link.springer.com

Standardizing the Benefit-Risk Assessment of New Medicines - Pharmaceutical Medicine

  • ️Walker, Stuart
  • ️Thu Aug 23 2012

Abstract

Pharmaceutical scientists and healthcare professionals participating in the development of new medicines bring important practical perspectives to the evaluation of benefits and risks. Within pharmaceutical companies, these specialists can serve to inform the benefit-risk (BR) assessment process, particularly in the latter stages of drug development. However, pharmaceutical scientists may not be aware of the current state of activity in the ongoing efforts to standardize the BR assessment process. In this article, we discuss the role of BR assessment frameworks, activities that are underpinning the standardization of these approaches, and suggest considerations for pharmaceutical scientists to incorporate these into medicine development programmes, regulatory dossiers and clinician communications. Over the past decade there has been an increasing awareness of the potential benefits that can derive from the use of a standardized methodology to assess and communicate a product’s BR profile. Frameworks (in this context defined as the tools and guidelines for their use to facilitate communication of benefits and risks) being developed by the European Medicines Agency, the Pharmaceutical Research and Manufacturers of America Benefit-Risk Action Team (PhRMA BRAT) initiative and the Centre for Innovation in Regulatory Sciences (CIRS), share a common basis in multi-criteria decision analysis and are introduced in this article. To date, quantitative approaches to BRhave been used cautiously because they have lacked the appropriate sophistication, flexibility, ease of use and ability to communicate BR findings. As a result, while a number of quantitative methods have been developed, none have yet achieved widespread endorsement or adoption. Nevertheless, weighting and valuing the underlying criteria can drive a more visual-based presentation of the results, such as through the use of forest plots. BR criteria can be applied to all stage-gate decisions in the lifecycle of a new medicine. Companies should consider developing a skeletal BR model (one based on a consistently applied BR framework) early in a product’s development cycle by assessing whether the product is likely to meet the minimally acceptable thresholds for benefits and risks based on preclinical data and mechanism of action. This process can be used to identify important areas from which to collect information to narrow gaps in knowledge about the BR profile of the product. BR criteria can also inform phase III go/no go decisions. These criteria are then described within the regulatory application to present data using comparable scales. By using a standardized assessment approach that can easily accommodate the parameters associated with the medicine under development, methods can be designed to help communicate the BR profile to a variety of decision stakeholders.

Access this article

Log in via an institution

Subscribe and save

  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

References

  1. Eichler H-G, Bloechl-Daum B, Abadie E, et al. Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers. Nat Rev Drug Discov 2010; 9: 277–91

    Article  PubMed  CAS  Google Scholar 

  2. Unger EF. Weighing benefits and risks: the FDA’s review of prasugrel. N Engl J Med 2009; 361: 942–5

    Article  PubMed  CAS  Google Scholar 

  3. Breckenridge A. Regulatory challenges, reimbursement, and risk-benefit assessment. Clin Pharmacol Ther 2010; 88 (2): 153–4

    Article  PubMed  CAS  Google Scholar 

  4. US Food andDrugAdministration, Center forDrug Evaluation and Research. Guidance for industry: premarketing risk [online]. Available from URL: http://www.fda.gov/CDER/guidance/6357fnl.htm. [Accessed 2010 Oct 22]

  5. Department of Health and Human Services. Food and Drug Administration [docket no. FDA-2008-N-0174]. Identification of drug and biological products deemed to have risk evaluation and mitigation strategies for purposes of the Food and Drug Administration Amendments Act of 2007. Federal Register/ Vol. 73, No. 60/Thursday, March 27/Notices [online]. Available from URL: http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-6201.pdf [Accessed 2011 Mar 16]

  6. Walker S, McAuslane N, Liberti L, et al. Refining the benefit-risk framework for the assessment of medicines: valuing and weighting benefit and risk parameters. Workshop Report, CMR International Institute for Regulatory Science; 2010 Jun 17–18; Washington, DC. London: CMR, 2010 Sep

