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Ethical justification of single-blind and double-blind placebo-controlled response tests in neuropathic pain and N-of-1 treatment paradigm in clinical settings

Authors Keppel Hesselink JM, Kopsky DJ, Bhaskar AK

Received 19 July 2018

Accepted for publication 6 December 2018

Published 14 January 2019 Volume 2019:12 Pages 345—352


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr E Alfonso Romero-Sandoval

Jan M Keppel Hesselink,1 David J Kopsky,2 Arun K Bhaskar3

1Institute for Neuropathic Pain, Bosch en Duin, The Netherlands; 2Institute for Neuropathic Pain, Amsterdam, The Netherlands; 3Pain Management Centre, Charing Cross Hospital Imperial Healthcare NHS Trust, London, UK

Abstract: At our center in the Netherlands, patients, who very often are treatment resistant to the analgesics recommended in the guidelines, suffering from symmetrical peripheral neuropathic pain are treated exclusively. We have developed a number of compounded topical formulations containing classical co-analgesics such as ketamine, baclofen, amitriptyline, and phenytoin for the treatment of neuropathic pain in treatment-resistant patients. In order to identify putative responders and exclude an (initial) placebo-response, we developed single-blind and double-blind placebo-controlled response tests. The test can be performed when the patient has a symmetrical polyneuropathy with a pain score difference of not more than 1 point on the 11-point numerical rating scale (NRS) between bilateral pain areas. On one area (eg, left foot) the placebo cream and on the other area (eg, right foot) the active cream will be applied. Within a time frame of 30 minutes, patients are considered responders if they rate a pain difference of at least 2 points on the NRS between the bilateral areas on which the active cream and placebo cream are applied. Response tests can be easily conducted during the first consultation. In this paper, we explore the ethical context of using a placebo in clinical practice in a single-blind and double-blind fashion to improve and individualize treatment of neuropathic pain outside a context of a formal clinical trial.

Keywords: ethics, trial, topical, treatment, enrichment

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