February 18, 2014
By K. Kimberly McCleary, Director, Strategic Initiatives, FasterCures
Mountain climbing. Hang gliding. Wave jumping. Are these extreme sports worth the risk for the exhilarating view? Your answer might indicate something about your personal risk tolerance.
Assessing benefits and risks is core to medical product development, regulation, and healthcare decision-making. The tradeoffs between desired benefits and tolerable risks may look quite different whether you’re a patient, a physician, a regulator, or a drug/device developer. They also might change over time.
The need for greater consistency and transparency in benefit-risk assessment is gaining a lot of attention. Over the past week, stakeholders came together in three different venues to share perspectives and explore the evolving science and practice:
- On Feb. 7, the U.S. Food & Drug Administration (FDA) hosted its fifth meeting of the Patient-Focused Drug Development Initiative. Hundreds of sickle cell disease patients and caregivers participated, giving emotional testimony about how their lives are impacted by the disease and risks they accept and challenges they face getting appropriate care and treatment.
- Beginning on Feb. 9, the Drug Information Association(DIA)sponsored “Benefit-Risk Assessment from Inception to Maturation: Aligning Regulatory and Industry Goals,” which attracted nearly 200 professionals from around the world representing various disciplines, pharmaceutical companies, and several countries’ regulatory bodies.
- On Feb. 12, the Institute of Medicine (IOM) Forum on Drug Discovery, Development, and Translation convened “Characterizing and Communicating Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products.” Regulators, academic researchers, and industry staff heard presentations on decision-making science and risk management from a number of different fields and reviewed case studies of FDA decisions.
FasterCures was represented at each of these meetings and is actively engaged in dialogue about benefit-risk, especially from the patient perspective. Below we share five things we believe you should know about benefit-risk:
1. The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 dramatically changed the landscape for benefit-risk assessment. Over the past several years, there have been a number of collaborative initiatives to develop systematic methods to guide, justify, and communicate benefit-risk decisions in a transparent and consistent manner:
- The Pharmaceutical Research and Manufacturers Association (PhRMA) shepherded the Benefit-Risk Action Team and a framework it developed and piloted over the past eight years, now transitioned to the Centre for Innovation in Regulatory Science.
- In Europe, the Innovative Medicines Initiative has sponsored the PROTECT program to evaluate 13 benefit-risk frameworks.
- In February 2013 the FDA released a draft five-year implementation plan that describes its proposed approach and introduces the FDA’s Benefit-Risk Framework for regulatory decision-making for drugs.
2. Patient perspectives on benefit-risk are vital to the structured assessment process across the lifecycle of developing drugs and devices. There is growing acceptance of the value of eliciting, understanding, and incorporating patient preferences for benefits and tolerances for risks at every stage from early clinical development to marketing medical products:
- FDA’s Patient Focused Drug Development Initiative (PFDDI) created under FDASIA will focus attention on 20 serious and/or life-threatening conditions where there is unmet medical need. Public sessions like the one held on Feb. 7 create an opportunity for FDA reviewers and decision-makers to hear directly from patients.
- The FDA’s “Voice of the Patient” report series provides a template for structuring qualitative information and could be used to inform more structured exercises like the pilot study sponsored by Parent Project Muscular Dystrophy to elicit parent preferences for their sons with a rare, genetic, progressive, and ultimately fatal condition called Duchenne muscular dystrophy.
- For devices, the FDA’s Center for Devices and Radiological Health launched its Patient Preference Initiative with a two-day meeting last fall.
- The National Health Council has published a Patient Stratification Tool to help disease communities collect and organize information of potential interest to regulators and drug/device development partners.
- Genetic Alliance and PhRMA have partnered to provide three patient communities preparing for upcoming PFDDI meetings with a secure platform to crowdsource input from stakeholders.
- Some pharmaceutical and biotechnology companies are forming patient advisory bodies to invite their expertise, and others are exploring means to gather this valuable input.
- During a presentation at the DIA meeting, I offered recommendations for how industry could connect to TRAIN and other patient-based organizations’ resources and ways to integrate patient perspectives into drug development and marketing processes.
3. Benefit-risk assessment requires participation from multiple scientific disciplines. During the recent DIA meeting, several speakers emphasized the need to bring teams from different functions together to understand and engage in the ongoing benefit-risk assessment, helping refine it as more information about drugs and their effects is gathered from development to clinical trials to approval and post-marketing surveillance. Systems have been constructed to capture adverse events and pick up potentially harmful signals, but there is little systematic capture of benefits beyond those approved in the label. This can lead to an imbalance in the benefit-risk profile over time. The need for a common lexicon for benefits and to identify new sources of ongoing information about benefits could help to resolve the imbalance. In some cases, products are withdrawn from the market while further assessments of safety and/or efficacy are made. This was the case with Tysabri in the treatment of multiple sclerosis. Patients’ willingness to tolerate a greater level of risk in exchange for benefits that contribute to greater quality of life and/or life expectancy was a key factor in the FDA’s decision to allow marketing of Tysabri again 16 months later with additional restrictions on its distribution and warnings to prescribers and patients.
4. The need to reduce uncertainty in decision-making about benefits and risks is being actively addressed. Patients also face uncertainty, not only about new products coming on to the market, but about choices among therapies. Here are examples of organizations addressing this need:
- To help fill major gaps in the knowledge base, especially from the patient perspective, the Patient-Centered Outcomes Research Institute is making substantial investments in new comparative effectiveness research and mechanisms to better communicate existing information that could enhance shared decision-making between patients and healthcare professionals (our Jan. 29 Webinar focused on the launch of PCORnet, a $100 million national patient-centered research network).
- HealthCanada determined that developing a construct for assessing and communicating benefits-harms-uncertainties was a means to help all stakeholders better understand what is known and what is unknown based on available evidence.
- The European Medicines Agency is developing processes for reducing uncertainty and managing complexity in its regulatory actions.
5. FasterCures will continue collaborating with other stakeholders to enhance patient participation in medical product development and regulation – so that products patients value advance more rapidly from bench to bedside.
- View the archived slides and recording from our Webinar on the FDA’s benefit-risk framework and patient-focused drug development, as well as the National Health Council’s patient stratification tool.
- Connect with us to stay informed about our activities in this and other areas.