In February 2018, Evgeny Degtyarev from Novartis and myself started an informal working group to discuss how to implement the ICH E9 draft addendum on estimands in oncological clinical trials.
Goals of the working group
Bring together statisticians from industry, regulators, and academia to ensure common understanding and consistent definitions for key estimands in oncology across and share experiences, intercurrent events, and the used sensitivity analyses. Key questions that are discussed are:
- How can time-to-event (T2E) endpoints be embedded in the addendum framework?
- What are key estimands and intercurrent events in Oncology?
- How do the five strategies to handle intercurrent events proposed in the ICH E9 addendum apply to T2E endpoints?
- How can established methods to answer questions in oncology, e.g. treatment switching or various censoring schemes, be embedded in the addendum framework, what estimands has been usually targeted?
- The addendum in its current version does not require a causal interpretation of a proposed estimand. However, are there parts in the drug development lifecycle that require a causal interpretation of an estimand?
- Being aware that the hazard ratio from Cox regression does not admit a causal interpretation, what are effect measures for T2E endpoints that are amenable to a causal interpretation?
Ways of working
The working group operates within five subteams:
- Causal estimands in time-to-event setting
- Treatment switching
- Censoring mechanisms and their impact on interpretation of estimands
- Case studies in solid tumors
- Case studies in hematology
These subteams hold regular TCs and work on white papers and presentations.
As of August 2019, the working group
- has 32 members (14 from Europe and 18 from US) representing 20 companies,
- regularly interacts with seven Health Authorities globally,
- has started to interact with academic colleagues,
- has organized invited sessions at LIDS 2019 and JSM 2019,
- has given contributed talks at the following conferences:
|Year||Event||Number of talks|
|2019||HTA EFSPI SIG 1-day event||1|
|2019||DIA annual meeting||1|
|2019||ISCB40||1 (+ 1 poster)|
|2019||JSM||4 + FDA discussant|
|2019||EFSPI Regulatory statistics workshop||1|
|2019||ASA biopharmaceutical workshop||3|
In November 2018 EFSPI has granted the WG the official status as EFSPI Special Interest Group for Estimands in Oncology and in June 2019 the ASA biopharmaceutical section has granted the official status as ASA scientific working group.