Sample Size Estimation for a Non-Inferiority Pain Management Trial

Abstract

Measuring pain and pain relief are the primary concerns in pain management. Sample size estimation in pain management with non-inferiority (NI) study design and assessment of endpoint specific -NI margins may be challenging as pain and its improvement are measured and reported on different endpoints. Multiple endpoints were reported frequently to measure pain and pain improvement. Sum of pain intensity difference (SPID[0-t]) at a specific time is the recommended endpoint for measurement of pain by the United States Food and Drug Administration. Statistical information on SPID and multiple literature reported other endpoints (preferably from placebo-controlled trials) was collected and compared to identify a suitable NI margin. A difference of 20% was considered as the default NI margin for evaluation, and the sample size was calculated for each endpoint. The sample size based on FDA-recommended primary endpoint SPID, found to be on higher side. This may be a concern for overall clinical operation and availability patients for recruitments in time. Though, the sample size obtained for the minimum clinically important difference (MCID) endpoint was feasible and justifiable from an operational and clinical standpoint. Evaluation and assessment of multiple endpoints before designing an NI study enables rapid decision-making on endpoint selection and increases operational efficiency.