Pharmacovigilance Principles: The Building Blocks of Benefit-Risk Assessment Open Access

Rosa A. Piccirillo, MD and Jennifer Parish, MD MPH

October 17, 2022

DOI: 10.36316/gcatr.04.0045.

Abstract

A medicinal product must demonstrate a favorable benefit-risk balance to remain on the market. That the benefits of use outweigh the risks is established using analyses referred to as benefit-risk assessments, which are conducted on an ongoing basis throughout the lifecycle of a medicinal product. While fundamental to maintaining a product’s marketing authorization, few regulatory guidance documents have been developed to provide information on the specific content and structure of a benefit-risk assessment. This paper aims to provide an overview of the key concepts in pharmacovigilance that contribute to the creation of a structured benefit-risk assessment, particularly through qualitative analysis.

Keywords

Pharmacovigilance; Benefit-risk assessments; Drug safety profile

Copyright©2022 by the author(s). Licensee Global Clinical and Translational Research. This is an open-access article distributed under the terms and conditions of the Creative Commons Attribution License (CCBY4.0, https://creative-commons,org/license/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.

How to cite this article. Piccirillo R and Parish J. Pharmacovigilance Principles: The Building Blocks of Benefit-Risk Assessments. Glob Clin Transl Res. 2022; 4(4): 1-7. DOI:10.36316/gcatr.04.0045.

References

1.         Lezotre PL. Recommendations to Support the Next Phase of International Cooperation, Convergence, and Harmonization in the Pharmaceutical Domain. In: International Cooperation, Convergence and Harmonization of Pharmaceutical Regulations [Internet]. Elsevier; 2014 [cited 2022 May 31]. p. 221–94. DOI

2.         Vargesson N. Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Res Part C Embryo Today Rev. 2015;105(2):140–56. PubMed  DOI

3.         Center for Drug Evaluation and Research. Drugs@FDA Glossary of Terms. FDA [Internet]. 2018 Nov 3 [cited 2021 Oct 15]; Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/drugsfda-glossary-terms

4.         CFR - Code of Federal Regulations Title 21 [Internet]. [cited 2021 Oct 15]. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=314.3

5.         International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH E2A Guideline [Internet]. 1994 [cited 2022 Apr 28]. Available from: https://database.ich.org/sites/default/files/E2A_Guideline.pdf

6.         Aronson JK, Ferner RE. Clarification of Terminology in Drug Safety: Drug Saf. 2005;28(10):851–70. PubMed  DOI

7.         Caster O. Benefit-Risk Assessment in Pharmacovigilance. In: Bate A, editor. Evidence-Based Pharmacovigilance [Internet]. New York, NY: Springer New York; 2018 [cited 2021 Oct 20]. p. 233–57. (Methods in Pharmacology and Toxicology). Available from: http://link.springer.com/10.1007/978-1-4939-8818-1_13.

8.         International conference on harmonization of technical requirements, for registration of pharmaceuticals for human use. Periodic Benefit-Risk Evaluation Report (PBRER) E2C(R2) [Internet]. 2012. Available from: https://database.ich.org/sites/default/files/E2C_R2_Guideline.pdf

9.         ICH Official web site: ICH [Internet]. [cited 2020 Mar 30]. Available from: https://www.ich.org/page/mission

10.      Dal Pan GJ, Arlett PR. The US Food and Drug Administration-European Medicines Agency Collaboration in Pharmacovigilance: Common Objectives and Common Challenges. Drug Saf. 2015;38(1):13–5. PubMed  DOI

11.      Council for International Organizations of Medical Sciences, Working Group IV. Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals Report of CIOMS Working Group IV. CIOMS; 1998.

12.      Council for International Organizations of Medical Sciences, Working Group VIII. Practical aspects of signal detection in pharmacovigilance: report of CIOMS Working Group VIII. Geneva: CIOMS; 2010.

13.      U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). FDA Guidance for Industry. Developing Medical Imaging Drug and Biological Products. Part 1: Conducting Safety Assessments [Internet]. 2004. Available from: https://www.fda.gov/downloads/Drugs/Guidances/ucm071600.pdf.

14.      European Medicines Agency and Heads of Medicines Agencies. Guideline on good pharmacovigilance practices (GVP) Module V – Risk management systems (Rev 2), EMA/838713/2011 Rev 2 [Internet]. 2017 [cited 2022 Jun 14]. Available from:

https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-module-v-risk-management-systems-rev-2_en.pdf.

15.      Center for Drug Evaluation and research. Benefit-Risk Assessment for New Drug and Biological Products [Internet]. The United States Food and Drug Administration; 2021 [cited 2021 Oct 20]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-assessment-new-drug-and-biological-products.

16.      Kisic V, Parish J. False-positive results of radionuclide imaging in lactating breasts: a pharmacovigilance perspective. Glob Clin Transl Res. 2020;2(2):38–45. DOI

17.      Davies M, Osborne V, Lane S, Roy D, Dhanda S, Evans A, et al. Remdesivir in Treatment of COVID-19: A Systematic Benefit-Risk Assessment. Drug Saf. 2020;43(7):645–56. PubMed  DOI

18.      Principles of benefit-risk assessment: A focus on some practical applications [Internet]. FPM. 2020 [cited 2022 Jun 14]. Available from: https://www.fpm.org.uk/blog/principles-of-benefit-risk-assessment-a-focus-on-some-practical-applications/.

19.      NDMA discovered in samples of ranitidine medicines [Internet]. European Pharmaceutical Review. [cited 2021 Oct 15]. Available from: https://www.europeanpharmaceuticalreview.com/news/100017/ndma-discovered-ranitidine-medicines/.

20.      Infarmed. Summary Public Assessment Report: Paracetamol Rompharm 10 mg/ml solution for infusion [Internet]. 2016. Available from: https://mri.cts-mrp.eu/Human/Downloads/PT_H_1556_001_PAR.pdf.

21.      Medicines Evaluation Board in the Netherlands. Public Assessment Report: Paracetamol PharmaMatch 1000 mg, tablets Pharmamatch B.V., the Netherlands. 2011.

22.      Chandler RE, Aoki Y, Sandberg L. WHO Pharmaceuticals Newsletter. 2018;(6):12–9.

23.      Decentralized Procedure - Public Assessment Report: Paracetamol Farmalider 500 / 1000 mg Tabletten Paracetamol (DE/H/6226/001-002/DC) [Internet]. 2019. Available from: https://mri.cts-mrp.eu/human/downloads/DE_H_6226_002_PAR.pdf.

24.    Cranshaw J, McCabe S, Granger L. Guideline for paracetamol use. The Royal Bournemouth and Christchurch Hospital [Internet]. 2012 [cited 2020 Mar 30]. Available from: https://www.dorsetccg.nhs.uk/Downloads/aboutus/medicines-management/Other%20Guidelines/Guideline%20for%20paracetamol%20use%20RBCH.pdf.