Skip to main content

Advertisement

SpringerLink
Log in

Structured Approaches to Benefit-Risk Assessment: A Case Study and the Patient Perspective

  • Patient Focus
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

Assessing the utility of structured approaches to benefit-risk assessment of medicinal products is challenging, in part due to the lack of a gold standard for results and the uncertainty inherent in the data. In place of conducting formal testing, obtaining feedback from users of structured approaches provides insight into their value and limitations. The authors conducted a simulated single-session benefit-risk decision in which 3 groups applied the PhRMA BRAT(Pharmaceutical Research and Manufacturers of America Benefit-Risk Action Team) framework or the multicriteria decision analysis approach. The groups were provided with background and data for a hypothetical triptan for acute migraine in a population with cardiovascular risk factors and were asked to determine and defend an approval decision. Three insights emerged consistently from the groups: (1) the value of a structured approach to benefit-risk assessment, (2) the clarity provided by real-time visualization tools, and, most critically, (3) the importance of bringing the patient into the discussion early.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Walker S, Liberti L, McAuslane N, Levitan BS. Refining the benefit-risk framework for the assessment of medicines: valuing and weighting benefit and risk parameters. Clin Pharmacol Ther. 2011;89:179–182.

    Article  CAS  Google Scholar 

  2. European Medicines Agency. Benefit-risk methodology project: EMA/213482/2010. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2010/04/WC500089603.pdf. Accessed April 25, 2014.

  3. Coplan PM, Noel RA, Levitan BS, Ferguson J, Mussen F. Development of a framework for enhancing the transparency, reproducibility and communication of the benefit-risk balance of medicines. Clin Pharmacol Ther. 2011;89:312–315.

    Article  CAS  Google Scholar 

  4. Levitan BS, Andrews EB, Gilsenan A, et al. Application of the BRAT framework to case studies: observations and insights. Clin Pharmacol Ther. 2011;89:217–224.

    Article  CAS  Google Scholar 

  5. FDA Center for Devices and Radiological Health. Guidance for industry and Food and Drug Administration staff: factors to consider when making benefit-risk determinations in medical device premarket approval and de novo classifications. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM296379.pdf. Published March 28, 2012. Accessed April 25, 2014.

  6. FDA. Structured approach to benefit-risk assessment in drug regulatory decision-making. http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM329758.pdf. Published 2013.

  7. Innovative Medicines Initiative PROTECT Project. http://www.imi-protect.eu/index.shtml. Published 2012. Accessed October 22, 2012.

  8. Nixon R, Waddingham E, Mt-Isa S, et al. IMI PROTECT WP5 IMI report 2:b:iv natalizumab wave 2 case study report. http://www.imi-protect.eu/documents/NixonetalBenefitRiskWave2CasestudyReportNatalizumabMarch2013.pdf. Published 2013.

  9. Nixon R, Stoeckert I, Hodgson G, Pears J, Tzoulaki I, Montero D. IMI WP5 report 1:b:iv benefit-risk wave 1 case study report: NATALIZUMAB. http://www.imi-protect.eu/documents/NixonetalBenefitRiskWave1casestudyreportNatalizumabMay2013.pdf. Published 2013.

  10. Juhaeri J, Mt-Isa S, Chan E, Genov G, Hirsch I, Bring J. IMI work package 5: report 1:b:i benefit-risk wave 1 case study report: rimonabant. http://www.imi-protect.eu/documents/JuhaerietalBenefitRiskWave1CasestudyreportRimonabantOct2011.pdf. Published 2011.

  11. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343–349.

    Article  CAS  Google Scholar 

  12. Straube A, Pfaffenrath V, Ladwig KH, et al. Prevalence of chronic migraine and medication overuse headache in Germany: the German DMKG headache study. Cephalalgia. 2010;30:207–213.

    Article  CAS  Google Scholar 

  13. National Headache Foundation. Migraine fact sheet. http://www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed October 22, 2012.

