Meeting Summary: CIHR Personalized Medicine Planning Meeting - May 2-3, 2011

Scope of Personalized Medicine

Personalized Medicine, as defined by the Personalized Medicine Working Group (Health Canada) refers to the tailoring of preventative, diagnostic or therapeutic interventions to the characteristics of an individual or population. It does not mean the creation of health interventions targeted directly to an individual, but rather that the scientific advancements that underpin personalized medicine provide the ability to classify individuals into sub-populations based on their susceptibility to a disease, or response to a specific treatment. This can allow for prevention/intervention strategies and earlier and/or targeted interventions to improve health outcomes.

Personalized medicine aims to transform the delivery of healthcare to patients such that it will evolve from a “one-size-fits-all” system towards a custom tailored system delivering more predictive, preventive, and precision care. Personalized medicine will also enhance awareness about lifestyle and preventive lifestyle changes based on individual risk factors. A personalized molecular medicine approach is expected to lead to better health outcomes, improved treatments, and a reduction in unnecessary treatment with its associated costs and adverse events.

The CIHR Institutes of Cancer Research (ICR), Genetics (IG), and Health Services and Policy Research (IHSPR), in consultation with the Institutes of Population and Public Health (IPPH), Infection and Immunity (III), and Circulatory and Respiratory Health (ICRH), are leading the CIHR signature initiative in Personalized Medicine, which is one of a suite of CIHR “signature” initiatives which align with the CIHR strategic plan known as Roadmap. This initiative will engage biomedical, clinical, population health, health economics, ethics and policy researchers, as well as provincial health authorities and decision makers, in an undertaking to identify health care burdens in disease that are suitable for a personalized medicine approach within the Canadian health care system. It will build on Canadian strengths in discovery research, clinical trials, biomarkers, and nanotechnology. It will also further develop Canada's strong existing infrastructure, including genome centers, large-scale cohort studies, and tissue/tumor/serum banks.

This initiative will support translational research for the effective prevention, diagnosis, and treatment of disease. A first goal will develop a framework to enable effective policy leading to preventative interventions as well as molecular, evidence-based medicine and the integration of personalized medicine into the health care system. The specific objectives of the initiative are:

1. To develop an evidence base on how to assess and, where appropriate, integrate innovative diagnostics (including laboratory diagnostics and medical imaging) into health policy and practice.
2. To stimulate the discovery, clinical validation, and translation of biomarkers, targets and genomic signatures for risk assessment and for diseases detection, which have the potential to improve the outcomes of therapeutic interventions by enabling the selection of treatment choices tailored to individual patient characteristics.
3. To foster the development and validation of diagnostics based on such biomarkers, targets and genomic signatures, and of innovative devices for the application to patient practice.

Objectives of the CIHR Personalized Medicine Planning Meeting

The planning meeting on May 2-3, 2011 in Montreal brought together researchers and provincial funders to help develop a framework for a national health research agenda that would address personalized medicine within the Canadian context. The objectives of the workshop were:

• To identify required components for a framework that would support the successful integration of personalized medicine approaches in the Canadian context.
• To identify priorities for research addressing health care challenges towards integrating personalized medicine.

Planning Meeting Overview

The format of the workshop consisted of talks by provincial funders/agency representatives as well as researchers on different aspects of personalized medicine and its integration into the Canadian Health Care system. This was followed by a breakout session to realize the workshop objectives and propose the top priorities for strategic research funding.

Session 1 – Presentations from provincial funders/agencies:

The one-and-a-half day workshop began with provincial funders/agencies providing their perspectives towards a Canadian personalized medicine approach. There was a general consensus for a need to build health research, as well as receptor capacity, in the area of personalized medicine. Priorities include, but are not limited to:

• how to better assess and evaluate personalized medicine innovations
• how to enable uptake and correct utilization by the healthcare system and the population
• how to educate and/or inform the public and healthcare professionals in the area of personalized medicine.

A collaborative and cross-functional approach between the provinces and other stakeholders would enable Canada to position itself appropriately to transform the delivery of health care as well as to improve health outcomes.

