• risk minimization intervention;
  • therapeutic risk management;
  • REMS;
  • effectiveness;
  • pharmacoepidemiology



Since the introduction of therapeutic risk management regulatory guidance, an increase in the number of risk minimization interventions (RMIs) published in the literature has been observed. Methods used to evaluate their effectiveness remain, however, poorly examined.


This paper aimed to conduct a literature review on the methods of evaluation of effectiveness of RMIs and to identify methodological gaps.


The search was conducted using MEDLINE and Embase between 1 January 2000 and 31 December 2010, and updated on 1 April 2013. The following characteristics were extracted from each study: target population for the RMI, target population for the assessment of effectiveness, study design, data sources, and effectiveness outcome(s).


A total of 188 unique RMIs were identified in the literature, of which effectiveness was evaluated in only 65 (34.6%) at the time of publication. The largest proportion of studies reviewed (n = 49, 75.4%) attempted to evaluate changes in behavior through prescribing or laboratory test practices. One quarter of studies evaluated the effect of RMIs on the occurrence of adverse events. Only a minority of studies used robust designs, such as randomized controlled trials (n = 6, 9.2%) or a quasi-experimental design with a parallel comparison group (n = 8, 12.3%).


Lack of robust methodological design used in published studies on RMI effectiveness evaluation is an important methodological gap in the evaluation of RMI effectiveness. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.