E-drug: Research Ethics Action Alert
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July 31, 2000
We are writing to request your urgent assistance in preventing
changes to the World Medical Association's Declaration of Helsinki
that would seriously erode protections for volunteers in medical
research. Over the last couple of years, we have kept you up to date
on various proposals to water down these and other critical research
protections. To a significant degree, our efforts to resist these
changes have been successful. In the latest draft of the revised
Declaration, most of the offending language contained in a previous
draft revision of the Declaration has been removed. There are,
however, two major areas of concern.
First, the proposed Declaration has removed the phrase "best proven"
from the section that describes what treatments must be provided to
volunteers in studies. Instead, the phrase "proven effective"
appears. This is, of course, a significant watering-down of the
Declaration and one that we feel must be resisted strongly. Rather
than providing the "best," researchers would now only be ethically
obligated to provide anything that works, no matter how inferior to
existing "best" therapy. Second, there is now a section on
availability of effective treatments after clinical trials, which is
a first for the Declaration. However, we think it is still very
vague and not likely to yield practical results on the ground.
We have written a letter to Delon Human of the World Medical
Association making these points. The letter can be found at
http://www.citizen.org/hrg/PUBLICATIONS/1531.htm. It is also
appended to the end of this email and attached as a Microsoft Word
document.
Comments on the current proposed draft are due at the World Medical
Association on August 1. This can be done either through a letter or
by filling out a structured questionnaire on the Association's
website: http://www.wma.net/e/helsinki.html. We suggest that you
provide comments, even if you do not represent a national medical
association. However, national medical associations are likely to
particularly influential.
We apologize for the late notification, but we only recently learned
when the comments were due. We expect that comments received shortly
after the deadline could still influence the debate.
After the comments are received, a new version of the Declaration
will be circulated to national medical associations in September
2000. The new Declaration will presumably come up for a vote at the
full World Medical Association General Assembly in Edinburgh on
October 3-7, 2000.
Now is the time to express your rejection of any proposals to reduce
research participants' protections. Please address your letters to:
Dr. Delon Human
World Medical Association
28 Avenue des Alpes
01212 Ferney-Voltaire Cedex
France
Fax: 011-33-4-50405937
We would appreciate a copy of any letter you send. These can be sent
to us through any of the contacts below.
PLEASE POST THIS INFORMATION ON ALL APPROPRIATE LISTSERVES AND
FORWARD IT TO INTERESTED COLLEAGUES. IF YOU HAVE NOT ALREADY DONE
SO, WE INVITE YOU TO BECOME A PART OF OUR INTERNATIONAL CAMPAIGN TO
PROTECT THE RIGHTS OF INTERNATIONAL STUDY PARTICIPANTS BY SENDING AN
EMAIL TO plurie@citizen.org. We will continue to provide periodic
information regarding the proposed revisions as we receive it, in
order to plan a coordinated strategy to protect participants' rights.
Your sincerely,
Peter Lurie, MD, MPH
Deputy Director
Public Citizen's Health Research Group
[References not included, but are included in the Internet version of this letter.]
July 31, 2000
Dr. Delon Human
World Medical Association
28 Avenue des Alpes
01212 Ferney-Voltaire Cedex
France
Fax: 011-33-4-50405937
Dear Dr. Human:
We are writing to offer our comments on the May 2000 version of the
World Medical Association's Declaration of Helsinki. While there
remain two major aspects of the current draft that we still find
exceedingly objectionable, we do congratulate you for withstanding
the insidious assault on research ethics represented by the previous
draft document (that prepared for the April 15, 1999 World Medical
Association Council session in Santiago, Chile). That document was a
transparent attempt by the research industry to open the world to
potentially exploitative research, which, under the then-proposed
draft, could masquerade as ethical research. The present draft has
rejected essentially all of that language, including particularly
dangerous language on the use of placebos. It is even stronger than
the current Declaration in several respects and is better organized.
However, we do remain deeply troubled by two aspects of the current
draft Declaration. The first is an apparently minor change in
language: while the current Declaration states unequivocally that "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," the draft Declaration states that "In any
medical study, every patient - including those of a control group, if
any - should be assured of proven effective prophylactic, diagnostic,
and therapeutic methods" (paragraph 24b). The addition of
"prophylactic" is welcome: there is no ethical justification for
setting preventive methods in a category apart from diagnostic or
treatment methods. The dangers of so doing were graphically
illustrated in the unethical Alaska needle exchange trial where
researchers sought to deny some injection drug users access to two
proven effective preventive interventions: needle exchange programs
and hepatitis B vaccine.
