Ensayos clínicos sobre dolor neuropático: factores asociados con disminuciones en la eficacia estimada del fármaco: Publicado originalmente en la Revista PAIN 159 (2018) 2339–2346. Traducción. Neurotarget.

Nanna B. Finnerup; Simon Haroutounian; Ralf Baron; Robert H. Dworkin; Ian Gilron; Maija Haanpaa; Troels S. Jensen; Peter R. Kamerman; Ewan McNicol; Andrew Moore; Srinivasa N. Raja; Niels T. Andersen; Emily S. Sena; Blair H. Smith; Andrew S.C. Rice; Nadine Attal

doi:10.47924/neurotarget201953

Authors

Nanna B. Finnerup Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Simon Haroutounian Washington University in St. Louis School of Medicine, St Louis, MO, United States
Ralf Baron Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Robert H. Dworkin University of Rochester School of Medicine and Dentistry, Rochester, NY, United States.
Ian Gilron Queen's University and Kingston General Hospital, Kingston, ON, Canada.
Maija Haanpaa Ilmarinen Mutual Insurance Company, Helsinki, Finland.
Troels S. Jensen Danish Pain Research Center, Aarhus University, Aarhus, Denmark.
Peter R. Kamerman Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Ewan McNicol Tufts Medical Center, Tufts University School of Medicine, Boston MA, United States.
Andrew Moore University of Oxford, The Churchill, Oxford, United Kingdom.
Srinivasa N. Raja Johns Hopkins University, Baltimore, MD, United States.
Niels T. Andersen Aarhus University, Aarhus, Denmark.
Emily S. Sena Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Blair H. Smith Division of Population Health Sciences, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland.
Andrew S.C. Rice Imperial College London, London, United Kingdom.
Nadine Attal Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne-Billancourt, France.

DOI:

https://doi.org/10.47924/neurotarget201953

Keywords:

Neuropathic pain, Clinical trial, Numbers needed to treat, Placebo response, Trial design

Abstract

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.

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