Project:

Registry Trials

overview icon Overview

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.

“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.”

John Laschinger, MD U.S. Food and Drug Administration

“Conducting randomized clinical trials within registries can increase efficiencies in data collection and decrease site workload, potentially leading to significant cost savings.”

Sunil Rao, MD Duke University

in detail icon In Detail

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:

  • Identify the appropriate registries
  • Ensure data quality/comparability
  • Meet regulatory/legal requirements
  • Protect participant privacy/security
  • Clarify processes that are necessary to implement a registry-based clinical trial

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)

  • Identify essential elements of registries needed to successfully embed and conduct registry-based clinical trials
  • Determine requirements to utilize a data registry for a clinical trial (e.g. electronic transfer of data from registry to a case report form, communication between registry personnel and site coordinators)
  • Identify regulatory requirements for using registry data for regulatory purpose
    • IND-based submissions for drug/biologic trials and device/IDE applications
  • Describe the potential barriers to the conduct of clinical trials within a registry, and leverage learning from successful trials in order to overcome those barriers
  • Outline the lessons learned from post-market registry device trials that may be applied to earlier phase device trials and drug trials in the context of different regulatory requirements
  • Recommend best practices for conducting randomized registry trials for regulatory purposes

Increase in the practice of leveraging clinical observational registries to facilitate high-quality clinical trials at lower costs

  • Literature review
  • Expert interviews
  • Landscape assessment
  • Expert meeting

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:

  • Data harmonization and standardization
  • Reliability of data
  • Regulatory flexibility
  • Need to persuade leaders

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.

Project Team Members

Role Name Affiliationsort descending
Team Member Magnus Petterson AstraZeneca Pharmaceuticals LP
Team Member Arlene Swern Celgene
Team Leader E. Dawn Flick Celgene
Project Manager Sara Calvert Clinical Trials Transformation Initiative
Team Member Christopher Dowd Cystic Fibrosis Foundation
Team Leader James Tcheng Duke University
Team Member Sunil Rao Duke University
Team Member Emily Zeitler Duke University
Team Member Chunrong Cheng Food and Drug Administration
Team Member Kristen Miller Food and Drug Administration
Team Leader John Laschinger Food and Drug Administration
Team Member Stephen Mikita Individual Patient/Caregiver
Team Leader Ted Lystig Medtronic
Team Member Daniel Mines Merck & Co, Inc
Executive Committee Champion Mike Lauer National Heart, Lung, and Blood Institute
Team Member Nicolle Gatto Pfizer Inc
Team Member Jules Mitchel Target Health, Inc
Team Member Lauren Mclaughin The Michael J Fox Foundation for Parkinson's Research