When Should We Start Randomized Trials for New Devices ?

This year marks the 20th anniversary of the publication of Gruentzig’s landmark work in development of percutaneous transluminal coronary angioplasty (PTCA) (1). In the 20 years since its inception, angioplasty has evolved from a crude, often unsuccessful, often dangerous intervention to a mainstay in the treatment of symptomatic coronary artery disease (2). As an early observer and investigator of this technique, I marvel at the extraordinary advances that have occurred over the last two decades. At its inception, angioplasty was performed by skilled but inexperienced operators, working with crude fluoroscopic images, no replay capability and crude, bulky, rigid, nonsteerable catheters. It is little wonder that even with stringent selection of soft, short, concentric lesions in proximal vessels, only a 64% success rate was achieved (3). I can clearly recall performing angioplasty on a patient in 1983 and observing a major non–flow-limiting dissection in the dilated vessel. I called numerous colleagues (including Dr. Hartzler and Dr. Gruentzig) to seek advice on whether the patient would require an urgent operation and whether coronary aneurysm or rupture would occur in the convalescent phase. No one had definitive answers on how to treat this patient. In the early 1980s these types of questions often arose. The early operators were not only hampered by inadequate equipment but also by a dearth of data with which to make important decisions. Despite these shortcomings, the field of angioplasty rapidly evolved. A few committed, intrepid investigators pushed the field of angioplasty and carefully documented their results (4). Information was informally exchanged at small demonstration courses and prospective registries were published (5). The late 1980s saw an explosion in popularity of PTCA. Formal interventional fellowship programs were formed, and dramatic advances in imaging equipment and dramatic improvements in flexibility and steerability of catheters occurred. By 1990, 500,000 patients a year were being treated with PTCA. These accomplishments occurred without the benefit of randomized clinical trials (RCTs). The first RCT of angioplasty therapy validated its use in acute infarction (6). The predominant indication for angioplasty in the 1980s was for treatment of symptomatic angina. A RCT of angioplasty for symptomatic angina was not published until 1992, or 15 years after the inception of the technique (7). Shortly after this study, comparisons of angioplasty to coronary artery bypass graft surgery for treatment of multivessel disease occurred (8). By the time balloon angioplasty was subjected to formal, randomized comparison, it was a mature discipline with large numbers of trained operators, excellent refined equipment and a large data base for intelligent patient selection and periprocedural management. A simple question must be asked: Was society harmed or benefitted by the way in which coronary balloon angioplasty was developed and validated? The reason this fundamental question must be asked is because this proved, successful method for new device development may never be repeated. Imagine a young Andreas Gruentzig trying to introduce coronary angioplasty in 1999 rather than 1979. Two major hurdles would assuredly thwart his efforts. First, federal regulations would place enormous road blocks. Extensive animal testing would be required. Not only would acute animal safety experiments be required but long-term healing data would also be needed. The expense of this extensive preclinical testing data would mandate venture capital funding. This in turn would place enormous time pressures for start and completion of RCTs. Today the RCT completion is imperative because without it, no insurance coverage for hospital stay or reimbursement for catheter costs would occur. Thus, in 1999, a young Gruentzig would quickly lose control of his idea and be totally stymied by regulatory road blocks. In addition, his new idea would be forced into immediate randomized comparisons. Imagine using the original Gruentzig balloon catheter today in comparison to single-vessel bypass! Balloon angioplasty would never have been validated and developed; atherectomy would never have existed; and coronary stent implantation would not have its delivery platform. Again, the fundamental question must be asked: Was society harmed or benefitted by the way in which coronary balloon angioplasty was developed? In this issue of the Journal, Tsuchikane et al. (9) report the final results of the STent versus Directional Coronary Atherectomy Randomized Trial (START). The operators