Low Trial Participation Rate of MI Patients Raises Questions of Applicability

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The percentage of patients hospitalized with a myocardial infarction (MI) who opt to participate in clinical trials is low, with a decline seen in recent years, according to a research letter published in the August 27, 2014, issue of the Journal of the American Medical Association. Those who chose to participate generally had better risk profiles—and lower rates of in-hospital mortality—compared with those who did not, raising questions about the generalizability of trial findings.

Taking advantage of existing quality improvement registries could help address these issues, lead author Jacob A. Udell, MD, MPH, of Women’s College Hospital (Toronto, Canada), told TCTMD in a telephone interview. “[I]f we nest a clinical trial within those observational registries we could harness the capabilities and a lot of the infrastructure … to make the clinical trial much easier to do, allow for a broader recruitment of patients, and—at a fraction of the cost—get questions and answers that would be applicable to more patients.”

Small Fraction of Patients Say ‘Yes’ to Trials

Overall, 2.8% of the patients were trial participants, meaning they provided consent and enrolled in a trial while hospitalized, regardless of whether investigational drugs, devices, or procedures were actually used. More than half of the centers (54.7%) enrolled at least 1 patient in a trial. 

Compared with nonparticipants, trial enrollees tended to be younger and to have a lower burden of cardiovascular disease, a lower predicted risk of in-hospital mortality, shorter hospital stays, and higher rates of use of evidence-based therapy. 

Of the nonparticipants, 68% were considered eligible for 3 antiplatelet trials that were ongoing during the study period. The rest were deemed ineligible, commonly because of uncontrolled hypertension (42%), elevated INR (20%), severe anemia (15%), or cardiogenic shock (14%). 

The rate of participation among eligible patients declined over time from 5.2% in 2008 to 3.4% in 2011 (P < .001 for trend).

The rate of in-hospital mortality was lowest for trial participants (1.5%), with significantly higher rates among eligible nonparticipants (2.5%; adjusted OR 1.63; 95% CI 1.11-2.41) and ineligible nonparticipants (8.4%; adjusted OR 1.91; 95% CI 1.29-2.83). The composite endpoint of death or MI, as well as cardiogenic shock, showed similar patterns. 

Multiple Possible Reasons for Low Participation

Many factors come into play when trying to understand trial participation rates, Dr. Udell said, including whether patients are willing to accept a 50/50 chance of getting a certain intervention to benefit future patients, are well enough to consent, or meet eligibility criteria. In addition, some centers do not participate in clinical trials. 

Although the study cannot identify reasons for participating or failing to participate in a trial, it does suggest that eligibility is not a major barrier, Dr. Udell pointed out.

Regardless of the reason for low participation, it is not a new problem, John Rumsfeld, MD, PhD, chief science officer for the NCDR and national director of cardiology for the Veterans Health Administration, told TCTMD in a telephone interview, pointing to the roughly 5% enrollment rate in the pivotal trials of CABG. “This has been a long-standing challenge for clinical research and it’s one that—if we want to continue to generate evidence that advances our guidelines, that advances what drugs or devices are approved in the United States—we are going to have to overcome,” he stressed.

Registry-Based Trials Hold Promise

There are 2 ways to simplify the clinical trials process that could increase participation rates and broaden patient populations, Dr. Rumsfeld said: reduce the number of exclusion criteria or use the infrastructure from existing quality improvement registries to find patients and conduct trials. Proof of the latter concept has been shown in the TASTE trial out of Sweden and the SAFE-PCI trial out of the United States, he noted. 

But, he added, “right now this is more about promise than it is about delivery.” 

Several barriers have to be overcome before the idea of the registry-based clinical trial can really take off, Dr. Rumsfeld said, including the fact that most hospitals and practices have different staff members handling registry and clinical trial activities, the general need for more data collection in a trial compared with a registry, the delivery of an intervention within the registry framework, and a requirement for longer-term follow-up in a trial.

Despite the barriers, however, Dr. Rumsfeld said that he thinks the concept will bloom in the coming years. 

“I think we have to work through all the barriers first to prove it’s efficient and to prove its value,” he said. “I am confident that will happen, but I suspect that it will grow slowly over a number of years. That being said, I hope over the next decade a significant number of clinical trials will be run this way in the United States.”

Source:
Udell JA, Wang TY, Li S, et al. Clinical trial participation after myocardial infarction in a national cardiovascular data registry [research letter]. JAMA. 2014;312:841-843.

Disclosures:

• The research was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry (NCDR). The Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry-Get With The Guidelines (GWTG) is sponsored in part by the partnership between Bristol-Myers Squibb and Sanofi. Dr. Udell was supported in part by a postdoctoral research fellowship from the Canadian Institutes of Health Research and the Canadian Foundation for Women’s Health.
• Dr. Udell reports receiving honoraria from the American College of Cardiology Foundation.
• Dr. Rumsfeld reports no relevant conflicts of interest aside from working for the NCDR.

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