Pragmatic pharmacoeconomic analyses by using post-market adverse drug reaction reports: an illustration using infliximab, adalimumab, and the Canada vigilance adverse reaction database

Christopher Longo,Tuhin Maity

doi:10.1186/s12913-021-07260-z

Abstract

BackgroundThe prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT). However, trial conditions do not always reflect the real-world applications of pharmaceutical products; hence, they may not accurately portray the actual risks of ADRs associated with them. The objective of this study is two-fold: (a) demonstrate whether and how post-market and RCT ADR data could lead to different conclusions for a set of drugs of interest, and (b) evaluate the potential economic impact of the post-market ADRs associated with those drugs.MethodsWe selected two TNF-α inhibitor biologics, infliximab and adalimumab, and used the Canada Vigilance Adverse Reaction (CVAR) online database as a source of post-market ADR data. Adverse reaction data from RCTs were obtained from ClinicalTrials.gov. Direct healthcare costs associated with adverse reactions were obtained from Canadian Institute for Health Information (CIHI) or Interactive Health Data Application, Alberta. We calculated post-market ADR rates and compared them with those found in the randomized controlled trials of these two drugs. Using the post-market data, we estimated the costs associated with serious ADRs from three perspectives: patient, health system, and societal.ResultsFor both drugs, the post-market and RCT data exhibited significantly different adverse reaction rates for several different clinical outcomes. As a general trend, more serious adverse reactions, such as death, appeared to have a higher rate in post-market applications compared to the clinical trials. The estimated average annual economic burden of the severe adverse reaction outcomes ranged from $10 million to $20 million for infliximab and $6 million to $19 million for adalimumab.ConclusionsThe frequency and severity of post-market adverse reactions associated with pharmaceutical products may significantly differ from those detected in the clinical trials. Despite possible methodological differences, this is due to the fact that post-market data reflect the externalities of the real-world that are absent in RCTs. The economic burden of adverse reactions can be substantial, and the cost calculated using post-market data is better reflective of the cost of ADRs in the real-world.

Highlights

The prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT)
The frequency and severity of post-market adverse reactions associated with pharmaceutical products may significantly differ from those detected in the clinical trials
This is due to the fact that post-market data reflect the externalities of the real-world that are absent in RCTs

Summary

Introduction

The prediction of the real-world cost of adverse drug reactions (ADRs) has historically relied on the data from randomized controlled trials (RCT). Adverse Drug Reaction (ADR) refers to a harmful and sometimes life-threatening reaction to the use of medicinal products, whether taken as recommended or otherwise [1, 2] It is one of the major causes of morbidity and mortality among hospital patients and in the general population [3, 4]. The economic evaluation of ADRs associated with pharmaceutical products has relied on data from randomized controlled trials (RCTs). Clinical trials are often not powered to detect low-frequency ADRs. Third, an increased level of patient-safety vigilance in RCTs helps avoid serious negative health outcomes, such as fatality, which is typically not present in the real-world setting. As a remedy to this obstacle, the use of postmarket data will be beneficial in more accurately understanding the frequency of ADRs and their actual economic burden

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