Interpreting discordant indirect and multiple treatment comparison meta-analyses: an evaluation of direct acting antivirals for chronic hepatitis C infection

Abstract

Indirect treatment comparison (ITC) and multiple treatment comparison (MTC) meta-analyses are increasingly being used to estimate the comparative effectiveness of interventions when head-to-head data do not exist. ITC meta-analyses can be conducted using simple methodology to compare two interventions. MTC meta-analyses can be conducted using more complex methodology, often employing Bayesian approaches, to compare multiple interventions. As the number of ITC and MTC meta-analyses increase, it is common to find multiple analyses evaluating the same interventions in similar therapeutic areas. Depending on the choice of the methodological approach, the conclusions about relative treatment efficacy may differ. Such situations create uncertainty for decision makers. An illustration of this is provided by four ITC and MTC meta-analyses assessing the efficacy of boceprevir and telaprevir for chronic hepatitis C virus infection. This paper examines why these evaluations provide discordant results by examining specific methodological issues that can strengthen or weaken inferences.

Keywords:

• indirect treatment comparison
• multiple treatment comparison
• meta-analysis
• hepatitis C virus

Supplementary table

Table S1 Approved treatment labels for boceprevir and telaprevir in Europe and North America

Acknowledgments

The academic researchers received funding from Merck Sharp and Dohme to support this study. No restrictions have been placed on the analysis or the interpretation on the results.

Author contributions

KT and EJM have consulted to Merck Sharp and Dohme, Inc, Pfizer Ltd, Novartis, or Takeda on MTC issues. KT and EJM have received grant funding from the Canadian Institutes of Health Research (CIHR) Drug Safety and Effectiveness Network (DSEN) to develop methods and educational materials on MTCs. DSEN had no role in the design and conduct of the study. EJM receives salary support from the CIHR through a Canada Research Chair. KT receives salary support from the CIHR DSEN Netman project. SH and ML are employees of Merck Sharp and Dohme. ED and CLC report no conflicts of interest related to this work.

Disclosure

ED, KT, CLC, and EJM conceived the design of the study. ED drafted the first manuscript. ED, SH, ML extracted the necessary data. All authors contributed equally to the interpretation and final write up of the manuscript.