{"id":3762,"date":"2017-01-20T11:53:54","date_gmt":"2017-01-20T11:53:54","guid":{"rendered":"https:\/\/www.wma.net\/wp-content\/uploads\/2017\/01\/van-der-graaf.pdf"},"modified":"2017-01-20T11:53:54","modified_gmt":"2017-01-20T11:53:54","slug":"van-der-graaf-2","status":"inherit","type":"attachment","link":"https:\/\/www.wma.net\/es\/van-der-graaf-2\/","title":{"rendered":"van-der-graaf"},"author":2,"comment_status":"open","ping_status":"closed","template":"","meta":[],"acf":[],"description":{"rendered":"

van-der-graaf<\/a><\/p>\n

Dr Rieke van der Graaf
\nProf dr Hans van Delden
\nJulius Center, Dpt Medical Humanities
\nUMC Utrecht, Netherlands
\nWMA Satellite Meeting during the 11th World Congress of
\nBioethics, 26 June 2012
\nOn the necessity of embedding clinical equipoise
\nin the Declaration of Helsinki
\nOutline
\n\u2022 Equipoise paradox
\n\u2022 What is equipoise?
\n\u2022 Perceived problems
\n\u2022 Answers
\n\u2022 Moral status
\n\u2022 Why embed equipoise?
\n\u2022 Conclusions
\nEquipoise paradox
\n\u2022 Many regard it as a fundamental ethical concept of
\nhuman subjects research
\n\u2022 Ethicists are criticial & not embedded in guidelines
\nClaim presentation:
\n\u2022 Time to focus on merits > weaknesses of the concept
\n\u2022 Sufficient reason to incorporate the concept in main
\nethical guidelines
\nOutline
\n\u2022 Equipoise paradox
\n\u2022 What is equipoise?
\n\u2022 Perceived problems
\n\u2022 Answers
\n\u2022 Moral status
\n\u2022 Why embed equipoise?
\n\u2022 Conclusions
\nWhat is clinical equipoise?
\nFreedman 1987
\ngenuine uncertainty in the expert medical community
\nabout the preferred treatment
\n3 elements definition
\n1. Expert medical community
\n2. Preferred treatment
\n3. Genuine uncertainty
\n1. Expert medical community
\n\u2022 Uncertainty not in the mind of a single investigator,
\nbut in broader community of clinical experts
\n2. Preferred treatment
\nStandard drug (S)
\n2. Preferred treatment
\nStandard drug (S) Experimental drug (E)
\n2. If S is superior to E\u2026
\nStandard drug (S)
\n\u2026participants have to be
\nprovided with S
\n\u201cMust be offered best
\ntreatment known\u201d
\n(Freedman)
\n3. Genuine uncertainty
\n\u2022 Equipoise not only grounded in therapeutic
\nobligation, but also in scientific duties
\n\u2013 Epistemic reasons to conduct a controlled trial
\n\u2013 Focus trials on solving questions that may
\ninfluence clinical decisions > theoretical questions
\nOutline
\n\u2022 Equipoise paradox
\n\u2022 What is equipoise?
\n\u2022 Perceived problems
\n\u2022 Answers
\n\u2022 Moral status
\n\u2022 Why embed equipoise?
\n\u2022 Conclusions
\nPerceived problems
\n\u2022 Expert community:
\n\u2013 Who are the members?
\n\u2013 How many?
\n\u2013 Patient should be in equipoise
\n\u2022 Preferred treatment
\n\u2013 May rule out many placebo-controlled trials
\n\u2013 Impossible to always offer best proven care
\n\u2013 Patients may still be harmed
\n\u2022 Genuine uncertainty
\n\u2013 What does it mean?
\n\u2013 When is it disturbed?
