Letter on New Version of Declaration of Helsinki

Dr. Delon Human
World Medical Association
28 Avenue des Alpes
01212 Ferney-Voltaire Cedex
France

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.[1]

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.[2] 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.[3] 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.”[4] 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,[5] 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, M.D., M.P.H.
Deputy Director

Sidney M. Wolfe, M.D.
Director
Public Citizen’s Health Research Group


References

[1] The details of this experiment are available at https://www.citizen.org/our-work/health-and-safety/articles/letter-cancellation-nih-funding-research-needle-exchange and also in the following publications: Lurie P. Le Mystere de Montreal (invited editorial). American Journal of Epidemiology 1997;146:1-4 and Lurie P. Dr. Lurie replies [to letters regarding his editorial on the Montreal and Alaska needle exchange studies] (letter). American Journal of Epidemiology 1998;148:715-6.

[2] For reasons that remain obscure to us, the draft version of the Declaration used strike-through software to indicate all changes to the current Declaration, but failed to indicate that “best” had been removed.

[3] Glantz LH, Annas GJ, Grodin MA, Mariner WK. Research in developing countries: taking “benefit” seriously. Hastings Center Report 1998;28:38-42.

[4] Council for International Organizations of Medical Sciences, World Health Organization. International ethical guidelines for biomedical research involving human subjects. Geneva, 1993.

[5] Gibbs Brown J. Recruiting human subjects: pressures in industry-sponsored clinical research. Office of the Inspector General, Department of Health and Human Services, June 2000 (OEI-01-97-00195).