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.

• EMA Guideline on good pharmacovigilance practices (GVP)
• FDA Draft Guidance on Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices
• Real-World Evidence — What Is It and What Can It Tell Us? (Sherman RE, et al. N Engl J Med 2016)
• Accelerating Development of Scientific Evidence for Medical Products Within the Existing US Regulatory Framework (Sherman RE, et al. Nat Rev Drug Disc 2017)
• RoPR Database: Registry of Patient Registries by the U.S. Department of Health and Human Services Agency for Healthcare Research and Quality (AHRQ)

Organization affiliations are listed as active affiliations during the project.

*Indicates former project manager, team leader, or team member.