Randomized Controlled Trials: Overview and Updates

This page presents an overview of new and innovative approaches to the conduct of randomized controlled trials as a means of providing mentorship and support to clinicians, academics, students, and research trainees. Mentorship within research is a professional responsibility for all scientists. Dr. Fredericks has chosen to provide mentorship that focuses on randomized controlled trial methodology, as she has received specific training in this area.

Controlled Trials

Below are a list articles that addresses key issues and/or approaches to the conduct of randomized controlled trials:

Aebi, M. (2009). Vertebroplasty: about sense and nonsense of uncontrolled “controlled randomized prospective trials”. European spine journal, 18(9), 1247-1248.

Eneling, J., Darsaut, T. E., Patel, M., & Raymond, J. (2023). Understanding explanatory and pragmatic trials: Examples from randomized controlled trials on vertebroplasty. Neurochirurgie, 69(1), 101403.

Eneling, J., Darsaut, T. E., Veilleux, C., & Raymond, J. (2023). Understanding the choice of control group: A systematic review of vertebroplasty trials for osteoporotic vertebral compression fractures. Neurochirurgie, 69(1), 101401.

Eneling, J., Darsaut, T. E., Veilleux, C., & Raymond, J. (2023). Understanding power in randomized trials: The example of vertebroplasty. Neurochirurgie, 69(1), 101402.

Evans, S. R., & Hamasaki, T. (2023). Weighing evidence: robustness vs quantity. JNCI: Journal of the National Cancer Institute, 115(1), 1-3.

Deaton, A., & Cartwright, N. (2018). Understanding and misunderstanding randomized controlled trials. Social Science & Medicine, 210, 2-21.

Fanaroff, A. C., Califf, R. M., & Lopes, R. D. (2020). New approaches to conducting randomized controlled trials. Journal of the American College of Cardiology, 75(5), 556-559.

Frieden, T. R. (2017). Evidence for health decision making - beyond randomized, controlled trials. New England Journal of Medicine, 377(5), 465-475.

Yap, T. A., Jacobs, I., Baumfeld Andre, E., Lee, L. J., Beaupre, D., & Azoulay, L. (2022). Application of real-world data to external control groups in oncology clinical trial drug development. Frontiers in Oncology, 11, 5569.

Complex interventions

These interventions typically contain a number of components that can include multiple control and experimental groups, numerous techniques for delivering the intervention, a variety of groups for receiving the intervention and variability in terms of outcomes being assessed.

Complex interventions pose a significant challenge for researcher by way of introduction of error. Below are a few suggested readings that address fundamental issues related to the design and implementation of complex interventions:

Annweiler, C., Noublanche, F., Boureau, A. S., & Berrut, G. (2023). Design thinking and clinical living labs: Two complementary approaches for addressing complex health challenges in geriatric medicine. Maturitas.

Horton, T. J., Illingworth, J. H., & Warburton, W. H. (2018). Overcoming challenges in codifying and replicating complex health care interventions. Health Affairs, 37(2), 191-197.

O'Cathain, A., Croot, L., Duncan, E., Rousseau, N., Sworn, K., Turner, K. M., ... & Hoddinott, P. (2019). Guidance on how to develop complex interventions to improve health and healthcare. BMJ open, 9(8), e029954.

McNair, A. G., Hoffmann, C., Macefield, R. C., Elliott, D., Blazeby, J. M., Avery, K. L., & Potter, S. (2023). A standardized measurement instrument was recommended for evaluating operator experience in complex healthcare interventions. Journal of Clinical Epidemiology, 153, 55-65.

Movsisyan, A. (2018). Applying GRADE in systematic reviews of complex interventions: Challenges and considerations for a new guidance (Doctoral dissertation, University of Oxford).

Paparini, S., Green, J., Papoutsi, C., Murdoch, J., Petticrew, M., Greenhalgh, T., ... & Shaw, S. (2020). Case study research for better evaluations of complex interventions: rationale and challenges. BMC medicine, 18(1), 1-6.

Tanner-Smith, E. E., & Grant, S. (2018). Meta-analysis of complex interventions. Annual Review of Public Health, 39, 135-151.