Standards for Clinical Research

Abstract

Approximately 70 years ago, the concept of randomization of individual participants in clinical trials was first introduced, along with informed consent, the ethics of randomized, controlled trials (RCTs), and blinding of treatment assignment.1 A decade later Kaplan and Meier described a mathematical approach to estimating event-free survival at any time T , allowing comparison of the response to treatments over time.2 Building on this strong foundation, clinical investigators began performing a rich array of RCTs that attempted to answer the question of whether a medical intervention was effective, under the ideal circumstances of a circumscribed population and defined treatment protocol (Figure). Blinded RCTs are useful for evaluating investigational products and are central to the development pathway of new medical products. The efficacy and safety data generated in an RCT provide regulatory authorities with the information they need to judge whether a product can be approved for use in clinical practice. Figure. Interface of the continuum of clinical research and research standards. On the left is shown the spectrum of trials where research subjects are randomized to medical interventions and followed prospectively. These range from those conducted under ideal circumstances to those conducted under usual conditions of clinical care. A mapping tool is shown where investigators use a Likert scale to score a trial design along nine domains as to whether it is predominantly explanatory (score=1) or pragmatic (score=5). The typical purpose of the trial type and the ethics and focus of research standards are shown at the bottom left. The core principles of human investigation apply across the spectrum, but the focus of the research standards varies. Big Data analyses incorporate inputs (not shown) of previously acquired data into a predictive analytic system and generate recommendations for more precise care of individuals and populations. Depending on the type of …