Neuropathic pain clinical trials

factors associated with decreases in estimated drug efficacy

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 Naga Raja, Niels T. Andersen, Emily S. Sena, Blair H. Smith, Andrew S.C. Rice, Nadine Attal

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2339-2346
Number of pages8
JournalPain
Volume159
Issue number11
DOIs
StatePublished - Nov 1 2018

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Neuralgia
Clinical Trials
Pain
Numbers Needed To Treat
Pharmaceutical Preparations
Meta-Analysis
Pharmacology
Randomized Controlled Trials
Placebos
Therapeutics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Finnerup, N. B., Haroutounian, S., Baron, R., Dworkin, R. H., Gilron, I., Haanpaa, M., ... Attal, N. (2018). Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy. Pain, 159(11), 2339-2346. https://doi.org/10.1097/j.pain.0000000000001340

Neuropathic pain clinical trials : factors associated with decreases in estimated drug efficacy. / Finnerup, Nanna B.; Haroutounian, Simon; Baron, Ralf; Dworkin, Robert H.; Gilron, Ian; Haanpaa, Maija; Jensen, Troels S.; Kamerman, Peter R.; McNicol, Ewan; Moore, Andrew; Raja, Srinivasa Naga; Andersen, Niels T.; Sena, Emily S.; Smith, Blair H.; Rice, Andrew S.C.; Attal, Nadine.

In: Pain, Vol. 159, No. 11, 01.11.2018, p. 2339-2346.

Research output: Contribution to journalArticle

Finnerup, NB, Haroutounian, S, Baron, R, Dworkin, RH, Gilron, I, Haanpaa, M, Jensen, TS, Kamerman, PR, McNicol, E, Moore, A, Raja, SN, Andersen, NT, Sena, ES, Smith, BH, Rice, ASC & Attal, N 2018, 'Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy', Pain, vol. 159, no. 11, pp. 2339-2346. https://doi.org/10.1097/j.pain.0000000000001340
Finnerup NB, Haroutounian S, Baron R, Dworkin RH, Gilron I, Haanpaa M et al. Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy. Pain. 2018 Nov 1;159(11):2339-2346. https://doi.org/10.1097/j.pain.0000000000001340
Finnerup, Nanna B. ; Haroutounian, Simon ; Baron, Ralf ; Dworkin, Robert H. ; Gilron, Ian ; Haanpaa, Maija ; Jensen, Troels S. ; Kamerman, Peter R. ; McNicol, Ewan ; Moore, Andrew ; Raja, Srinivasa Naga ; Andersen, Niels T. ; Sena, Emily S. ; Smith, Blair H. ; Rice, Andrew S.C. ; Attal, Nadine. / Neuropathic pain clinical trials : factors associated with decreases in estimated drug efficacy. In: Pain. 2018 ; Vol. 159, No. 11. pp. 2339-2346.
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