{"id":3808,"date":"2017-01-20T12:26:06","date_gmt":"2017-01-20T12:26:06","guid":{"rendered":"https:\/\/www.wma.net\/wp-content\/uploads\/2017\/01\/HHS_Comments_on_DOH_for_Cape_Town_Conference_12-5-7-2012.pdf"},"modified":"2017-01-20T12:26:06","modified_gmt":"2017-01-20T12:26:06","slug":"hhs_comments_on_doh_for_cape_town_conference_12-5-7-2012-2","status":"inherit","type":"attachment","link":"https:\/\/www.wma.net\/fr\/hhs_comments_on_doh_for_cape_town_conference_12-5-7-2012-2\/","title":{"rendered":"HHS_Comments_on_DOH_for_Cape_Town_Conference_12-5-7-2012"},"author":2,"comment_status":"open","ping_status":"closed","template":"","meta":[],"acf":[],"description":{"rendered":"

HHS_Comments_on_DOH_for_Cape_Town_Conference_12-5-7-2012<\/a><\/p>\n

1
\n1
\nU.S. Department of Health and Human Services
\nPerspectives on the Revision of the Declaration of Helsinki
\nWorld Medical Association Expert Conference
\nDecember 5-7, 2012
\nThe Declaration of Helsinki (DOH) has been an important source of ethical guidance in the
\nconduct of clinical research throughout the world for nearly half a century. The DOH is highly
\nregarded and respected for its reflection of fundamental principles and widely-held values. As
\nthe process to revise the 2008 version of the Declaration of Helsinki begins, we wish to
\ncommend the World Medical Association (WMA) for the integrity and transparency of its
\nconsultative and deliberative processes and for giving due consideration to the perspectives of all
\nstakeholders and interested parties.
\nDOH\u2019s strength and influence lies in its articulation of basic ethical guidance for the conduct of
\nclinical research. While ethical principles are enduring, clinical research is a dynamic enterprise.
\nNew frontiers of clinical science and new opportunities to address human diseases and advance
\nhuman health can raise ethical questions. We support efforts to augment the DOH where new
\nethical challenges arise and to adjust current content to reflect new research practices and
\ndirections. At the same time, it is important to resist calls to add procedural specifics to the
\nDOH. Prescribing specific procedural steps leads to conflicts between the DOH and the
\nmandatory procedures that countries have in place to protect human research participants. Such
\nconflicts weaken DOH\u2019s influence and diminish its value as a source of fundamental ethical
\nguidance.
\nWe appreciate the opportunity to provide our perspectives on the specific topics being discussed
\nat this Expert Conference, to raise several issues with regard to the content and structure of the
\ncurrent document, and to listen to the thoughtful perspectives of other participants. We also look
\nforward to providing further input during the next phases of the revision process when specific
\nrevisions to the current version will be considered.
\nDiscussion Topics
\nVulnerable Groups
\nIn the current DOH, attention is given to the ethical issue of vulnerability in two separate
\nparagraphs, 9 and 17. Taking note of the definition provided in Paragraph 9, we would
\nrecommend that the reference to disadvantaged populations in Paragraph 17 be dropped. Its
\ninclusion effectively and, in our view, inappropriately characterizes every disadvantaged
\npopulation or community as incapable of giving or refusing consent for themselves or as
\nvulnerable to coercion or undue influence. In addition, the second \u201cif\u201d clause currently makes no
\nreference to the fact that research participation in itself can be beneficial to a population or
\ncommunity. We would suggest that this issue be addressed by dropping the phrase \u201cresults of
\nthe.\u201d
\n2
\n2
\nPost-Study Arrangements
\nThe current DOH approach to post-trial arrangements, expressed in Paragraphs 33 and 14,
\nwarrants reconsideration and revision, particularly Paragraph 33. The expectation in Paragraph
\n33 that investigators will provide access to interventions identified as beneficial or to other
\nappropriate care or benefits is a standard that most investigators cannot meet. Especially
\ntroubling is the statement that study participants \u201care entitled\u201d to share in the benefits that result
\nfrom the study. Investigators may face any number of challenges and impediments to providing
\naccess to such benefits, including lack of funding, insufficient supplies, the country\u2019s health care
\nsituation and its national regulations and health care policies. Moreover, requiring post-study
\naccess may restrict the number of countries where research involving potentially beneficial
\ninterventions can be conducted and could have profoundly adverse consequences across the
\nglobe on the ability of the public and private sectors to carry out research on investigational
\ntherapies, diagnostics, and preventive measures.
