Inferential reproduction analysis demonstrated that “paracetamol for acute low back pain” trial conclusions were reproducible

Abstract

Objectives: The aim of this study was to reanalyze and reinterpret data obtained in Paracetamol in Acute Low Back Pain (PACE), the first large randomized controlled trial evaluating the efficacy of paracetamol in acute low back pain, to assess the inferential reproducibility of the original conclusions.Study Design and Setting: Mixed effects models were used to reanalyze pain intensity (primary outcome; 11-point Numeric Rating Scale) and physical functioning, health-related quality of life, sleep quality, and time until recovery (as secondary outcomes), according to the intention-to-treat principle. The original authors of the PACE study were not involved in the development of the methods for this reanalysis.Results: The reproduction analyses indicated no effect of treatment on pain intensity and confidence intervals excluded clinically worthwhile effects (adjusted main effect for regular paracetamol vs. placebo 0.00 [À0.02, 0.01; P 5 0.85]; adjusted main effect for paracetamol as-needed vs. placebo 0.00 [À0.02, 0.01; P 5 0.92]). Similar results were obtained for all secondary outcomes.Conclusion: This study indicates that the conclusions of the PACE trial are inferentially reproducible, even when using a different analytical approach. This reinforces the notion that the management of acute low back pain should focus on providing patients advice and reassurance without the addition of paracetamol.

Paracetamol for low back pain: the state of the research field

“…no difference between paracetamol vs placebo) were also found in the subgroups of patients with severe pain-intensity and severe impairment of physical functioning. Overall, the re-analysis confirmed the original analysis and results of the PACE-trial and strengthen its conclusions [40].…”

Effectiveness of placebo interventions for patients with nonspecific low back pain: a systematic review and meta-analysis

“…In the field of low back pain (LBP, the most disabling condition worldwide 13,24 ), conservative interventions are often administered to patients, 63 despite evidence suggesting that such interventions have modest effects(0-9 points on a scale of 0-100) at best when compared with placebo. 11,55,57 It has been suggested that sham oral medication could produce clinically meaningful change in pain scores in patients with LBP without a specific nociceptive source for their complaints (eg, LBP 24 ), 52 thus contradicting earlier evidence regarding the magnitude of placebo interventions for pain. 31 However, studies with a no intervention group were not included in this systematic review, which makes it impossible to actually estimate the magnitude of the placebo effect vs no intervention in LBP.…”

Teaching reproducible research for medical students and postgraduate pharmaceutical scientists

“…There are indeed positive examples for well-reproduced analyses and their added value in the current literature. In particular, in their re-analysis pursuing inferential reproducibility of the PACE ("paracetamol for acute low back pain") trial data, Schreijenberg et al were able to confirm the results from earlier analyses of the same data [10]. This re-analysis demonstrated that trial conclusions were reproducible even after replication with a different methodological approach.…”