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Ethics of genetic and biomarker test disclosures in neurodegenerative disease prevention trials.

ABSTRACT: OBJECTIVE:Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research. METHODS:Normative analysis applying 4 key ethical criteria-favorable risk-benefit ratio, informed consent, fair subject selection, and scientific validity-to blinded vs transparent enrollment, using current evidence and state of Alzheimer disease (AD) and other prevention trials. RESULTS:Current evidence on the psychosocial impact of risk marker disclosure and considerations of scientific benefit do not support an obligation to use blinded enrollment in prevention trials. Nor does transparent enrollment coerce or involve undue influence of potential participants. Transparent enrollment does not unfairly exploit vulnerable participants or limit generalizability of scientific findings of prevention trials. However, if the preferences of a community of potential participants would affect the rigor or feasibility of a prevention trial using transparent enrollment, then investigators are required by considerations of scientific validity to use blinded enrollment. CONCLUSIONS:Considerations of risks and benefits, informed consent, and fair subject selection do not require the use of blinded enrollment for AD prevention trials. Blinded enrollment in AD prevention trials may sometimes be necessary because of the need for scientific validity, not because it prevents coercion or undue influence.

SUBMITTER: Kim SY

PROVIDER: S-EPMC4395889 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Ethics of genetic and biomarker test disclosures in neurodegenerative disease prevention trials.

Kim Scott Y H SY Karlawish Jason J Berkman Benjamin E BE

Neurology 20150311 14

<h4>Objective</h4>Prevention trials for neurodegenerative diseases use genetic or other risk marker tests to select participants but there is concern that this could involve coercive disclosure of unwanted information. This has led some trials to use blinded enrollment (participants are tested but not told of their risk marker status). We examined the ethics of blinded vs transparent enrollment using well-established criteria for assessing the ethics of clinical research.<h4>Methods</h4>Normativ ...[more]

PMID: 25762713

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Project description:Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers.Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression.Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn.BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years.349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples.Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, A?42 and their ratio.Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample.An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials.

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Ethics of genetic and biomarker test disclosures in neurodegenerative disease prevention trials.

Publications

Ethics of genetic and biomarker test disclosures in neurodegenerative disease prevention trials.

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