Background & Aims
Adverse Events (AEs) in clinical trials are usually collected only at designated timepoints and rely on participant recall and self-report. Participant recall has limited accuracy (even for serious AEs) and likely results in missing minor AEs altogether, especially with long-term follow-up. This has two important implications: 1) Because AEs are not reported in real-time, researchers/ethics committees are unable to judge whether the participant is safe to continue with the treatment; 2) we may be vastly underestimating the frequency of AEs from treatment, meaning that the information underlying informed patient consent is faulty. Underestimating AEs also underestimates an intervention’s ‘cost’, resulting in inaccurate information regarding treatment safety, increasing risk to the community. We aimed to develop and implement a new system to collect accurate AE data to enable informed consent and decision making by patients, clinicians and policy makers.
Methods
We conducted a clinical trial investigating an exercise program for people with knee osteoarthritis [1]. Treatments were delivered by physiotherapists across Adelaide and Melbourne (Australia). 187 participants (target 198) have been followed over 12 months. To comprehensively evaluate AEs, our system used real-time data capture (via online participant-specific and treatment session-specific forms) paired with gold standard training of physiotherapists to report AEs on participants’ behalf throughout the intervention. Physiotherapists were required to know the Good Clinical Practice Guidelines definition of AEs and were mandated to ask participants about AEs at every treatment session. Real-time AEs were captured and followed up by the trial coordinator. Minor AEs were defined as any health event that lasted ?2 days and/or caused the participant to seek treatment or take medication, and serious AEs were defined as an event that caused the participant to attend/be admitted to hospital.
Results
Data collection is ongoing with 11 participants yet to complete the final 12 month follow up. To date, 179 AEs (25 serious, 154 minor) have been captured. Of the identified AEs, only 1 potentially serious AE was related to the trial. This occurred during a fall while the participant was undertaking the trial’s walking program. The participant presented to hospital but was cleared of serious injury. 8 minor AEs were related to the trial and included increased pain in the knee (x1) or other body parts (x6) because of the exercise/walking program. Treatment sessions were delayed/cancelled in 50 instances, and an additional 37 sessions were provided to 27 participants due to AEs Many of the serious AEs not related to the trial were unrelated medical events (e.g., cancer diagnosis or a cardiac condition), not unexpected in this age demographic. The most common reason for delays was a Covid-19 diagnosis.
Conclusions
A review of 54 trials investigating exercise for knee osteoarthritis [2] found that only 20% reported AEs, none reported any serious AEs, with the maximum number of AEs in a single trial of 11 (sample size comparable). These reports are highly unlikely to reflect reality given these trials involved vulnerable older populations paired with challenging exercise programs (i.e., with inherent risk of injury or increased pain/discomfort). Our enhanced AE capture system, involving real-time data capture, paired with gold standard training of physiotherapists to report AEs on participants’ behalf, revealed a much higher rate of AEs. This protocol has allowed us to take immediate action to mitigate AEs (e.g., pausing treatment until medically cleared, or providing additional treatment in line with the National Statement on Ethical Conduct – we have funded 37 additional treatments) that would have otherwise been missed.
References
1. Stanton, T. R., Braithwaite, F. A., Butler, D., Moseley, G. L., Hill, C., Milte, R., … & Bennell, K. (2021). The EPIPHA-KNEE trial: Explaining Pain to target unhelpful pain beliefs to Increase PHysical Activity in KNEE osteoarthritis–a protocol for a multicentre, randomised controlled trial with clinical-and cost-effectiveness analysis. BMC Musculoskeletal Disorders, 22, 1-22.
2. Fransen, M., McConnell, S., Harmer, A. R., Van der Esch, M., Simic, M., & Bennell, K. L. (2015). Exercise for osteoarthritis of the knee. Cochrane database of systematic reviews, (1).
Presenting Author
Dianne Wilson
Poster Authors
Dianne Wilson
PhD.
University of South Australia
Lead Author
Erin MacIntyre
University of South Australia
Lead Author
Felicity Braithwaite
BPT (Hons)
University of South Australia
Lead Author
Tasha Stanton
BScPT
University of South Australia
Lead Author
Brian Pulling
BSci
University of South Australia
Lead Author
Topics
- Access to Care