Abstract
Background
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.
Objectives
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.
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.
Results
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.
Conclusions
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.
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.
Objectives
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.
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.
Results
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.
Conclusions
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.
| Original language | English |
|---|---|
| Number of pages | 20 |
| Journal | Health Technology Assessment |
| Volume | 29 |
| Issue number | 43 |
| DOIs | |
| Publication status | Published - 31 Aug 2025 |
Bibliographical note
We thank the advisory board for their guidance (Eleanor Mitchell, Senior Trial Manager, University of Nottingham; Ginette Hampshire, Senior Manager, Global Regulatory Strategy, Eisai Ltd; Imogen Goold, Associate Professor of Law, University of Oxford; Lauren Sutherland, QC, Ambersand Advocates; Jono Broad, Patient Experience Representative; Sheuli Porkess, Vice President, Faculty of Pharmaceutical Medicine; Fida Issa, Safety Surveillance Specialist, Novo Nordisk)Data Availability Statement
The qualitative data in this study are not suitable for sharing beyond that contained within the cited publications and this manuscript. Further information, and requests for other data should be addressed to the corresponding author.Funding
This award was funded by the Medical Research Council and the National Institute for Health and Care Research (NIHR) Better Methods, Better Research programme (MRC Award Reference: MR/V020706/1)
| Funders | Funder number |
|---|---|
| National Institute for Health and Care Research | MR/V020706/1 |