Table 2 Overview of key findings by theme and subtheme

Theme 1: Perception and understanding of harms

 Importance of harms recording

• Essential for BCI trials

• Range of opinion on risk level; seen as both low risk (because not a CTIMP) or high risk (harms unknown therefore risky)

• Important to patient and public representatives

 Perceptions of what is a harm

• Largely informed by individual experience, knowledge of clinical trials and colleague influence due to the lack of guidance.

• Greater understanding on what constitutes a Serious Adverse event in BCI trials; confusion around what constitutes a non-serious harm or AE.

• Safeguarding/AEs/SAEs- lack of distinction and overlap

• Participants found harm difficult to quantify and define in BCIs and most agreed there was a subjective nature to harms in BCI trials, i.e. what might be considered harmful to one person might be different to another.

 Factors influencing harms

• Study population

• Intervention; established or novel

• Plausibility of being related to the intervention

• Outcomes already being collected within the trial which may capture harms

• Meaningfulness to patients

• Importance of collecting different perspectives on harms (family member, significant other) as well as the trial participant.

 Approaches to harms recording

• Majority applied the ICH-GCP definitions for harms, AEs and SAEs given they are responsible and standard in clinical trials

• Importance of embedded qualitative research routinely asking for harms (currently few participants report qualitative research did this).

• Importance of feasibility and pilot studies capturing harms

 Awareness of literature

• Lack of awareness about the literature on harms in BCIs

• Most participants viewed a literature summary on categories and mechanisms of harms, methods, and recommendations as useful to stimulate discussion amongst trial teams around harms from an intervention.

Theme 2: Proportionate reporting and plausibility

 Burden of recording harms

• Most participants perceived a lack of pragmatism on determining the events to record as harms, with over-reporting of harms in BCI trials unrelated to the intervention.

• Large burden of reporting on trial staff and trial participants

• Data wastage and difficulty in finding signals in the data.

 Plausibility

• A proportionate approach should be taken to avoid wasting resources and improve data quality.

• Plausibility is the key factor for a proportionate approach, there must be a plausible link that the intervention could cause the harm.

Theme 3: The need for a multi-disciplinary approach

• Essential for multi-disciplinary team input; variety of perspectives required on recording harms.

• Lack of knowledge or understanding of harms from BCIs or lack of input could make decision making difficult.

• Difference in opinion and conflict on recording harms decisions.

• Trial manager burdened with responsibility of making decisions.

Theme 4: Language of BCI harms

 Medical language

• Lack of suitable alternative definition for harm, therefore ICH-GCP used

• Led to highly medicalised language which was deemed inappropriate in context of BCI trials.

• SAEs easier to identify than AEs.

• New harms language for BCIs is considered essential.

Theme 5: Complex harms for complex interventions

 Causality

• Driven by direct contact with the participant, requiring contextual information and therefore resources

• Case-by-case decisions on attribution of a harm to the intervention.

• Participants reported instances where it was not appropriate to keep asking for further information to determine causality of an intervention where an event or data may be sensitive.

 Future guidance

• Future guidance would be welcomed, particularly practical application for e.g. protocol template wording.

• Direction and endorsement or support from regulatory bodies like the Heath Research Authority was also sought.

• Providing a summary of relevant literature in an accessible document was thought useful.

• Details on basic theorising of harms from interventions was requested.

• Difficulty in writing guidance was noted because it was unlikely to be a one size fits all, but generic guidance may not be useful.

• Guidance on recording hams would be another guidance document to follow and ‘another thing to do’ within limited trial resources.