The "Efficacy-Effectiveness Gap": Historical Background and Current Conceptualization

Abstract

Background: The concept of the "efficacy-effectiveness gap" (EEG) has started to challenge confidence in decisions made for drugs when based on randomized controlled trials alone. Launched by the Innovative Medicines Initiative, the GetReal project aims to improve understanding of how to reconcile evidence to support efficacy and effectiveness and at proposing operational solutions.

Objectives: The objectives of the present narrative review were 1) to understand the historical background in which the concept of the EEG has emerged and 2) to describe the conceptualization of EEG.

Methods: A focused literature review was conducted across the gray literature and articles published in English reporting insights on the EEG concept. The identification of different "paradigms" was performed by simple inductive analysis of the documents' content.

Results: The literature on the EEG falls into three major paradigms, in which EEG is related to 1) real-life characteristics of the health care system; 2) the method used to measure the drug's effect; and 3) a complex interaction between the drug's biological effect and contextual factors.

Conclusions: The third paradigm provides an opportunity to look beyond any dichotomy between "standardized" versus "real-life" characteristics of the health care system and study designs. Namely, future research will determine whether the identification of these contextual factors can help to best design randomized controlled trials that provide better estimates of drugs' effectiveness.

Keywords: efficacy-effectiveness gap; outcomes research; pharmaceuticals; pragmatic clinical trials.