Systematic evaluation of the ‘efficacy‐effectiveness gap’ in the treatment of depression with venlafaxine and duloxetine

Abstract

Evidence of larger drug effects in highly standardized studies (efficacy) compared to clinical routine (effectiveness) is discussed as efficacy-effectiveness gap. This study aimed to quantify effect size differences of RCTs and non-RCTs in the treatment of depression with venlafaxine and duloxetine and to identify effect modifying predictors. Methods: A comprehensive systematic review and meta-analysis was conducted, including all prospective trials, which evaluated the treatment effects of duloxetine or venlafaxine in patients with depression. The primary outcome was the pre-post effect size after acute therapy, which were compared between RCTs and non-RCTs.Moreover, an exploratory analysis of predictors in a mixed meta-regression model within an information-theoretic approach was performed. Results: 171 RCTs and 74 non-RCTs were included. The pre-post effect size differed significantly between RCTs and non-RCTs (−3.04 vs. −2.62, Δ = 0.41, p = 0.012, high heterogeneity). Study characteristics were very similar between RCTs and non-RCTs. Most important variables to predict effect sizes were 'depression severity', 'dose' and 'number of participants'. Conclusion: Despite differences in effect sizes between RCTs and non-RCTs, study design is not clearly an important predictor for the effect sizes. Our results question the common assumption that non-RCTs are generally better suited to describe a drug's effectiveness in clinical practice than RCTs. Future studies and their reporting should put more emphasis on the description of external validity, in order to allow better assessments of clinical relevance. K E Y W O R D Smeta-analysis, depression, psychopharmacology, antidepressives Summations• RCTs showed higher effect sizes than non-RCTs, but the two study designs were very similar in most study characteristics.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Antidepressant treatment effects and country income: meta‐regression analysis of individual participant data from duloxetine trials

“…In preparation of the request, we conducted a systematic review of randomised controlled duloxetine trials for the treatment of depression in major electronic databases (eg Medline, Embase and PsycInfo), public clinical trial registers (eg http://www.clinicaltrials.gov, http://www.clinicaltrialsregister.eu) and the manufacturer database (http://www.lillytrials.com) to identify all published and unpublished trials. Search for and selection of studies followed the same approach that has been described in more detail elsewhere 25 …”

“…Search for and selection of studies followed the same approach that has been described in more detail elsewhere. 25 We submitted the research protocol together with a list of requested trial data. 26 The protocol (see Document S1) was reviewed by an Independent Review Panel at 'http:// www.clini calst udyda tareq uest.com' before the data-sharing agreement was signed.…”

Representation and Outcomes of Individuals With Schizophrenia Seen in Everyday Practice Who Are Ineligible for Randomized Clinical Trials

“…RCT outcomes (efficacy) may differ from the utility of interventions in routine clinical practice (effectiveness), in what has been termed the efficacy-effectiveness gap. Efficacy-effectiveness gaps have been identified in several health care areas, including pneumology, oncology, infectology, and internal medicine; nonpharmacological interventions in psychology; and antidepressants …”

“…Efficacyeffectiveness gaps have been identified in several health care areas, including pneumology, 1,2 oncology, 3 infectology, 4 and internal medicine 5 ; nonpharmacological interventions in psychology 6 ; and antidepressants. 7 A possible efficacy-effectiveness gap in effectiveness and safety of antipsychotics in individuals with schizophrenia, which, to our knowledge, has not been investigated so far, may stem from the strict exclusion criteria applied in typical RCTs aiming at marketing approval. Therefore, a broad and diverse set of individuals is excluded from these trials, such as those experiencing suicidal ideations, substance use disorders, or somatic and psychiatric comorbidities.…”