Integrating the Broader Public Health Consequences of Opioid Abuse and Misuse into the Evaluation of New Opioid Products

Transcription

1 Integrating the Broader Public Health Consequences of Opioid Abuse and Misuse into the Evaluation of New Opioid Products Peter Lurie, MD, MPH Associate Commissioner Office of Public Health Strategy and Analysis US Food and Drug Administration Presented before National Academies of Science, Engineering, and Medicine November 4, 2016

2 Acknowledgements Marisa Cruz Ann Witt Lisa Rovin Disclaimer This presentation offers broad reflections on the topic at hand and does necessarily represent FDA policy. This presentation should not be construed to be an endorsement of either the policy or the legality of any approaches discussed.

3 Overview Current FDA legal framework Current FDA benefit-risk approach Examples where FDA has integrated population health into premarket approval decisions Examples where other Federal agencies have integrated population health into premarket approval decisions Examples where other countries have integrated population health into benefit-risk assessments Potential approaches for further integrating population health into regulatory decision-making 3

4 Current FDA Legal Framework: Statutory Considerations By law, in reviewing a NDA, FDA is required to consider: Whether such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof Whether the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof USC 355(d) (emphasis added) 4

5 Current FDA Legal Framework: Regulatory Considerations While the statutory standards apply to all drugs, the many kinds of drugs that are subject to the statutory standards and the wide range of uses for those drugs demand flexibility in applying the standards. Thus FDA is required to exercise its scientific judgment to determine the kind and quantity of data and information an applicant is required to provide for a particular drug to meet the statutory standards CFR (c) 5

6 Current FDA Legal Framework: Regulatory Considerations A required element in a NDA, but not an approval criterion: Environmental impact. The application is required to contain either a claim for categorical exclusion under or of this chapter or an environmental assessment under of this chapter CFR (d)(1)(iii) 6

7 FDA s Current Approach to Benefit-Risk Determinations for Medical Products Decision Factor Evidence and Uncertainties Conclusions and Reasons Analysis of Condition Current Treatment Options Benefit Risk Risk Management Benefit-Risk Summary Assessment Source: Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making Draft PDUFA V Implementation Plan, February

8 FDA s Current Approach to Benefit-Risk Determinations for Medical Products Qualitative; does not prescribe how each factor should be weighed Does not explicitly consider population or environmental health factors Sources: CDER/CBER: Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making Draft PDUFA V Implementation Plan, February 2013; CDRH: Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications, Final Guidance, March 28,

9 FDA Integration of Population Health Perspectives into Safety Issues Testosterone warning: potential for children to come into contact with topical formulations For drugs of abuse, NDA sponsors must provide a description and analysis of studies or information related to abuse of the drug CFR (c)(5)(vii) Drugs of abuse: Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing OxyContin in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. -- Oxycontin prescribing information 9

10 FDA Integration of Population Health Perspectives into Safety Issues REMS for Transmucosal Immediate Release Fentanyl (TIRF) includes measures to prevent accidental exposure to children Post-Marketing Requirements in REMS for Extended-Release/Long-Acting opioids include study of abuse potential Requirements for adverse event reporting including drug overdose, whether accidental or intentional and drug abuse CFR (a) 10

11 FDA Integration of Population Health Perspectives into Safety Issues Human antibiotics Traditionally approved according to standard FDA benefit-risk approach Human labels: To reduce the development of drug-resistant bacteria and maintain the effectiveness of (insert name of antibacterial drug product) and other antibacterial drugs, (insert name of antibacterial drug product) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. Veterinary antibiotics Process of voluntary withdrawal for growth promotion indications scheduled to be completed by end of 2016 Impact of antimicrobial resistance on general population being considered as evaluation criterion for future approvals 11

12 FDA Integration of Population Health Perspectives into Safety Issues Genetically engineered line of Aedes aegypti mosquitoes Self-limiting gene prevents males from surviving to adulthood Intended to suppress local Aedes aegypti population at release site Species is known to transmit human viral diseases such as Zika, dengue, yellow fever and chikungunya Company wished to conduct field trial in Key Haven, FL Under National Environmental Policy Act, required to conduct Environmental Assessment August 2016: Finding of No Significant Impact Must still meet all other local, state, and federal requirements 12

13 FDA Integration of Population Health Perspectives into Safety Issues Vaccines: Fundamental premise of herd immunity entails incorporating a population health approach to more fully assess efficacy Influenza vaccine: vaccinating the general population to disproportionately benefit atrisk populations Human Papilloma Virus vaccine: vaccinating boys to disproportionately benefit women 13

