Canadas Drug Regulation Renewal: Are Improved Access and Safety in our Sights?

A Roundtable Exploring the New Paradigm of Benefit-Risk Evaluation

Summary Report March 5, 2010

Format
On Friday, March 5, 2010, over thirty Canadian health stakeholders (representing patients, providers, government, academics and industry) participated in a roundtable meeting to discuss the new paradigm of benefit-risk introduced in Bill C-51. The day featured a rich discussion (moderated by Dr. Stuart MacLeod) that effectively framed the issues in benefit-risk evaluation and set the stage for a continuing dialogue. Prior to the Roundtable, surveys were conducted with stakeholders from diverse backgrounds and areas of interest to identify the best format to enable an open, honest discussion and ensure that key issues would be addressed. An Advisory Committee was formed to further guide the Roundtable planning, ensure a balanced approach, and review background materials. Health Canada was engaged and informed throughout the process.

Key Themes
While many issues were raised during the vigorous discussions, five key themes emerged from the Roundtable meeting: 1. Consideration of quality of life should be central to the new approach to evaluation of benefit from innovative therapies. The evaluation will require a combination of quantitative and qualitative methods. 2. Enhanced patient engagement (including the relationship with stakeholder advocacy groups) is certain to be a key feature of any future process. 3. There should be a change in emphasis to benefit-risk from risk-benefit. This shift is appropriate and significant as it leads to a more patient-centered approach where costs arent the only deciding factor. 4. Change in the drug regulatory system (and by extension in the review of drug reimbursement/access decisions) is inevitable. The active process of change in which we are now engaged is driven by our vastly improved understanding of the social and biological determinants of health and these will affect the assessment of drug benefits and drug safety. 5. New approaches and new methods are needed for the assessment of both benefit and risk. Importantly, methodological innovation is required and will be facilitated by the legislative renewal process as described by David Lee and Robyn Lim from the Office of Legislative and Regulatory Modernization. Canadas forthcoming renewed legislation describing a life-cycle approach to the evaluation of new therapies will be a driver of therapeutic innovation and will facilitate a more patient-centered approach to treatment, which should correspond to improved access to new drug treatments. Page 1 / 6

Roundtable Summary Report: Canadas Drug Regulation Renewal

March 5, 2010

Overview
Russell Williams, President of Rx&D, welcomed a diverse group of over thirty Canadian health stakeholders to the roundtable meeting and encouraged a robust discussion on the new paradigm of benefit-risk introduced in Bill C-51. Bill C-51 represents an attempt to modernize Canadas Food and Drugs Act for the first time in 50 years and contains an increased emphasis on the concepts of benefit and risk. The proposed Bill has the potential to significantly impact the manner in which drugs are regulated, monitored, and delivered to patients. It is everyones role: governments, approval agencies and innovators, to ensure that this benefitrisk ratio is appropriate. We must also ensure that we do not become risk-averse to the point where we potentially delay or deny access to medicines that could provide significant benefits to patients. The day featured a rich discussion that effectively framed the issues in benefit risk evaluation and set the stage for a continuing dialogue. From the viewpoints heard at the symposium it can be concluded that the current system does not meet the standards of accountability for reasonableness as laid out by Daniels and Sabin in the their landmark position paper of 1998 (Health Affairs;17:50-64). Specifically, the current approach to drug regulation does not meet the desired standard for openness and transparency, including the wide dissemination of the basis for decision-making. Neither does the current system, in spite of some recent improvements, meet the objectives of diverse stakeholder involvement in the decision making process with regard to either regulation or reimbursement recommendations. It was pointed out during the days discussions that proposed improvements in the regulatory system without corresponding progress on decision-making around access would be futile. Unless provincial authorities start to consistently offer Health Canada approved medicines for reimbursement, were only dealing with half the issue and are taking healthcare decisions out of the hands of patients and physicians.

