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. 2008 Aug;66(2):266-75.
doi: 10.1111/j.1365-2125.2008.03200.x. Epub 2008 Apr 11.

Enriched enrollment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review

Sebastian Straube  1 , Sheena Derry, Henry J McQuay, R Andrew Moore
Affiliations

Enriched enrollment: definition and effects of enrichment and dose in trials of pregabalin and gabapentin in neuropathic pain. A systematic review

Sebastian Straube et al. Br J Clin Pharmacol. 2008 Aug.

Abstract

Aims: Enriched enrollment study designs have been suggested to be useful for proof of concept when only a proportion of the diseased population responds to a treatment intervention. We aim to investigate whether this really is the case in trials of pregabalin and gabapentin in neuropathic pain.

Methods: We defined 'complete', 'partial' and 'non-enriched' enrollment, and examined pregabalin and gabapentin trials for the extent of enrichment and for effects of enrichment on efficacy and adverse event outcomes.

Results: There were no studies using complete enriched enrollment; seven trials used partial enriched enrollment and 14 non-enriched enrollment. In pregabalin trials the maximum extent of enrichment was estimated at about 12%. Partial enriched enrollment did not change estimates of efficacy or harm. Over 150-600 mg maximum daily dose there was strong dose dependence for pregabalin.

Conclusions: A benefit of partial over non-enriched enrollment could not be demonstrated because the degree of enrichment was rather small, and possibly because enrichment produced little enhancement of treatment effect. Whether a greater degree of enrichment would result in important differences is unknown. Researchers reporting clinical trials with any enrichment must describe both process and extent of enrichment. As things stand, the effects of enriched enrollment remain unknown for neuropathic pain trials.

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Figures

Figure 1
Figure 1
Rate of at least 50% pain relief with pregabalin according to the use of partial enriched enrolment (PEE) (formula image) or non-enriched enrolment (NEE) (formula image). Response to placebo was 12, 14, and 19% in PEE trials, and 14, 6, and 14% in NEE trials, for studies with titration to 150, 300, and 600 mg respectively
Figure 2
Figure 2
NNT (at least 50% pain relief compared with placebo) for dose response in pregabalin trials according to the use of partial enriched enrolment (PEE) or non-enriched enrolment (NEE)
See this image and copyright information in PMC

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