Wien, 21.08.2023 – Text: Catarina Carrão
Schwartz and Lellouch pragmatic views
The Merriam-Webster dictionary defines Pragmatism has a practical approach to problems and affairs.1 In relation to clinical trials, pragmatism surfaced in 1967 with an article from Schwartz & Lellouch, due to concerns that many trials did not adequately inform practice because they were optimized to determine efficacy.2 At the time, authors complained that trials were performed with relatively small samples at sites with experienced investigators and a cohort of highly selected participants, so there could be an overestimation of benefits and an underestimation of harm.3 As such, this led to the belief that more pragmatic trials were needed designed to show the real-world (RW) effectiveness of the intervention in broader patient groups.
Pragmatism in clinical trials
A randomized pragmatic clinical trial is a type of clinical trial designed to compare an intervention and a comparator in participants who are more similar to those affected by the condition(s) under study in routine clinical practice settings. The intended purpose is to efficiently inform decision-making regarding the comparative balance of benefits, burdens, and risks of health interventions at the individual, community, or population level; and can integrate use of prospectively collected real-world data (RWD).4 In summa, pragmatic trials tend to focus on understanding how interventions work in real life, as opposed to “explanatory” studies where the goal is to determine if and how an intervention works.5
Pragmatic clinical trials can impact multiple design elements, such as broader eligibility criteria, ease of recruitment and follow-up, flexibility in delivery of the intervention, and use more patient-centric outcomes. This “real-world” setting of a clinical study can reduce the burden of trial participation, with hope to facilitate a more diverse trial population, quicker enrollment, and reduced attrition. Furthermore, pragmatic trials may result in evidence that is more broadly representative of the general population that is affected by the clinical question.6
Future trends in clinical trials
What we are witnessing today is a tendency for payors, government agencies, and researchers to put greater emphasis on clinical trials that focus on health care in a broader sense.7,8 There is a drive for trials to evaluate a combination of diet, drug treatment, education, and supervision to foster holistic approaches that are more readily adopted by the patients. Additionally, we might see more clinical trials gathering data to answer frequent questions from clinicians and patients, versus with the objective of obtaining approval from regulatory agencies by researchers and sponsors.7
The movement is for a more patient-focused approach of clinical trials; and to compare and evaluate real-world situations rather than equating an intervention to a placebo. The objective is to reduce the so-called efficacy-efficiency gap, defined as the problematic difference between outcomes generated from trials targeting a strictly selected patient population in highly controlled environments, and those observed in real-world clinical practice, optimizing treatments by independent clinical research.
All references assessed 15 August 2023.
1 Merriam-Webster.com. Pragmatism. Dictionary https://www.merriam-webster.com/dictionary/pragmatism(2023).
2 Schwartz, D. & Lellouch, J. Explanatory and pragmatic attitudes in therapeutical trials. Journal of chronic diseases 20, 637-648 (1967).
3 Ford, I. & Norrie, J. Pragmatic Trials. New England Journal of Medicine 375, 454-463 (2016). https://doi.org:10.1056/NEJMra1510059
4 Califf, R. M. & Sugarman, J. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials12, 436-441 (2015). https://doi.org:10.1177/1740774515598334
5 Anderson, M. L. et al. The Food and Drug Administration and pragmatic clinical trials of marketed medical products. Clin Trials 12, 511-519 (2015). https://doi.org:10.1177/1740774515597700
6 FDA.org. Project Pragmatica: Advancing evidence generation for approved oncology medical products. Oncology Center of Excelence https://www.fda.gov/about-fda/oncology-center-excellence/project-pragmatica(2023).
7 Cooper, J. A. Pragmatic Clinical Trials: What You Need to Know. Ethics in clinical research: whitepaper wcgclinical https://www.wcgclinical.com/insights/pragmatic-clinical-trials-what-you-need-to-know/ (2023).
8 EORTC.org. Three new EORTC clinical trials funded by the EU. European Organisation for Research and Treatment of Cancer (EORTC): News https://www.eortc.org/blog/2023/04/24/clinical-trials-funded-by-the-eu/(2023).