E-drug: Final revisions to Declaration of Helsinki
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WARNING: LONG MESSAGE
This email is to update everyone on the latest developments in the
debate over the Declaration of Helsinki and other ethics documents.
The most important news is that, through our collective efforts, the
attempts by some elements of the research industry to weaken the
Declaration of Helsinki have been repulsed, particularly in the
all-important area of what to provide to participants during trials.
In addition, there is new language governing availability of
interventions shown to be effective after the trial. This is a major
victory for those who resisted these changes.
**ACTION REQUESTED**
A. WRITE TO THE US NATIONAL BIOETHICS ADVISORY COMMISSION COMMENTING
ON THEIR RECENTLY RELEASED DRAFT REPORT ON INTERNATIONAL RESEARCH
B. POST THIS EMAIL ON ALL APPROPRIATE LISTSERVES
1. Declaration of Helsinki
As you may recall from my last email, the World Medical Association
met on October 3-7, 2000 in Edinburgh, Scotland to evaluate the
latest proposed changes in the Declaration. In Public Citizen's
letter to them (http://www.citizen.org/hrg/PUBLICATIONS/1538.htm), we
stressed that the addition of the phrase "at the conclusion of the
study" to a section that had in the past dealt with intra-trial
availability of treatment in effect meant that there was no guidance
on what to provide participants during the trial. We asked you to
write to WMA and about 2 dozen people cc'ed me on their letters.
Thank you so much for your efforts!
I spoke to WMA representatives during the week of the meeting and
learned that the offending phrase "at the conclusion of the study"
had not been removed by the Ethics Committee and was about to go
before the Council, the last step before a final vote by the full
Assembly. I pointed out that this left the Declaration with
essentially nothing to say about in-trial availability, though it did
make a strong statement about what needed to be provided to
participants after the trial. The WMA's representative pointed to a
principle in the Declaration that said "The potential benefits,
hazards and discomfort of a new method should be weighed against the
advantages of the best current diagnostic and therapeutic methods."
I pointed out that "weighed" was a very vague term and suggested
"tested" instead.
The other major change that the Ethics Committee had made was in the
section dealing with post-trial availability to the general
community. Previous Declarations had no specific statements on this
crucial issue. The draft of September 2000 had two sentences on this
issue, but the Ethics Committee removed one, that requiring that
researchers develop a "realistic plan" for ensuring post-trial
availability of effective interventions.
In the end, the Council substituted "tested" for "weighed" so that
when there are known effective therapies, new therapies must be
tested against them, rather than against placebo. The second part of
the section dealing with post-trial availability was not restored.
The version passed by the Assembly was essentially identical to that
passed by the Council and can be viewed on the WMA's website at
www.wma.net. Articles describing the results of this process
appeared in BMJ (14 October, p. 913), Lancet (14 October, p. 1336)
and Science (October 20, p. 418).
Here is where this leaves us:
a. The language requiring "best proven" interventions has been
restored. Because the industry had a more-than-adequate opportunity
to make its case for not providing "best proven" interventions to
poor people and this approach (after being incorporated in an earlier
draft) was squarely rejected, the return to the original language
means that there can now be no question as to what is meant by the
phrase "best proven."
b. There is now clear language that people in clinical trials must be
provided with the best intervention after the trial.
c. For the first time, there is language on post-trial availability
for the general community, even if this language is far from perfect
("Medical research is only justified if there is a reasonable
likelihood that the populations in which the research is carried out
stand to benefit from the results of the research.").
d. Left unaddressed, despite the efforts of Dirceu Greco of Brazil,
is the issue of whether other interventions need to be provided to
participants during the trial. For example, in an HIV vaccine trial,
would researchers need to provide treatment to people who become
infected during the trial? This was not addressed directly in the
Declaration.
e. In several other respects, the Declaration is much strengthened, including:
1. Need to publish negative results
2. Need to inform participants of researchers' relevant
financial and other interests
3. Stipulation that certain populations who are not competent
to provide consent should not be the subjects of experiments unless
other subjects are not suitable.
In sum, the efforts of those committed to expanding protections for
research participants have carried the day. Dr. Delon Human of WMA
told me that literally thousands of people had written in with their
concerns. There will be resistance from the U.S. FDA, in particular,
which is concerned that the language on placebos is too restrictive.
But for now, the attempt to water down the protections for
participants, and to retrospectively justify the provision of
placebos to HIV-positive pregnant women in the studies in Africa and
Asia, has failed.
2. Perinatal HIV transmission studies
Ironically, about a week before the WMA meeting, another of the
perinatal HIV studies was published. In our original article
criticising the provision of placebos and unproven therapies to
HIV-positive women (New England Journal of Medicine, September 18,
1997, p. 853-6), we mentioned the one study, by Thai and Harvard
researchers, that used an active-controlled design (no placebo) to
study less-expensive regimens of AZT. The results of the Lallemant
study have now been published (New England Journal of Medicine,
October 5, pp. 982-91). The results show that the shortest regimen
of AZT was not as effective as the longer versions (in fact the
researchers terminated the shortest version prematurely to protect
the participants), but still clearly superior to all previous placebo
or untreated groups. The study permits a clearer assessment of which
portion of the AZT regimen is most important than any prior study,
including the unethical placebo-controlled trials. It demonstrates
that it is possible to design a study that is optimal from both a
scientific and an ethical perspective. Public Citizen's press
release on the study can be found at
http://www.citizen.org/hrg/PUBLICATIONS/1539.htm.
3. U.S. National Bioethics Advisory Commission
The NBAC has now released its draft report on international research
for comment. Comments are due at the commission by November 13,
2000. The report can be downloaded at
http://bioethics.gov/report.html. The address for comments is:
By email: nbac@od.nih.gov
NBAC Website: Comments
By Mail: 6705 Rockledge Drive, Suite 700, Bethesda, MD 20892-7979
By Fax: 1-301-480-6900
We have not examined the report in detail yet, but from a cursory
review we have noted the following:
a. Researchers are required to provide participants in control groups
with "an established, effective treatment," not the "best" treatment
(Recommendation 2.2). As you may recall, the April 2000 draft
version of the Declaration of Helsinki had similar language; one was
obligated to provide something that is better than nothing, not the
best. It is this same language that was removed from the draft
Declaration after many protested. The NBAC would therefore create a
standard that is lower than the Declaration, in a sense creating a
second and lower standard for ethics in international trials.
b. Research would now be permitted even if there was no reason to
think that any intervention proved effective would be made available
to the community after the trial (Recommendation 4.2): "Where
investigators do not believe that successful interventions will
become available to the host country population, they should explain
to the relevant IRB(s) why the research is nonetheless responsive to
the health needs of the country and presents a reasonable
risk/benefit ratio." This is an outrageous invitation to
experimenting on poor patients for purposes that would
disproportionately benefit richer patients.
Please send your comments to the NBAC with cc's to us.
We will continue to keep you informed as events develop, including
with the CIOMS revision process.
Peter Lurie
Peter Lurie, MD, MPH
Deputy Director
Public Citizen's Health Research Group
1600 20th Street, NW
Washington, DC 20009
Phone: (202)588-7781
Fax: (202)588-7796
Email: plurie@citizen.org
Web address: http://www.citizen.org
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