Table 1 Development of the paragraph on placebo use in the Declaration of Helsinki 1975–2013

29th WMA General Assembly, Tokyo, Japan, October 1975

“II.2 The potential benefits, hazards and discomfort of a new method should be weighed against the advantages of the best current diagnostic and therapeutic methods.

II.3 In any medical study, every patient – including those of a control group, if any – should be assured of the best proven diagnostic and therapeutic method.” [23]

48th WMA General Assembly, Somerset West, South Africa, October 1996

“II.3 In any medical study, every patient – including those of a control group, if any – should be assured of the best proven diagnostic and therapeutic method. This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists”. [24]

52nd WMA General Assembly, Edinburgh, Scotland, October 2000

“§29 The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists”. [25]

53rd WMA General Assembly, Washington DC, USA, October 2002

Ҥ29 The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.

Note of Clarification added:

However, a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances:

1. Where for compelling and scientifically sound methodological reasons it is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or

2. Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm.” [26]

59th WMA General Assembly, Seoul, Korea, October 2008

Ҥ32 The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances:

-The use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or

-Where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of this option.” [27]

64th WMA General Assembly, Fortaleza, Brazil 2013

Ҥ33 The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best proven intervention(s), except in the following circumstances:

- Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or

- Where, for compelling and scientifically sound methodological reasons, the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is necessary to determine the efficacy or safety of an intervention and the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention. Extreme care must be taken to avoid abuse of this option.” [2]