{"id":3917,"date":"2017-01-20T13:44:59","date_gmt":"2017-01-20T13:44:59","guid":{"rendered":"https:\/\/www.wma.net\/wp-content\/uploads\/2017\/01\/Blackmer-DoH-Helsinki-20141111.pdf"},"modified":"2017-01-20T13:44:59","modified_gmt":"2017-01-20T13:44:59","slug":"blackmer-doh-helsinki-20141111-2","status":"inherit","type":"attachment","link":"https:\/\/www.wma.net\/fr\/blackmer-doh-helsinki-20141111-2\/","title":{"rendered":"Blackmer-DoH-Helsinki-20141111"},"author":2,"comment_status":"open","ping_status":"closed","template":"","meta":[],"acf":[],"description":{"rendered":"

Blackmer-DoH-Helsinki-20141111<\/a><\/p>\n

18\/11\/14
\n1
\n1
\nImplementation of the DoH in the Americas:
\nChallenges and successes
\nDr. Jeff Blackmer
\nDirector of Ethics
\nCanadian Medical Association
\n2
\nOutline
\n!\u202f Background and context
\n!\u202f United States
\n!\u202f Canada
\n!\u202f South America
\n18\/11\/14
\n2
\n3
\nBackground and context
\n!\u202f The Declaration of Helsinki (DoH) is not a legally binding document
\nunder international laws.
\n!\u202f However, it exerts authority through the extent to which it has directly
\nand indirectly influenced national and international legislation and
\nregulations.
\n!\u202f In some cases, it has been codified into those laws and regulations.
\n4
\n!\u202f It is important to always keep in mind, however, that the Declaration is
\nmorally binding on physicians, and that this obligation is generally
\nconsidered to override any national or local laws or regulations.
\n!\u202f Paragraph 10 of the 2013 version of the DoH states:
\n!\u202f No national or international ethical, legal or regulatory requirement
\nshould reduce or eliminate any of the protections for research
\nsubjects set forth in this Declaration.
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\n3
\n5
\n!\u202f Since the publication of the original version of the DoH in 1964, there
\nhas been a proliferation of numerous national and international research
\nethics guidelines and documents.
\n!\u202f While there is some degree of alignment and overlap between many of
\nthese documents, there are points of divergence as well, particularly in
\nmore controversial areas such as post-trial access and the use of
\nplacebos.
\n6
\n!\u202f Amongst international documents, the DoH is relatively unique in that it
\nrepresents a set of ethical principles combined with some degree of
\nproscriptive detail, while many of the other documents are more
\ntechnical in nature.
\n!\u202f However, their presence has meant that a number of national regulatory
\nbodies have decided to make reference primarily to one particular
\ndocument or standard.
\n!\u202f For some, this has meant \u201cchoosing\u201d between using the DoH as a
\nstandard versus another more static and\/or technical document.
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\n!\u202f Such documents include, but are not limited to
\n!\u202f The World Health Organization (WHO) and its Standards and Operational
\nGuidance for Ethics Review of Health-Related Research with Human
\nParticipants
\n!\u202f The Council for International Organizations of Medical Sciences (CIOMS)
\nInternational Ethical Guidelines for Biomedical Research Involving Human
\nSubjects
\n!\u202f Good Clinical Practice standards developed by the International Conference
\non Harmonization of Technical Requirements for Registration of
\nPharmaceuticals for Human Use (ICH-GCP)
\n8
\n!\u202f The DoH is unique amongst these policies and guidelines in that it is
\nwritten and updated by physicians for physicians and final approval of
\nthe document rests solely with the physician representatives of the
\nWorld Medical Association.
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\n5
\n9
\nUnited States of America
\n!\u202f In April 2006, the United States Food and Drug Administration (FDA)
\npublished a regulatory change ending the need for clinical trials
\nconducted outside of the US to comply with the Declaration of Helsinki.
\n!\u202f Previous to this, the FDA had already rejected the 2000 version of the
\nDoH and all subsequent revisions, recognizing only the 1989 version in
\nits regulations.
\n10
\n!\u202f These decisions were made largely over the question of whether
\nplacebos should be allowed in clinical trials in resource-poor settings
\n(and to a lesser extent on the issue of post-trial access).
\n!\u202f Representatives from the FDA have actively engaged on the placebo
\nissue with the WMA, including during the DoH revision processes and as
\npart of the placebo-control meetings held in Sao Paulo.
