Medical Writing Patient-reported outcomes Estimands – closing the gap between study design and analysis

Volume 27, Issue 4 - Patient-reported outcomes

Estimands – closing the gap between study design and analysis


Estimands represent a new way to look at key aspects of clinical research and will become increasingly important for medical writers. Estimands are detailed definitions of quantities to be estimated using clinical trial data, which make allowance for events that happen after randomisation. Such postrandomisation events include, for example, treatment discontinuation due to poor tolerability or lack of efficacy, and use of rescue medication. Through a worked example, this article elucidates several different kinds of estimands and shows how the estimands approach has the potential to improve the quality of clinical research. Estimands foster a more complete alignment of study objectives, study design, study conduct, data analysis, and interpretation of results.

Download the full article


  1. International Council for Harmonisation of Technical Requirements for Pharma ceuti - cals for Human Use [Internet]. Estimands and sensitivity analysis in clinical trials. E9 (R1). Current Step 2 version. 2017 Jun 16 [cited 2018 Aug 19]. Available from: Available from: Web_Site/ICH_Products/Guidelines/ Efficacy/E9/E9-R1EWG_Step2_ Guideline_ 2017_0616.pdf.
  2. European Medicines Agency [Internet]. Overview of comments received on draft ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. EMA/744060/2017. 2017 Nov 09 [cited 2018 Aug 19]. Available from: Available from: http://www.ema.europa. eu/docs/en_GB/document_library/Over view_of_comments/2018/04/WC500247 968.pdf.
  3. ICH E9(R1) Expert Working Group [Internet]. Draft (Step 2) guideline ICH E9(R1) Estimands and Sensitivity Analysis in Clinical Trials (training material). 2018 Jun [cited 2018 Oct 21]. Available from: Available from: Public_Web_Site/ICH_Products/ Guidelines/Efficacy/E9/E9-R1EWG_ Modules1–3_Step2_COMPILATION _Training Material_2018_0703.pdf.
  4. Hemmings R, Akacha M [Internet]. ICH E9 (R1) Addendum on ‘Estimands and Sensitivity Analysis’. Presentation at the Annual Conference of the International Society of Clinical Biostatistics 2017 – Mini Symposia. 2017 [cited 2018 Aug 19]. Available from: Available from: uploadedFiles/ISCB2017.y23bw/file Manager/09%2045%20ROB%20 HEMMINGS%20MOUNA%20AKACHA %20 Estimands%20Vigo%20 Final.pdf.
  5. Akacha M, Bretz F, Ruberg S. Estimands in clinical trials – broadening the perspective. Stat Med. 2017;36:5–19. Available from: http://
  6. Ruberg SJ, Akacha M. Considerations for evaluating treatment effects from randomized clinical trials. Clin Pharmacol Ther. 2017;102:917–23. Available from: http://
  7. Akacha M, Kothny W. Estimands: a more strategic approach to study design and analysis. Clin Pharmacol Ther. 2018;102:894–96. Available from: http://
  8. Mallinckrodt C, Molenberghs G, Rathmann S. Choosing estimands in clinical trials with missing data. Pharm Stat. 2017;16:29–36. Available from: http://
  9. Phillips A, Abellan-Andres J, Soren A, et al. Estimands: discussion points from the PSI estimands and sensitivity expert group. Pharm Stat. 2017;16:6–11. Available from: http://
  10. Holzhauer B, Akacha M, Bermann G. Choice of estimand and analysis methods in diabetes trials with rescue medication. Pharm Stat. 2015;14:433–47. Available from: http://
  11. Leuchs A-K, Zinserling J, Brandt A, et al. Choosing appropriate estimands in clinical trials. Ther Innov Regul Sci. 2015;49: 584–92. Available from: http://
  12. Food and Drug Administration [Internet]. Presentations for the July 19, 2011 meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. 2011 [cited 2018 Aug 19]. Available from: Available from: 20170405220520/ downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/ EndocrinologicandMetabolicDrugs AdvisoryCommittee/UCM264312. pdf
  13. Bridge H, Schindler TM. The perils of the unknown: missing data in clinical studies. Med Writ. 2018;27:56–9. Available from: http://



Patient reported outcomes
President's Message
Measuring health outcomes: The foundation of contemporary healthcare decision-making
Measuring quality of life – theoretical background
Quality of life measures – an overview
Publication planning and patient-reported outcomes: Demonstrating value in a multi-stakeholder era
Patient-reported outcome measure translation: An overview
Systematic hospital collection of patient-reported outcome data via patient apps
The PROMIS of electronic patient-reported outcomes
Interview with Professor Matthias Rose on developing patient-reported outcomes and the PROMIS initiative
The UK pharmaceutical industry braces for Brexit, be it mild, severe, or doomsday
Awareness of medical writing as a profession and its career prospects
Estimands – closing the gap between study design and analysis
Protecting the rights of clinical trial patients through disclosure: The significance of plain language
News from the EMA
Regulatory Matters & Regulatory Public Disclosure
Medical Communications
Medical Devices
Journal Watch
In the Bookstores
Good Writing Practice
Getting Your Foot In The Door
My First Medical Writing
Out on Our Own

Member Login


The Write Stuff Archive Contact Instructions for Authors Feature Article Template (Word) Journal Policies

Editoral Board



Managing Editor

show all +

Associate Editors:

Section Editors:

Ad-hoc Editors:

  • Amy Whereat (SpeaktheSpeech Consulting, Asnieres sur Seine, France)

Editor Emeritus: