Systematic review of enriched enrolment, randomised withdrawal trial designs in chronic pain

a new framework for design and reporting

R. Andrew Moore, Philip J. Wiffen, Christopher Eccleston, Sheena Derry, Ralf Baron, Rae F. Bell, Andrea D. Furlan, Ian Gilron, Simon Haroutounian, Nathaniel P. Katz, Arthur G. Lipman, Stephen Morley, Paul M. Peloso, Steve N. Quessy, Kate Seers, Scott A. Strassels, Sebastian Straube

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Enriched enrolment, randomised withdrawal (EERW) pain trials select, before randomisation, patients who respond by demonstrating a predetermined degree of pain relief and acceptance of adverse events. There is uncertainty over the value of this design. We report a systematic review of EERW trials in chronic noncancer pain together with a critical appraisal of methods and potential biases in the methods used and recommendations for the design and reporting of future EERWtrials. Electronic and other searches found 25 EERW trials published between 1995 and June 2014, involving 5669 patients in a randomised withdrawal phase comparing drug with placebo; 13 (median, 107 patients) had a randomised withdrawal phase of 6weeks or less, and 12 (median, 334) lasted 12 to 26weeks. Risks of bias included short duration, inadequate outcome definition, incomplete outcome data reporting, small size, and inadequate dose tapering on randomisation to placebo. Active treatment was usually better than placebo (22/25 trials). This review reduces the uncertainty around the value of EERW trials in pain. If properly designed, conducted, and reported, they are feasible and useful for making decisions about pain therapies. Shorter, small studies can be explanatory; longer, larger studies can inform practice. Current evidence is inadequate for valid comparisons in outcome between EERW and classical trials, although no gross differences were found. This systematic review provides a framework for assessing potential biases and the value of the EERW trials, and for the design of future studies by making recommendations for the conduct and reporting of EERW trials.

Original languageEnglish
Pages (from-to)1382-1395
Number of pages14
JournalPain
Volume156
Issue number8
DOIs
Publication statusPublished - 1 Aug 2015

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Chronic Pain
Pain
Placebos
Random Allocation
Uncertainty
Decision Making
Research Design
Therapeutics
Pharmaceutical Preparations

Keywords

  • Enriched enrolment
  • Methods
  • Randomised withdrawal
  • Recommendations
  • Systematic review

Cite this

Systematic review of enriched enrolment, randomised withdrawal trial designs in chronic pain : a new framework for design and reporting. / Moore, R. Andrew; Wiffen, Philip J.; Eccleston, Christopher; Derry, Sheena; Baron, Ralf; Bell, Rae F.; Furlan, Andrea D.; Gilron, Ian; Haroutounian, Simon; Katz, Nathaniel P.; Lipman, Arthur G.; Morley, Stephen; Peloso, Paul M.; Quessy, Steve N.; Seers, Kate; Strassels, Scott A.; Straube, Sebastian.

In: Pain, Vol. 156, No. 8, 01.08.2015, p. 1382-1395.

Research output: Contribution to journalArticle

Moore, RA, Wiffen, PJ, Eccleston, C, Derry, S, Baron, R, Bell, RF, Furlan, AD, Gilron, I, Haroutounian, S, Katz, NP, Lipman, AG, Morley, S, Peloso, PM, Quessy, SN, Seers, K, Strassels, SA & Straube, S 2015, 'Systematic review of enriched enrolment, randomised withdrawal trial designs in chronic pain: a new framework for design and reporting', Pain, vol. 156, no. 8, pp. 1382-1395. https://doi.org/10.1097/j.pain.0000000000000088
Moore, R. Andrew ; Wiffen, Philip J. ; Eccleston, Christopher ; Derry, Sheena ; Baron, Ralf ; Bell, Rae F. ; Furlan, Andrea D. ; Gilron, Ian ; Haroutounian, Simon ; Katz, Nathaniel P. ; Lipman, Arthur G. ; Morley, Stephen ; Peloso, Paul M. ; Quessy, Steve N. ; Seers, Kate ; Strassels, Scott A. ; Straube, Sebastian. / Systematic review of enriched enrolment, randomised withdrawal trial designs in chronic pain : a new framework for design and reporting. In: Pain. 2015 ; Vol. 156, No. 8. pp. 1382-1395.
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