Abstract
In the past two decades more than 20 high-profile brand-name drugs including rofecoxib, troglitazone, cisapride, cerivastatin, natalizumab, gemtuzumab, and sibutramine were withdrawn from the market due to drug safety concerns related to severe adverse events. In 2005, the Food and Drug Administration (FDA) issued risk management guidance for the pharmaceutical industry. Subsequently the FDA Amendments Act in 2007 gave the FDA the authority to require pharmaceutical companies to develop and implement a Risk Evaluation and Mitigation Strategy (REMS) for specified prescription drugs and initiated the FDA Sentinel safety surveillance program in order to enhance the benefit-risk balance for pharmaceutical products. This chapter describes some basic concepts of drug safety, post-marketing surveillance, pharmacovigilance, and risk management. The safety signal detection algorithms and regulatory interventions will be also discussed. Finally some commonly used benefit-risk assessments (BRA) will be reviewed and discussed briefly in this chapter since the BRA methods are becoming critical tools for the life cycle of drug development and enhancing decision-making and regulatory interventions. The BRA is only one of unique analyses for clinical trials. Some concepts and methods of BRA may crossover with other analyses discussed in other chapters like “Intention to treat and alternative approaches,” “Cost effectiveness analyses,” and “Development and validation of risk prediction models” Bayesian adaptive designs.
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References
Almenoff JS, Tonning JM, Gould AL et al (2005) Perspectives on the use of data Mining in Pharmacovigilance. Drug Saf 28:981–1007
Bate A, Lindquist M, Edwards IR, Orre R (2002) A data mining approach for signal detection and analysis. Drug Saf 25:393–397
DuMouchel W (1999) Bayesian data mining in large frequency tables, with an application to FDA spontaneous reporting system. Am Stats 53:177–190
Chen Y, Guo JJ, Healy D, Lin X, Patel NC (2008a) Risk of hepatotoxicity associated with the use of Telithromycin: signal detection based upon the FDA’s spontaneous reporting system. Annals Pharmacotherapy 42(12):1791–1796
Chen Y, Guo JJ, Steinbuck M, Lin XD, Buncher CR, Patel C (2008b) Comparisons of data mining algorithms for adverse drug reactions: an empirical study based on the adverse event reporting system of the Food and Drug Administration. J Pharm Med 22(6):359–365
Chuang-Stein C (1994) A New Proposal for Benefit-Less-Risk Analysis in Clinical Trials. Controlled Clinical Trials 15:30–43
Djulbegovic B, Hozo I, Fields K, Sullivan D (1998) High-dose chemotherapy in the adjuvant treatment of breast cancer: benefit/risk analysis. Cancer Control 5:394–405
Evans SJV, Waller PC, Davis S (2001) Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf 10:483–486
Food and Drug Administration (FDA) (2005) FDA Guidance for industry: Premarketing risk assessment. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. Development and use of risk minimization action plans (RiskMAP). Online available at: https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071696.pdf
Food and Drug Administration (FDA) (2018) Benefit-risk assessment in drug regulatory decision-making. Online available at: https://www.fda.gov/files/about%20fda/published/Benefit-Risk-Assessment-in-Drug-Regulatory-Decision-Making.pdf
FDA. (2019) Federal Food, Drug, and Cosmetic Act (FD&C Act). Kefauver-Harris Amendments revolutionized drug development. U.S. Department of Health and Human Services. Online available at: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm322856.htm.https://www.fda.gov/regulatoryinformation/lawsenforcedbyfda/federalfooddrugandcosmeticactfdcact/default.htm. Accessed on January 22, 2019
Garrison LP, Towse A, Bresnahan BW (2007) Assessing a structured, quantitative health outcomes approach to drug risk-benefit analysis. Health Aff 26(3):684–695
