Stroke is a potentially debilitating medical event that affects approximately 800,000 people in the United States each year, leaving as many as 30% of survivors permanently disabled. Given this impact, there is great demand for treatments that significantly improve functional outcome after a stroke. To date, few clinical trials for the treatment of acute stroke have succeeded. Suppose you and a team of collaborators have a new treatment that you would like to test for use in patients who have had strokes. Where do you begin? How many patients do you need to sample to know if your treatment is safe and effective? How do you choose a comparison group and allocate treatment? How do you choose the outcome of interest and conduct the analysis of your data? These questions will be addressed in the following sections.
A clinical trial is a prospective research study conducted in humans to assess the impact of an experimental intervention. The intervention can be a drug product, a device such as a surgical stent or diagnostic tool, a procedure such as a surgical treatment, or a behavioral intervention. Clinical trials are a critical step to therapeutic development because they provide the necessary methodology to make inferences with minimal bias and the best possible precision. Clinical trials have been in existence since the 1700s, although the primary concepts and terminology of trials were not identified until much later (Figure 7-1, Timeline), and clinical trial methods and regulations continue to be developed.
Clinical trial history. CE, Comparative Effectiveness; CFR, Code of Federal Regulations; CONSORT, Consolidated Standards of Reporting Trials; FDA, Food and Drug Administration; GCP, Good Clinical Practice; ICH, International Conference on Harmonization; IRB, Institutional Review Board; NCI, National Cancer Institute; NIH, National Institutes of Health; SCT, Society for Clinical Trials.
The history of clinical trials is important for understanding the impetus for good clinical practice guidelines, as well as the evolution of the drug and device development process. On average, the typical time from initial development to introduction into clinical practice for a drug in the United States is 15 years (Woosley and Cossman, 2007). Because therapeutic development is a time-consuming and costly process, it is important to take the time to develop the most appropriate study design and ensure proper conduct and analysis of the trial. There are plenty of examples of failed clinical trials, and the cause is not necessarily the absence of a treatment effect. For example, several trials were conducted in acute stroke only to conclude that patients may not have been treated early enough after the injury. Similarly, hundreds of AIDS trials were conducted before it was determined that CD4 cell levels might not be a reliable surrogate for AIDS. There are examples in areas where technology is evolving quickly ...