Article Text

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression
  1. Rocio Roji1,
  2. Patrick Stone1,
  3. Federico Ricciardi2 and
  4. Bridget Candy1
  1. 1Marie Curie Palliative Care Research Department, University College London, London, UK
  2. 2Department of Statistical Science, University College London, London, UK
  1. Correspondence to Dr Bridget Candy, Marie Curie Palliative Care Research Department, UCL, London WC1E 6BT, UK; b.candy{at}ucl.ac.uk

Abstract

Background Cancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors.

Method RCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool.

Results From 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was −0.23 (95% confidence intervals −0.42 to −0.04). None of the variables analysed in the meta-regression were statistically significant related to PR.

Conclusion There is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results.

  • cancer
  • methodological research
  • fatigue
https://creativecommons.org/licenses/by/4.0/

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Footnotes

  • Contributors All authors were responsible for the study concept and design; RR and BC were responsible to the acquisition of the trial data; all authors were responsible for analysis or interpretation of the data; RR drafted the initial manuscript; BC, FR and PS revised the manuscript critically for important intellectual content; all authors gave the final approval of the version to be published.

  • Funding This work is supported by the Marie Curie I-CAN-CARE Programme grant (MCCC-FPO-16-U) and Core grant (MCCC-FCO-16-U). PS is supported by the Marie Curie Chair’s grant. The department is supported by the UCLH NIHR Biomedical Research Centre.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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