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Updated: May 11, 2026

Establishing a Competing Risk Regression Nomogram Model for Survival Data
Published on: October 23, 2020
Missing data and measurement variability in assessing progression-free survival endpoint in randomized clinical
Rajeshwari Sridhara1, Sumithra J Mandrekar, Lori E Dodd
1CDER/OTS/OB/DBV, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA. rajeshwari.sridhara@fda.hhs.gov
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.
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