Session 2 – Existing frameworks to assess and implement evidence-based medicine:

A second session focused on describing two frameworks used to assess and implement evidence-based medicine. The first framework (Figure 1) described the pipeline between gene/biomarker discovery and health outcomes, and outlined the various research methods and questions that are required to move through this pipeline. Such research methods include but are not limited to:

• analytical and clinical validation when considering genomic discovery and the pertinence of this discovery to health application
• clinical utility, cost-effectiveness studies, and health technology assessment when considering the development of evidence and evidence-based guidelines
• dissemination and policy research when considering the implementation of guidelines into health practice
• outcomes and public health research when considering the impact of these discoveries on the health of the population.

Although there are various research activities between discovery and health outcomes, it is clear that ethical, legal, and social issues surround the entire process.

Figure 1: (courtesy of François Rousseau)

Pipeline between gene discovery and health outcomes

The second framework outlined a proposed structure for the approval of drug-test pairs into clinical practice (Figure 2). In the current landscape, there are two separate routes for the submission of drugs and tests. New drugs are reviewed by the Committee to Evaluate Drugs and tests are reviewed by a Health Technology Advisory Committee. It was emphasized that as drugs that require companion tests are developed, strict guidelines will be needed to evaluate the two components as a pair. As in the framework described above, there will be pre-clinical, clinical, and evidence-based research, but also a committee to evaluate test/drug pairs before they are approved and implemented. A part of the decision making process will also include the possibility to perform real-world evaluation if necessary.

Figure 2: (courtesy of Carol Sawka)

Session 3 – Implementation of biomarkers:

A third session focused on examples of biomarker implementation as well as the current challenges, successes and lessons learned within the personalized medicine landscape. Topics for presentation included:

• health economics
• cost-effectiveness analysis
• health services issues
• ethical-legal-social issues
• commercialization of technology platforms
• education

While one can argue that health care providers currently practice personalized medicine, there was an understanding that new research is required to enable the enhanced discovery of appropriate biomarkers and molecular-based medicine approaches suitable for the Canadian health care system.

Session 4 – Challenges, successes and lessons learned:

The fourth session involved a discussion on the current challenges and priorities for personalized medicine within the Canadian context. Questions that were addressed during the breakout session and plenary discussion were:

• What are the gaps within the current frameworks?
• What elements in the frameworks require additional research?
• What are some of the obstacles to getting measures of personalized medicine accepted and funded in clinical practice?
• What are the critical issues that will face decision-makers regarding personalized medicine and how might these be informed by research?
• What are the top two priorities for strategic research funding (within the health services, policy, and ethical, legal, social issues) that will have an impact on implementing personalized medicine?
• What should CIHR's role in a personalized medicine strategy be? How should CIHR prepare for a national consultation? Would this require a series of smaller workshops followed by a larger consensus conference? If so, what should their objectives be? Should an outcome of this planning workshop include the formation of small defined working groups?

Key Messages

The key messages from the Personalized Medicine Planning Meeting are summarized below.

Requirement for More Evidence-Based Medicine and Real-World Evidence

• Evidence-based medicine uses our understanding of disease processes and our knowledge of scientific evidence to evaluate laboratory tests or innovative diagnostics for clinical decision making. Such studies of evidence include i) Analytical validity: whether a test accurately identifies a genetics variant or biomarker; ii) Clinical validity: does a genetic variant or biomarker accurately predict the presence of disease, and iii) Clinical utility: what are the risks and benefits of the test and does it improve health outcomes. In addition, studies are carried out to perform cost-effectiveness analysis, as well as to evaluate the evidence at a population health level, and how the consequences of knowledge will impact on health outcomes. While evidence-based medicine encompasses a variety of research tool sets and criteria, the need for more rigorous data collection and evaluation of this science was brought forward. It was agreed that high-quality evidence is required throughout the process of translating research findings such that this evidence is used in decision-making and only drugs, laboratory tests, and innovative diagnostics that meet strict pre-identified criteria are evaluated and implemented.
• Real-world evidence encompasses comparative effectiveness research, and is defined as the knowledge gained from developing, implementing, and evaluating personalized medicine approaches in the real-world. In addition to evidence-based medicine, research into real-world evaluation was identified as a pressing priority in personalized medicine. It was also agreed that dedicated test-centers and platforms were needed to generate real-world evidence for genomic-based tests.
• There is currently insufficient data or data that does not address the appropriate questions when it comes to the evaluation of scientific evidence. Emphasis was placed on the need for gold-standard evidence, quality indicators, quality data, and coverage with evidence-development. In addition to these, research into policy and decision making, regulatory research, and research on standardization of regulatory processes was deemed necessary.

