Task forces

Published

April 1, 2024

After a first phase where five subteams have written several publications (see publications) the working group now operates within seven task forces. Objectives and member rosters of these task forces are available below.

Task forces that are active and take new members

Principal stratification in clinical trials

Lead: Yufei Wang (GSK)

Objective: This task force performs periodical literature reviews of principal stratum applied to treatment switching, focusing on the analysis of overall survival. It aims to evaluate and improve existing methods, develop new principal stratification models for treatment switching, e.g. through simulation studies to compare operating characteristics, relaxation/stress test of key assumptions, prior selection for Bayesian analysis, and software for implementation.

Communication of results is intended to happen through publication(s) for peer-reviewed journals, presentations/round-table discussions/trainings at various forums (JSM, DIA, FDA workshop, ISCB, …).

Firstname Lastname Institution Location
Yufei Wang GSK Europe
Natalia Kan-Dobrosky Abbvie NorAm
Kaifeng Lu Beigene NorAm
Mehreteab Aregay Daiichi Sankyo NorAm
Peixin Zhang Incyte NorAm
Satrajit Roychoudhury Pfizer NorAm
Songzi Li NA NorAm

Conditional vs. marginal effects

Lead: Jiawei Wei (Novartis)

Objective: We would like to bring the complex concept and methods about conditional and marginal treatment effect into a simplified and interpretable way. Potential topics including adjusted or unadjusted analysis; stratified vs unstratified hazard ratio; collapsibility and subgroup; p-values; etc. We will give clinically relevant opinions and recommendations based on our interpretation, and illustrate the idea using some case studies.

The conditional and marginal effects task force will continue its work beyond 2024 under the ASA BIOP Covariate Adjustment SWG.

Firstname Lastname Institution Location
Jiajun Xu J&J Asia
Bingying Xie Junshi Pharma Asia
Jiawei Wei Novartis Asia
Ziqiang Zhao Novartis Asia
Xin Zhang Pfizer Asia
Liming Li Roche Asia
Sarwar Mozumder AstraZeneca Europe
Björn Bornkamp Novartis Europe
Hong Tian Beigene NorAm
Dong Xi Gilead NorAm
Alex Sverdlov Novartis NorAm
Satrajit Roychoudhury Pfizer NorAm
Ray Lin Roche NorAm
Qing Xu Taiho Oncology NorAm
Jonathan Chipman University of Utah NorAm

Time to event endpoints with prognostic or predictive biomarker subgroups

Lead: Hong Tian (Beigene), Miao Yang (Seagen)

Objective: Our goal is to understand various efficacy estimands of biomarker subgroups and its relationship to the overall population for binary and time-to-event endpoints. For continuous outcomes with difference of means as efficacy estimand, Least Square estimates from the full model containing treatment, subgroup, and its interaction term enable an unbiased estimation of efficacy for the overall population by linearly combining estimands of the two subgroups. Following the same process for binary or time-to-event efficacy estimands such as hazard ratio or odds ratio, although guaranteeing logical inference in appearance, does not lead to the correct efficacy estimand of the overall population. In fact, the correct HR (or OR) may be outside of the interval of subgroup HRs (or ORs) leading to illogical interpretations. The task force will investigate which efficacy measures are logic respecting on the population level and make recommendations on how to analyze real clinical trial data so that analysis results based on these efficacy measures will always be logical for either prognostic or predictive biomarkers.

Firstname Lastname Institution Location
Siyoen Kil LSK Global Pharma Services Asia
Hong Sun BMS Europe
Min-Hua Jen Lilly Europe
Francois Mercier Roche Europe
Shoubhik Mondal AstraZeneca NorAm
Hong Tian Beigene NorAm
Yue Shentu Daiichi Sankyo NorAm
Haiming Zhou Daiichi Sankyo NorAm
Liwei Wang Genmab NorAm
Yi Liu Nektar NorAm
Wenchuan Guo Seagen NorAm
Miao Yang Seagen NorAm

Task forces that are active but do not take any new members

Real-world data and estimands

Lead: Evgeny Degtyarev (Novartis)

Objective: Illustrate the value and promote the use of target trial framework and estimand framework for design of comparisons including real-world data. The frameworks allows to clarify the definition of the causal question of interest ensuring alignment between the research objective and analysis. Its application in submission documents would facilitate regulatory review in a transparent and structured way.

Firstname Lastname Institution Location
Rajat Mukherjee Alira Health Europe
Annette Sauter J&J Europe
Evgeny Degtyarev Novartis Europe
Lisa Hampson Novartis Europe
Zhaohui Wang GSK NorAm
Benjamin Li Pfizer NorAm
Rui Tang Servier NorAm
Jianchang Lin Takeda NorAm
Feng Xiao Vanda Pharma NorAm
Cheng Zheng Zentalis NorAm
Lei Gao NA NorAm

Estimands for Safety

Lead: Jonathan Siegel (Bayer)

Objective: Key issues of interest for this task force are: (1) Estimands for safety-focused studies (2) Safety estimands within the context of a conventional efficacy study (3) Implementing estimands principles in general safety reporting and analysis (including what to change and what to leave in place) (4) Implementing estimands principles in associated CRF and data standards. The mission of the group is up for discussion and I would appreciate your interest.

The envisioned output for the group would be white papers, one focused on study design and statistical methodological considerations in safety estimands, and one focused on more nuts-and-bolts implementation issues including recommendations for general safety reporting, visit schedule and withdrawal criteria issues, monitoring, CRF considerations, data considerations and changes in data standards etc. In addition, the TF plans to involve itself in WG discussions with and recommendations to regulatory authorities, conference presentations, outreach webinars and workshops, etc.

Firstname Lastname Institution Location
Jiawei Wei Novartis Asia
Alan Phillips AJPStatistics Europe
Luc Boone EORTC Europe
Murielle Maurer EORTC Europe
Marie-Laure Casadebaig Incyte Europe
Anja-Helena Loos Merck Europe
Pedro Lopez Romero Novartis Europe
Remi Aprahamian Servier Europe
Alexander Stemke NA Europe
Greg Ball ASAP Process Planning NorAm
Natalia Kan-Dobrosky Abbvie NorAm
Jonathan Siegel Bayer NorAm
James Buchanan Covilance NorAm
Philip He DSI NorAm
Shayami Thanabalasundrum Exelis NorAm
Shanti Gomatam FDA NorAm
Isabel Huang ICON NorAm
Steven Sun J&J NorAm
Mary Nilsson Lilly NorAm
Mengchun Li Merck NorAm
Hongtao Zhang Merck NorAm
Yi Lan Novartis NorAm
Craig Mallinckrodt Pentara Corp NorAm
Rui Tang Servier NorAm

Task forces or subteams that have concluded their work (apart from ongoing paper revisions)

Patient-reported outcomes

Lead: Rachael Lawrance (Adelphi)

Objective: Clarify what questions are we answering with typical analyses conducted on HRQoL endpoints in regulatory clinical trials. We are going to consider longitudinal mixed models and time to event analyses initially; “mapping” potential common questions into the estimand framework. The task force is also going to dig into the question of “how to handle death” in HRQoL analyses. We are keen to build collaborative approaches with statisticians and others active in this topic area, such as SISAQoL and ISOQoL working groups.

2021 summary on backfitting MMRM

This taskforce has concluded its work. As a spin-off a new EFSPI SIG is to be initiated in early 2024. If you are interested to join please reach out to Rachael Lawrance.

Firstname Lastname Institution Location
Rachael Lawrance Adelphi Europe
Rajat Mukherjee Alira Health Europe
Xiangning Huang AstraZeneca Europe
Konstantina Skaltsa IQVIA Europe
Antoine Regnault Modus Outcomes Europe
Evgeny Degtyarev Novartis Europe
Stephen Corson Phastar Europe
Jonathan Siegel Bayer NorAm
Libby Floden ClinOutSolutions NorAm
Devin Peipert Northwestern University Feinberg School of Medicine NorAm
Dave Andrae NA NorAm

Quantification of follow-up

Lead: Kaspar Rufibach (Roche)

Objective: This task force has submitted a paper entitled Quantification of Follow-up Time in Oncology Clinical Trials with a Time-to-Event Endpoint: Asking the Right Questions, find the link on the publications page. All questions initially asked have been discussed in this paper and the task force is therefore currently inactive.