    Google Scholar 

  7. EMA. Reflection paper on benefit-risk assessment methods in the context of the evaluation of marketing authorisation applications of medicinal products for human use, EMEA/CHMP/15404/2007, London 19 March 2008 [online] Available from URL: http://www.emea.europa.eu. [Accessed 2011 Mar 18]

    Google Scholar 

  8. Cone M, Lisinski T. Measuring benefit and balancing risk: strategies for the benefit-risk assessment of new medicines in a risk-averse environment. Workshop Report, CMR International Institute for Regulatory Science; 2008 Jun 19–20; Washington, DC. London: CMR, 2008 Sep

    Google Scholar 

  9. European Medicines Agency. European Medicines Agency benefit-risk methodology project. Description of the current practice of benefit-risk assessment for centralised procedure products. EMA/213482/2010, London, 30 March 2010 [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2010/04/WC500089603.pdf [Accessed 2011Mar 18]

    Google Scholar 

  10. Phillips LD, Fasolo B, Zafiropoulos N, et al. Benefit-risk methodology project work package 2 report: applicability of current tools and processes for regulatory benefit-risk assessment 31 August 2010 EMA/549682/2010 — revision 1 [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2010/10/WC500097750.pdf [Accessed 2011Mar 18]

  11. Hutton JL. Number needed to treat and number needed to harm are not the best way to report and assess the results of randomised clinical trials. Br J Haematol 2009; 146 (1): 27–30

    Article  PubMed  Google Scholar 

  12. Nexøe J, Kristiansen IS, Gyrd-Hansen D, et al. Influence of number needed to treat, costs and outcome on preferences for a preventive drug. Fam Pract 2005; 22: 126–31

    Article  PubMed  Google Scholar 

  13. Tallarida RJ, Murray RB, Eiben C. A scale for assessing the severity of diseases and adverse drug reactions: application to drug benefit and risk. Clin Pharmacol Ther 1979; 25 (4): 381–90

    Google Scholar 

  14. Gelber RD, Cole BF, Gelber S, et al. Comparing treatments using qualityadjusted survival: the Q-TWiST method. Am Stat 1995; 49: 161–9

    Google Scholar 

  15. Mussen F, Salek S, Walker SR. Benefit-risk appraisal of medicines: a systematic approach to decisionmaking. West Sussex: John Wiley & Sons, Ltd, 2009

    Google Scholar 

  16. Nutt DJ, King LA, Phillips LD, Independent Scientific Committee on Drugs. Drug harms in the UK: a multicriteria decision analysis. Lancet 2010; 376 (9752): 1558–65

    Article  PubMed  Google Scholar 

  17. Chuang-Stein C, Entsuah R, Pritchett Y. Measures for conducting comparative benefit:risk assessment. Drug Inf J 2008; 42: 223–33

    Article  Google Scholar 

  18. Walker S, McAuslane N, Liberti L, et al. Measuring benefit and balancing risk: strategies for the benefit-risk assessment of new medicines in a risk-averse environment. Clin Pharmacol Ther 2009 85; 241–6

    Article  PubMed  CAS  Google Scholar 

  19. Felli JC, Noel RA, Cavazzoni PA. A multiattribute model for evaluating the benefit-risk profiles of treatment alternatives. Med Decis Making 2009 Jan–Feb; 29 (1): 104–15

    Article  PubMed  Google Scholar 

  20. Noel R. Goals and progress of the PhRMA benefit-risk assessment team in developing a structured benefit-risk framework [online]. Available from URL: http://www.diahome.org/cgi-in/MsmGo.exe?grab_id=0&page_id=13600&query=BRATA&hiword=BRAT. [Accessed 2010 Oct 22]

  21. Coplan PM, Noel RA, Levitan BS, et al. Development of a framework for enhancing the transparency, reproducibility and communication of the benefitrisk balance of medicines. Clin Pharm Ther 2011; 89 (2) 312–5

