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Licensed Unlicensed Requires Authentication Published by De Gruyter February 27, 2020

Meta-analysis comparing placebo responses in clinical trials of painful HIV-associated sensory neuropathy and diabetic polyneuropathy

Harriet I. Kemp, Joseph Eliahoo, Lene Vase, Steffany Nguyen, Arbi Ben Abdallah, Andrew S.C. Rice, Nanna B. Finnerup and Simon Haroutounian


Background and aims

The placebo response has been identified as one factor responsible for the lack of therapeutic trials with positive outcomes in neuropathic pain. Reviews have suggested that certain neuropathic pain conditions, including HIV-associated sensory neuropathy (HIV-SN), exhibit a greater placebo response than other neuropathic aetiologies. If true, such a finding could substantially affect clinical trial design and therapeutic developments for these conditions. This study aimed to identify any difference in placebo response between trials of systemic pharmacological intervention in HIV-SN and a comparable neuropathic condition, diabetic polyneuropathy (DPN) and to identify factors influencing the placebo response.


A systematic review search to identify randomised, double-blind studies of systemic pharmacological interventions for painful HIV-SN and DPN published between January 1966 and June 2019 was performed. A meta-analysis of the magnitude of placebo response and the proportion of placebo responders was conducted and compared between the two disease conditions. A meta-regression was used to assess for any study and participant characteristics that were associated with the placebo response. Only studies meeting a methodological quality threshold were included.


Seventy-five trials were identified. There was no statistically significant difference in the proportion of placebo responders (HIV-SN = 0.35; versus DPN = 0.27, p = 0.129). The difference observed in the magnitude of the placebo response [pain reduction of 1.68 (1.47–1.88) DPN; 2.38 (1.87–2.98) in HIV-SN] was based on only 2 trials of HIV-SN and 35 of DPN. Potential factors influencing the placebo response such as psychological measures, were reported inconsistently.


We found no statistically significant difference in the placebo response rate between painful HIV-SN and DPN. Too few studies were available that reported the necessary information to clarify potential differences in the magnitude of placebo response or to elucidate parameters that could be contributing such differences.


The placebo response is one factor that may contribute to a lack of positive trials in neuropathic pain; some etiologies may display larger responses than others. This meta-analysis found no significant difference in placebo response between trials of HIV-associated sensory neuropathy and painful diabetic polyneuropathy, although limited data were available.

Corresponding author: Dr. Harriet I. Kemp, Pain Research Group, Imperial College London, Chelsea and Westminster Campus, 369 Fulham Road, London SW10 9NH, UK

  1. Authors’ statements

  2. Research funding: HIK was funded by a European Commission, NeuroPain FP7 Grant EC (#2013-602891). The funder provided financial support for the conduct and reporting of this research, they did not contribute to study design; nor collection, analysis or interpretation of data; in the writing of this report; nor in the decision to submit the article for publication.

  3. Conflict of interest: NBF has received fees for serving on advisory boards from Grünenthal, Mitsubishi Tanabe, Novartis, Teva Pharmaceuticals, and Merck Selbstmedikation, lecture fees from Astellas, and grant support from Innovative Medicines Initiative. ASCR undertakes consultancy and advisory board work for Imperial College Consultants- in the last 12 months this has included remunerated work for: Merck, Galapagos, Toray, Quartet, Lateral, Novartis and Orion. ASCR was the owner of share options in Spinifex Pharmaceuticals from which personal benefit accrued upon the acquisition of Spinifex by Novartis in July 2015 and from which future milestone payments may occur. ASCR is named as an inventor on patents: Rice A.S.C., Vandevoorde S. and Lambert D.M Methods using N-(2-propenyl)hexadecanamide and related amides to relieve pain. WO 2005/079771; Okuse K. et al. Methods of treating pain by inhibition of vgf activity EP13702262.0/WO2013 110945. SH reports receiving research support from Pfizer Inc. and Disarm Therapeutics, and personal fees from Medoc Ltd. SH reports no conflicts of interest. HIK, LV, JE, ABA, SN report no conflicts of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2019-11-04
Revised: 2020-01-08
Accepted: 2020-01-15
Published Online: 2020-02-27
Published in Print: 2020-07-28

©2020 Scandinavian Association for the Study of Pain. Published by Walter de Gruyter GmbH, Berlin/Boston. All rights reserved.

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