Characterizing and Communicating Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products Workshop Summary (2014) / Chapter Skim
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3 The Regulators' Challenge
3 The Regulators' Challenge
Pages 19-30
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From page 19... ...
• Canadian regulators are working to incorporate transpar ency about the benefit, harm, and uncertainty considerations in regulatory decisions, with the goal of aligning decisions and accompanying communication strategies to better serve patients. • Developing an understanding of what matters most to patients could help FDA craft regulatory decisions and outreach that meaningfully communicates uncertain issues in a manner most relevant to patients.
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From page 20... ...
Frey indicated that expert elicitation methods might be applicable in the drug regulatory setting, allowing FDA drug reviewers to participate in a process that has been effective for quantifying uncertainty in other areas. Frey noted that such decision science methods have potential in the drug regulatory setting for developing a systematic approach to uncertainty that is both scientifically rigorous and can be practically implemented in FDA's existing benefit–risk framework.
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From page 21... ...
Parks, Deputy Director, Office of Drug Evaluation II, Office of New Drugs, CDER, FDA, spoke about the uncertainties inherent in the interpretation of scientific evidence in the drug review process, and how those uncertainties are communicated both within the agency and outside. The FDA PDUFA V Plan states: "To be approved for marketing, a drug must be safe and effective for its intended use." Parks emphasized that the statement does not mean that an approved drug is risk free.
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From page 22... ...
. TABLE 3-1 Hierarchy of Scientific Evidence Level Type of Scientiic Evidence Ia Scientific evidence obtained from meta-analyses of randomized clinical trials Ib Scientific evidence obtained from at least one randomized clinical trial IIa Scientific evidence obtained from at least one well-designed, non randomized controlled prospective study IIb Scientific evidence obtained from at least one well-designed, quasi experimental study III Scientific evidence obtained from well-designed observational studies, such as comparative studies, correlation study, or case-control studies IV Scientific evidence obtained from documents or opinions of experts, committees, and/or clinical experiences of renowned opinion leaders NOTES: Category Ib, scientific evidence from at least one randomized clinical trial (RCT)
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From page 23... ...
COMMUNICATING WITH THE PUBLIC ABOUT BENEFIT, HARM, AND UNCERTAINTY3 Robyn Lim, Senior Science Advisor, Office of Legislative and Regulatory Modernization, Health Products and Food Branch, Health Canada, presented Health Canada's Benefit–Harm–Uncertainty Initiative (BHU) , a new regulatory approach focused on communication and patients.
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From page 24... ...
The new system will include mandated transparency about the benefit, harm, and uncertainty considerations in regulatory decisions with the goal of aligning regulatory decisions and accompanying communication strategies to better serve the needs of health partners, particularly patients. The guiding principle behind BHU, according to Lim, is that pairing the terms "benefit" and "risk" is inherently confusing because there is an asymmetrical acknowledgment of uncertainty in the terms, and that confusion undermines patients' ability to think about choices and trade-offs in a disciplined way.
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From page 25... ...
Although uncertainty is not the main focus for PFDD meetings, Mullin noted that patients often must 4 This subsection is based on the presentation by Theresa Mullin, Director, Office of Strategic Programs, CDER, FDA. 5 FDA patient engagement tools include FDA Patient Representative Program; Patient Consultant Program; Patient Liaison and Patient Network programs; and CDER's Professional Affairs and Stakeholder Engagement.
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From page 26... ...
Patient discussions and conversations strengthen the agency's understanding of the relative importance of clinical outcomes, and what types of risks might be considered acceptable to patients. Patient input could also support drug development more broadly, for instance, by identifying specific symptoms, such as fatigue, that are not being remedied by current treatment options.
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From page 27... ...
Mullin noted that hosting meetings in the Washington area, and generally in close proximity to Silver Spring or Bethesda, would facilitate attendance by FDA staff. To provide context for workshop discussions surrounding regulatory decision making under uncertainty, FDA developed two case studies to illustrate the types of uncertainties that FDA reviewers face in weighing the evidence for a particular product to receive market approval (see Box 3-3 and Appendix B for complete case studies)
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From page 28... ...
. Robert Temple, Deputy Director for Clinical Science, and Acting Deputy Director, Office of Drug Evaluation I, CDER, FDA, described the Tysabri case study.
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From page 29... ...
The low numbers of major cardiac events in Anoro Ellipta's premarket clinical trials made it difficult to draw definitive conclusions about CV risk. According to Pippins, FDA's view was that the observational studies the sponsor proposed would not be able to provide a definitive assessment of cardiac risk; as a result, the agency decided not to require postmarket monitoring.
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