Advancing evidence generation for approved oncology medical products
Traditional prospective randomized controlled trials in oncology are typically associated with significant monitoring, assessments, tests, and clinical follow up visits that can be burdensome to trial participants, investigators, and trial sponsors.
Project Pragmatica seeks to introduce functional efficiencies and enhance patient centricity by integrating aspects of clinical trials with real-world routine clinical practice through appropriate use of pragmatic design elements.
- Pragmatic clinical trials may incorporate various design elements that are more reflective of routine clinical practice. Pragmatic trial elements take advantage of functional efficiencies such as fewer and simpler eligibility criteria and flexibilities in trial delivery and outcome measurement. The degree of flexibility is tailored to the trial context, keeping the safety of patients and the integrity of trial data at the forefront. This more "real-world" setting can reduce the burden of trial participation, with the hope to facilitate more diverse trial populations, more rapid enrollment, and reduced attrition. Pragmatic trials may have the potential to result in evidence that is more broadly representative of the general population affected by the clinical question.
As part of a broader effort to modernize evidence generation, the FDA Oncology Center of Excellence launched Project Pragmatica in 2022 to explore the appropriate use of pragmatic design elements in trials for approved oncology medical products.
What is a randomized pragmatic clinical trial (PCT)?
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). 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 (Califf et al). Along a continuum from explanatory to pragmatic, trials can be more or less pragmatic depending on the various elements that can be deployed to streamline procedures and data collection (Thorp et al).
Project Pragmatica Objectives
- Explore the range of pragmatic elements that are feasible and appropriate to implement in cancer trials across a range of clinical and regulatory contexts while maintaining patient safety and data integrity.
- Collaborate with patients, trial investigators, pharmaceutical companies, government agencies and international healthcare policy stakeholders to evaluate opportunities and challenges in incorporating pragmatic elements into multiregional cancer trials.
- Foster research into evaluating potential benefits of pragmatic trial elements to patients, investigators and trial sponsors. (e.g., more rapid accrual, more heterogeneous population, less attrition, cost and time savings).
Project Pragmatica leads include Drs. Donna Rivera, Harpreet Singh, and Paul Kluetz in addition to a multidisciplinary team of FDA scientists interested in efforts to make trials more efficient and patient-centric.
Additional OCE programs intersecting with Pragmatica include the Oncology Real World Evidence Program, Project Silver, Patient Focused Drug Development Program, Project Significant and Project Equity.
- Jungmeyer E. Pragmatic Approach to Trial Design Born from Lung-MAP Substudy IASLC Lung Cancer News. 21 March 2023.
- Ong M, Goldberg P. Conversation with The Cancer Letter: FDA’s Singh and Rivera describe the “new normal”—and the future—in cancer pragmatic trials The Cancer Letter, 9 December 2022; Vol. 48, No. 44.
- For questions specifically on Project Pragmatica, please email: OCERWE@fda.hhs.gov
- For application-associated regulatory questions, please contact the relevant Office of Oncologic Diseases review division early and often to discuss innovative trial designs.