Conducting Clinical Trials Using Clinical Observational Registries
CTTI’s Registry Trials Recommendations provide a pathway for registries to be used for the conduct of more efficient clinical trials, bringing new treatments to patients faster. Registries are data collection tools typically used to better understand long-term trends in a specific population, such as patients with a particular disease or exposure to a certain treatment. However, if designed appropriately, registries can be used as a data source within which clinical trials can be performed.
FDA recently signaled a commitment to developing policies regarding the use of registries and other forms of “real-world evidence” for research, including clinical trials. While registries have long been used to support safety evaluations, their use for efficacy evaluations is a newer practice.
CTTI’s recommendations outline best practices for assessing and designing registries so that the data should be able to meet expectations for FDA review of new products. The recommendations can be applied to existing registries or for developing new registries. The goal is to increase the practice of leveraging registries to facilitate high-quality clinical trials at lower costs.
John Laschinger, MD U.S. Food and Drug Administration
“High-quality registries are an increasingly important source of evidence for regulatory decisions and surveillance, conveying important information, for example, regarding real-world medical product use and outcomes throughout the total product lifecycle. Use of high-quality registries as a vehicle for efficient conduct of randomized clinical trials is a proven concept that can be considered for future pre-market trials.”
Sunil Rao, MD Duke University
“Conducting randomized clinical trials within registries can increase efficiencies in data collection and decrease site workload, potentially leading to significant cost savings.”
Demographic, disease, and outcome data collected in clinical observational registries can be a valuable resource when these data overlap with those needed to support clinical trials. Integrating clinical trials within registries may offer considerable benefits and improve overall trial conduct; however, methods are needed to inform key decisions or activities, including the following:
The Registry Trials Project focuses on the feasibility of using registries to conduct prospective, embedded clinical trials that can support FDA review of new products, including efficacy as well as safety evaluations.*
*Note: Study designers and sponsors should meet with FDA for official determination if registry trial data is acceptable for regulatory purposes.
Registry Trials: Conducting Clinical Trials Using Clinical Observational Registries (2013-2017)
Increase in the practice of leveraging clinical observational registries to facilitate high-quality clinical trials at lower costs
The literature review revealed that the type and purpose of a registry are important to determine if embedding a clinical trial is possible and appropriate. Considerations include data completeness, data quality, interoperability, representativeness, informed consent, and privacy. There are also cost and operational questions, such as who will fund the registry, which party will pay for adjustments required for clinical trials, and who will be responsible for maintenance costs.
In multi-stakeholder interviews, experts described weaknesses and strengths of registries. Data quality was consistently identified as a potential weakness. Multiple strengths were noted, including efficiency/cost efficiency, recruitment, study design, large datasets, and a more real-life population. Experts suggested several issues to address to encourage the use of registries, including:
After input at a multi-stakeholder expert meeting, CTTI developed recommendations to facilitate determination of a registry’s suitability for conducting an embedded clinical trial intended for regulatory submission.
|Executive Committee Champion||Mike Lauer||National Heart, Lung, and Blood Institute|
|Project Manager||Sara Calvert||Clinical Trials Transformation Initiative|
|Team Leader||E. Dawn Flick||Celgene|
|Team Leader||John Laschinger||Food and Drug Administration|
|Team Leader||Ted Lystig||Medtronic|
|Team Leader||James Tcheng||Duke University|
|Team Member||Magnus Petterson||AstraZeneca Pharmaceuticals LP|
|Team Member||Sunil Rao||Duke University|
|Team Member||Arlene Swern||Celgene|
|Team Member||Emily Zeitler||Duke University|
|Team Member||Stephen Mikita||Individual Patient/Caregiver|
|Team Member||Chunrong Cheng||Food and Drug Administration|
|Team Member||Christopher Dowd||Cystic Fibrosis Foundation|
|Team Member||Nicolle Gatto||Pfizer Inc|
|Team Member||Lauren Mclaughin||The Michael J Fox Foundation for Parkinson's Research|
|Team Member||Kristen Miller||Food and Drug Administration|
|Team Member||Daniel Mines||Merck & Co, Inc|
|Team Member||Jules Mitchel||Target Health, Inc|