Jens Laigaard1, Casper Pedersen2, Thea Nørgaard Rønsbo2, Ole Mathiesen3, Anders Peder Højer Karlsen2. 1. Centre for Anaesthesiological Research, Department of Anaesthesia, Zealand University Hospital, Køge, Denmark. Electronic address: Jenslaigaard@hotmail.com. 2. Centre for Anaesthesiological Research, Department of Anaesthesia, Zealand University Hospital, Køge, Denmark. 3. Centre for Anaesthesiological Research, Department of Anaesthesia, Zealand University Hospital, Køge, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND: Sample size determination is essential for reliable hypothesis testing in clinical trials and should rely on adequate sample size calculations with alpha, beta, variance, and an effect size being the minimal clinically important difference (MCID). This facilitates interpretation of the clinical relevance of statistically significant results. No gold standard for MCIDs exists in postoperative pain research. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for English language articles on randomised trials investigating analgesic interventions after total hip or knee arthroplasty. Primary outcomes were the reported MCIDs for pain score and cumulated rescue opioid consumption. Secondary outcomes included reported sample size calculations and propensity to report statistical significance without reaching MCID. Trend analyses were conducted using statistical process control. RESULTS: We included 570 trials. Median MCID for 0-24 h opioid consumption was 10 mg i.v. morphine equivalents for absolute reductions (interquartile range [IQR]: 6.8-14.5) and relative 40% (IQR: 30-50%). Median MCIDs for pain scores were absolute 15 mm at rest (IQR: 10-20) and 18 mm during movement (IQR: 10-20) on a 0-100 mm VAS and relative 30% (IQR: 20-30%). No trends were demonstrated for MCIDs. Adequate sample size calculations were reported in 34% of trials. In 46% of trials with statistically significant primary outcomes, the differences did not reach the predetermined MCID. CONCLUSIONS: We provide clinician-perceived MCID estimates for rescue opioid consumption and pain scores that can be used for sample size calculations until reliable evidence-based patient-rated MCIDs emerge. Nearly half of the trials with significant findings did not reach the predetermined MCID.
BACKGROUND: Sample size determination is essential for reliable hypothesis testing in clinical trials and should rely on adequate sample size calculations with alpha, beta, variance, and an effect size being the minimal clinically important difference (MCID). This facilitates interpretation of the clinical relevance of statistically significant results. No gold standard for MCIDs exists in postoperative pain research. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for English language articles on randomised trials investigating analgesic interventions after total hip or knee arthroplasty. Primary outcomes were the reported MCIDs for pain score and cumulated rescue opioid consumption. Secondary outcomes included reported sample size calculations and propensity to report statistical significance without reaching MCID. Trend analyses were conducted using statistical process control. RESULTS: We included 570 trials. Median MCID for 0-24 h opioid consumption was 10 mg i.v. morphine equivalents for absolute reductions (interquartile range [IQR]: 6.8-14.5) and relative 40% (IQR: 30-50%). Median MCIDs for pain scores were absolute 15 mm at rest (IQR: 10-20) and 18 mm during movement (IQR: 10-20) on a 0-100 mm VAS and relative 30% (IQR: 20-30%). No trends were demonstrated for MCIDs. Adequate sample size calculations were reported in 34% of trials. In 46% of trials with statistically significant primary outcomes, the differences did not reach the predetermined MCID. CONCLUSIONS: We provide clinician-perceived MCID estimates for rescue opioid consumption and pain scores that can be used for sample size calculations until reliable evidence-based patient-rated MCIDs emerge. Nearly half of the trials with significant findings did not reach the predetermined MCID.