Regulatory Focus™ > News Articles > Major Clinical Trials Ethics Framework Gets Update, Emphasizing Post-Trial Responsibilities

Major Clinical Trials Ethics Framework Gets Update, Emphasizing Post-Trial Responsibilities

Posted 16 April 2013 | By Alexander Gaffney, RAC

A cornerstone of the global clinical trials ethical framework, the Declaration of Helsinki, has undergone a major revision and is now being released for public consultation, the World Medical Association (WMA), the document's steward, has said.


The Declaration of Helsinki was first adopted by the WMA during its Helsinki meeting in June 1964, and has since been amended eight additional times. Its most current revision, if formally adopted, would mark its tenth, and its fifth since the year 2000.

The document is known to be a major cornerstone of many country's ethical frameworks for the government of clinical trials.

Though an important landmark for ethical research standards, it is not legally binding for countries, industry or individuals. The US Food and Drug Administration (FDA), for instance, has not signed on to any revision made since 1996 after changes were made to abandon the use of placebo controls in studies where no therapeutic benefit currently exists.

Still, the declaration is often referenced as a benchmark for many other ethical frameworks. Until 2008, FDA required clinical trials conducted in foreign countries on behalf of pending products before the agency to adhere to the 1989 iteration of the declaration. Many other countries reference other versions of the declaration, such as the 1996 version referenced by the European Commission.

A New Framework

The WMA has been working on the draft document for months with an end goal of publication by 2014-the 50th anniversary of the initial declaration.

It is now being released for public consultation for the first time, incorporating a number of significant and minor changes.

For example, the declaration for the first time calls for "adequate compensation and treatment for subjects who are harmed as a result of participating in the research," a frequent source of contention in developing countries where clinical trials are often not as strictly regulated.

In addition, researchers themselves would for the first time be charged with monitoring trial risks on an ongoing basis and directed to mitigate those risks. Those are more traditionally assigned to ethics committees and safety monitors, though the concept itself is already widely practiced and a part of other general ethical frameworks.

So-called "vulnerable populations"-traditionally defined as the sick, the old, the young and the mentally incapacitated-are also given special emphasis in the revision, which calls for special considerations to be given to those populations to ensure that research is first done (if able) in non-vulnerable populations, and that the population stands to benefit.

In another edit, the WMA calls for measures to be taken to ensure that patients enrolled in a study are still able to access the product or intervention after the study's conclusion, with the caveat that the intervention must be known to be beneficial to the patient.

Changes to Placebo Policy

As expected, changes are also being made to the use of placebo controls in the document, which introduces new levels of nuance to its existing policy.

"The use of placebo, or no intervention, is acceptable in studies where no proven intervention exists; or Where for compelling and scientifically sound methodological reasons the use of any intervention less effective than the best proven one, placebo or no treatment 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 treatment will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention," the document states.

Other Changes

Other changes are more minor in scope. For example, physicians involved in clinical trials are now asked to safeguard not only the health of patients but also their "well-being," implying a broader standard of care. Those same physicians now "must"-rather than the normative "should"-"consider the ethical, legal and regulatory norms and standards for research involving human subjects in their own countries."

The document, complete with highlighted changes, may be found here. Comments on the document are due no later than 15 June 2013.

Regulatory Focus newsletters

All the biggest regulatory news and happenings.