Background of the efficacy-effectiveness gap

A narrative review completed by GetReal examined the literature related to the concept of the efficacy-effectiveness gap (Nordon et al., 2016). The authors used inductive analysis to identify the different ways, here called ‘paradigms’ used to understand the efficacy-effectiveness gap (see Clarify the Issues) that have evolved over the last few decades. These are summarised in the table below.

Paradigm  Description
1. Method used to assess the effects of a medicine
  • The efficacy-effectiveness gap is an issue of measurement: different study designs (RCT vs effectiveness) give different results
  • The efficacy is the real effect whereas effectiveness is a distorted one resulting from biased studies
  • It is acknowledged that RCTs lack external validity or generalisability
2. Impact of patient and clinician’s behaviour or real-life characteristics of the healthcare system
  • A medicine’s ideal effects (efficacy) are distorted by real-life factors, such as clinician and patient behaviour, or adherence to treatment
  • Pragmatic randomised trials have been introduced to combine characteristics of RCTs and observational studies (see Study Design: Pragmatic Trial)
3. Interaction between a medicine’s biological effect and contextual factors
  • The difference between a medicine’s effect in experimental settings and routine practice is because of an interaction of multiple real-life characteristics (or contextual factors) on the biological effect of the medicine (i.e. real-life contextual factors)
  • The current view on understanding the efficacy-effectiveness gap

Current view on the efficacy-effectiveness gap

The third and current paradigm provides the opportunity to look beyond the differences between ‘standardised’ and ‘real-life’ characteristics of the healthcare system and study designs. Many experts consider there to be a continuum between explanatory and pragmatic trials, rather than a simple dichotomy: explanatory vs pragmatic: ‘the explanatory‑pragmatic continuum’. Future research will determine if the identification of these contextual factors can help to design RCTs that provide better estimates of medicines’ effectiveness.

Key contributor

Clementine Nordon, LASER