Authors' objectives: Variation in the way information about potential trial intervention benefits and harms is conveyed within patient information leaflets can cause avoidable information-induced (‘nocebo’) harm, research waste, and may be unethical. To develop stakeholder-informed principles to guide how to describe information about potential trial intervention benefits and harms within patient information leaflets. To test whether using these principles are feasible for testing in trials that measure whether they improve recruitment and adverse event rates. To develop and disseminate guidance on how to implement the principles.

Authors' results and conclusions: For work package 1, 250 participants completed the Delphi survey and 7 principles were agreed upon: (1) all potential intervention harms should be listed, (2) potential harms should be separated into ‘serious’ and ‘less serious’, (3) if not all potential harms are known, this needs to be explicitly stated, (4) all potential benefits should be listed, (5) potential benefits and harms associated with trial participation need to be compared with those associated with non-participation, (6) suitable visual representations should be added where appropriate, and (7) information about potential benefits and harms should not be separated by more than one page. For work package 2, we developed principled patient information leaflets for five host trials and interviewed two members of each host trial team. Two host trials agreed to compare the patient information leaflets with principled patient information leaflets using Studies Within a Trial, and we published a protocol for a meta-analysis that will synthesise the results. For work package 3, 25 participants attended a hybrid workshop and recommended that researchers and Research Ethics Committee members should use the principles to design and evaluate patient information leaflets. We produced a guidance booklet and website, which are currently being used by some Health Research Authority Research Ethics Committees. A strong consensus was reached regarding seven principles that can harmonise the way information about the potential benefits and harms of trial interventions is shared. The principles are likely to reduce research waste and avoidable information-induced harm, and may enhance clinical trial ethics.

Authors' methods: We used a mixed methodology consisting of three work packages. Work package 1 involved a modified Delphi survey and consensus meeting to develop the principles for harmonising the way information regarding potential benefits and harms are shared. Work package 2 involved testing whether the principles could be used to transform existing patient information leaflets by recruiting host trials to compare standard patient information leaflets with patient information leaflets developed using the principles ‘principled patient information leaflets’. We also set up an infrastructure to test whether they could reduce variation, impact trial recruitment and reduce reported adverse events. Work package 3 involved developing and disseminating guidance for using the principles. Due to COVID-19, the National Institute for Health and Care Research review of ongoing trials that resulted in funding termination for several trials, and highly pressured trial staff with limited capacity to add Studies Within a Trial to their trials, we had to modify our second objective. Whereas we initially intended to actually conduct the Studies Within a Trial, we replaced this with: a protocol for a meta-analysis of Studies Within a Trial, additional research on the need to reduce variation, additional dissemination work, and a paper on the ethical requirement to mention potential benefits and harms of trial interventions in patient information leaflets.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR136246

Year Published: 2025

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/GJJH2402

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/GJJH2402

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk