Estimands in Clinical Trials: The Practical Reference the Drug Development Community Has Been Waiting For
In 2019, the International Council for Harmonisation released the E9(R1) addendum on estimands and sensitivity analysis in clinical trials. Seven years later, the implementation gap has not fully closed. Clinical teams still struggle to translate the framework's five intercurrent event strategies into concrete protocol language. Regulatory submissions still reveal misalignment between stated trial objectives and the statistical methods actually applied. And biostatisticians — from junior analysts to senior directors at major pharmaceutical companies — still lack a single, authoritative reference that covers the framework comprehensively and practically.
Estimands in Clinical Trials: A Practical Guide (Springer, January 2026) fills that gap.
Who Wrote It and Why It Matters
The author team is the strongest possible credential for this book. Jiawei Wei (Senior Director Biostatistician at Novartis, Advanced Methodology and Data Science) and Frank Bretz (Distinguished Quantitative Research Scientist at Novartis and ICH E9(R1) Expert Working Group member) bring direct experience from the development and operationalisation of the framework itself. Leslie Meng (Boehringer Ingelheim) contributes from large-scale drug development across therapeutic areas. Feng Chen (Nanjing Medical University, Chair of China Clinical Trial Statistics Working Group) and Jun Wang (Center for Drug Evaluation, NMPA, China) ensure that the regulatory perspective covers not only FDA and EMA but also the rapidly maturing Chinese regulatory environment.
What the Book Covers
The five-part structure mirrors the lifecycle of an estimand:
- Part I introduces core concepts and provides detailed guidance on describing estimands in clinical trial protocols and statistical analysis plans
- Part II presents case studies across therapeutic areas including oncology, neurology, cardiology, and diabetes — supporting direct implementation
- Part III summarises estimand-related content from regulatory guidelines across major jurisdictions
- Part IV covers statistical methods for handling missing data: multiple imputation, controlled imputation, and sensitivity analysis across continuous, binary, recurrent, and time-to-event endpoints
- Part V applies the framework to adaptive designs, master protocols, non-inferiority trials, multiregional trials, and decentralised clinical trials
Why 2026 Is the Right Moment
FDA and EMA have both intensified expectations around estimand specification in regulatory submissions. The adoption of the framework in China under NMPA is accelerating. And the expansion of decentralised and adaptive trial designs has created new intercurrent event scenarios that the original guidance did not anticipate. This book reflects the accumulated experience of seven years of real-world implementation — and the regulatory community's current expectations.
Q&A
What is the ICH E9(R1) estimand framework?
A structured methodology requiring clinical trial teams to precisely define the treatment effect they intend to estimate — including the population, endpoint, intercurrent event strategies, and population-level summary — before making design and analysis decisions. Introduced in 2019, now expected by FDA, EMA, and NMPA in regulatory submissions.
What are intercurrent events and why do they matter?
Intercurrent events are post-randomisation occurrences that affect either the interpretation or existence of the endpoint — such as treatment discontinuation, use of rescue medication, or death. How these events are handled directly determines what treatment effect is being estimated. The book covers all five ICH E9(R1) strategies in detail, with case studies.
Is this book relevant for regulatory affairs teams, not just statisticians?
Yes. Part III specifically addresses regulatory guidance content from FDA, EMA, and NMPA perspectives, making it directly relevant for regulatory affairs professionals preparing or reviewing submissions.
Who are the authors?
A team of senior biostatisticians and regulatory scientists from Novartis (including an ICH E9(R1) Expert Working Group member), Boehringer Ingelheim, Nanjing Medical University, and China's National Medical Products Administration.
Where can pharmaceutical and medical libraries order this title?
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