\nEquipoise controversy
\n\u2022 \u201cRehabilitate the concept\u201d (PB Miller\/Weijer 2003)
\n\u2022 \u201cNot yet time to give up on equipoise\u201d (Ashcroft 2004)
\n\u2022 \u201cEquipoise is fundamentally flawed\u201d (F Miller\/Joffe
\n2011)
\n\u2022 \u201cEquipoise is bankrupt, pull the plug\u201d (Gifford 2007)
\n\u2022 \u201cEquipoise is a muddy concept, beyond rehabilitation\u201d
\n(Menikoff 2003)
\nProposals of opponents: alternatives
\n\u2022 Alternative conceptions that can justify why we allow
\ncompromises to individual interests patients
\n\u2022 Problems of alternatives:
\n\u2013 Conceive equipoise as overarching justification of
\nhuman subjects research
\n\u2013 opponents of the concept \u2018resolve the ethical
\nproblems of equipoise by abandoning the need for
\nequipoise\u2019 (Freedman 1987)
\nOutline
\n\u2022 Equipoise paradox
\n\u2022 What is equipoise?
\n\u2022 Perceived problems
\n\u2022 Answers
\n\u2022 Moral status
\n\u2022 Why embed equipoise?
\n\u2022 Conclusions
\n1. Expert medical community
\n\u2022 Distinguish between
\n\u2013 those who are uncertain (virtual community of
\nexperts)
\n\u2013 those who have to determine whether experts are
\nuncertain
\n\u2022 IRB, researchers, sponsors (also experts!)
\n\u2022 Physicians and patients may have own treatment
\npreferences \u2260 clinical equipoise
\n2. Preferred treatment
\n\u2022 Extensive debate whether clinicians have therapeutic
\nduties as researchers
\n\u2022 Even proponents of the concept: unnecessary to
\nalways offer the \u201cbest possible care\u201d
\n\u2022 Focus on what cannot reasonably be withheld > what
\nshould be provided
\n3. Genuine uncertainty: semantics
\n\u2022 Semantics of equipoise creates confusion over the
\nconcept
\n\u2022 Alex London (2007):
\n\u2013 Distinguish between \u2018agnosticism\u2019 (don\u2019t know)
\nand \u2018conflict\u2019
\n3. Genuine uncertainty: don\u2019t know
\n\u2022Safe?
\n\u2022Effective?
\n\u2022Efficacious?
\n\u2022No balance in this
\nsituation
\nE
\n3. Genuine uncertainty: conflict
\n\u2022Both E and S standard
\ndrugs for given condition
\n\u2022Some experts favor E,
\nothers favor S
\nE
\nS
\n3. Genuine uncertainty: conflict
\n\u2022 In the case of a conflict
\nexperts are seldom
\n\u201cequally poised\u201d
\n3. Genuine uncertainty: conflict
\n\u2022 More experts favor E>S
\n\u2022 Researchers\/IRBs
\ndetermine whether
\nexperts are in equipoise
\nES
\n3. Genuine uncertainty: conflict
\n\u2022 Irrelevant how many
\n\u2022 Strength of the
\nevidence matters
\nES
\nEquipoise vs balance of trial arms
\nES S E
\nDisturbance trial arms \u2260 disturbance
\nequipoise
\nES S E
\nDisturbance trial arms \u2260 disturbance
\nequipoise
\nES S E
\n3. Genuine uncertainty: disturbance
\n\u2022 Freedman: trial must be
\ndesigned to disturb
\nclinical equipoise
\n\u2022 Unrealistic: often many
\nRCTs, meta-analyses
\nES
\nOutline
\n\u2022 Equipoise paradox
\n\u2022 What is equipoise?
\n\u2022 Perceived problems
\n\u2022 Answers
\n\u2022 Moral status
\n\u2022 Why embed equipoise?
\n\u2022 Conclusions
\nWhat does clinical equipoise require?
\n\u2022 Expert medical community should be in a state of
\ngenuine agnosticism or conflict about the net
\npreferred medically established procedure for the
\ncondition under study
\n\u2022 Those who consider initiating or continuing an RCT
\n1. Is there sufficient disagreement, or absence of
\nagreement among experts? (scientific component)
\n2. Can standard of care reasonably be withheld all-
\nthings-considered (\u201ctherapeutic\u201d component)
\nMoral status of equipoise
\n\u2022 Fundamental > foundational concept of research
\nethics
\n\u2022 Prima facie obligation
\n\u2022 Deduced from scientific validity\/social value and
\nfavorable risk-benefit
\n\u2013 Adds substance to these norms
\n\u2022 Not a specific rule that determines comparator
\n\u2022 Threshold requirement
\nIf equipoise cannot be met\u2026
\n\u2022 \u2026trial not necessarily unethical, but
\n\u2022 Burden of proof on researchers\/IRBs to explicate
\n\u2013 Why it is necessary to conduct RCT (and not
\nobservational study e.g.)
