The 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.
We 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.
For 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.
The 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.