  14. World Health Organization. Global Burden of Disease Study. Geneva, Switzerland: World Health Organization; 2000.

    Google Scholar 

  15. Bigal ME. Migraine and cardiovascular disease. Arquivos de neuro-psiquiatria. 2011;69:122–129.

    Article  Google Scholar 

  16. Schurks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.

    Article  Google Scholar 

  17. Catalyze Ltd. Hiview3. http://www.catalyze.co.uk/.

  18. Dodgson JS, Spackman M, Pearman A, Phillips LD. Multi-criteria Analysis: A Manual. London, UK: Department for Communities and Local Government; 2009.

    Google Scholar 

  19. Zafiropoulos N, Phillips L, Pignatti F. Evaluating benefit-risk: an agency perspective. Regulatory Rapporteur. 2012;9(6):5–8.

    Google Scholar 

  20. Levitan B. A concise display of multiple end points for benefit-risk assessment. Clin Pharmacol Ther. 2011;89:56–59.

    Article  CAS  Google Scholar 

  21. FDA. Rivaroxaban Cardiovascular and Renal Drugs Advisory Committee [briefing document]. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM272005.pdf. Published September 8, 2011.

  22. FDA. Belatacept Cardiovascular and Renal Drugs Advisory Committee [briefing document]. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM203517.pdf. Published March 1, 2010.

  23. FDA. Tanezumab Arthritis Advisory Committee [briefing document]. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM295205.pdf. Published February 8, 2012.

  24. Miller GA. The magical number seven plus or minus two: some limits on our capacity for processing information. Psychological Review. 1956;63:81–97.

    Article  CAS  Google Scholar 

  25. Felli JC, Noel RA, Cavazzoni PA. A multiattribute model for evaluating the benefit-risk profiles of treatment alternatives. Med Decis Making. 2009;29:104–115.

    Article  Google Scholar 

  26. Kirkwood CW. Strategic Decision Making: Multiobjective Decision Analysis With Spreadsheets. Pacific Grove, CA: Duxbury Press; 1996.

    Google Scholar 

  27. Phillips LD. Decision conferencing. In: Edwards W, Miles RF, von Winterfeldt D, eds. Advances in Decision Analysis: From Foundations to Applications. Cambridge, UK: Cambridge University Press; 2007:375–399.

    Chapter  Google Scholar 

  28. Bond SD, Carlson KA, Keeney RL. Generating objectives: can decision makers articulate what they want? Manage Sci. 2008;54:56–70.

    Article  Google Scholar 

  29. Belton V, Stewart TJ. Multiple Criteria Decision Analysis: An Integrated Approach. Boston, MA: Kluwer; 2001.

    Google Scholar 

  30. FDA. Structured approach to benefit-risk assessment in drug regulatory decision-making. http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM329758.pdf. Published 2013.

  31. FDA. The voice of the patient: chronic fatigue syndrome and myalgic encephalomyelitis. http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM368806.pdf. Published 2013.

  32. FDA. The voice of the patient: lung cancer. http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM379698.pdf. Published 2013.

  33. European Medicines Agency. The Patient’s Voice in the Evaluation of Medicines. London, UK: European Medicines Agency; 2013. EMA/607864/2013.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Epidemiology, Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA

    Bennett Levitan MD, PhD

  2. Department of Management, Management Science Group, London School of Economics, London, UK

    Lawrence D. Phillips PhD

  3. Centre for Innovation in Regulatory Science, London, UK

    Stuart Walker PhD MFPM, FIBiol, FRCPath

Authors
  1. Bennett Levitan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lawrence D. Phillips PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stuart Walker PhD MFPM, FIBiol, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bennett Levitan MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Levitan, B., Phillips, L.D. & Walker, S. Structured Approaches to Benefit-Risk Assessment: A Case Study and the Patient Perspective. Ther Innov Regul Sci 48, 564–573 (2014). https://doi.org/10.1177/2168479014536500

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/2168479014536500

Keywords

Search

Navigation