Short answers, pulled from the story.
James Lind conducted the first reported clinical trial for scurvy in 1747 while serving as a Scottish physician on the HMS Salisbury. He divided twelve scurvy patients into six pairs and tested different treatments including cider, vinegar, and citrus fruits. The pair receiving oranges and lemons showed rapid recovery while the others showed little improvement.
The first randomized controlled trial in medicine was published in 1948 by the Medical Research Council. The paper titled Streptomycin treatment of pulmonary tuberculosis was authored by Austin Bradford Hill who conceived the modern RCT by randomly assigning patients to receive either streptomycin or bed rest alone. This trial demonstrated that randomization could eliminate selection bias and confounding factors.
Studies since 1982 have shown that many subjects believe they are certain to receive the best treatment for their condition which is known as the therapeutic misconception. This misunderstanding complicates the process of obtaining informed consent as patients may not fully grasp the difference between research and treatment. Placebo-controlled trials have faced ethical scrutiny especially when withholding treatment could lead to harm or death.
A study of 28 Phase III RCTs funded by the National Institute of Neurological Disorders and Stroke prior to 2000 revealed a total cost of US$335 million. The average cost per trial was US$12 million despite the high financial burden. The same study projected that these 28 RCTs produced a net benefit to society at 10 years of 46 times the cost of the trials program.
A 2011 study reviewing 29 meta-analyses found that 219 out of 509 RCTs were industry-funded which represents 69% of the total. Of these 509 RCTs 91 studies disclosed industry financial ties with one or more authors. A systematic review published in 2003 found a correlation between industry sponsorship and positive study outcomes with industry-funded RCTs being more likely to report statistically significant pro-industry findings.