Demonstrating heterogeneity of treatment effects among patients: an overlooked but important step toward precision medicine.

  • Competence Center for Methodology and Statistics
July 01, 2019 By:
  • Gewandter JS
  • McDermott MP
  • He H
  • Gao S
  • Cai X
  • Farrar JT
  • Katz NP
  • Markman JD
  • Senn S
  • Turk DC
  • Dworkin RH.

Although heterogeneity in the observed outcomes in clinical trials is often assumed to reflect a true heterogeneous response, it could actually be due to random variability. This retrospective analysis of four randomized, double-blind, placebo-controlled multiperiod (i.e., episode) crossover trials of fentanyl for breakthrough cancer pain illustrates the use of multiperiod crossover trials to examine heterogeneity of treatment response. A mixed-effects model, including fixed effects for treatment and episode and random effects for patient and treatment-by-patient interaction, was used to assess the heterogeneity in patients' responses to treatment during each episode. A significant treatment-by-patient interaction was found for three of four trials (P < 0.05), suggesting heterogeneity of the effect of fentanyl among different patients in each trial. Similar analyses in other therapeutic areas could identify conditions and therapies that should be investigated further for predictors of treatment response in efforts to maximize the efficiency of developing precision medicine strategies.

2019 Jul. Clin Pharmacol Ther.106(1):204-210. Epub 2019 Mar 12.
Other information