Firstname Lastname Institution Location
Lynda Grinsted AstraZeneca Europe
Hans-Jochen Weber Novartis Europe
Kaspar Rufibach Roche Europe
Jiang Li Beigene NorAm
Yue Shentu Daiichi Sankyo NorAm
Jiangxiu Zhou J&J NorAm
Cheng Zheng Zentalis NorAm

Early development estimand nexus (EDEN)

Lead: Francois Mercier (Roche)

Objective: In oncology Phase 1a (dose-escalation) and Phase 1b (expansion cohort) studies, the designs are complex because the objectives are often multiple and ambitious. Defining estimands and the associated estimators in this setting can be difficult. In this WG, we intend to implement the ICH-E9 addendum and to reflect on the challenges it presents in early clinical development studies. Such challenges may include: (1) absence of control group (2) varying dose, but also dosing schedule across treatment arms (a.k.a. cohorts) (3) presence of anti-drug antibody (ADA) (4) prophylactic treatment or co-medication for toxicity mitigation (e.g. using steroids) (5) compassionate within-patient dose escalation. The taskforce will give clinically relevant opinions and recommendations based on our analysis and interpretation of the selected case studies. Contact to other task forces will be sought based on need.

Firstname Lastname Institution Location
Elizabeth Pilling AstraZeneca Europe
Victoria Homer Cancer Research UK Clinical Trials Unit Europe
Stefan Englert J&J Europe
Christina Habermehl Merck Europe
Anja Victor Merck Europe
Francois Mercier Roche Europe
Natalia Kan-Dobrosky Abbvie NorAm
Atalanta Ghosh BMS NorAm
Junxian Geng Boehringer NorAm
Hongtao Zhang Merck NorAm
Guillaume Lecorps Sanofi NorAm
Xiaojiang Zhan Servier NorAm

Estimands engagement

Lead: NA NA (NA)

Objective: Develop basic introductory material that can be used by all study team members to educate themselves on Oncology Estimands. Translate key messages from the working group activities to a non-statistical audience, targeting especially clinical functions.

This taskforce has concluded its work. Further activities will be organized under the Estimand Implementation Working Group (EWIG). If you are interested to contribute please reach out to Stefan Englert.

Firstname Lastname Institution Location
Jiawei Wei Novartis Asia
Stefan Englert J&J Europe
Jonathan Siegel Bayer NorAm
Feng Liu Marengo Therapeutics NorAm
Rui Tang Servier NorAm

Duration of responses

Lead: NA NA (NA)

Objective: Duration of response and also time to response are standard secondary endpoints in clinical studies in oncology. The tasks force has concluded its work, see publication #12 on the list.

Firstname Lastname Institution Location
Alex Todd AstraZeneca Europe
Hong Sun BMS Europe
Martin-Oliver Sailer Boehringer Europe
Min-Hua Jen Lilly Europe
Hans-Jochen Weber Novartis Europe
Stephen Corson Phastar Europe
Francois Mercier Roche Europe
Jiang Li Beigene NorAm
Steven Sun J&J NorAm
Satrajit Roychoudhury Pfizer NorAm
Godwin Yung Roche NorAm
Wenchuan Guo Seagen NorAm

Treatment Switching

Lead: Viktoriya Stalbovskaya (Merus)

Objective: Subteam that looked into treatment switching. Published paper, see publications.