But there is an additional, subtle change: whereas researchers are
currently obligated to provide the "best proven" intervention, the
draft Declaration would only obligate them to provide a "proven
effective" intervention. The implications of this change are
significant. While science proceeds forward and identifies
increasingly effective interventions for particular conditions, the
current draft Declaration amounts to a blank check for researchers to
provide any intervention ever proved effective -- not necessarily the
most effective one. Is this the world of clinical research we would
like to see: Patients with infectious diseases treated with
antibiotic-resistant drugs? Tuberculosis patients treated with
streptomycin only? Patients with severe pain treated with aspirin or
acetaminophen? All of these are "effective" medications, but none
are the best. These examples make clear that the impact of this
one-word change could have a heavy impact even on those living in
developed countries, particularly vulnerable populations in those
countries.
But the greatest impact will be in developing countries. Even at a
time when the "best proven" language is still in place, we have seen
the following, just in the AIDS arena: 1. a protocol for the Vaxgen
HIV vaccine trial in Thailand in which newly infected patients would
be treated with "best available" (and in this case "proven
effective") treatments (usually two-drug therapy) for HIV infection
instead of superior triple-drug therapy; 2. HIV treatment studies
using two instead of three drugs in Brazil; and 3. patients in one
arm of a sexually transmitted disease treatment trial being referred
to syphilis treatment, while the other arm was treated on site.
While the "proven effective" standard may abolish some of the more
exploitative of these trials (assuming that researchers actually
follow it), it still leaves open a very clear double standard in
research: Best therapy for the rich; anything that can arguably be
said to be better than nothing for the poor. A two-tiered medical
research system is exactly what the World Medical Association should
be standing four-square against. Instead this language would give
your blessing to these double standards.
We therefore propose the phrase "best proven prophylactic, diagnostic
and therapeutic method." While we acknowledge that there are some
situations in which the provision of "best" interventions would be
impractical (e.g., we would not require that coronary care units be
in place before an anti-hypertensive drug could be tested in a
developing country), the Declaration should represent the highest of
our aspirations for the ethical conduct of clinical trials. If
exceptions must be noted in the Declaration, they should be labeled
as exceptions; otherwise we risk the exception becoming the rule.
The default should be "best" interventions.
Our second point deals with post-trial availability of interventions
proved to be effective. We are gratified to see that, for the first
time, there is mention of this issue in the current draft Declaration
(paragraph 24a). But this draft requires only "a reasonable
likelihood that the populations in which the research is carried out
stand to benefit from the results of the research." Given past
behavior, it does not seem likely to us that the research industry
will interpret this expansively. What is needed instead is a
recommendation that researchers discuss post-trial availability of
interventions proved effective as a condition of commencing research
and develop concrete plans in writing for the delivery of such
interventions. Even the language in the Council for International
Organizations of Medical Sciences (CIOMS) document is clearer: "As a
general rule, the sponsoring agency should agree in advance of the
research that any product developed through such research will be
made reasonably available to the inhabitants of the host community or
country at the completion of successful testing." But even this
document fails to require agreements in writing or to provide real
teeth to its recommendation. In the absence of this, we can
anticipate numbing repetitions of recent situations such as the lack
of availability of hepatitis B vaccine and antiretroviral drugs for
perinatal HIV transmission, even after developing world studies
proved them effective.
In conclusion, we commend you on many of the changes you have made
and on your apparent decision to reject the dangerous excesses of the
previous draft Declaration. As you know, researchers and patients
the world over look to the Declaration as the most authoritative word
on research ethics. At a time that international research is
exploding (the number of new foreign investigators in the U.S. Food
and Drug Administration's clinical researcher database grew from 988
in 1990-1992 period to 5,380 in 1996-1998) and reports of improper
recruiting practices continue to grow, the Declaration should be
amended to provide more protection for the increasingly vulnerable
patients the industry is pursuing. In the two respects discussed in
this letter, the effect of the currently proposed Declaration will be
the opposite.
Yours sincerely,
Peter Lurie, MD, MPH
Deputy Director
Sidney M. Wolfe, MD
Director
Public Citizen's Health Research Group
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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