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\n11
\nWhat the FDA says
\n!\u202f \u201cWe didn\u2019t think the World Medical Association understood you really do
\nneed placebos to learn something in a lot of cases. Fundamentally, in a
\nlot of symptomatic conditions, it\u2019s common for studies that compare a
\nnew drug with placebo to fail. If doing the right design, or doing an
\ninformative design would mean denying somebody a therapy that would
\nreally save their lives, then you just can\u2019t do the study at all. Everybody
\nagrees on that. But if it\u2019s just a matter of symptoms, having a headache
\na little longer, being depressed for a few more days, I would say most
\npeople and certainly we believe that you could ask a person to
\nparticipate in a study [using placebos]. But it\u2019s not unethical to do a trial
\nlike that.\u201d
\n12
\n!\u202f \u201cWhat I think has happened to some extent is that the Declaration has
\nmoved from a purely ethical document to a document that is increasingly
\ninterested in social justice. For example, they clearly are very upset that
\npeople in poor countries don\u2019t have really good medical care. And I\u2019m
\nupset by that too. But I don\u2019t think that determines the ethics of a trial.\u201d
\n!\u202f Robert Temple, Director of the Office of Medical Policy at the FDA\u2019s
\nCenter for Drug Evaluation and Research, EBMO Reports, 2006
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\n13
\nPharmaceutical industry concerns
\n!\u202f Fearing that these new obligations (to use a comparator other than
\nplacebo) would make it harder to prove the efficacy of a new drug and
\nwould drive up the costs of development, drug developers, particularly in
\nthe USA, are protesting.
\n!\u202f EBMO Reports, 2006
\n14
\nCriticism of the FDA decision
\n!\u202f \u201cFor the last 30 years, US organizations said they loved the Declaration
\nof Helsinki. All of a sudden, people effectively lobbied to make some
\nchanges to the DoH after the HIV\/AIDS trials. And now the FDA says,
\n\u2018Helsinki? What is that? That doesn\u2019t mean anything.\u2019 It\u2019s just totally
\nhypocritical on their part to follow the DoH as long as it says what they
\nwant it to say, and as soon as it\u2019s changed, say it doesn\u2019t mean
\nanything.\u201d
\n!\u202f George Annas, Chairman of the Health Law Department at Boston University\u2019s
\nSchool of Public Health, 2006
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\n8
\n15
\n!\u202f The FDA now references the ICH-GCP document instead, a change
\nmade in April 2008.
\n!\u202f Unlike the declaration, those standards are developed by regulators in
\nJapan, the US and Europe, in conjunction with the pharmaceutical
\nindustry.
\n16
\nConcerns about pharma influence
\n!\u202f Pharmaceutical companies ultimately look to see what are the
\nregulations and laws they must comply with in whatever countries they
\nare going to seek approval to market a particular product. To the extent
\nthat it\u2019s easier and perhaps less costly to conduct their research in
\nsettings that appear to have looser standards or less rigorous ethical
\nprocesses, then we\u2019ve seen a trend in which they have been moving
\nmore towards doing research in that setting.
\n!\u202f CMAJ November 6, 2012
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\n17
\n!\u202f The FDA\u2019s adoption of less morally stringent guidelines could encourage
\npharmaceutical companies to take ethical short cuts. It could also have
\npractical consequences for trial ethics in developing countries, especially
\nwhere research ethics committees may not be promoting high standards
\nof protection for participants in clinical trials, due to lack of financial and
\nhuman resources.
\n!\u202f Pharmaceutical companies may also pressurise research ethics
\ncommittees to relax guidelines and legislation, in order to facilitate future
\nclinical trials in developing and emerging countries that lack the
\nresources to conduct their own clinical research on epidemics such as
\nHIV\/AIDS, which have devastating effects on their populations.
\n!\u202f South African J of Bioethics and Law 2012
\n18
\nThe Common Rule
\n!\u202f Several US departments and agencies subscribe to subpart A of the
\nrelevant section of the Code of Federal Regulations, often referred to as
\nthe \u201cCommon Rule\u201d.
\n!\u202f The Common Rule is intended to establish a comprehensive framework
\nfor the review and conduct of proposed human research to ensure that it
\nwill be performed ethically.
\n!\u202f It includes provisions concerning research conducted in foreign
\ncountries.
\n18\/11\/14
\n10
\n19
\n!\u202f According to 45 CFR 46.10110:
\n!\u202f When research covered by this policy takes place in foreign countries,
\nprocedures normally followed in the foreign countries to protect human
\nsubjects may differ from those set forth in this policy.
\n!\u202f An example is a foreign institution which complies with guidelines consistent
\nwith the World Medical Assembly Declaration of Helsinki (amended 1989)
\nissued either by sovereign states or by an organisation whose function for the
\nprotection of human research subjects is internationally recognized.
\n!\u202f In these circumstances, if a department or agency head determines that the
\nprocedures prescribed by the institution afford protections that are at least
\nequivalent to those provided in this policy, the department or agency head
\nmay approve the substitution of the foreign procedures in lieu of the
\nprocedural requirements provided in this policy.
\n20
\nCanada
\n!\u202f Canada does not have a uniform and comprehensive legislative or
\nregulatory framework pertaining to research involving human subjects.
\n!\u202f Two different sets of documents are the main sources that govern
\nresearch involving human subjects in Canada.
\n!\u202f One of them (Health Canada\u2019s Food and Drug Regulations) addresses
\nclinical trials that test new drugs or medical devices for approval in
\nCanada, and the other (The Tricouncil Policy Statement, or TCPS)
\naddresses studies that have received federal research funding.
\n18\/11\/14
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\n21
\n!\u202f The Food and Drug Regulations do not reference the DoH.
