[Note: to read the full text of this article free click here. "Number needed to treat" represents the number of subjects who would need to be treated for one to achieve a greater benefit (e.g., 50% greater, considered significantly greater in this analysis) than those taking placebo in a clinical trial.]
Background: Population mean [average] changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.
Methods: We obtained individual patient data from four randomized double blind trials of pregabalin [Lyrica] in fibromyalgia lasting 8 to 14 weeks.
We calculated response for all efficacy outcomes using:
• Any improvement ([greater than or equal to] 0%),
• Minimal improvement ([greater than or equal to]15%),
• Moderate improvement ([greater than or equal to] 30%),
• Substantial improvement ([greater than or equal to] 50%), and
• Extensive improvement ([greater than or equal to]70%)...
with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.
Results: Information from 2,757 patients was available.
Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses.
Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter.
Numbers needed to treat (with 95% confidence intervals) for [greater than or equal to]50% improvement in pain intensity compared with placebo after 12 weeks were:
• 22 (11 to 870) for pregabalin 300 mg, [that is, one in 22 patients taking this dose would achieve a "substantial improvement" in pain of 50% or more above those taking fake dose/placebo]
• 16 (9.3 to 59) for pregabalin 450 mg, and
• 13 (8.1 to 31) for pregabalin 600 mg daily.
Numbers needed to treat for [greater than or equal to]50% improvement in sleep interference compared with placebo after 12 weeks were:
• 13 (8.2 to 30) for pregabalin 300 mg,[that is one in 13 patients taking this dose would achieve a "substantial" 50% or more improvement in sleep above those taking fake dose/placebo]
• 8.4 (6.0 to 14) for pregabalin 450 mg, and
• 8.4 (6.1 to 14) for pregabalin 600 mg.
Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response.
Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.
Conclusions: Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time.
Short trials using 'any improvement' as an outcome overestimate treatment effects.
Source: BMC [BioMedCentral] Musculoskeletal Disorders, Jul 5, 2010;11:150. DOI:10.1186/1471-2474-11-150, by Straube S, Derry S, Moore RA, Paine J, McQuay HJ. Department of Occupational and Social Medicine, University of Göttingen, Germany and Pain Research and Nuffield Department of Anesthetics, University of Oxford, John Radcliffe Hospital, Oxford, UK. [Email firstname.lastname@example.org]