In the recent blog post Harnessing the engines of finance and commerce for life-extension, I characterized a new approach to health, medicine and longevity called Personalized Predictive Preventative Participatory Medicine (PPPPM). I also promised to describe specific examples in subsequent blog entries. This posting is concerned with a Canadian initiative on the way to becoming a full PPPPM. The initiative is called the PROOF Centre of Excellence, where PROOF stands for prevention of organ failure. A presentation on this topic was made at the Bio-IT World Conference & Expo last week by Raymond Ng. His talk was on Developing Combinatorial Biomarker Panels for End-stage Organ Failures. PROOF represents a medium-scale PPPPM in early-stage development, where focus is presently on identification and development of biomarkers.
As stated on the PROOF website “The Centre of Excellence for the Prevention of Organ Failure (PROOF Centre) discovers, develops, commercializes and implements bio-molecular markers (biomarkers) to prevent, predict, diagnose and better treat heart, lung and kidney failure. The PROOF Centre is a cross-disciplinary engine of devoted partners including industry, academia, health care, government, patients and the public focused on reducing the enormous socioeconomic burdens of heart, lung and kidney failure and on improving health.”
I will review elements of PROOF paying particular attention to the criteria by which I characterized PPPPM.
1. PROOF addresses an important category of disease processes. Organ failure is a condition where an organ does not perform its expected function. There are many possible types of organ failure and multiple possible causes. “Epidemics of inactivity, dietary imbalance, hypertension, obesity, diabetes, air pollution and tobacco use set the stage for accelerated risk for, and occurrence of, vital organ failure. One in four Canadians are believed to be at risk of organ failure; similar to the incidence worldwide. Current methods of detecting organ failure are frequently ineffectual, often costly, at times invasive and generally unsuitable for early diagnosis(ref).” In Canada alone, the personal, societal and economic consequences of vital organ failure (heart, lung and kidney) has a cost of more than $35 billion a year.
2. Availability of reliable predictive biomarkers for various kinds of organ failure could make a big difference. “Precise and accurate recognition of a patient’s risk of organ failure has the potential to dramatically improve preventive care, treatment decisions and clinical outcomes, while lowering both social and economic costs(ref).” This web page illustrates how PROOF views the importance of biomarkers and articulates the core strategy of a PPPPM initiative. “Current treatment strategies are reactive in that, for the most part, interventions are initiated after significant pathological changes have occurred and are often irreversible, which greatly increases the management costs, disease burden, and results in poorer outcomes. The typical current intervention occurs after the disease is irreversible and costly –. However, a new treatment strategy that makes use of predictive, diagnostic, or prognostic biomarker information may help to guide earlier effective interventions when the disease process is still modifiable. As such, overall treatment costs may be reduced and outcomes can be improved.”
3. PROOF is a highly collaborative activity. Proof is a not-for-profit center established in 2008, funded initially by the Canadian Networks for Centres of Excellence for Commercialization and Research, hosted by the University of British Columbia and based at the St. Paul hospital in Vancouver BC. It defines itself as the hub of a multi-disciplinary group of partners drawn from industry, academia, government, health care and the public.
Among the PROOF Centre partners are Luminex, Pfizer of Canada, Genome BC, Astellas Pharma Canada and UVic Genome BC Proteomics Centre. “The PROOF Centre has partnered with Genome British Columbia to bring new blood tests into clinical practice for heart and kidney transplant patients. IO Informatics have partnered with the PROOF Centre to provide a data integration and knowledge explorer infrastructure. This will allow investigators involved in the Centre to access data from all biomarker programs within the PROOF Centre(ref).”
Among the PROOF Centre partners are:
â€¢ “clinical and academic leaders to define decision-points in patient management when/where a biomarker panel could change care and then implement observational biomarker discovery studies,
â€¢ technology leaders in the public and private sectors to pilot or augment technology platforms for multiplexed analysis,
â€¢ leaders of established patient cohorts at the “right” stage of disease to assess the power of biomarker panels in changing care,
â€¢ health economics leaders to evaluate clinical settings and patient groups in which biomarker solutions would change healthcare costs and/or lead to a wealth creation opportunity, and
â€¢ “front-line” health care and laboratory professionals who understand the harsh practicalities of bringing new tests based on biomarkers into care systems(ref).”
4. PROOF envisages the following stages of evolution which are characteristic of a PPPPM:
a. “Biomarker discovery: cohort – single site, high performance platforms – genomics, proteomics, metabolomics, and computation & analysis to develop sets of biomarkers,
b. Biomarker development: multi-site biomarker trial, high performance platforms/assay validation, computation & analysis to validate sets of biomarker signals,
c. Clinical drug development: develop assays and platforms that can move into the clinical laboratory, assay development partnerships,
d. Regulatory filing: voluntary exploratory data submission (VXDS). FDA and Health Canada submissions
e. Clinical implication and experience feedback(ref).”
5. PROOF is already a going concern. Representative of PROOF’s initial impacts:
· “Through its flagship program, “Biomarkers in Transplantation”, the PROOF Centre team has discovered levels of genes and proteins in the blood that allow the diagnosis or prediction of acute rejection in heart and kidney(ref).” Put differently: “The PROOF Centre has discovered and internally validated blood-based proteomic and genomic biomarker tests to diagnose and predict allograft immune rejection in heart and kidney transplantation(ref).”
· A Canada-Wide Biomarker Trial is underway and will test this new method to provide better care for heart and kidney transplant patients in preparation for a submission to regulatory agencies(ref)”
My impression is that PROOF is somewhere in the middle of the scale in size and reach as far as existing PPPPMs go. I suspect PROOF will grow in scale, in sophistication of techniques and in partnering activities as time progresses. Dimensions of expansion will probably include more “omics” screening, enhanced collaborative computer networking among its partners and active relationships with care agencies with active feedback from clinical experience.
PROOF may seem small-scale given US standards and appears tucked up in the Canadian NorthWest. But its biomarkers, once validated and in widespread use, may be of immense help to everybody.