High costs and slow recruitment have hampered many a randomized controlled clinical trial in recent years. Those limitations have prompted some cardiovascular researchers to get creative, using electronic resources to enroll and follow patients at a fraction of the cost of a traditional trial.
Sponsors of a clinical trial for a cardiovascular pharmaceutical can expect to shell out on average $64.1 million, according to an analysis prepared for the U.S. Department of Health and Human Services. The authors at Eastern Research Group warned that slow patient recruitment can lead to costly delays and sometimes even derail the study. Add in flameouts and the total cost estimates soar beyond $1 billion.
Incorporating EHRs could lop 5.78 percent off the costs off a Phase 1 cardiovascular study, with even greater savings achieved in Phase 3 trials, they calculated in the report, “Examination of Clinical Trial Costs and Barriers for Drug Development.” While that sounds attractive, actual implementation with EHRs may be difficult.
“The challenges for the U.S. are many,” says Robert Harrington, MD, an interventional cardiologist and chair of the Department of Medicine at Stanford University School of Medicine in California. “[First], we don’t have the ability to have all of our data in common data networks. Second, the fragmentation of our healthcare system means the longitudinal follow-up in these kinds of trials can be problematic. And third is trying to deal with this in real time across a fragmented and diverse healthcare system.”
Harrington has been at the forefront of clinical trial innovation. As director of the Duke Clinical Research Institute (DCRI) in Durham, N.C., until 2012, he served as the principal investigator of the National Cardiovascular Research Infrastructure (NCRI) network, an effort to facilitate clinical research using the American College of Cardiology’s National Cardiovascular Data Registry (NCDR). Fast forward to today and he is co-study chair of the first demonstration conducted through another potential data goldmine, the National Patient-Centered Clinical Research Network (PCORnet).
The DCRI received $14 million in May to conduct the three-year study, which sets out to answer a question that has vexed cardiologists for many years: Which is better for preventing secondary cardiovascular disease in high-risk patients, high- or low-dose aspirin? ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness) will use PCORnet to enroll 20,000 patients with a previous MI or diagnosed coronary stenosis and randomize them to receive 81 mg or 325 mg of aspirin daily. Researchers will track mortality, hospitalizations and bleeding events through data collected and stored in six of PCORnet’s clinical data research networks.
Given the cost of large clinical trials and little incentive for industry to pay, studies on aspirin dosing were limited to observational and other designs that can’t provide definitive results. “It is a ripe question looking for a simple and efficient approach,” says Adrian Hernandez, MD, MHS, a cardiologist, director of the DCRI’s Outcomes and Health Services Research and ADAPTABLE’s co-principal investigator.
“We are interested in the specific question being studied but maybe more importantly we are interested in demonstrating that the methodology of using EHRs through a common data network can be pulled off,” notes Harrington.
The NCRI was funded through the American Recovery and Reinvestment Act of 2009, which set aside $8.2 billion in extramural funding for National Institutes of Health grants and contracts. The NCRI team received about $2.6 million over two years to build a clinical investigator network that leveraged the data collection power of the NCDR, whose members submit quality data through EHRs. The NCRI centralized network was designed to help recruit and retain trial participants, facilitate and stimulate cardiovascular research and develop and share an informatics platform.
“The infrastructure allowed us to do a clinical trial,” says Harrington. That was SAFE-PCI (Study of Access Site for Enhancement of PCI for Women), a registry-based randomized pragmatic trial that compared radial and femoral access PCI in women. The NCRI allowed the researchers to identify facilities with radial expertise, which helped to jumpstart site participation and enrollment. Using the NCRI also streamlined data collection and reduced the site-level workload. All in all, the trial cost approximately $5 million, “which is far less than a comparably sized trial would have cost without the NCRI model,” the SAFE-PCI researchers observed (J Am Coll Cardiol 2014; 7:858-867).
Like SAFE-PCI, ADAPTABLE is both a pragmatic clinical trial and a proof of concept. Using PCORnet, researchers will draw collaborators and patients from the six networks’ various clinics, which should represent many settings and patient populations. ADAPTABLE, which was funded by the Patient-Centered Outcomes Research Institute (PCORI), will allow researchers to develop and refine the PCORnet infrastructure. Hernandez says they will evaluate PCORnet’s ability to harness EHR data, assess the quality of data, monitor patient and investigator experiences and determine what part of PCORnet can be recycled in other large-scale trials.
“Right now we have patients coming into the hospital every day and there are probably hundreds if not thousands of questions that lack evidence in terms of what is the right choice for a given therapy or strategy and risk-benefit,” he says. “What has limited us is being able to seamlessly answer those questions without having to build and rebuild networks or sites to do this. This allows us to have a reusable research network that can answer questions hopefully better, faster and cheaper.”
The Holy Grail may be the randomized registry-controlled TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) trial. The researchers enrolled 7,244 patients through the Swedish Coronary Angiography and Angioplasty Registry, which is part of a national Internet-based real-time registry. By one account, TASTE cost a mere $350,000 to conduct, excluding infrastructure costs shouldered by the Swedish government.
“I think there are great lessons from the Swedish example, from the NCRI example and hopefully from PCORI, that there will be better ways of doing clinical research,” Harrington says. Registry-based randomized clinical trials in the U.S. may never reach the efficiencies of a small and well-networked nation like Sweden, he admits. But applying knowledge gained to create a robust infrastructure in the U.S. should help usher in a new way of providing evidence-based care.