September 16th, 2013

Combining Randomized Trials And Registries: A New Paradigm

Ultimately, we need clinical trials to know what drugs and medical devices work. Without them, we will not have the evidence we need for clinical practice guidelines, and clinical care will not evolve. But traditional clinical trial approaches are not sustainable – too expensive and too inefficient. The new hope for clinical trials is to use clinical registry programs to conduct them more efficiently. And that new hope is now a reality. The Swedish registry proves the concept. And the U.S. registries-– especially those in the cardiovascular area-– have also done ‘proof of concept’. The remaining barrier to this becoming the way clinical trials are conducted is to gain the collaboration-– and trust-– of industry to work with the professional society registry programs to conduct the trials. The FDA and NIH and other stakeholders support it, so I believe it will now happen. And the primary beneficiary is patients, because we can spend less to gain critical new knowledge in a shorter time.

Randomized clinical trials remain the centerpiece for scientific evidence– the evidence for what medical therapies work and should be recommended in clinical practice guidelines.

Unfortunately, traditional clinical trials are very costly and inefficient. In essence, each new clinical trial starts “from scratch,” including identifying hospitals or practices to participate, developing new case report forms, etc. And each trial includes selected patients from selected centers, who participate in the trial for a specified, usually limited, amount of time.

The expense and inefficiency of traditional clinical trials is a threat to their existence. Already we see fewer and fewer of these conducted in the U.S.

But there is a potential new paradigm for conducting clinical trials-– piggy-backing on existing clinical registries to make the trial more efficient.

The hope is that large clinical registry programs-– like those of the American College of Cardiology in the U.S. or the Swedish registry that was used for the TASTE trial published in the NEJM-– may be able to serve as a more efficient infrastructure for clinical trials.

Here is why this hope exists:

1. Large national clinical registry programs are already a network of hospitals or practices. Participants already have contracts in place to collect and combine data, for quality measurement but also for aggregated research.

2. The data elements collected in registry programs largely represent the ‘data standards’ for a given clinical area. At least 80% of the necessary data for a clinical trial is already being collected in the registries.

3. Thus, it is easy to see how a clinical registry can be used to recruit sites from the existing registry network for a clinical trial, and that only a modest amount of additional data collection may be necessary for the trial. Both of these would greatly contribute to more efficient clinical trials, from both cost and time standpoints.

4. There are other appealing aspects of this. For example:

a. Existing registry data can be used to plan clinical trials-– we know what sites provide which types of care, so a given clinical trial can use that data to target specific centers for participation (for example, for doing a certain type of procedure not done at all hospitals).

b. When a clinical trial ends, the clinical registry program will continue to document care and patient outcomes. This suggests that ‘post-trial’ surveillance can continue-– which can become ‘post-market’ surveillance for new drugs and devices. The FDA is working closely with clinical registry programs in the cardiovascular area, supporting the idea of conducting more efficient clinical trials, but then to have the registry data available for post-market safety surveillance.

Traditionally, the two worlds of clinical trials and clinical registry programs have just not overlapped, but that is no longer true. And the hope of using clinical registries to conduct clinical trials is now a reality. The Swedish registry is proof that the two can be combined to run a more efficient clinical trial. In the U.S. the American College of Cardiology’s National Cardiovascular Data Registry (NCDR) has also recently proved the concept, conducting a randomized clinical trial of angioplasty in women (called SAFE-PCI) using the registry infrastructure.


2 Responses to “Combining Randomized Trials And Registries: A New Paradigm”

  1. I get the “conducting clinical trials-– piggy-backing on existing clinical registries to make the trial more efficient.” I find the concept challenging to extend to trials which require longer follow up or test a novel drug. If the algorithms are standardized as they should be in a trial and followed for extended periods of time, then one would defeat the purpose of the registry (collect real-world practice data).

  2. John S Rumsfeld, MD, PhD says:

    Good comment. I think you rightly highlight that some clinical trials will be a better ‘fit’ than others for this model. However, even with such trials (e.g. more intensive study intervention / longer study / etc), only select centers in the overall registry network will be in the trial, and only patients meeting entry criteria for the given trial (and consented) will participate in the trial. For example, in the SAFE-PCI trial (reference: Hess CN et al., Am Heart J. 2013 Sep;166(3):421-428), 60 of the over 1500 hospitals that participate in the NCDR CathPCI registry were trial sites. Hence, the patients enrolled in the trial at those sites will be following the clinical trial protocol, but that doesn’t change the usual registry functioning for all other patients at those sites, or for all the other hospitals in the registry that did not opt to participate in a given clinical trial.