Influence of flare design on symptomatic efficacy of non-steroidal anti-inflammatory drugs in osteoarthritis: a meta-analysis of randomized placebo-controlled trials

Abstract

Our study suggests that the flare design used in clinical trials evaluating NSAIDs results in a treatment effect of higher magnitude. These results should be considered when designing a trial and/or interpreting the results of a trial.

Does flare trial design affect the effect size of non-steroidal anti-inflammatory drugs in symptomatic osteoarthritis? A systematic review and meta-analysis

“…Mean change in pain at short-term follow-up was significantly higher in non-flare than flare and possible flare trial designs. These results differ from previous findings 8. The current study included an increased number of trials: while the earlier paper assessed 33 studies, all of which were included in the current analysis, an additional 24 trials contributed to our analysis.…”

“…Trijau et al 8 previously presented a well designed meta-analysis comparing the efficacy of NSAIDs in flare and non-flare design trials. They reported that flare trials evaluating NSAIDs resulted in a higher magnitude of treatment effect compared with non-flare trials.…”

Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement

“…Further improvement of study design could be reached by requiring a flaring design in knee OA patients 30 and considering the documented differences in the outcome between knee and hip OA by assessing the locations separately 19 .…”

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

“…Other studies often use a wash-out period, 11,14 or even need a flare of symptoms after a wash-out period 25 prior to randomisation. Use of a flare design might result in higher treatment effects, 26 and this might reduce generalisability of the results in daily practice. Although placebocontrolled trials are important as proof of principle, pragmatic trials (open label) are also needed to assess the effectiveness of treatments in daily practice.…”