    Article  CAS  Google Scholar 

  22. Liberti L, McAuslane N, Walker SR. Progress on the development of a benefit/ risk framework for evaluating medicines. Reg Focus 2010; 15: 32–7

    Google Scholar 

  23. Working CIOMS Group IV. Benefit-risk balance for marketed drugs: evaluating safety signals. Geneva: Council for International Organizations of Medical Sciences, 1998 [online]. Available from URL: http://www.cioms.ch/publications/g4-benefit-risk.pdf [Accessed 2011 Mar 18]

    Google Scholar 

  24. ICH Harmonised Tripartite Guideline. The common technical document for the registration of pharmaceuticals for human use. Efficacy M4E(R1) 12 September 2002 [online]. Available from URL: http://www.deyounghayden.com/files/ICH_CTD_Overview.pdf [Accessed 2010 Oct 22]

    Google Scholar 

  25. Daemmrich A, Krücken G. Risk versus risk: decision-making dilemmas of drug regulation in the United States and Germany. Sci Cult (Lond.) 2000; 9: 505–34

    Article  CAS  Google Scholar 

  26. Breckenridge A, Woods K. Medicines regulation and the pharmaceutical industry. BMJ 2005; 331: 834–6

    Article  PubMed  Google Scholar 

  27. Eichler H-G, Pignatti F, Flamion B, et al. Balancing early market access to new drugs with the need for benefit/risk data: a mounting dilemma. Nat Rev Drug Discov 2008; 7: 818–26

    Article  PubMed  CAS  Google Scholar 

  28. Liberti L, Walker S, McAuslaneN, et al. Strategies for communicating benefits and risks to decision-makers: explaining methods, findings and conclusions through a common language approach. Workshop Report, CMR International Institute for Regulatory Science; 2009 Jun 17–19; Washington, DC. London: CMR, 200

    Google Scholar 

  29. Baglin T. Communicating benefit and risk. Br J Haematol 2009; 146 (1): 31–3

    Article  PubMed  Google Scholar 

  30. Carling CL, Kristoffersen DT, Montori VM, et al. The effect of alternative summary statistics for communicating risk reduction on decisions about taking statins: a randomized trial. PLoS Med 2009 Aug; 6 (8): E1000134

  31. Schwartz LM, Woloshin S, Welch HG. Using a drug facts box to communicate drug benefits and harms: two randomized trials. Ann Intern Med 2009; 150 (8): 516–27

    PubMed  Google Scholar 

  32. EUNetHTA and EMA joint communications. European Medicines Agency and EUnetHTA Joint Action start collaboration on European Public Assessment Report (EPAR) contribution to relative effectiveness assessments. 2010 Feb 16 [online]. Available from URL: http://www.eunethta.net/upload/Joint%20Action/JA%20WP1/News/EMA_EUnetHTA_16022010.pdf. [Accessed 2010 Oct 22]

    Google Scholar 

Download references

Acknowledgements

The authors have no conflicts of interest to disclose. No sources of funding were used to prepare this article. The authors acknowledge the editorial assistance of Patricia Connelly, ELS in the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Centre for Innovation in Regulatory Science (CIRS), formerly the CMR International Institute for Regulatory Science, The Johnson Building, 77 Hatton Garden, London, EC1N 8JS, UK

    Lawrence Liberti, James Neil McAuslane & Stuart Walker

Authors

  1. Lawrence Liberti

    You can also search for this author in PubMed Google Scholar

  2. James Neil McAuslane

    You can also search for this author in PubMed Google Scholar

  3. Stuart Walker

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence Liberti.

About this article

Cite this article

Liberti, L., McAuslane, J.N. & Walker, S. Standardizing the Benefit-Risk Assessment of New Medicines. Pharm Med 25, 139–146 (2011). https://doi.org/10.1007/BF03256855

Download citation

  • Published: 23 August 2012

  • Issue Date: June 2011

  • DOI: https://doi.org/10.1007/BF03256855

Keywords