Baseline Pain And Analgesic Consumption Over Time As A Determinant of Post Op Pain Severity

Introduction: There has been much discussion in the context of analgesic drug development regarding which surgical procedures produce mild, moderate and severe pain. Furthermore, related discussion as to what constitutes major or minor surgery often confuses drug developers attempting to select appropriate inclusion/exclusion criteria for acute pain studies. The authors have compiled from numerous published study results various surgical selection criteria such as baseline pain one should consider when designing analgesic clinical trials.

Methods: The authors reviewed and selected over 20 published analgesic clinical trials in an effort to catalog specific surgical criteria to better explain pain severity and durability of various surgical procedures. Surgical procedures evaluated include third molar extraction, hysterectomy, bunionectomy, hip and/or knee replacement, hernia repair, and hammertoe repair. In addition to using baseline pain scores and analgesic consumption over time to compare between surgical procedures the authors also used established efficacy end-points (PI, PID, PR, TOTPAR, SPID) to compare drug response within a clinical study, between studies utilizing the same model, or between models. Comparisons are aided by transforming these variables into quantities known as effect sizes. An effect size is defined as the difference between two means divided by an estimate of the common standard deviation. By looking at differences of means rather than individual means, effect sizes may account for systematic “shifts” due solely to variations in mean starting pain. For several recent investigations on treatments for acute pain, the authors matched studies using the same active treatments, both compared to placebo, and measuring the same efficacy variables, where one study was in a specific post-surgical setting, and the other was in another post-surgical pain setting. Effect sizes were calculated for each study comparing the active treatment to placebo.

Conclusion: Meaningful differences exist between various surgical procedures which could significantly impact analgesic trial outcomes.