{"id":3764,"date":"2017-01-20T11:53:59","date_gmt":"2017-01-20T11:53:59","guid":{"rendered":"https:\/\/www.wma.net\/wp-content\/uploads\/2017\/01\/Westra.pdf"},"modified":"2017-01-20T11:53:59","modified_gmt":"2017-01-20T11:53:59","slug":"westra-2","status":"inherit","type":"attachment","link":"https:\/\/www.wma.net\/fr\/westra-2\/","title":{"rendered":"Westra"},"author":2,"comment_status":"open","ping_status":"closed","template":"","meta":[],"acf":[],"description":{"rendered":"

Westra<\/a><\/p>\n

A N N A W E S T R A , M A , M D , P H D
\nJ U L I A N A C H I L D R E N \u2019 S H O S P I T A L , T H E H A G U E \/
\nD E P . O F M E D I C A L E T H I C S , E R A S M U S M C , R O T T E R D A M
\n1 1 T H W O R L D C O N G R E S S O F B I O E T H I C S
\nW M A S A T E L L I T E M E E T I N G :
\nT H E F U T U R E O F T H E D E C L A R A T I O N O F H E L S I N K I
\nR O T T E R D A M , J U N E 2 6 T H , 2 0 1 2
\nRefining the Declaration of
\nHelsinki\u2019s additional protections
\nfor research in children
\na.e.westra@lumc.nl
\n1
\nAnna E. Westra
\nHelsinki\u2019s Paragraph 27
\n\uf097 For a potential research subject who is incompetent,
\nthe physician must seek informed consent from the
\nlegally authorized representative.
\n\uf097 These individuals must not be included in a research
\nstudy that has no likelihood of benefit for them
\nunless it is intended to promote the health of the
\npopulation represented by the potential subject, the
\nresearch cannot instead be performed with
\ncompetent persons, and the research entails only
\nminimal risk and minimal burden.
\na.e.westra@lumc.nl
\n2
\nAnna E. Westra
\nPresentation
\nI will argue
\n1. Why I endorse the focus on protection of this group
\nof subjects, as well as the central role of the
\nrequirement of minimal risk and burden
\n2.That Paragraph 27 however is not very subtle,
\nand how the two issues that deserve most attention
\ncould be dealt with
\n3.Why now, time has come for refinement
\na.e.westra@lumc.nl
\n3
\nAnna E. Westra
\na.e.westra@lumc.nlAnna E. Westra 4
\nPresentation
\nI will argue
\n1. Why I endorse the focus on protection of this group
\nof subjects, as well as the central role of the
\nrequirement of minimal risk and burden
\n2.That paragraph 27 however is not very subtle,
\nand how the two issues that deserve most attention
\ncould be dealt with
\n3.Why now, time has come for refinement
\na.e.westra@lumc.nl
\n5
\nAnna E. Westra
\nBackground: the ethical dilemma
\n\u2022 Research with children is necessary to improve
\nprevention and medical care for children as a group
\n\u2022 Not all necessary data can be provided by studies that
\nare likely to benefit the subjects themselves
\n\u2022 Risks and burdens that are not compensated for by
\npotential benefits are faced purely for research reasons:
\nthe so called \u2018net\u2019 research risks and burdens
\n\u2022 Children cannot consent to facing these risks\/burdens
\na.e.westra@lumc.nl
\n6
\nAnna E. Westra
\nWays of dealing with this dilemma
\na.e.westra@lumc.nlAnna E. Westra
\n7
\nFocus on the importance of the research
\n1. No additional protective measures at all
\n2. Only some basic additional safeguards: benefit for the group;
\nnot possible with competent adults; risks and burdens as low as
\npossible (European CTD)
\nFocus on protection: such research only acceptable if
\n1. No risks or burdens at all
\n2. Minimal risk and burden (Helsinki; European Convention)
\n3. Subjects that are healthy: Minimal risk and burden;
\nSubjects with the disease: A minor increase over minimal (US)
\nHelsinki\u2019s choice seems best
\na.e.westra@lumc.nlAnna E. Westra
\n8
\n\uf097 Focus on protection seems valid:
\n\uf0a1 Proxy consent does not have the same moral value as informed
\nconsent (altruism seems to be rather personal)
\n\uf0a1 Risk of using children merely as a means
\n\uf097 Minimal risk and burden requirement seems valid:
\n\uf0a1 No risk and burden at all, is not necessary1
\n\uf0a1 No valid grounds for allowing a minor increase over minimal
\nrisk for all subjects with the disease under study2
\n1.Wendler D. The ethics of pediatric research, 2010; 2.Westra AE et al. Regulating \u2018\u2018Higher Risk, No Direct Benefit\u2019\u2019 Studies
\nwith Children: Challenging the US Federal Regulations. In: Schildmann J et al, eds. Human Medical Research, 2012
\nPresentation
\nI will argue
\n1. Why I endorse the focus on protection of this group
\nof subjects, as well as the central role of the
\nrequirement of minimal risk and burden
\n2.That paragraph 27 however is not very subtle,
\nand how the two issues that deserve most attention
\ncould be dealt with
\n3.Why now, time has come for refinement
\na.e.westra@lumc.nl
\n9
\nAnna E. Westra
\nParagraph 27: not very subtle
\na.e.westra@lumc.nlAnna E. Westra
\n10
\n\uf097 Issue 1:
\nWhen distinguishing between studies with and
\nwithout potential benefit, the \u2018net\u2019 research risks and
\nburdens often cannot accurately be identified
\n\uf097 Issue 2:
\nNot all children need the same level of protection
\nResearch in children versus in adults
\n\uf097 More complex ethical review process:
\nThe net research risks and burdens should be minimal
\n\uf0d8 More need to identify the net research risks and burdens
\n\uf097 More complex study designs:
\n\uf0d8 More often combined with medical care
\n\uf0d8 More often a mixture of components
\n\uf0d8 More difficult to identify the net risks and burdens
\na.e.westra@lumc.nl
\n11
\nAnna E. Westra
\na.e.westra@lumc.nlAnna Westra
\n12
\nExample study (ADHD)
\n1. Visits to hospital (30x)
\n2. Medication washout
\n3. Treatment with the new drug (initial 12 wks)
\n4. Treatment with the new drug after good response,
\nor placebo treatment (6 or 9 months)
\n5. Blood draw (6x); ECG (6x); physical examination
\nincluding pubertal staging (5x)
\nBuitelaar JK et al. Biological Psychiatry 2007;61:694-699
\nStudy-level approach is inadequate
\n\uf097 Paragraph 27 distinguishes between studies
\nwith\/without potential benefit
\n\uf097 To adequately identify the net research risks\/burdens,
\nstudy components require separate moral evaluation
\n\uf0a1 Procedures that are performed pure for research reasons:
\n\uf0d8 risks and burdens should be minimal
\n\uf0a1 Procedures that have potential benefits for the subjects
\n(i.e., those that are combined with medical care):
\n\uf0d8 risk\/benefit profile should be acceptable
\na.e.westra@lumc.nl
\n13
\nAnna E. Westra
\nRecommendation 1
\na.e.westra@lumc.nlAnna E. Westra
\n14
\n\uf097 To stimulate research ethics committees to more
\naccurately identify those risks and burdens that the
\nresearch subjects have to undergo purely for research
\nreasons and that thus have to be minimal,
\n\uf097 by distinguishing between research procedures with
\nand without potential benefit instead of between
\nstudies with and without potential benefit
\nWestra AE et al. The merits of procedure-level risk-benefit assessment. IRB 2011;33(5):7-13.
\nParagraph 27: not very subtle
\na.e.westra@lumc.nlAnna E. Westra
\n15
\n\uf097 Issue 1:
\nWhen distinguishing between studies with and
\nwithout potential benefit, the \u2018net\u2019 research risks and
\nburdens often cannot accurately be identified
\n\uf097 Issue 2:
\nNot all children need the same level of protection
\nNot all children need equal level of protection
\n\uf097 With increasing age, children are increasingly capable
\n\uf0a1 of understanding the proposed study
\n\uf0a1 of making their own informed decisions
\n\uf097 If a child is generally capable of doing so, it can be
\nasked for its assent
\n\uf097 If a child can give assent: less need for protection
\n(although still extra protection as compared to adults)
\nWestra AE et al. Am J Bioeth. 2011;11(6):29-31. a.e.westra@lumc.nl
\n16
\nAnna E. Westra
\nHelsinki\u2019s Paragraph 28
\n\u2022 When a potential research subject who is deemed
\nincompetent is able to give assent to decisions
\nabout participation in research, the physician must
\nseek that assent in addition to the consent of the
\nlegally authorized representative.
\n\u2022 The potential subject\u2019s dissent should be respected
\na.e.westra@lumc.nl
\n17
\nAnna E. Westra
\nRecommendation 2
\nTo allow for exceptions to the minimal risk and
\nburden requirement in cases of studies that involve
\nchildren who can give their assent to participate in
\nthe study; and that involve at most a minor increase
\nover minimal risk
\na.e.westra@lumc.nlAnna E. Westra
\n18
\nParagraph 27 with revisions (1)
\n\uf097 For a potential research subject who is incompetent,
\nthe physician must seek informed consent from the
\nlegally authorized representative.
\n\uf097 These individuals must not be included in research
\nprocedures that have no likelihood of direct benefit
\nfor them unless these procedures are essential parts
\nof a research study that is intended to promote the
\nhealth of the population represented by the potential
\nsubject and that cannot instead be performed with
\ncompetent persons, and all together, these
\nprocedures entail only minimal risk and burden.
\na.e.westra@lumc.nl
\n19
\nAnna E. Westra
\nParagraph 27 with revisions (2)
\n\u2022 The minimal risk and burden requirement does
\nnot apply to studies involving subjects who are
\nable to give assent and involving at most a minor
\nincrease over minimal risk and\/or burden.
\na.e.westra@lumc.nl
\n20
\nAnna E. Westra
\nPresentation
\nI will argue
\n1. Why I endorse the focus on protection of this group
\nof subjects, as well as the central role of the
\nrequirement of minimal risk and burden
\n2.That paragraph 27 however is not very subtle,
\nand how the two issues that deserve most attention
\ncould be dealt with
\n3.Why now, time has come for refinement
\na.e.westra@lumc.nl
\n21
\nAnna E. Westra
\nRefining paragraph 27: why now?
\na.e.westra@lumc.nlAnna E. Westra
\n22
\n\uf097 Currently, many drugs prescribed for children have
\nnot been proven safe and effective for them
\n\uf097 Extrapolation from adult studies: often inappropriate
\n\uf097 Need for trials has been increasingly recognised: US
\nand EU have taken stimulative measures (financially)
\n\uf097 These measures have made optimizing the system
\nthat protects the subjects all the more pressing
\na.e.westra@lumc.nlAnna E. Westra
\n23<\/p>\n"},"caption":{"rendered":"

Westra A N N A W E S T R A , M A , M D , P H D J U L I A N A C H I L D R E N \u2019 S H O S P I T A L , T H E H A G U E […]<\/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\/Westra.pdf","_links":{"self":[{"href":"https:\/\/www.wma.net\/fr\/wp-json\/wp\/v2\/media\/3764"}],"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=3764"}]}}