Consideration of quality of life should be central to the new approach to evaluation of benefit from innovative therapies.
The evaluation will require a combination of quantitative and qualitative methods. It was clear from the days discussion that many international regulatory agencies, especially in Europe and the United States, have made progress with new evaluation systems and Canada will need to learn from them and mesh with international trends. The development of better systems for qualitative research in therapeutic evaluation will require a major focus on patient-reported outcomes. Page 2 / 6

Roundtable Summary Report: Canadas Drug Regulation Renewal

March 5, 2010

Enhanced patient engagement (including the relationship with stakeholder advocacy groups) is certain to be a key feature of any future process.
The Roundtable heard very important messages from patient advocates in regard to the evaluation of drug benefit-risk. Patients viewpoints on benefit-risk will vary greatly depending on their perspective and can be influenced by factors such as their condition, severity of illness, who their physician is, impact on caregivers, their view of risk and their beliefs. Patient advocates stressed that: Patient groups should demand access to the evidence forming the basis for decisions. Patients (lay individuals) should not be afraid of science. Science literacy should be improved across the board. Patients who are affected by benefit-risk evaluations should not be reticent about involvement in the process and in taking ownership of the eventual decision.

Definition: Life-Cycle
The entire spectrum of activities that happen over the course of a drug's "life," which includes its discovery; the early testing done to understand the drug; the trials to determine its safety and efficacy in humans; its approval; and its marketing and use in larger populations. -- Health Canada1

There should be a change in emphasis to benefit-risk from risk-benefit.

This shift is appropriate and significant as it leads to a more patient-centered approach where costs arent the only deciding factor. Safety issues should certainly not be ignored but we should not lose sight of the fact that most severe adverse drug reactions are rare and greatly outweighed by therapeutic benefits. Drugs with a higher potential for adverse reaction (though still rare) can be an important option in situations where patients decide that the benefits outweigh the risks, such as cancer treatment, antiretroviral therapy, and use of therapies such as anti-TNF biologicals. All recipients of drug therapy have a major stake in improving our methodology for the measurement of benefit including a more nuanced understanding of improvements in quality of life.

Change in the drug regulatory system (and by extension in the review of drug reimbursement/access decisions) is inevitable.
The active process of change in which we are now engaged is driven by our vastly improved understanding of the social and biological determinants of health and these will affect the assessment of drug benefits and drug safety. We have greatly expanded our knowledge of biology as it relates to drug action and drug risk. This improved understanding is leading us inevitably toward a system in which drug therapy will be tailored much more closely to the characteristics of individual patients. We are on the threshold of an era of personalized or individualized treatment that will in many cases supplant the more general, population approaches to evaluation of therapy that have been taken in the past. Page 3 / 6

Roundtable Summary Report: Canadas Drug Regulation Renewal

March 5, 2010

New approaches and new methods are needed for the assessment of both benefit and risk.
Importantly, methodological innovation is required and will be

Current Drug Development and Regulatory Process in Canada

facilitated by the legislative renewal process as described by David Lee and Robyn Lim from the Office of Legislative and Regulatory Modernization. Canadas forthcoming renewed legislation describing a lifecycle approach to the evaluation of new therapies will be a driver of therapeutic innovation and will lead directly to improved access to new drug treatments. Randomized controlled trials will remain a gold standard for evidence of efficacy but there will be an inevitable shift to decisions made on the basis of a deliberative process that takes context into account. Decision-making will increasingly be evidence informed rather than based exclusively on RCTs. Decision makers will need to take into account observational studies particularly in relationship to quality of life and adverse drug reactions. Consideration of composite outcomes will drive the final decision and colloquial evidence will be accepted. The proposed life-cycle approach requires government to be an active participant, and for manufacturers to be more invested in all stages of product life-cycle regarding benefit-risk

Health Canadas Proposed Life-Cycle Model

Additional discussion
It is important that the new system be able to integrate with global reporting networks for adverse drug events. The government is mandated to not develop uniquely Canadian laws unless absolutely necessary. Canadas population isnt large enough to draw out necessary health data. The drug review and reimbursement processes shouldnt be detached from the patient voice and outcomes. The lifecycle approach isnt absolutely watching everything, 24 hours a day. Its the ability to intervene and assess as appropriate. Clearly were all in favour of achieving the best access with minimal risk, but the devils in the details. Page 4 / 6

