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Article Dans Une Revue Alcoholism: Clinical and Experimental Research Année : 2021

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta‐regression analysis to develop an enrichment strategy

1 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
2 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo
3 CESP - Centre de recherche en épidémiologie et santé des populations
4 Hôpital Paul Brousse
5 GU - Göteborgs Universitet = University of Gothenburg
6 UP11 - Université Paris-Sud - Paris 11
7 UniFE - Università degli Studi di Ferrara = University of Ferrara
8 UGA - Université Grenoble Alpes
9 Amsterdam Public Health Research Institute [The Netherlands]
10 IDIBAPS - Hospital Clinic
11 Universität Heidelberg [Heidelberg] = Heidelberg University
12 Brown University
13 JHU - Johns Hopkins University
14 Georgetown University Medical Center
15 NIH - National Institutes of Health [Bethesda, MD, USA]
16 University of Vienna [Vienna]
17 University of Pisa - Università di Pisa
18 Imperial College London
19 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
20 CHU Nîmes - Hôpital Universitaire de Réadaptation, de Rééducation et d'Addictologie du CHU de Nîmes [Grau-du-Roi]
21 University of Toronto
22 TU Dresden - Technische Universität Dresden = Dresden University of Technology
23 Sechenov First Moscow State Medical University
24 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
25 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
26 Hôpitaux Sud - Hôpital Sainte-Marguerite [CHU - APHM]
27 University of Heidelberg, Medical Faculty
Bruno Scherrer
  • Fonction : Auteur
Giovanni Addolorato
Maurice Dematteis
  • Fonction : Auteur
  • PersonId : 860218
Antoni Gual
  • Fonction : Auteur
  • PersonId : 924142
Roch Poulnais
  • Fonction : Auteur
Quentin Raffaillac
  • Fonction : Auteur
Henriette Walter
  • Fonction : Auteur
  • PersonId : 836235

Résumé

Background: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. Methods: We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. Results: Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). Conclusions: Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.
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hal-03629845 , version 1 (01-06-2022)

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Bruno Scherrer, Julien Guiraud, Giovanni Addolorato, Henri-Jean Aubin, Andrea de Bejczy, et al.. Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta‐regression analysis to develop an enrichment strategy. Alcoholism: Clinical and Experimental Research, 2021, 45 (9), pp.1722-1734. ⟨10.1111/acer.14670⟩. ⟨hal-03629845⟩
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