14 New Statutory Authorities Enabling Consideration of Population Health Premarket Authorization Standard for New Tobacco Products The Secretary shall deny an application... if... there is a lack of showing that permitting such tobacco product to be marketed would be appropriate for the protection of the public health -- FD&C Act Sec. 910 (c)(2)(a) 14

15 Potential Considerations in the Assessment of Public Health Effects Smokers who Might have Quit do Not Smokers Reduce Amount of Exposure Net Public Health Effect Smokers Quit Facilitates Entry of New Smokers Undermines Social Sanctions Against Smoking 15

16 Practices of Other Federal Agencies: Registration of Pesticides Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) in weighing any regulatory action concerning a public health pesticide under this subchapter, [EPA] shall weigh any risks of the pesticide against the health risks such as the disease transmitted by the vector to be controlled USC 136(bb) 16

17 Practices of Other Federal Agencies: Approval of New Nuclear Power Plants Need construction permit and operating license No explicit criteria for approval Multiple opportunities for public input Environmental Impact Statement issued under National Environmental Policy Act Essentially a procedural approach Source: U.S. Nuclear Regulatory Commission. Nuclear Power Plant Licensing Process,

18 Practices of Other Governments: Norwegian Medical Need Clause Drugs assessed from both a scientific and technical viewpoint and also in relation to medical need Introduced social perspective Other elements: Limited fixed combination drugs Approval and registration limited to 5 years Eliminated in 1994 when Norway entered the European Union Sources: Brooks, Geyer. Sociol Health Illn 2016; Andrew, Joldal, Tomson. Develop Dialogue

19 Practices of Other Governments: European Food Safety Agency Guidance on Human Health Risk-Benefit Assessment of Foods Made general recommendations Considered two paradigmatic cases: Dietary fish consumption: methylmercury v. benefits of other components of fish Selenium: indispensable nutrient with risks (selenosis) and potential benefits (cancer prevention) Source: EFSA Journal 2010; 8:

20 Health Impact Assessment Defined HIA is a systematic process that uses an array of data sources and analytic methods and considers input from stakeholders to determine the potential effects of a proposed policy, plan, program, or project on the health of a population and the distribution of those effects within the population. Source: NAS. Improving Health in the United States: The Role of Health Impact Assessment,

21 Review of Health Impact Assessment Tools Real-life Population Dynamic Projection Explicit Risk-Factor Status Modest Data Requirements Rich Model Output General Accessibility ARMADA GBD * POHEM PREVENT MSLT * RIVM CDM * + - *With some restrictions Source: Lhachimi, et al. Am J Prev Med

22 Dynamic Population Model for New Tobacco Products Source: Vugrin, et al. PLoS ONE

23 Alternative Approaches to Benefit-Risk Assessment in Regulatory Decision-Making European Medicines Agency Combines qualitative generic framework (PrOACT-URL) with multi-criteria decision analysis model Can be used across product life-cycle Can capture population health and patient perspectives Australia/Canada/Switzerland/Singapore (UMBRA) Semi-quantitative value tree model Still under development Pharmacoepidemiological Research on Outcomes of Therapeutics (PROTECT) Umbrella group to analyze and harmonize benefit-risk efforts Sources: PrOACT-URL: UMBRA: PROTECT: 23

24 Conclusions FDA s mandate has traditionally been interpreted as focused on individual health Opportunities to further introduce population health considerations exist in statute, regulations, guidances, labeling, post-marketing requirements, adverse event reporting, and research Certain provisions of FDA s tobacco product authorities explicitly require a population health framework Several other FDA-regulated products lend themselves to a population health approach Opioids Antibiotics Environmental contamination by FDA-regulated products Several benefit-risk assessment tools have been developed, but all have strengths and weaknesses 24

25 Supplementary Slides 25

26 Health Impact Assessment Tools ARMADA: models real-life populations over time with a generic disease model with explicit risk factor states GBD: Static model measuring life-years lost, disability-adjusted life-years (DALY) and healthy life expectancy POHEM: models the risk factor and health status of individuals, who jointly form a real-life population, throughout their lifetime Source: Lhachimi, et al. Am J Prev Med

27 Health Impact Assessment Tools (Continued) PREVENT: models real-life population over time based on multi-state life table of chronic diseases MSLT: extension of a simple life table that incorporates competing causes of death RIVM CDM: models real-life population over time clearly linking explicit risk-factor states to multiple diseases and death Source: Lhachimi, et al. Am J Prev Med

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