Firstname Lastname Institution Location
Jianhong Pan China Asia
Jun Wang China Asia
Yuki Ando Japan Asia
Ayako Hara Japan Asia
Xin Zhang Pfizer Asia
Guei-Feng Tsai Taiwan Asia
Hong Sun BMS Europe
Marie-Laure Casadebaig Incyte Europe
Min-Hua Jen Lilly Europe
Viktoriya Stalbovskaya Merus Europe
Anja Schiel Norway Europe
Evgeny Degtyarev Novartis Europe
Hannes Buchner Staburo Europe
Natalia Kan-Dobrosky Abbvie NorAm
Catherine Njue Canada NorAm
Yue Shentu Daiichi Sankyo NorAm
Juliane Manitz EMD Serono NorAm
Emily Martin EMD Serono NorAm
Jiangxiu Zhou J&J NorAm
Godwin Yung Roche NorAm
Wenchuan Guo Seagen NorAm
Rui Tang Servier NorAm

Causal estimands

Lead: Kaspar Rufibach (Roche)

Objective: Subteam that looked into how to merge causal inference with the ICH E9 addendum. Published a paper on the principal stratum strategy, see publications.

Firstname Lastname Institution Location
Jianhong Pan China Asia
Jun Wang China Asia
Yuki Ando Japan Asia
Ayako Hara Japan Asia
Guei-Feng Tsai Taiwan Asia
Alan Phillips AJPStatistics Europe
Andreas Brandt Germany Europe
Marie-Laure Casadebaig Incyte Europe
Anja Schiel Norway Europe
Björn Bornkamp Novartis Europe
Kaspar Rufibach Roche Europe
An Vandebosch argenx Europe
Catherine Njue Canada NorAm
Yue Shentu Daiichi Sankyo NorAm
Emily Martin EMD Serono NorAm
Feng Liu Marengo Therapeutics NorAm
Devan Mehrotra Merck NorAm
Yi Liu Nektar NorAm
Satrajit Roychoudhury Pfizer NorAm
Audrey Boruvka Roche NorAm
Jianchang Lin Takeda NorAm

Censoring

Lead: Jonathan Siegel (Bayer)

Objective: Subteam that looked into how to embed censoring into the ICH E9 addendum framework. Two papers currently under review, see publications.

Firstname Lastname Institution Location
Jianhong Pan China Asia
Jun Wang China Asia
Yuki Ando Japan Asia
Ayako Hara Japan Asia
Xin Zhang Pfizer Asia
Guei-Feng Tsai Taiwan Asia
Lynda Grinsted AstraZeneca Europe
Sarwar Mozumder AstraZeneca Europe
Andreas Brandt Germany Europe
Stefan Englert J&J Europe
Anja Schiel Norway Europe
Hans-Jochen Weber Novartis Europe
Kaspar Rufibach Roche Europe
Natalia Kan-Dobrosky Abbvie NorAm
Shoubhik Mondal AstraZeneca NorAm
Jonathan Siegel Bayer NorAm
Catherine Njue Canada NorAm
Steven Sun J&J NorAm
Jiangxiu Zhou J&J NorAm
Feng Liu Marengo Therapeutics NorAm
Michelle Casey Mural Oncology NorAm

Hematology

Lead: Evgeny Degtyarev (Novartis)

Objective: Subteam that looked into estimands for solid tumors. Published paper, see publications.

Firstname Lastname Institution Location
Jianhong Pan China Asia
Jun Wang China Asia
Yuki Ando Japan Asia
Ayako Hara Japan Asia
Guei-Feng Tsai Taiwan Asia
Martin-Oliver Sailer Boehringer Europe
Viktoriya Stalbovskaya Merus Europe
Anja Schiel Norway Europe
Evgeny Degtyarev Novartis Europe
Catherine Njue Canada NorAm
Feng Liu Marengo Therapeutics NorAm
Rui Tang Servier NorAm

Solid tumors

Lead: Steven Sun (J&J)

Objective: Subteam that looked into estimands in hematology indications. Published paper, see publications.

Firstname Lastname Institution Location
Jianhong Pan China Asia
Jun Wang China Asia
Yuki Ando Japan Asia
Ayako Hara Japan Asia
Guei-Feng Tsai Taiwan Asia
Lucy DeCosta Amgen Europe
Viktoriya Stalbovskaya Merus Europe
Anja Schiel Norway Europe
Hans-Jochen Weber Novartis Europe
Kaspar Rufibach Roche Europe
Catherine Njue Canada NorAm
Steven Sun J&J NorAm
Satrajit Roychoudhury Pfizer NorAm