1. Clinical trials: A history

2. First clinical Trial

3. 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

5. 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

6. 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

7. 19th century
Placebo- literally “I Will Please” developed in clinical trials

8. 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

9. 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

10. 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

11. 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

12. Declaration of Helsinki
Fundamental ethical principles
Respect for Persons
Beneficence
Justice