Beyond "Intent-to-treat" and "Per protocol": Improving assessment of treatment effects in clinical trials through the specification of an estimand
Frank Pétavy, Lorenzo Guizzaro, Inês Antunes Dos Reis, Steven Teerenstra, Kit C B Roes, Frank Pétavy, Lorenzo Guizzaro, Inês Antunes Dos Reis, Steven Teerenstra, Kit C B Roes
Abstract
There is a key problem in randomised clinical trials as outcomes can be distorted due to informative post-randomisation events. This is inadequately addressed by the use of traditional intention-to-treat or per protocol analysis sets and often either ignored or wrongly labelled as missing data. As a consequence, the treatment effects of interest in a clinical trial are not well defined and their estimates might be misinterpreted. The estimand framework should help all those planning, conducting and analysing clinical trials as well as those interpreting the results to better define, estimate and understand the treatment effects of interest. This framework is described in the addendum to ICH E9 and addresses precisely this problem. It is relevant for regulatory drug trials and academic-run trials, as well as for trials of nonpharmacological interventions.
Conflict of interest statement
The authors have no conflicts of interest to declare. The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made onbehalf of or reflecting the position of the agencies or organisations with which the authors are affiliated.
© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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Source: PubMed