Engagement with Decision Makers and Health Technology Assessment Groups: Breaking Down the “Silo” Effect

• From the frameworks presented, it was clear that better interactions between researchers, decision makers, and health technology assessors are critical to ensure the generation and use of high-quality information in order to support and inform health policy and clinical practice.
• A major gap discussed was the siloing effect and the consequent lack of coordinated/integrated funding. These silos exist in the healthcare system, within hospitals, between funders, and also between payers.
• There is a need for a systems based approach to quality assurance that will allow for the regulation of drugs and diagnostics together.

Need for Platforms and Data Access/Management

• One of the challenges in personalized medicine will be to create appropriate platforms in which innovations will be appropriately evaluated and subsequently linked with decision makers and technology assessors.
• To enable the infrastructure required to carry out personalized medicine, linkages with electronic health records will be necessary. Indeed, appropriate infrastructure is needed to collect large amounts of population data and link to biobanks and clinical data. Large cohorts that are appropriately sampled and phenotyped are critical, and research is therefore needed to address data sharing (biobanks, clinical data, health records, cohorts, etc.)

Health Economics and Cost-effectiveness Analysis

The role of health economists and the importance of cost-effectiveness / cost-benefit analysis was emphasized and it was agreed that this type of analysis will be needed up-front in collaboration with policy makers, clinical epidemiologists, clinicians and researchers.

Ethical, Legal, Social Issues and Population Health Issues

• Ethical, legal, and social issues associated with the implementation of personalized medicine approaches need to be integrated throughout the translation of personalized medicine approaches into the healthcare system.
• Population health research must be considered as personalized medicine will evolve to a broader 'bench to the community and back' philosophy to facilitate resolution of conflicts between population-based and individual priorities and how the agreed parties recognize the legitimacy of decisions and the evidence supporting these decisions.
• The societal impact of personalized medicine will need to be addressed as social perceptions, expectations, and values between stakeholders may be different and will have an impact on decision making. The difference in values between patients and practitioners must also be addressed.
• The commercialization of personalized medicine tools will require research related to the ethical, legal, and social implication of these tools.

Education and Engagement of Health Professionals and the Community

• Education and training for primary health care providers and clinician scientists on personalized medicine, direct-to consumer testing, personalized prevention and management, genetics was identified as a priority.
• Education of the public was also identified as a priority. Improvements in communication are required to ensure patient empowerment and better dialogue with the public about how treatment reimbursement decisions are made. Research into the public and patient's expectations is needed and the impact of social media will need to be addressed. The public, including advocacy groups, vulnerable populations, etc. need to be engaged from the beginning and throughout the process of any personalized medicine approach.
• Education of health care providers and patients about personalized disease prevention, detection, and treatment

Next Steps and CIHR's Role in a Personalized Medicine Strategy

• A requirement that interventions, biomarkers, diagnostic and imaging tools, etc., are medically necessary and they improve outcomes over standard of care
• For personalized medicine to be effective, there must be standards for integrating techniques into health care, as well as changes in regulatory and reimbursement policies.
• There will be a shift towards prospective and retrospective studies, which will greatly rely on biobanks, cohorts, and datasets, such that comparative-effectiveness research will analyze how personalized medicine discoveries work in the real-world.
• A successful national strategy for personalized medicine will engage all major stakeholders, namely the public, provinces, provincial funders, provincial health authorities, decision makers, industry, diagnostic and IT companies.
• A broad consultative process will formulate the principles and the evidence needed to make decisions about how personalized medicine interventions should be implemented/integrated into practice in the Canadian health care system.