Regulatory Focus™ > News Articles > Revised Declaration of Helsinki Published for Comment, Earning Scathing Reviews

Revised Declaration of Helsinki Published for Comment, Earning Scathing Reviews

Posted 21 October 2013 | By Alexander Gaffney, RAC

Since 2012, the World Medical Association (WMA) has been working to update The Declaration of Helsinki, a document whose iterations form much of the backbone of the current practice of clinical trials ethics. And now, nearly a month after WMA officials said revisions had been completed, industry and the public is getting its first glimpses at the group's work.


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 will mark its 10th, and its fifth since the year 2000.

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.

Revision Process

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.

As Focus reported in August 2013, the WMA recently announced it had finished making changes to the document since its original unveiling in April 2013.

The April 2013 unveiling had shown a focus on "adequate compensation and treatment for subjects who are harmed as a result of participating in the research." Some countries, and in particular those in developing regions, do not currently have in place those requirements, though many other regions already do.

In addition, WMA said that 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.

The document also called for changes to the use of placebo controls, saying it 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 that the best proven one … is necessary to determine the efficacy or safety of an intervention." Under such a paradigm, it would need to be shown that patients would not be subject to any additional risks, the document adds.


WMA's latest iteration of the document, published in the Journal of the American Medical Association (JAMA), contains few substantive changes relative to the April 2013 iteration.

For example, Section 15 of the April document had originally called for "adequate" compensation. The new revision, however, called for "appropriate" compensation instead.

Another change: The April revision called for risks to "always be monitored by the researcher throughout the trial." It now called for risks to be "monitored, assessed and documented" by the same.

In another example, WMA struck the sentence (Section 20): "Consideration should also be given to ensuring that the community receives a fair level of additional benefits."

Many other minor word changes exist in the document.


The JAMA posting was accompanied by an extensive analysis of the document by Joseph Millum, David Wendler and Ezekiel Emanuel, who wrote that the document "contains persistent flaws."

"While the document purports to be a statement of enduring ethical principles, the nearly continuous process of revision undermines its authority," the authors observed.

They also argued that while WMA maintains that the primary audience of the Helsinki Declaration is physicians, such a focus "is a mistake."

"It is time for the WMA to recognize that the Declaration of Helsinki should address physicians as well other health professionals and personnel involved in research. A statement of ethical principles does not require a mandate from the people who ought to follow those principles."

They also faulted the revised document's informed consent provisions as being "inadequate," saying it "fails to recognize the possibility of waiving consent for some research involving competent adults, even though such research is common and widely endorsed." They similarly added that the document does not allow for broad consent to be given for use of biological samples obtained during the course of a trial, which could be used in subsequent research.

"In addition, the declaration prohibits individuals who cannot consent from participating in research that does not address the condition that caused their incapacity (paragraph 30), even when the research offers participants the potential for important medical benefit and there are no-or few-potential participants who can consent," they added. "This approach transforms a protection into a barrier."

While the authors conceded that the revised declaration "represents a significant improvement over previous versions," they concluded that "important problems and confusion remain" and "await response" by the WMA.

Revised Declaration of Helsinki

JAMA Analysis

Tags: WMA

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