BMC Med Ethics. 2018 Mar 15;19(1):24. doi: 10.1186/s12910-018-0262-9.

Ethical principles and placebo-controlled trials - interpretation and implementation of the Declaration of Helsinki's placebo paragraph in medical research.

Skierka AS1, Michels KB2,3,4.

Author information

1

Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. antoniaskierka@hotmail.com.

2

Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. kmichels@hsph.harvard.edu.

3

Department of Obstetrics, Gynecology and Reproductive Biology, Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. kmichels@hsph.harvard.edu.

4

Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. kmichels@hsph.harvard.edu.

Abstract

BACKGROUND:

In October 2013, the Declaration of Helsinki was revised a seventh time in its 50 year history. While it is the most widely accepted set of ethical principles for the protection of patients participating in medical research, the Declaration of Helsinki has also been subject of constant controversy. In particular, its paragraph on the use of placebo controls in clinical trials divides the research community into active-control and placebo orthodox proponents, both continuously demanding revisions of the Declaration of Helsinki in favour of their position. The goal of the present project is to compare the mainly theoretical controversy with regulatory implementation.

METHODS:

We distributed a questionnaire to national drug regulatory authorities from different countries to collect information on the authorities' respective approaches to interpretation and implementation of the Declarations' placebo paragraph in the conduct of medical research.

RESULTS:

Our findings suggest that the majority of drug regulatory authorities have established a practice of a middle ground, allowing placebo controls in some instances. Various interpretations of "serious harm" and "methodological reasons" are proposed as well as safeguards to avoid abuse of the option to use placebo-controls.

CONCLUSION:

Leaving the placebo paragraph open to various interpretation is a result of the Declaration of Helsinki's character as a guidance document. With the current version controversy will continue. The Declaration should be continued to be strengthened to enforce the appreciation of conducting medical research with the highest ethical standard.