Tell me what you want, what you really really want: Estimands in observational pharmacoepidemiologic comparative effectiveness and safety studies

Kim Luijken*, Rik van Eekelen, Helga Gardarsdottir, Rolf H H Groenwold, Nan van Geloven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: Ideally, the objectives of a pharmacoepidemiologic comparative effectiveness or safety study should dictate its design and data analysis. This paper discusses how defining an estimand is instrumental to this process.

METHODS: We applied the ICH-E9 (Statistical Principles for Clinical Trials) R1 addendum on estimands - which originally focused on randomized trials - to three examples of observational pharmacoepidemiologic comparative effectiveness and safety studies. Five key elements specify the estimand: the population, contrasted treatments, endpoint, intercurrent events, and population-level summary measure.

RESULTS: Different estimands were defined for case studies representing three types of pharmacological treatments: (1) single-dose treatments using a case study about the effect of influenza vaccination versus no vaccination on mortality risk in an adult population of ≥60 years of age; (2) sustained-treatments using a case study about the effect of dipeptidyl peptidase 4 inhibitor versus glucagon-like peptide-1 agonist on hypoglycemia risk in treatment of uncontrolled diabetes; and (3) as needed treatments using a case study on the effect of nitroglycerin spray as-needed versus no nitroglycerin on syncope risk in treatment of stabile angina pectoris.

CONCLUSIONS: The case studies illustrated that a seemingly clear research question can still be open to multiple interpretations. Defining an estimand ensures that the study targets a treatment effect that aligns with the treatment decision the study aims to inform. Estimand definitions further help to inform choices regarding study design and data-analysis and clarify how to interpret study findings.

Original languageEnglish
Pages (from-to)863-872
Number of pages10
JournalPharmacoepidemiology and Drug Safety
Volume32
Issue number8
Early online date22 Mar 2023
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Funding Information:
We acknowledge Victoria Beckham, Melanie Brown, Emma Bunton, Melanie Chisholm, and Geri Halliwell for inspiring the title of this work. Rolf H. H. Groenwold was supported by grants from the Leiden University Medical Center.

Publisher Copyright:
© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Keywords

  • ICH-E9(R1) addendum
  • causal inference
  • comparative effectiveness and safety research
  • estimand

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