\nCertainly, researchers must be attentive to the ongoing health needs of research participants, but
\nestablishing a standard that is largely impossible to achieve does not advance the ethical conduct
\nof research. We urge WMA to consider a more reasonable articulation of the investigator\u2019s
\nobligations to the future well-being of the participants enrolled in their studies. In our view, the
\nWMA should adopt a more measured ethical approach that would call upon researchers to
\nconsider the issue of post-trial access in the context of local needs, the local healthcare
\ninfrastructure, national regulations and health care policies, and the availability of effective
\ntreatments and, where such access is possible, to describe arrangements for access to
\ninterventions identified as beneficial in the study, such as continued therapy with an
\ninvestigational intervention or other appropriate care or benefits.
\nFor reasons we will describe later, the concepts in Paragraph 33 should be moved to Part B.
\nBiobanks
\nBiobanks raise many important ethical issues, and they will likely play a role of growing
\nimportance in the world of research. The debate with regard to the ethical issues surrounding
\nbiobanks is ongoing, and there is as yet no consensus. It is premature to establish ethical
\nrequirements in areas where a consensus on the appropriate ethical course to take has not been
\nestablished.
\nEthics Committees
\nOne important element regarding the composition and role of ethics review committees is
\nmissing from Paragraph 15. Language should be added to specify that Ethics Review
\nCommittees should be comprised of members with the appropriate expertise to review the
\nresearch protocols that are submitted to them. Addressing this gap would strengthen the DOH.
\nEnhancement
\nHHS does not see a need for the DOH to address the ethical issues related to physical or
\ncognitive enhancement research. To the extent that such research involves the same ethical
\n3
\n3
\nissues that apply to other types of research, the DOH already provides guidance. If there are
\nunique ethical issues with enhancement research, those issues have not yet been identified or
\nresolved. As such, it would be premature to attempt to articulate specific ethical guidance.
\nGeneral Consultation Topics
\nHHS looks forward to learning more about the specific aspects of the four consultation topics
\nthat may be under consideration for inclusion into the DOH. As the thinking advances and the
\nintentions become clearer, we will likely have more specific comments. Below are some of our
\npreliminary thoughts.
\nInsurance\/Compensation\/Protection
\nWe agree that clinical researchers have an ethical obligation to provide for treatment of
\nindividuals who experience adverse events or injuries as a result of their participation in
\nresearch. Compensation for harms or costs of long-term care is a much more complex issue. In
\nthis regard, the U.S. Presidential Commission on the Study of Bioethics Issues addressed the
\nissue in a recent report, which is currently under consideration by HHS. Articulating the ethical
\nprinciple that research participants should not bear the cost of unforeseen harms related to their
\nstudy participation may be an appropriate addition to the DOH. However, given the different
\napproaches that nations take in addressing this issue, it would be counterproductive to go farther
\nby attempting to identify a specific implementation mechanism.
\nUse of Unproven Interventions\/Off-label Use
\nHHS does not see a need to modify or expand on the current text in the DOH that addresses
\nunproven interventions. Paragraph 35 speaks to the issues that should guide a physician\u2019s
\ndecision-making when considering the use of an unproven intervention. Moreover, existing
\nnational regulations and guidance provide more detailed explanation of requirements for the use
\nof unproven interventions with therapeutic intent for an individual patient. More detailed text on
\nthis topic is likely to conflict with national regulations that vary in their requirements for dealing
\nwith the use of investigational drugs for therapeutic purposes.
\nAlso, we advise against addressing the topic of off-label use of approved products. It is a
\nmedical practice, rather than a research, matter. Moreover, attempting to address the issue of
\noff-label use in the DOH is likely to lead to conflicts with national regulations that vary in their
\npolicies or requirements.
\nBroad Consent
\nThe ethical acceptability of the use of broad consent in certain types of research is an important
\nand timely issue. HHS is currently considering regulatory changes to allow the use of broad
\nconsent for research involving biospecimens and data. Such a change will facilitate important
\nresearch and, if properly designed and implemented, would be in keeping with applicable ethical
\nprinciples.
\n4
\n4
\nMedical Research Involving Children
\nSpecific ethical guidance on research involving children need not be added to the DOH. The
\nprinciples outlined in the DOH generally apply to research with children and, together with the
\nprinciple outlined in Paragraph 17 that covers vulnerable populations, the DOH provides
\nsufficient ethical guidance for studies involving pediatric populations. Articulating detailed
\nstandards for pediatric research would require a significant expansion of the DOH. However,
\nsuch an expansion would be inappropriate because adding specific details in this area to the
\nDOH may conflict with specific and comprehensive regulations for pediatric studies already in
\nplace for many countries.
\nOther Issues with the 2008 Version of the DOH
\nDeference to National Human Subjects Protections Requirements on Specific Details
\nWhile much of the DOH appropriately remains at the level of broad principles, there are
\nprovisions that detail specific requirements. Some of these are, moreover, at odds with national
\nlaws and\/or regulatory requirements. Excessive specificity undermines the value of DOH as a
\nsource of basic ethical guidance and leads to unnecessary conflicts with national approaches that
\nare based on the same fundamental ethical principles. This problem is exacerbated because of
\nlanguage in the DOH that claims moral supremacy over national requirements and standards.
\nWe urge WMA to modify Paragraphs 10 and 15. Both Paragraphs include statements that
\ninappropriately call on researchers to disregard their obligations to follow their national laws and
\nregulations when they conflict with the provisions of the DOH. Paragraph 10\u2019s statement that
\n\u201cNo national or international ethical, legal or regulatory requirement should reduce or eliminate
\nany of the protections for research subjects set forth in this Declaration\u201d and the similar
\nstatement in Paragraph 15 should be deleted.
\nClarifying the Intent of Paragraph 6
\nParagraphs 6 conflates medical research with medical care and, in so doing, incorrectly creates a
\nstandard for the well-being of the subject that is akin to that which applies to patients in clinical
\ncare. That standard is not the one that is currently being applied in the research setting, for if it
\nwere, much of the research conducted today would be in violation of the standard. Paragraph 6
\nshould be revised and combined with paragraph 21, which more closely reflects the applicable
\nstandard.
\nRegistration of Clinical Trials
\nHHS agrees with the importance of the goals of transparency and accountability articulated in
\nParagraph 19 and that information about clinical trials should be available through registration in
\na publicly accessible database. However, specifying a timeframe for registration does not relate
\nto an ethical principle, i.e., whether the registration occurs before recruitment or sometime after
\nrecruitment begins is not important for the protection of the study participants. Moreover, there
\nis no international consensus on best practices about the scope and timing of registration.
\n5
\n5
\nAccordingly, Paragraph 19 should be revised to become a statement of principle that \u201cEvery
\nclinical trial should be registered in a publicly accessible database as early as possible in order to
\nfacilitate transparency and accountability.\u201d
\nArtificial Distinction between Medical Research (Section B) and Medical Research
\nCombined with Medical Care (Section C)
\nThe distinction that the DOH is drawing between \u201cmedical research\u201d and \u201cmedical research
\ncombined with medical care\u201d is confusing. In fact, there do not appear to be conceptual
\ndifferences that would warrant separate ethical guidance sections. As such, we recommend
\ndeleting Part C \u201cAdditional Principles for Medical Research Combined with Medical Care,\u201d and
\nincorporating sections of Paragraphs 31-35 into sections A and\/or B, as follows.
\n\uf0b7 Paragraph 31 repeats concepts already covered in Paragraphs 3, 6, and 16 and can be
\ndeleted altogether.
\n\uf0b7 Paragraph 32 addresses the use of placebos and should be moved to follow Paragraph 16.
\n\uf0b7 Paragraph 33 should be deleted. An exhortation to inform participants of the outcome of
\nthe study should become part of Paragraph 14 (this should not be worded as an
\nentitlement since it may not always be possible). For reasons discussed above in Post-
\nstudy Arrangements, the second part of Paragraph 33 that reads \u201cand to share any
\nbenefits that result from it, for example, access to interventions identified as beneficial in
\nthe study or to other appropriate care or benefits\u201d should be deleted.
\n\uf0b7 The second sentence in Paragraph 34 regarding refusal to consent and withdrawal repeats
\nconcepts in Paragraphs 4 and 9 and should be deleted. The concept in the first sentence
\nthat care and treatment should be distinguished should be addressed in Paragraph 24.
\n\uf0b7 The guidance regarding the use of unproven interventions in Paragraph 35 should be
\nmoved to follow Paragraph 18.
\nEnhancing DOH\u2019s Readability
\nThe paragraphs in Section B should be reorganized so that related issues are presented together
\nand in a logical order. It would be helpful to add descriptive topic headings as well. Currently,
\nrelated items are scattered throughout Section B. A restructuring would help readers navigate
\nthe document more easily, enhance its readability, and facilitate adherence to ethical guidance in
\nthe DOH. For example, the information in Paragraphs15, 25 and 29 concerning the
\nresponsibilities of Research Ethics Committees could be grouped together under the topic
\nheading \u201cResearch Ethics Committees.\u201d
\nExceptions to Requirements for Informed Consent
\nParagraph 22 should allow for the fact that, in certain limited circumstances, some research
\ninvolving competent subjects can ethically be conducted without consent. Specifically,
\nParagraph 22 should be expanded to state that the requirement for informed consent may be
\nwaived or altered in situations where risk to research subjects is no more than minimal and
\nconsent would be impossible or impractical to obtain for such research or would pose a threat to
\nthe validity of the research.
\n6
\n6
\nEmergency Research
\nChanges should be made to clarify Paragraph 29. Although the text applies to pre-planned
\nemergency research situations, its focus is not evident until midway through the paragraph. Pre-
\nplanned emergency research includes, for example, studies to evaluate the effectiveness of
\nautomated defibrillators in reducing mortality in out-of-hospital cardiac arrest. Since people who
\nhave suffered cardiac arrest are incapable of providing consent for themselves and the urgent
\nneed for the intervention does not, in most instances, permit additional time to seek consent from
\na legally authorized representative, the research cannot be carried out without a waiver of
\nconsent. Specifically, Paragraph 29 should be reorganized and revised to make clear that it
\npertains to the waiver of consent in pre-planned emergency research situations and not to an
\nindividual emergency situation. These revisions, which are shown below, will also distinguish it
\nfrom Paragraph 35 which addresses consent from the patient or a legally authorized
\nrepresentative for administering an unproven intervention to an individual in an emergency
\nsituation.
\n\u201c29. The requirement for informed consent may be waived in certain emergency
\nresearch situations. These waivers of consent are justified when all the following
\nconditions are met: research involves subjects in life-threatening situations where
\nthere are no proven or effective treatments and the initiation of the experimental
\nintervention cannot be delayed; research involvinges subjects who are physically or
\nmentally incapable of giving consent due to the life-threatening situation; for
\nexample, unconscious patients, may be done only if the physical or mental
\ncondition that prevents giving informed consent is a necessary characteristic of the
\nresearch population. In such circumstances the physician should seek informed
\nconsent from the legally authorized representative. Participation in the research
\nholds out the prospect of direct benefit for the subjects; If no such legally
\nauthorized representative is available to provide informed consent; and if the
\nresearch cannot be delayed, the study may proceed without informed consent
\nprovided that the research cannot practicably be carried out without a waiver of
\nconsent; and the specific reasons for involving subjects with a condition that
\nrenders them unable to give informed consent have been stated in the research
\nprotocol and the study has been approved by a research ethics committee. Consent
\nto remain in the research should be obtained as soon as possible from the subject or
\na legally authorized representative.
\nPlacebo Controls in Clinical Research
\nAlthough the use of placebo controls in clinical trials was the subject of much discussion and
\ndebate in the past, we are pleased with the consensus wording achieved in 2008. The 2008
\nversion appropriately outlines the ethical criteria that justify the use of placebos when a proven
\nintervention exists, including that the study has scientific merit and clinical value and that it does
\nnot pose risks of serious or irreversible harm. Paragraph 32 thus offers appropriate ethical
\nguidance as currently written, and the WMA should resist calls for substantive changes.
\n7
\n7
\nConclusion
\nWe appreciate the opportunity to present HHS perspectives on the DOH and the additional topics
\nunder discussion and to hear thoughtful perspectives from colleagues around the world. We
\nstand ready, during the next phase of the revision process, to provide additional perspectives as
\nwell as more specific comments regarding revisions to the 2008 DOH.<\/p>\n"},"caption":{"rendered":"

HHS_Comments_on_DOH_for_Cape_Town_Conference_12-5-7-2012 1 1 U.S. Department of Health and Human Services Perspectives on the Revision of the Declaration of Helsinki World Medical Association Expert Conference December 5-7, 2012 The Declaration of Helsinki (DOH) has been an important source of ethical guidance in the conduct of clinical research throughout the world for nearly half a century. The […]<\/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\/HHS_Comments_on_DOH_for_Cape_Town_Conference_12-5-7-2012.pdf","_links":{"self":[{"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/media\/3808"}],"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=3808"}]}}