Randomized controlled trial

A randomized controlled trial (or randomized control trial; RCT) is a type of scientific (often medical) experiment that aims to reduce certain sources of bias when testing the effectiveness of new treatments; this is accomplished by randomly allocating subjects to two or more groups, treating them differently, and then comparing them with respect to a measured response. One group—the experimental group—has the intervention being assessed, while the other—usually called the control group—has an alternative condition, such as a placebo or no intervention. The groups are followed under conditions of the trial design to see how effective the experimental intervention was. Treatment efficacy is assessed in comparison to the control. There may be more than one treatment group or more than one control group.Ronald A. Fisher was 'interested in application and in the popularizationof statistical methods and his early book Statistical Methods for Research Workers, published in 1925, went through many editions andmotivated and influenced the practical use of statistics in many fields ofstudy. His Design of Experiments (1935) statistical technique and application. In that book heemphasized examples and how to design experiments systematically froma statistical point of view. The mathematical justification of the methodsdescribed was not stressed and, indeed, proofs were often barely sketchedor omitted altogether ..., a fact which led H. B. Mann to fill the gaps with a rigorous mathematical treatment in his well known treatise, Mann (1949).'Page 87: Conniffe, Denis (1990–1991). 'R. A. Fisher and the development of statistics—a view in his centenary year'. Journal of the Statistical and Social Inquiry Society of Ireland. XXVI (3). Dublin: Statistical and Social Inquiry Society of Ireland. pp. 55–108. ISSN 0081-4776. A randomized controlled trial (or randomized control trial; RCT) is a type of scientific (often medical) experiment that aims to reduce certain sources of bias when testing the effectiveness of new treatments; this is accomplished by randomly allocating subjects to two or more groups, treating them differently, and then comparing them with respect to a measured response. One group—the experimental group—has the intervention being assessed, while the other—usually called the control group—has an alternative condition, such as a placebo or no intervention. The groups are followed under conditions of the trial design to see how effective the experimental intervention was. Treatment efficacy is assessed in comparison to the control. There may be more than one treatment group or more than one control group. The trial may be blinded, in which information which may influence the participants is withheld until after the experiment is complete. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. Good blinding may reduce or eliminate some sources of experimental bias. The randomness in the assignment of subjects to groups reduces selection bias and allocation bias, balancing both known and unknown prognostic factors, in the assignment of treatments. Blinding reduces other forms of experimenter and subject biases. A well-blinded RCT is often considered the gold standard for clinical trials. Blinded RCTs are commonly used to test the efficacy of medical interventions and may additionally provide information about adverse effects, such as drug reactions. The terms 'RCT' and 'randomized trial' are sometimes used synonymously, but the latter term omits mention of controls and can therefore describe studies that compare multiple treatment groups with each other in the absence of a control group. Similarly, the initialism is sometimes expanded as 'randomized clinical trial' or 'randomized comparative trial', leading to ambiguity in the scientific literature. Not all randomized clinical trials are randomized controlled trials (and some of them could never be, as in cases where controls would be impractical or unethical to institute). The term randomized controlled clinical trial is an alternative term used in clinical research; however, RCTs are also employed in other research areas, including many of the social sciences. The first reported clinical trial was conducted by James Lind in 1747 to identify treatment for scurvy. Randomized experiments appeared in psychology, where they were introduced by Charles Sanders Peirce and Joseph Jastrow in the 1880s, and in education. Later, in the early 20th century, randomized experiments appeared in agriculture, due to Jerzy Neyman and Ronald A. Fisher. Fisher's experimental research and his writings popularized randomized experiments. The first published RCT in medicine appeared in the 1948 paper entitled 'Streptomycin treatment of pulmonary tuberculosis', which described a Medical Research Council investigation. One of the authors of that paper was Austin Bradford Hill, who is credited as having conceived the modern RCT. By the late 20th century, RCTs were recognized as the standard method for 'rational therapeutics' in medicine. As of 2004, more than 150,000 RCTs were in the Cochrane Library. To improve the reporting of RCTs in the medical literature, an international group of scientists and editors published Consolidated Standards of Reporting Trials (CONSORT) Statements in 1996, 2001 and 2010, and these have become widely accepted. Randomization is the process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce the bias. Although the principle of clinical equipoise ('genuine uncertainty within the expert medical community... about the preferred treatment') common to clinical trials has been applied to RCTs, the ethics of RCTs have special considerations. For one, it has been argued that equipoise itself is insufficient to justify RCTs. For another, 'collective equipoise' can conflict with a lack of personal equipoise (e.g., a personal belief that an intervention is effective). Finally, Zelen's design, which has been used for some RCTs, randomizes subjects before they provide informed consent, which may be ethical for RCTs of screening and selected therapies, but is likely unethical 'for most therapeutic trials.'