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. 2025 Mar 18;26(1):95.
doi: 10.1186/s13063-025-08801-1.

Improving the capture and reporting of adverse events in clinical trials of non-pharmacological interventions: learnings from the PaCCSC/CST membership

Rayan Saleh Moussa #  1 , Jack Power #  1 , Vanessa Yenson  1 , Belinda Fazekas  1 , Celia Marston  1   2   3   4 , Annmarie Hosie  1   5 , Layla Edwards  1 , Domenica Disalvo  1 , Linda Brown  1   6 , Imelda Gilmore  1 , John Stubbs  1 , Andrea Cross  1 , Sally Fielding  1 , Meera R Agar  7
Affiliations

Improving the capture and reporting of adverse events in clinical trials of non-pharmacological interventions: learnings from the PaCCSC/CST membership

Rayan Saleh Moussa et al. Trials. .

Abstract

Background: Accurate capture and reporting of adverse events (AEs) in clinical trials is critical to understanding the potential harms of prospective interventions. Current AE-reporting frameworks are specifically constructed for pharmacological interventions and adaptation of these frameworks imparts the risk of excluding AEs unique to non-pharmacological interventions that have not yet been defined. As a result, clinical trials of non-pharmacological interventions seldom include a systematic method to capturing and reporting AEs, often using no method at all. These gaps make it likely that AEs in trials of non-pharmacological interventions are underreported, providing insufficient information about the safety of such interventions prior to their implementation in clinical practice. In addition, clinical trials focus primarily on participants receiving the intervention, with current AE-reporting frameworks not designed to capture potential harms to other personnel involved (i.e. family/carers, and clinical and research staff). A series of collaborative group discussions with consumers and interdisciplinary clinical trialists, and case study analyses were conducted to explore gaps in the capture and reporting of AEs specific to non-pharmacological trials, and their mitigation.

Main body: Two case examples are provided. The first case example highlights that current methods are inadequate, resulting in inconsistencies in capturing AEs, influenced by the environmental context of the clinical trial. The second case example highlights the need for both systematic and simplified AE-reporting frameworks, particularly for clinical trials conducted in medically complex populations where participants may be at high risk of experiencing AEs. We recommend future trials of non-pharmacological interventions adopt a four-step framework that incorporates: (1) enhanced trial protocol development to define the participant, environmental context in which the intervention is taking place and identify other personnel involved; (2) pre-specify anticipated AEs in trial protocol; (3) selection of the most appropriate measurement system to define, report and grade AEs; and (4) develop corrective and preventative action plans.

Conclusion: We provide recommendations for an AE-reporting framework for future trials that encompass risks unique to non-pharmacological interventions and all individuals involved. By focusing on these directions, we can streamline the process of capturing and reporting AEs and contribute to more impactful and sustainable outcomes.

Keywords: Adverse events; Case study; Clinical trials; Framework; Harm; Intervention; Non-pharmacological; Risk management; Safety.

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Conflict of interest statement

Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
PICO table for TIGER and PRESERVE case examples
Fig. 2
Fig. 2
A Traditional AE-reporting frameworks capture AEs that only impact trial participants that can be graded according to current measuring systems. B Sponsors and investigator teams need to consider potential AEs that cannot be graded in this way, as well as the importance of capturing AEs that may occur within the environmental context of a trial, and how to best capture and report them
Fig. 3
Fig. 3
A 4-step framework for the accurate capture and reporting of AEs in clinical trials
See this image and copyright information in PMC

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