SPOTLIGHTING THE PROOF CENTRE

BioMaRKeR signatURes and healthcaRe solUtions

in heart, lung and kidney failure management

Lifestyle, environmental and genetic factors are driving the epidemics of heart, lung and kidney disease in Canada and around the world. Heart, lung and kidney diseases together are responsible for more than 40 per cent of deaths and $3.46 trillion in healthcare spending worldwide. People with chronic conditions such as heart failure, diabetes, hypertension, chronic kidney disease, and chronic obstructive pulmonary disease, represent approximately 38 per cent of the BC population and consume approximately 80 per cent of the combined physician payment, PharmaCare and acute care budgets (BC Ministry of Health). Chronic diseases are more common in older populations and its prevalence is projected to increase 58 per cent in the next 25 years. In addition, for the fi rst time in history, our children are expected to have a shorter lifespan due to the epidemic of organ failure. Thus, any healthcare improvement focused on chronic disease will realize signifi cant benefi ts.

PROOF Centre Solution

The Centre of Excellence for the Prevention of Organ Failure (PROOF Centre), founded in 2008 by competitive federal funding from the Networks of Centres of Excellence, is a not-for-profi t Society hosted by Providence Health Care and the University of British Columbia. Working with a cross-sectoral multi-disciplinary team of clinicians, scientists, technologists, computational biologists, health care providers and authorities, health economists, and patients, the PROOF Centre develops cost-effective blood tests for heart, lung and kidney care, enabling the identifi cation of disease presence, rate of progression, and therapeutic responsiveness. We create health-relevant content for new blood tests, while strategically using systematic measures to ensure physician and health care adoption.

PROOF Centre Development Process

The PROOF Centre’s model begins with identifi cation of a clinical need where a cost-effective blood test would enhance patient experience and outcomes, and bring economic value to Canadians and others globally. Based on coordinated consultation with experts in academia, healthcare, and industry, the PROOF Centre delivers its commercially viable blood tests through a development process that includes collaborator input and resources. The PROOF Centre’s goal is to accelerate development of these cost-effective biomarker-based blood tests that address critical clinical needs and bring them to market.

The PROOF Centre is among a limited number of teams combining the value of RNAs, proteins, and metabolites in biosignatures. A computation pipeline has been developed using statistical ensembling and decision tree building to evaluate multicomponent marker panels. The team has developed SOPs and quality control measures

PROOF Centre Director, Dr. McManus, and graduate students from the James Hogg Research Centre, examine a venous blood sample – a precious source of “omic” biomarkers. Credit: Brian Smith, Providence Health Care

Dr. Raymond Ng, PROOF Centre, Chief Informatics Offi cer, and other PROOF Centre scientists, Zsuzsanna Hollander, Oliver Günther and Gabriela Cohen Freue, examine promising new data. Credit: Aaron Aubrey Photography

The goal of the program includes providing proper self-management education to these at-risk patients and to establish follow-up care procedures either with their family physician or the COPD clinic.

— Bruce McManus

PROOF Centre clinical coordinators consent a subject in one of our heart failure studies in the Heart Function Clinic at St. Paul’s Hospital. Credit: Aaron Aubrey Photography

for all aspects of data handling and storage. This quality-driven approach ensures that the vast amounts of data remain valuable assets. To this end, the PROOF Centre was awarded the 2010 Bio-IT World Best Practices Award for Personalized & Translational Medicine.

The PROOF Centre’s lead programs in chronic obstructive pulmonary disease (COPD), heart failure, and transplantation are projected to result in the commercialization of five biomarker blood tests by 2018. One of our tests that will improve care for COPD is discussed in more detail below.

Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and is expected to be the third leading cause of death worldwide by the year 2020, with much of this increase resulting from an exponential rise in COPD mortality among women.

Lung exacerbations, or ‘lung attacks’ are experienced by about a third of those who suffer from COPD – a progressive disease that causes reduced lung function in the form of shortness of breath and coughing. When a lung attack takes place, the symptoms of COPD worsen resulting in increased breathlessness, coughing, and wheezing. Lung exacerbations not only take a physical and emotional toll on those with COPD, but are also an enormous burden to the healthcare system. Such exacerbations are the leading cause of emergency room visits and hospitalizations among chronic disease sufferers in British Columbia (BC), and across the country. Consequently, lung attacks can incur over $5.7 billion in direct and $6.7 billion in indirect healthcare costs every year in Canada.

There is a large and compelling unmet medical need and a socioeconomic imperative for identifying markers of COPD exacerbation. Physicians lack objective measurements to accurately risk-stratify patients and monitor the effectiveness of interventions provided for their patients. Currently, the only test in clinical use is lung function measured by forced expiratory volume in one second (FEV1). However, FEV1 has limited utility because it cannot separate the different phenotypes nor reliably predict those who will exacerbate from those who will not.

To address the devastating and costly impacts of COPD exacerbations, the PROOF Centre, Genome BC, Siemens Healthcare Diagnostics, Providence Health Care, and HTG Molecular Diagnostics are providing much needed funding to develop a simple blood test that can determine if a person is at risk for a lung attack. The PROOF Centre team, working with Dr. Don Sin, project leader and head of Respiratory Medicine at St. Paul’s Hospital, and investigators from GlaxoSmithKline have identified unique gene and protein biomarkers that have the ability to predict which patients will likely have frequent lung attacks. Our blood tests outperformed the currently used test, FEV1. The goal is to put this test in the clinical laboratory and be available to any physician in BC. This would be a huge step forward from the current diagnosis method: a breathing test that is available only in certain centres in the province and which must be performed by specially trained staff. This predictive test will also provide a more accurate picture of a patient’s condition, and will allow physicians to better treat and manage COPD.

The development of a predictive test for COPD lung attacks highly complements the initiatives undertaken by the BC Ministry of Health to overcome COPD. Already, a plan is in place to mobilize COPD experts at three Lower Mainland hospitals who will identify lung attack patients seen at each site. The goal of the program includes providing proper self-management education to these at-risk patients and to establish follow-up care procedures either with their family physician or the COPD clinic. Such a program opens the door for a seamless transition from laboratory-based discovery to effective patient management targeting the prevention of fatal lung attacks.

Prospect

Thus, the PROOF Centre blood tests will save lives, improve quality of life, and save precious healthcare dollars with increasing rate of return. Our transplant, COPD, and heart failure tests combined are projected to save more than $3B in Canada and increase patient quality of life (QALY) five years after test implementation. Our blood tests will also be used by family practice physicians with practice guidelines integrated into the clinical reporting system for improved decision making.

To see this story online visit http://biotechnologyfocus. ca/biomarker-signatures-andhealthcare-solutions/