Getting to the heart of the cardiovascular indication
- M Hovde
The existence of effective therapies for most cardiovascular disease states, coupled with increased requirements that potential benefits of new drugs be evaluated on clinical rather than surrogate endpoints, makes it increasingly difficult to substantiate any incremental improvements in efficacy that these new drugs might offer. Compounding the problem is the highly controversial issue of comparing new agents with placebos rather than active pharmaceuticals in drug efficacy trials. Despite the recent consensus that placebos may be used ethically in well-defined, justifiable circumstances, the problem persists, in part because of increased scrutiny by ethics committees but also because of considerable lingering disagreement regarding the propriety and scientific value of placebo-controlled trials (and trials of antihypertensive drugs in particular). The disagreement also substantially affects the most viable alternative to placebo-controlled trials: actively controlled equivalence/noninferiority trials. To a great extent, this situation was prompted by numerous previous trials of this type that were marked by fundamental methodological flaws and consequent false claims, inconsistencies, and potential harm to patients. As the development and use of generic drugs continue to escalate, along with concurrent pressure to control medical costs by substituting less-expensive therapies for established ones, any claim that a new drug, intervention, or therapy is "equivalent" to another should not be accepted without close scrutiny. Adherence to proper methods in conducting studies of equivalence will help investigators to avoid false claims and inconsistencies. These matters will be addressed in the third article of this three-part series. The Magnitude and Scope of the Background Problem The cardiovascular therapeutic area The cardiovascular indication has been the largest or second-largest focus of clinical trials for the past decade (the central nervous system has occupied first place since 1999), making up 15.5% of all clinical investigator contracts Correspondingly, the cardiovascular therapeutic area commands the largest market for prescription drugs – nearly one fourth of branded prescription drug sales – as the dominant indication for branded medicines sold commercially during the past few years. The total worldwide cardiovascular market is expected to show revenues of $91.2 billion in 2008, an increase of 6.9% compared with 2003  The WHO ICD-9 coding system specifies 46 cardiovascular diseases within this therapeutic area; however, 65% of all cardiovascular trials address the top six of these subindications. Essential hypertension is in first place (27.1% of trials), followed by congestive heart failure (13.1%) and cerebrovascular disease (9.9%). Published: 04 June 2004 Current Controlled Trials in Cardiovascular Medicine 2004, 5:4 Received: 12 March 2004 Accepted: 04 June 2004 This article is available from: http://cvm.controlled-trials.com/content/5/1/4 © 2004 Pater; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.