Gelber RD, Goldhirsh A (1986) A new endpoint for the assessment of adjuvant therapy in postmenopausal women with operable breast cancer. J Clin Oncol 4:1772–1779
Gelber RD, Goldhirsch A, Cole BF, Wieand HS, Schroeder G, Krook JE (1996) A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer. J Natl Cancer Inst 88(15):1039–1045
Guo JJ, Curkendall S, Jones J, Fife D, Goehring E, She DW (2003) The impact of cisapride label change on codispending of contraindicated medications. J Pharmacoepidemiology Drug Safety 12:295–301
Guo JJ, Jang R, Louder A, Cluxton RJ (2005) Acute pancreatitis associated with different drug therapies among HIV-infected patients. Pharmacotherapy 25(8):1044–1054
Guo JJ, Goehring E, Jones JK (2008) The story of cisapride and its withdraw from market: a case study [book chapter 29]. In: Hartzema AG, Tilson HH, Chan AK (eds) Pharmacoepidemiology and therapeutic risk management. Harvey Whitney Books, Cincinnati, pp 727–738
Guo JJ, Pandey S, Doyle J, Bian B, Raisch D (2010) A review of current risk-benefit assessments for drug safety: report of ISPOR risk-benefit management working group. Value Health 13(5):657–666
Hauben M, Reich L (2004) Safety related drug-labeling changes: findings from two data mining algorithms. Drug Saf 27:735–744
Hauber AB, Mohamed AF, Johnson FR, Falvey H (2009) Treatment preferences and medication adherence of people with type 2 diabetes using oral glucose-lowering agents. Diabet Med 26:416–424
Holden WL, Juhaeri J, Dai W (2003) Benefit-risk analysis: a proposal using quantitative methods. Pharmacoepidemiol Drug Saf 12:611–616
International conference on harmonization (ICH) technical requirements for registration of pharmaceuticals for human use. (2004) ICH harmonized tripartite guideline pharmacovigilance planning E2E. November 2004. Online available at: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2E/Step4/E2E_Guideline.pdf. Accessed on Jan 22, 2019
Johal T, Kuruba N, Sule M, Mukhopadhyay S, Raje G (2018) Laparoscopic salpingectomy and removal of Essure hysteroscopic sterilization device: a case series. Eur J Contracept Reprod Health Care 23(3):227–230
Lis Y, Roberts MH, Kamble S, Guo JJ, Raisch DW (2012) Comparison of FDA and EMA risk management implementation for recent pharmaceutical approvals: report of the International Society for Pharmacoeconomics & outcomes research risk management working group. Value Health 15(8):1108–1118
Lynd LD, O’Brien BJ (2004) Advances in risk-benefit evaluation using probabilistic simulation methods: an application to the prophylaxis of deep vein thrombosis. J Clin Epidemiol 57:795–803
Mussen F, Salek S, Walker S (2007) A quantitative approach to benefit-risk assessment of medicines – part 1: the development of a new model using multi-criteria decision analysis. Pharmacoepidemiol Drug Saf 16:S2–S15
Pray WS, Pray GE (2011) Behind-the-counter products: a third class of drugs. US Pharmacist 36(9):11–15
Shakespeare TP, Gebski VJ, Veness MJ, Simes J (2001) Improving interpretation of clinical studies by use of confidence levels, clinical significance curves, and risk-benefit contours. Lancet 357:1349–1353
Stang PE, Ryan PB, Meng R, Racoosin JA, Overhage JM, Hartzema AG et al (2010) Advancing the science for active surveillance: rationale and design for the observational medical outcomes partnership. Ann Int Med 153:600–606
Zeldis JB, William BA, Thomas SD, Elsayed ME (1999) S.T.E.P.S. a comprehensive program for controlling and monitoring access to thalidomide. Clin Therap 21(2):319–330
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Guo, J.J. (2022). Safety and Risk Benefit Analyses. In: Piantadosi, S., Meinert, C.L. (eds) Principles and Practice of Clinical Trials. Springer, Cham. https://doi.org/10.1007/978-3-319-52636-2_136
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DOI: https://doi.org/10.1007/978-3-319-52636-2_136
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