<P> The AIDS Clinical Trials Group (ACTG) Study 076 of 100 Zidovudine in maternal - infant transmission of HIV had been published in 1994 . This was a placebo controlled trial which showed a reduction of nearly 70% in the risk of transmission, and Zidovudine became a de facto standard of care . The subsequent initiation of further placebo controlled trials carried out in developing countries and funded by the United States Centers for Disease Control or National Institutes of Health raised considerable concern when it was learned that patients in trials in the US had essentially unrestricted access to the drug, while those in developing countries did not . Justification was provided by a 1994 WHO group in Geneva which concluded "Placebo - controlled trials offer the best option for a rapid and scientifically valid assessment of alternative antiretroviral drug regimens to prevent transmission of HIV". These trials appeared to be in direct conflict with recently published guidelines for international research by CIOMS, which stated "The ethical standards applied should be no less exacting than they would be in the case of research carried out in country", referring to the sponsoring or initiating country . In fact a schism between ethical universalism and ethical pluralism was already apparent before the 1993 revision of the CIOMS guidelines . </P> <P> In retrospect, this was one of the most significant revisions because it added the phrase "This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists" to Article II. 3 ("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 ."). Critics claimed that the Zidovudine trials in developing countries were in breach of this because Zidovudine was now the best proven treatment and the placebo group should have been given it . This led to the US Food and Drug Administration (FDA) ignoring this and all subsequent revisions . </P> <P> Following the fourth revision in 1996 pressure began to build almost immediately for a more fundamental approach to revising the declaration . The later revision in 2000 would go on to require monitoring of scientific research on human subjects to assure ethical standards were being met . In 1997 Lurie and Wolfe published their seminal paper on HIV trials, raising awareness of a number of central issues . These included the claims that the continuing trials in developing countries were unethical, and pointing out a fundamental discrepancy in decisions to change the study design in Thailand but not Africa . The issue of the use of placebo in turn raised questions about the standard of care in developing counties and whether, as Marcia Angell wrote "Human subjects in any part of the world should be protected by an irreducible set of ethical standards" (1988). The American Medical Association put forward a proposed revision in November that year, and a proposed revision (17. C / Rev1 / 99) was circulated the following year, causing considerable debate and resulting in a number of symposia and conferences . Recommendations included limiting the document to basic guiding principles . Many editorials and commentaries were published reflecting a variety of views including concerns that the Declaration was being weakened by a shift towards efficiency - based and utilitarian standards (Rothman, Michaels and Baum 2000), and an entire issue of the Bulletin of Medical Ethics was devoted to the debate . Others saw it as an example of Angell's' Ethical Imperialism', an imposition of US needs on the developing world, and resisted any but the most minor changes, or even a partitioned document with firm principles and commentaries, as used by CIOMS . The idea of ethical imperialism was brought into high attention with HIV testing, as it was strongly debated from 1996 - 2000 because of its centrality to the issue of regimens to prevent its vertical transmission . Brennan summarises this by stating "The principles exemplified by the current Declaration of Helsinki represent a delicate compromise that we should modify only after careful deliberation". Nevertheless, what had started as a controversy over a specific series of trials and their designs in Sub-Saharan Africa, now had potential implications for all research . These implications further came into public view since the Helsinki declaration had stated, "In the treatment of the sick person, the physician must be free to use a new diagnostic and therapeutic measure, if in his or her judgement, it offers hope of saving life, reestablishing health or alleviating suffering ." </P> <P> Even though most meetings about the proposed revisions failed to achieve consensus, and many argued that the declaration should remain unchanged or only minimally altered, after extensive consultation the Workgroup eventually came up with a text that was endorsed by WMA's Council and passed by the General Assembly on October 7, 2000, and which proved to be the most far reaching and contentious revision to date . The justification for this was partly to take account of expanded scope of biomedical research since 1975 . This involved a restructuring of the document, including renumbering and re-ordering of all the articles, the changes in which are outlined in this Table . The Introduction establishes the rights of subjects and describes the inherent tension between the need for research to improve the common good, and the rights of the individual . The Basic Principles establish a guide for judging to what extent proposed research meets the expected ethical standards . The distinction between therapeutic and non-therapeutic research introduced in the original document, criticised by Levine was removed to emphasise the more general application of ethical principles, but the application of the principles to healthy volunteers is spelt out in Articles 18 - 9, and they are referred to in Article 8 (' those who will not benefit personally from the research') as being especially vulnerable . The scope of ethical review was increased to include human tissue and data (Article 1), the necessity to challenge accepted care was added (Article 6), as well as establishing the primacy of the ethical requirements over laws and regulations (Article 9). </P>

Laws related to the protection of human subjects world medical association declaration of helsinki