\n\u2013 Whether the control group can reasonably be
\nwithheld the standard of care
\nOutline
\n\u2022 Equipoise paradox
\n\u2022 What is equipoise?
\n\u2022 Perceived problems
\n\u2022 Answers
\n\u2022 Moral status?
\n\u2022 Why embed
\nequipoise?
\n\u2022 Conclusions
\n\u00a732 Declaration of Helsinki
\n\u2022 \u201cThe benefits, risks, burdens and effectiveness of a
\nnew intervention must be tested against those of the
\nbest current proven intervention\u201d
\n\u2022 Applied rule focusing on testing of new interventions
\nand on precise comparator
\n\u2022 Needs further grounding: why provide best proven
\ncare and when is it allowed to conduct controlled
\nstudies?
\nConclusions
\n\u2022 Weaknesses \u2260 equipoise is flawed
\n\u2022 If we give up on equipoise we may lose a
\nrequirement that explicitly asks for:
\n\u2013 scientific justifications of controlled trials
\n\u2013 taking professional standards into account when
\nconsidering these trials
\n\u2022 In order to protect the merits of equipoise and hence
\nthe interests of patient-subjects clinical equipoise
\nshould be incorporated in the Declaration
\nSome references
\n\u2022 Pictures: Istockphoto
\n\u2022 Ashcroft R. Equipoise, knowledge and ethics in clinical research in clinical research and
\npractice. Bioethics 1999;13:314-326.
\n\u2022 Freedman B. Equipoise and the ethics of clinical research. NEJM 1987;317(3):141-145.
\n\u2022 Gifford F. Pulling the plug on clinical equipoise: a critique of Miller and Weijer. Kennedy Inst
\nEthics J 2007;17:203-226.
\n\u2022 London AJ. Clinical equipoise foundational requirement or fundamental error? In Steinbock
\nB, et al (ed.). Te Oxford Handbook of bioethics. Oxford University Press, Oxford 2007a, pp.
\n571-596.
\n\u2022 Menikoff J. Equipoise: beyond rehabilitation? Kennedy Inst Ethics J 2003;13(4):347-351.
\n\u2022 Miller GF, Joffe S. Equipoise and the randomized clinical trial dilemma. NEJM
\n2011;364:476-480.
\n\u2022 Van der Graaf R, Van Delden JJM. Equipoise should be amended, not abandoned. Clinical
\nTrials 2011;8:408-416.
\n\u2022 Van der Graaf R, Van Delden JJM. On what we will lose in giving up on equipoise: a reply to
\nMiller. Clinical Trials, forthcoming.
\n\u2022 Weijer C, Miller PB. When are research risks reasonable in relation to anticipated benefits.
\nNat Med 2004;10(6): 570-573.<\/p>\n"},"caption":{"rendered":"

van-der-graaf Dr Rieke van der Graaf Prof dr Hans van Delden Julius Center, Dpt Medical Humanities UMC Utrecht, Netherlands WMA Satellite Meeting during the 11th World Congress of Bioethics, 26 June 2012 On the necessity of embedding clinical equipoise in the Declaration of Helsinki Outline \u2022 Equipoise paradox \u2022 What is equipoise? \u2022 Perceived problems […]<\/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\/van-der-graaf.pdf","_links":{"self":[{"href":"https:\/\/www.wma.net\/es\/wp-json\/wp\/v2\/media\/3762"}],"collection":[{"href":"https:\/\/www.wma.net\/es\/wp-json\/wp\/v2\/media"}],"about":[{"href":"https:\/\/www.wma.net\/es\/wp-json\/wp\/v2\/types\/attachment"}],"author":[{"embeddable":true,"href":"https:\/\/www.wma.net\/es\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.wma.net\/es\/wp-json\/wp\/v2\/comments?post=3762"}]}}