC tools.9
Research investment opportunities to seize
PHC is still in its early stages. The realization of current and future potential in PHC requires significant continued efforts in terms of research, new approaches and new collaborations. These new investigative developments are vital to the pursuit of desired innovation. Growth of the PHC tools market thereby represents a growth opportunity for research investments in Québec.
Currently, in many regions of the world, significant efforts are being invested to enhance PHC research and ensure it remains in line with user needs. Clinical validation with large cohorts is a prerequisite to the application of PHC. The means to assemble large stratified groups of patients and access to data, samples and patients constitute obstacles to the clinical validation of biomarkers and companion diagnostics. Québec already has an enviable reputation across North America and internationally in many areas of research, particularly in PHC-associated fields. The public research network has developed an effective infrastructure and can advantageously position itself so as to attract the analytical and clinical validation studies of PHC tools.
From this perspective, to stand out, we need to offer extensive clinical databases quality tissue banks. Aside from CARTaGENE1, Québec wealth is dispersed throughout several databanks and pathology-specialized biobanks. To promote this asset, we need to harmonize practices with respect to the collection and conservation of samples, based on recognized international standards.
Additionally, public databanks could prove to be a major competitive advantage for Québec, with its unique healthcare sys-
tem. Our public healthcare system should enable us to review problems related to healthcare and to the way in which healthcare is organized. However, in some cases, access to data is highly restrictive. Mechanisms (methods) designed to improve access and make better use of these databases are required to be able to fully capitalize on this Québec asset.
The clinical utility of PHC: demonstration and validation issues
Though recent developments in PHC have been significant, most PHC tools are still at the preclinical validation or proof of concept (analytical or clinical) stage. Many specialists nevertheless agree that the real challenge resides more in the implementation of PHC in healthcare systems than in the advancement of scientific knowledge.
Efforts must first be deployed to transform the existing knowledge into available products to treat patients. PHC’s tangible benefits on healthcare and healthcare systems must still be demonstrated, especially their measured cost-benefit ratio. A product’s clinical utility measures its impact on the healthcare professional’s clinical decision and on the improvement of an individual’s health. The impact of the implementation of PHC on healthcare costs and the efficiency of healthcare must also be clearly demonstrated.
To achieve this, we have to develop a more systematic vision of healthcare institutions. Considering the features of its healthcare system, Québec is well positioned to demonstrate the systemic effects of introducing PHC into a healthcare system. It’s a major undertaking but also an opportunity for international distinction. All the states understand the potential PHC represents but few among them know how to effectively implement it in their healthcare systems.
Digital infrastructures and connectivity
The technological limitations of dataprocessing platforms and the performance of ICT tools are also slowing down the development and implementation of PHC. Stratification of the patient cohorts requires a highly effective digital platform; our existing infrastructures need to evolve.
The development and deployment of PHC in Québec should be supported by the implementation of technological infrastructures required to improve the healthcare system and adapt the existing tools to PHC. The connectivity between the different data sources (patient’s clinical file, environment, family history, drugs, diagnostic test results, etc.) and the real-time access to this information will ensure successful implementation of PHC in a healthcare system.
Organizational and applicability issues within the healthcare system
The organizational impact is one of the key elements influencing the adoption of change and innovation in a given environment. While the clinical validation of PHC tools using large and well-characterized cohorts constitutes a key development stage, it is also vital to convince the healthcare sector of the necessity and relevance of adopting these new healthcare approaches.
PHC may bring about significant changes to the practice of medicine and other healthcare professions and to the organization of the healthcare system. For example,
where will the tests be administered, who will analyze them, who will absorb the costs, who will decide upon what treatment the patient will receive? Furthermore, the growing availability of PHC tests will also require further attention to be paid to the quality (predictability) of the results of these tests. The new tools used in PHC often use sophisticated techniques, less controlled than those currently found in hospital laboratories. In addition to assessing the cost-benefit ratio of the new personalized solutions, it will be important to measure the impact of the introduction of these solutions on the medical profession, the roles within the medical profession, the ways in which the services are organized, training needs, available tools, compensation, etc.
Ethical and regulatory issues
The PHC approach also raises important ethical questions on aspects such as the protection of personal information, social equity, and the interpretation and especially the transmission of diagnostic tests results. Most of predictive gene tests are not certified and can lead to misinterpretations, causing psychological impacts for those involved and inciting unwelcome practices.
Any major change in practice raises ethical questions on necessary, desirable intensity. For example, should an individual’s predisposition to a debilitating disease be measured if there exists no treatment? What are the acceptable societal risks of misinterpreting the results? Should the sale of “direct to consumer” sequencing services be permitted, knowing that the genetic predisposition is only responsible for a portion of the susceptibility factors?11
Faced with the proliferation in staff sequencing services, mainly in the United States, the use of data and results of such tests needs to be properly monitored. More specifically, it is vital to prevent an insurer from being able to adjust eligibility for insurance products on the basis of results of such tests and of a person’s relative risk of developing a given health problem. In this regard, in 2003, an inter-ministerial committee, the “Commission de l’éthique de la science et de la technologie” [Ethics of science and
technology commission] focused on genetic medicine.2 The committee’s recommendations concerned mainly the imposition of a moratorium on the use of genetic data by employers and insurers, until legislation is amended and adopted. Such a moratorium is still vital to progress toward deployment of PHC. In 2003, a declaration made by UNESCO3 also addressed this idea: “ …Every effort should be made to ensure that human genetic data and human proteomic data are not used for purposes that discriminate in a way that is intended to infringe, or has the effect of infringing human rights, fundamental freedoms or human dignity of an individual or for purposes that lead to the stigmatization of an individual, a family, or a group or communities…”
Furthermore, the regulatory authorization process is not yet ready and most of the discoveries in personalized therapeutic solutions have not yet been approved by regulatory agencies or have not been repaid, particularly in Canada. These are crucial issues and cannot be minimized.
