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Pro: Vaughn A. Starnes, M.D.
Con: Martin B. Leon, M.D.
Well-designed and properly executed randomized trials provide the best evidence on the efficacy of health care interventions. Randomization has two major advantages. First it eliminates bias in the treatment assignment. Without randomization, treatment comparisons may be prejudiced, whether consciously or not, by selection of participants of a particular kind or to receive a particular treatment. Second, random assignment permits the use of probability theory to express the likelihood that any difference in outcome between treatment groups merely reflects chance. Ideally, the randomization scheme, assignment is unknowable in advance. Preventing selection and confounding biases is the most important advantage of randomization.
Blinding is not inherent to randomized trials, although blinding requires placebo or use of alternate treatment that cannot be distinguished from treatment. That would not be possible in a trial comparing two valve interventions.
There is a concept that a trial should ideally reflect real-world conditions. A randomized trial may be performed after a more “experimental” trial in a select group of patients, such as a feasibility trial.
There are some ethical issues with randomization to either a percutaneous aortic valve insertion or a standard valve replacement. There is a point at which you are not sure which treatment is better. This is the concept of equipoise.
The REMATCH trial (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) compared a left ventricular assist device to a regimen of drug therapy, diet management and exercise for the treatment of end-stage heart failure. The FDA required the company to carry out a randomized trial. With the rigors of randomization, the outcomes showed that one-year survival for those with the LVAD was nearly double that of the drug therapy group.
Following the STS, AATS, and SCAI guidelines recently published in The Journal of Thoracic and Cardiovascular Surgery (2005;129:970-976) it would be prudent to perform a feasibility trial which would be unblinded, uncontrolled and would test safety of the insertion of the percutaneous heart valve. The patient population for the trial should include AS patients who are severely symptomatic. Such a trial should be
Pro Discussant: Vaughn A. Starnes, M.D.
- The Regulatory Approval Pathway for New Interventional Valve Therapies Requires Randomized Clinical Trials conducted at institutions where there is an experienced surgeon and an interventional cardiologist who has had specific training in the area of percutaneous heart valve technology (PHVT). These institutions should have a high volume of surgical valve operations a year (100-150 valve operations a year) and an interventional cardiologist who performs at least 100 percutaneous procedures a year.
The FDA has viewed the percutaneous heart valve systems as class III devices and they will be reviewed as pre-market approval (PMA) applications. Therefore to meet the FDA requirements for approval the gold standard for approval will be a controlled, randomized clinical trial.