Roundtable Summary Report: Canadas Drug Regulation Renewal

March 5, 2010

Roundtable presentations
Presenters Russell Williams Affiliation Canadas Research Based Pharmaceutical Companies Child & Family Research Institute, University of British Columbia University of Western Ontario Patient Advocate University of British Columbia Health Canada North Bay Blue Sky Family Health Team Kidney Cancer Canada Health Canada Topics Welcome and introductions

Dr. Stuart MacLeod

Moderators welcome Balancing benefit & risk Impact of benefit-risk from the paediatric perspective Patient perspective on the issue of benefit-risk Personalized medicine and benefit-risk Benefit, Risk within Federal Modernization Innovation in technology and healthcare: personal health records & health management Kidney Cancer: The impact of evidence on decision-making International Trends in Benefit/Risk

Dr. Michael Rieder Harlon Davey Dr. Bruce Carleton David Lee Dr. Wendy Graham Deb Maskens Robyn Lim, PhD.

Roundtable outcomes
The Roundtable brought together a broad cross section of views and it is hoped that the process can be continued through future in depth discussion of the convergence between benefit risk evaluation and consideration of access/reimbursement issues. Consideration of quality of life should be central to the new approach to evaluation of benefit from innovative therapies. The proposed life-cycle evaluation will require a combination of quantitative and qualitative methods, which is a significant change and follows international trends. Participants identified the need to ensure that public and private payers move in step with the lifecycle model vis--vis reimbursement and evidence requirements. (private payers were not represented at the Roundtable) Health stakeholders expressed a strong interest in remaining engaged on this issue and a willingness to participate in future events (based on evaluations and verbal feedback). Participants requested that Rx&D share a summary report from the roundtable, provide access to speaker presentation (as appropriate) and provide updates on Bill C-51.
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http://www.hc-sc.gc.ca/dhp-mps/homologation-licensing/gloss/index-eng.php#bm_l02 Page 5 / 6

Roundtable Summary Report: Canadas Drug Regulation Renewal

March 5, 2010 Leslie Turcotte, Rx&D Holly Vengroff, CARP, A New Vision for Ageing JoAnne Watton, Huntington Society of Canada Sandra Wainwright, Merck Canada Linda Wilhelm, Best Medicines Coalition Russell Williams, Canadas Research-Based Pharmaceutical Companies Durhane Wong-Rieger, Consumer Advocare/CORD * Presenter

Roundtable Attendees
Lembi Buchanan, Fighting for Fairness *Bruce Carleton, University of British Columbia *Harlon Davey, Patient Advocate Loretta Del Bosco, Abbott Laboratories Della Faulkner, Canadian Nurses Association Elisabeth Fowler, World Health Advocacy *Wendy Graham, Blue Sky Family Health Team Normand Laberge, Rx&D *David Lee, Office of Legislative and Regulatory Modernization, Health Canada *Robyn Lim, Office of Legislative and Regulatory Modernization, Health Canada Steven Lott, World Health Advocacy Anne Lyddiatt, Patient Partners in Arthritis

*Stuart MacLeod, Child & Family Research Institute, University of British Columbia Jean Marion, Rx&D *Deb Maskens, Kidney Cancer Canada Robin Moore-Orr, Canadian Institute for Child Health Wendy Morton, Merck Canada Elaine Orrbine, Canadian Association of Pediatric Health Centres Graeme Page, Alzheimers Society *Michael Rieder, University of Western Ontario Nancy Risebrough, Oxford Outcomes Aprile Royal, MS Society of Canada Stuart Reynolds, Heart and Stroke Foundation of Ontario Paul Shay, Kidney Foundation of Canada Kim Steele, MS Society of Canada Wayne Taylor, The Cameron Institute Jane Tsai, Canadian Diabetes Association

Advisory Committee
Jacqueline Cahill, Canadian Continence Foundation Elisabeth Fowler, World Health Advocacy Kavita Mehta, Toronto SouthEast Family Health Team Elaine Orrbine, Cdn. Ass. of Pediatric Health Centres Aprile Royal, MS Society Leslie Turcotte, Rx&D

Rx&D Contacts
Leslie Turcotte Director, Stakeholders and Partnerships lturcotte@canadapharma.org 613-236-0455 ext. 833 Normand Laberge Vice President, Regulatory and Scientific Affairs nlaberge@canadapharma.org 613-236-0455 ext. 250

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