In Québec, the Institut national d’excellence en santé et en services sociaux (INESSS) has been mandated to make recommendations concerning the assessment and development of practice guides, repayment of healthcare technologies and drugs (previously under
the responsibility of the Conseil du médicament), creation of registers and the obtaining of information on use and price.5 Section 7 of the Act Respecting the Institut national d’excellence en santé et services sociaux stipulates the criteria used by INESSS during the evaluation of a drug, including the drug’s therapeutic value, carried out using clinical studies provided by the manufacturer and the available evidence; fairness of the price; cost-effectiveness ratio; and the consequences of the drug’s registration on the health of the population and on the other components of the health and social services system. In light of the recent merging of responsibilities of the Conseil du médicament and those of INESSS, the terms of evaluation and repayment linked to a drug and a companion diagnostic test need to be defined.
Several states have adopted reimbursement processes focused on performance or the achievement of a therapeutic effectiveness threshold. The PHC tools will allow us to better select patients before having access to given treatments. PHC offers an opportunity to optimize our reimbursement evaluation processes for access. In the past, Québec was able to adopt flexible regulatory approaches that promoted innovation while respecting ethical aspects. New and additional efforts will, however, be required .
Involvement of the population and clinicians
Implementation of PHC in a healthcare system also requires the involvement of physicians and other clinicians, particularly regarding the choice of tests, treatments and healthcare protocols for patients. PHC solutions will therefore need to simplify clinical decisions and render the healthcare process more effective (clinical utility).
Finally, the PHC approach requires the population to be involved, whether in the management of its health or in its understanding of the solutions being proposed. Education of the population and management of expectations constitute basic aspects of the success of the PHC approach. Though Québec’s population is more informed than ever on health issues and patients know more about their illnesses and potential solutions, additional efforts are still required. The generalization of the PHC approach requires the full participation of the population and all stakeholders. This involvement will entail means other than those aimed simply at awareness-building and education and must lead to a participative approach.
Conclusion
Solutions and tools stemming from the PHC approach are currently being implemented and will especially gain prominence in Québec’s healthcare system in the years to come. Québec must prepare, plan and facilitate joint actions so that PHC becomes a differentiating factor to ensure higher quality patient services, better disease prevention and an efficient public healthcare system. The health of individuals and the population will improve, and Québec’s productive potential will increase.
References
1. http://www.cartagene.qc.ca/ 2. Recommendations February 13, 2003 by the Commission de l’éthique de la science et de la technologie, “Les enjeux éthiques des banques d’information génétique” [Ethical issues of genetic information banks”] 3. International declaration by UNESCO on human genetic data, October 23, 2003 4. Arrowhead Publishers (2010). Personalized Medicine 2010, May 2010, 261 pages. 5. An Act Respecting the Institut national d’excellence en santé et services sociaux
R.S.Q., Chapter I-13.03, (hereafter cited
“Loi sur l’INESSS »), art. 5, 12, 13, et 62. 6. Bergman, Howard (2010). Initiative to develop a personalized health care strategy for Québec, July 2010 7. Bange, J; Zwick E, Ullrich A. (2001). Molecular targets for breast cancer therapy and prevention.” Nature Medicine 7, pages 548–552. 8. Gianni et al. (2011). Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2positive early breast cancer: a 4-year follow-up of a randomised controlled trial. The Lancet Oncology, Vol.12, Issue 3, Pages 236- 244. 9. Little, Stephen (2008). Business op-
portunities and commercial challenge in personalized medicine, April 2008. http://www.ivdtechnology.com/article/ business-opportunities-and-commercialchallenges-personalized-medicine 10. An Act respecting the Institut national d’excellence en santé et services sociaux
R.S.Q., Chapter I-13.03.
“Ensuring that Québec capitalizes on the development of personalized health care – A business proposal by the Québec network for personalized healthcare,”
January 2011 11. Torr-Brown, Sheryl R (2010). Future of
Medicine/ Personalized medicine, “Regulatory and ethical challenges of personalized medicine,” September 2010, Vol. 7, No. 5, pages 465-468, DOI 10.2217/ pme.10.49
Michelle Savoie, MBA, MPH, Ph D is Co-President, Interim Steering Committee, Québec Network for Personalized Healthcare, General Manager, Montréal InVivo and Guest Professor, Faculty of Pharmacy, Université de Montréal
Dr. Howard Bergman is Former Co-President, Interim Steering Committee, Québec Network for Personalized Healthcare (PHC), the Dr. Joseph Kaufmann Professor of Geriatric Medicine, Professor of Medicine, Family Medicine and Oncology, McGill University and Jewish General Hospital
Daniel Denis, MSc is a partner, SECOR Conseil
Patrice Hugo, PhD is Expert Advisor, Québec Network for Personalized Healthcare and Chief Scientific Officer, Clearstone Central Laboratories, a Labcorp Company
Nathalie Ouimet, MSc, MBA is a Project Manager, Montréal InVivo
Acknowledgements:
This article was prepared for the “Quebec economic 2011” of the CIRANO (http://ge.cirano. qc.ca) and is drawn from consultations led by the Québec Network for Personalized Healthcare in 2010 and 2011.
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