\n!\u202f However, Health Canada has introduced the full text of the ICH-GCP
\nGuideline (with its own references to the DoH) into its regulatory regime
\nas a Guidance Document.
\n22
\n!\u202f In the Introduction to the Guidance Document, Health Canada states:
\n!\u202f Good Clinical Practice (GCP) is an international ethical and scientific
\nquality standard for designing, conducting, recording and reporting
\ntrials that involve the participation of human subjects. Compliance
\nwith this standard provides public assurance that the rights, safety
\nand well-being of trial subjects are protected, consistent with the
\nprinciples that have their origin in the Declaration of Helsinki, and that
\nthe clinical trial data are credible.
\n18\/11\/14
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\n23
\n!\u202f The TCPS applies to all research funded by the federal research
\ngranting agencies, and was most recently revised in 2010.
\n!\u202f It contains two references to the DoH, in the reference sections for
\nChapter 8 (Multi-Jurisdictional Research) and Chapter 11 (Clinical
\nTrials).
\n24
\nSouth America
\n!\u202f Uruguay
\n!\u202f The Declaration of Helsinki is used in Uruguay as the main research
\nethics guideline by which all researchers must abide.
\n!\u202f National legislation incorporates the 2000 revised version of the
\ndocument.
\n!\u202f Later modifications on the use of placebo are not part of the legislation.
\n18\/11\/14
\n13
\n25
\n!\u202f Brazil
\n!\u202f Following the 2008 revision, Brazil immediately contested the position
\nadopted by the WMA concerning the use of placebo in research
\ninvolving human beings.
\n!\u202f According to the position advocated officially by the Brazilian
\ngovernment, through a Resolution from its National Health Board, \u00ab\u00a0the
\nbenefits, risks, difficulties and effectiveness of a new method should be
\ntested by comparing them with the best present methods\u00a0\u00bb
\n26
\nDouble standard concern
\n!\u202f There remains in some parts of South America a concern about a
\n\u201cdouble standard\u201d for research that they feel is not fully addressed by the
\nDoH.
\n!\u202f Subjects in resource-poor settings may be exposed to placebo controls
\nor to controls that are less then standard of care in more developed
\ncountries.
\n!\u202f Research may not be responsive to the needs of the community in which
\nit is conducted.
\n!\u202f While revisions of the DoH have attempted to address some of these
\nconcerns, they have not done so to the satisfaction of all of those
\ninvolved.
\n18\/11\/14
\n14
\n27
\nDeclaration of Cordoba
\n!\u202f In November 2008, the Congress of the Latin-American and Caribbean
\nBioethics Network of UNESCO (Redbioetica) approved the Declaration
\nof Cordoba on Ethics in Research with Human Beings.
\n!\u202f This document proposed that Latin American countries, governments
\nand organisations should refuse to follow 2008 version of the
\nDeclaration of Helsinki, which was approved in Seoul, South Korea.
\n!\u202f It recommended instead as an ethical and normative frame of reference
\nthe principles of the Universal Declaration on Bioethics and Human
\nRights , proclaimed in October 2005 at the UNESCO General
\nConference.
\n28
\n!\u202f The Declaration of Cordoba states that:
\n!\u202f The new version of the DoH can seriously affect the safety, well-being
\nand rights of persons who participate as volunteers in medical
\nresearch studies.
\n!\u202f The acceptance of different standards of medical care, as well as the
\nnew possibilities for using placebo, are considered ethically
\nunacceptable practices and are contrary to the idea of human dignity
\nand human rights.
\n!\u202f The lack of hard post-study obligations in relation to the persons who
\nvolunteered to participate in the studies and to the host communities,
\noffends people’s integrity and amplifies social inequity.
\n18\/11\/14
\n15
\n29
\nSummary
\n!\u202f The use and implementation of the DoH in the Americas is, to say the
\nleast, inconsistent and controversial.
\n!\u202f In the United States, the FDA does not endorse the document, and only
\nreferences the 1989 version.
\n!\u202f In South American countries, there remains a concern that the DoH
\ndoes not contain sufficient safeguards when it comes to the issues of
\nplacebo controls and post-trial access.<\/p>\n"},"caption":{"rendered":"

Blackmer-DoH-Helsinki-20141111 18\/11\/14 1 1 Implementation of the DoH in the Americas: Challenges and successes Dr. Jeff Blackmer Director of Ethics Canadian Medical Association 2 Outline !\u202f Background and context !\u202f United States !\u202f Canada !\u202f South America 18\/11\/14 2 3 Background and context !\u202f The Declaration of Helsinki (DoH) is not a legally binding document […]<\/p>\n"},"alt_text":"","media_type":"file","mime_type":"application\/pdf","media_details":{},"post":null,"source_url":"https:\/\/www.wma.net\/wp-content\/uploads\/2017\/01\/Blackmer-DoH-Helsinki-20141111.pdf","_links":{"self":[{"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/media\/3917"}],"collection":[{"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/media"}],"about":[{"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/types\/attachment"}],"author":[{"embeddable":true,"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/comments?post=3917"}]}}