Clinical trials: A history www.bradfordvts.co.uk

First clinical Trial

Nebuchadnezzar II Instructed courtiers to follow strict diet of wine and meat Jewish courtiers refused to eat meat offered to idols and were allowed to eat vegetables, bread and water Daniel and colleagues were healthier than those on the meat and wine

Ambroise Parè 1537 Ran out of traditional dressing compound Mixed oil of rose, turpentine and egg yolk and dressed wounds with this Following day wounds dressed with his compound were healthier Unintentional

James Lind 1747 Controlled trial of crews in British navy 1 Crew given lemon juice 1 Crew normal diet No scurvy in treated crew First controlled trial

19th century Placebo- literally “I Will Please” developed in clinical trials

Austin Bradford Hill 1947 Streptomycin used in first double blind, randomised, placebo controlled clinical trial. Use of streptomycin already proven in advanced disease Pulmonary tuberculosis not always fatal so placebo considered ethical This trial was organised by the group that became the MRC Clinical Trials Unit

Ethical Considerations Following WWII, after atrocities carried out by Nazi doctors, the Nuremberg code (1947) was developed. voluntary consent Avoidance of unnecessary suffering High scientific standards

Tuskegee Observational study of men with syphilis Started in 1932 Despite availability of penicillin from early 1950s, study participants were observed without treatment until 1972

Declaration of Helsinki Statement of ethical principles for medical research first issued in 1962 Most recently revised 2000 Has legal force in most countries Embodied in EU good clinical practice guidelines since 1990

Declaration of Helsinki Fundamental ethical principles Respect for Persons Beneficence Justice