Estimands in oncology: are we censoring for the right reason?
July 1, 2021
Ensuring alignment between the key scientific question of interest, analysis and interpretation during clinical trial design.
The estimands framework, introduced in the ICH E9 (R1) guideline, facilitates discussions during design of clinical trials to ensure alignment between the key scientific question of interest, analysis and interpretation. In the context of oncology solid tumor randomized studies, commonly performed analyses of progression-free survival (PFS) will be reviewed, with a critical eye on which question they address, using the estimands terminology. The estimands framework will not necessarily change common analysis methods within oncology, but will describe in detail how intercurrent events (such as subsequent therapy) will be taken into account and increase transparency on the treatment effect being evaluated.
Since the ICH E9 (R1) guideline became effective, more attention has been given to the fact that censoring or not censoring for intercurrent events actually address different clinical questions.
- The different questions of interest will be mapped to the choice of estimands, with examples of wording for practical implementation in protocol.
- The common practice of censoring PFS for intercurrent events will be discussed. In particular, it may be justified in supplemental analyses but should not be used uncritically.
Corinne Jamoul, MSc: Principal Consultant at the International Drug Development Institute (IDDI)
Corinne holds Master’s degrees in mathematics (ULg) and biostatistics (UHasselt). She has more than 20 years of experience in biostatistics, clinical trials and drug development, and worked for various companies, including BMS, UCB, GSK, Astellas, Merck, and Galapagos. Throughout her career, she provided statistical expertise to cross-functional teams for the design, oversight, and evaluation and reporting of results of phase I to IV clinical trials in various therapeutic areas, including oncology and inflammation/autoimmune diseases.
Marc Buyse, ScD, Chief Scientific Officer at the International Drug Development Institute (IDDI).
Marc holds a ScD in biostatistics from the Harvard School of Public Health (Boston, MA). He is the founder of the International Drug Development Institute (IDDI) and of CluePoints, two biostatistical service organizations based in the US and Europe. He is interested in clinical trial design, meta-analysis, validation of biomarkers and surrogate endpoints, statistical methods in oncology, statistical detection of errors and fraud, statistical monitoring of clinical trials, and medical data sharing. See his works here.