Short answers, pulled from the story.
A randomized controlled trial, or RCT, is a type of statistical experiment that evaluates the efficacy or safety of an intervention by randomly allocating participants to comparison groups. At least one group receives the intervention under study, such as a drug, surgical procedure, medical device or diet, while other groups receive an alternative treatment, a placebo, or standard care.
Jan Baptist van Helmont made the first proposal for an RCT in the posthumously published Ortus Medicinae of 1648, to test two treatment regimes for fever, though he likely never conducted it. Austin Bradford Hill, an author of the 1948 paper Streptomycin treatment of pulmonary tuberculosis, is credited with conceiving the modern RCT.
The first published randomized controlled trial in medicine appeared in 1948, in a paper titled Streptomycin treatment of pulmonary tuberculosis that described a Medical Research Council investigation. By 2004, more than 150,000 RCTs were in the Cochrane Library.
Randomized controlled trials are considered the gold standard because random allocation reduces selection bias and balances both known and unknown prognostic factors across groups. As of 1998, Australia's National Health and Medical Research Council ranked a systematic review of all relevant RCTs as Level I evidence, and the GRADE Working Group concluded in 2008 that randomized trials without important limitations constitute high quality evidence.
The major RCT study designs are parallel-group, crossover, stepped-wedge, cluster, and factorial. An analysis of 616 RCTs indexed in PubMed during December 2006 found that 78% were parallel-group, 16% were crossover, and split-body, cluster and factorial were each 2%.
Randomized controlled trials can be expensive and slow, with one study of 28 Phase III trials finding a mean cost of US$12 million per RCT, and results often take years to publish. They may also be unethical when withholding treatment could harm patients, are poorly suited to studying rare events, and industry-funded RCTs have been associated with positive, pro-industry findings.