A clinical trial is a study designed to test hypotheses about comparative effects. Trials are based on experimental designs, within which the investigator systematically introduces changes into natural phenomena and then observes the consequences of those changes. The randomized controlled trial (RCT) is the standard explanatory design, intended to support a cause-and-effect relationship between an intervention (the independent variable) and an observed response or outcome (the dependent variable).
The purpose of this chapter is to describe the basic structure of clinical trials using the RCT as a model and to discuss the important elements that provide structure and control for both explanatory and pragmatic studies.
One of the most important influences in the advancement of scientific research over the past 60 years has been the development of the clinical trial as a prospective experiment on human subjects (see Box 14-1). Clinical trials have been classified as explanatory, focusing on efficacy, and pragmatic designs, focusing on effectiveness, differing in their degree of internal control and external generalizability (see Chapter 2). The National Institutes of Health (NIH) define a clinical trial as:
A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.1
Box 14-1 Clinical Trials Registries
Clinical trials registries are Web-based resources that catalog information on publicly and privately supported clinical studies. In the United States, ClinicalTrials.gov includes more than 300,000 trials.6 Registries are also available in more than 20 countries.7 The database was developed by NIH through the National Library of Medicine (NLM) in collaboration with the Food and Drug Administration (FDA), allowing broad availability of information to those with medical conditions, members of the public, healthcare providers, and researchers.
The intent of a clinical registry is to help patients find trials for which they may be eligible, to enhance the design of clinical trials, and to prevent duplication of unsuccessful or unsafe trials. It is also intended to improve the evidence base that informs clinical care, increase efficiency of drug and device development, improve clinical research practices, and build public trust in clinical research.8
Researchers can voluntarily register their studies when they begin using a Web-based entry system called the Protocol Registration and Results System (PRS).9 Not all studies must be registered, but those involving drug or device interventions are required to do so, and must also submit their results.10 Researchers are responsible for updating and maintaining accuracy of information, such as when the study is recruiting subjects, when results are obtained, and when the study is complete. Protocols for trials are also published, giving details about study methods. Trials are assigned a number which can be used to search for specific studies and ...