Missing data and measurement variability in assessing progression-free survival endpoint in randomized clinical trials

Clin Cancer Res. 2013 May 15;19(10):2613-20. doi: 10.1158/1078-0432.CCR-12-2938.

Abstract

Progression-free survival (PFS) is frequently used as the primary efficacy endpoint in the evaluation of cancer treatment that is considered for marketing approval. Missing or incomplete data problems become more acute with a PFS endpoint (compared with overall survival). In a given clinical trial, it is common to observe incomplete data due to premature treatment discontinuation, missed or flawed assessments, change of treatment, lack of follow-up, and unevaluable data. When incomplete data issues are substantial, interpretation of the data becomes tenuous. Plans to prevent, minimize, or properly analyze incomplete data are critical for generalizability of results from the clinical trial. Variability in progressive disease measurement between radiologists further contributes to data problems with a PFS endpoint. The repercussions of this on phase III clinical trials are complex and depend on several factors, including the magnitude of the variability and whether there is a systematic reader evaluation bias favoring one treatment arm particularly in open-label trials.

Publication types

  • Review

MeSH terms

  • Bias
  • Disease Progression
  • Disease-Free Survival
  • Endpoint Determination / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Outcome Assessment, Health Care / methods*
  • Outcome Assessment, Health Care / standards
  • Randomized Controlled Trials as Topic*
  • Research Design / standards