By Ted Lystig, Ph.D., Medtronic, and Sara Calvert, Pharm.D., Clinical Trials Transformation Initiative (CTTI)
Integrating clinical trials within registries offers several opportunities: avoiding duplicative data collection, identifying and recruiting patients more efficiently, and accelerating decision making, to name a few. These efficiencies have the potential to reduce clinical trial costs — especially when a registry is used to conduct multiple clinical trials.
While registries have been used often for observational research, there are far fewer instances of registries supporting clinical trials intended for regulatory submission. What is keeping the industry from using this valuable source of real-world evidence to support review of new treatments or indications?
The Clinical Trials Transformation Initiative (CTTI) brought together experts from multiple stakeholders across the clinical research enterprise to examine barriers and develop solutions for the use of registries in clinical trials for regulatory purposes. The resulting recommendations and tools can be used to help determine a registry’s suitability for conducting an embedded clinical trial. They also outline steps to modify existing registries or design new registries for use in research designed for regulatory decision making. Generally speaking, it will be easier to embed a clinical trial into a condition-based registry than into a therapy-based one.
In this article, we’ll go through the ins and outs of how to create a research-ready registry that is prepped to meet regulatory standards. We’ll also cover practical, evidence-based strategies for the following:
By following these best practices, owners and developers of clinical registries, along with their research partners, will be armed to make the most out of registry data and bring safe and effective new treatments to patients faster.
Is My Existing Registry Appropriate For Embedding Clinical Trials?
If there is an existing clinical registry that relates to the condition or treatment you’d like to study in a clinical trial, then it makes sense to see whether this registry can be used as the venue to conduct the trial — saving time, money, and the burden on participants. As trials such as SAFE-PCI and others have shown, the use of registries for clinical trials is not limited to post-market safety analyses. Rather, with the right qualities, registries have potential as platforms for conducting prospective randomized trials.
To use an existing data source to support a trial intended for regulatory decision making, the data must be sufficiently reliable, relevant, and robust. CTTI’s detailed tools offer suggested good practices, along with a decision tree, to help make these determinations. In addition to the data requirements, it is also necessary to ensure that adequate measures for patient protections, privacy, and data confidentiality are in place. This will include obtaining informed consent from participants or a waiver of informed consent from the institutional review board.
What To Do If A Registry Does Not Have All The Data Needed
If an existing registry does not have all the data needed for a given clinical trial, don’t give up hope. As long as the registry is appropriate for the condition or treatment of interest and the core data is present, there are several ways to modify the existing registry for the research purpose:
What Else Does A Registry Need To Support Clinical Trials?
Aside from the data needed to conduct a clinical trial, a registry also needs certain processes to facilitate research conduct. Examples include enhanced auditing functions, an ability to embed processes for documentation of informed consent, and an ability to embed processes for randomization. An existing registry may require modifications to support these research processes.
How To Design A Registry That Supports Embedded Clinical Trials
When designing a new registry, developers should consider the elements that will make the registry best able to support embedded clinical trials for regulatory decision making. Having a research-ready registry will make the most of registry participants’ donated data along with dollars spent by registry owners and research sponsors.
Understandably, it is likely not possible to conceive of all potential future uses of the registry for research purposes. The goal should be to include the processes for supporting research and the core data elements. To make up for any specific data needs for a trial, the registry should have the potential to accept data from other sources, whether from an electronic health record or other reliable external dataset.
A versatile registry will be able to support the study of different treatment types (e.g., drugs, devices, biologics), pre- and post-market regulatory decisions, and the evidence needs of other stakeholders. Following available guidance and standards will help to ensure the best chances for registry data to be able to support regulatory decision making.
Can This Really Work?
There are several examples of using registries for prospective randomized trials. One of these is the Thrombus Aspiration in ST-Elevation Myocardial Infarction (TASTE) trial. In TASTE, investigators used multiple interoperable national health registries to identify and randomize patients and collect all study data. By enrolling patients and collecting data through existing infrastructures, a large, representative patient sample was achieved and trial-specific work by clinical staff was minimized. As a result, this trial saw quicker enrollment and reduced costs compared with traditional trials. The same registries have been used to conduct additional randomized trials in Scandinavia. Because similar national health registries are not available in the U.S., conducting randomized registry-based trials may involve additional time and costs for up-front development but could still result in efficiencies — especially when a registry is reused for multiple trials. Though most registry-based trials to date have tested devices or procedures, registry-based trials of drugs are being planned.
Where To Go From Here
Careful consideration during registry development will help to maximize the potential for research use, but there are also ways to assess and modify existing registries for the capability of embedding clinical trials. Registries offer several advantages as a reusable platform for clinical trials. Review the complete CTTI Registry Trials recommendations for best practices in assessing and modifying existing registries or developing new registries to conduct clinical trials. As these methods are implemented, it will be important to share lessons and examples to benefit the wider research community.
About The Authors:
Theodore Lystig, Ph.D., is the director of corporate biostatistics at Medtronic, where he provides leadership and guidance in the use of robust statistical and research design methods throughout the company. He also holds the position of adjunct assistant professor within the Division of Biostatistics at the University of Minnesota. Lystig is an elected fellow of the American Statistical Association (ASA). He received his B.A. in mathematics from St. Olaf College, earned his M.S. and Ph.D. degrees in biostatistics from the University of Washington, and was a postdoctoral fellow in statistical genetics at Chalmers Technical University (Gothenburg, Sweden).
Sara Calvert, Pharm.D., is a senior project manager at the Clinical Trials Transformation Initiative (CTTI), where she is responsible for managing the development and implementation of CTTI projects. In collaboration with team leaders, she leads the creation of project plans and budgets, as well as the implementation of those plans. Prior to joining CTTI, she was a clinical pharmacist and project leader in the Outcomes Group at the Duke Clinical Research Institute. Calvert received her doctor of pharmacy from the University of Pittsburgh and completed a specialty residency in primary care pharmacy practice at Duke University Medical Center and Health System.