کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10451105 | 918389 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Impact of responder definition on the enriched enrollment randomized withdrawal trial design for establishing proof of concept in neuropathic pain
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Impact of responder definition on the enriched enrollment randomized withdrawal trial design for establishing proof of concept in neuropathic pain Impact of responder definition on the enriched enrollment randomized withdrawal trial design for establishing proof of concept in neuropathic pain](/preview/png/10451105.png)
چکیده انگلیسی
The objective of this study was to evaluate how enrichment for responders increases assay sensitivity in an enriched enrollment randomized withdrawal (EERW) proof-of-concept (POC) study in neuropathic pain. Adults with moderate to severe peripheral neuropathic pain entered a 3- to 4-day screening period, followed by a 12-day titration to the highest tolerated dose that provided pain control (pregabalin 50-200 mg t.i.d.), and then a 9-day maintenance period. Subjects were stratified as primary responders (⩾30%), secondary responders (⩾10% to <30%), or nonresponders (<10%) based on decrease in pain intensity and were randomized to placebo or pregabalin during the randomized withdrawal period. The primary endpoint was mean of average 24-h pain intensity during the last 3 days of treatment period relative to the 3 days before randomization. Time-to-efficacy-failure was the key secondary endpoint. Other features included not requiring discontinuation of current analgesic therapies and blinding investigators to study design elements that could contribute to non-treatment-related responses. Effect size (ES) (mean treatment difference/SD) was used to measure assay sensitivity. Pregabalin-treated subjects (n = 52) had significantly less pain than those receiving placebo (n = 51) (P ⩽ .003). Effect size of the primary endpoint was 0.72 for primary responders and decreased if secondary and nonresponders were included in the analysis. The highest ES (1.68) was demonstrated for the endpoint time-to-efficacy-failure seen in primary responders with painful diabetic neuropathy. The EERW trial design using time-to-efficacy-failure may provide a sensitive and efficient method to conduct POC studies of novel therapies in patients with neuropathic pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN® - Volume 152, Issue 3, March 2011, Pages 514-521
Journal: PAIN® - Volume 152, Issue 3, March 2011, Pages 514-521
نویسندگان
David J. Hewitt, Tony W. Ho, Bradley Galer, Miroslav Backonja, Paul Markovitz, Arnold Gammaitoni, David Michelson, James Bolognese, Achilles Alon, Elizabeth Rosenberg, Gary Herman, Hao Wang,