A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease

Robert C. Green, Kurt D. Christensen, L. Adrienne Cupples, Norman R. Relkin, Peter J. Whitehouse, Charmaine D M Royal, Thomas O. Obisesan, Robert Cook-Deegan, Erin Linnenbringer, Melissa Barber Butson, Grace Ann Fasaye, Elana Levinson, J. Scott Roberts, D. Bhatt, B. Biesecker, D. Blacker, C. Chen, E. Cox, J. G. Davis, L. FarrerP. Griffith, K. Harkins, S. Hiraki, M. Johnson, S. Johnson, E. Juengst, J. Karlawish, L. Le, E. McCarty Wood, T. Obisesan, S. Post, K. Quaid, L. Ravdin, D. Roter, R. Stern, A. Sadovnick, S. Sami, P. Sankar, E. Topol, W. Uhlmann, L. Waterston, L. Wright

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Introduction Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. Methods A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Results Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. Conclusions These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.

Original languageEnglish (US)
Pages (from-to)1222-1230
Number of pages9
JournalAlzheimer's and Dementia
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Disclosure
Clinical Protocols
Alzheimer Disease
Apolipoproteins E
Anxiety
Depression
African Americans
Genotype
Safety
Genetic Counseling
Multicenter Studies
Physicians
Counselors

Keywords

  • Alzheimer
  • APOE
  • Genetics
  • Genomics
  • Personalized medicine
  • Risk assessment

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Green, R. C., Christensen, K. D., Cupples, L. A., Relkin, N. R., Whitehouse, P. J., Royal, C. D. M., ... Wright, L. (2015). A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease. Alzheimer's and Dementia, 11(10), 1222-1230. https://doi.org/10.1016/j.jalz.2014.10.014

A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease. / Green, Robert C.; Christensen, Kurt D.; Cupples, L. Adrienne; Relkin, Norman R.; Whitehouse, Peter J.; Royal, Charmaine D M; Obisesan, Thomas O.; Cook-Deegan, Robert; Linnenbringer, Erin; Butson, Melissa Barber; Fasaye, Grace Ann; Levinson, Elana; Roberts, J. Scott; Bhatt, D.; Biesecker, B.; Blacker, D.; Chen, C.; Cox, E.; Davis, J. G.; Farrer, L.; Griffith, P.; Harkins, K.; Hiraki, S.; Johnson, M.; Johnson, S.; Juengst, E.; Karlawish, J.; Le, L.; McCarty Wood, E.; Obisesan, T.; Post, S.; Quaid, K.; Ravdin, L.; Roter, D.; Stern, R.; Sadovnick, A.; Sami, S.; Sankar, P.; Topol, E.; Uhlmann, W.; Waterston, L.; Wright, L.

In: Alzheimer's and Dementia, Vol. 11, No. 10, 01.10.2015, p. 1222-1230.

Research output: Contribution to journalArticle

Green, RC, Christensen, KD, Cupples, LA, Relkin, NR, Whitehouse, PJ, Royal, CDM, Obisesan, TO, Cook-Deegan, R, Linnenbringer, E, Butson, MB, Fasaye, GA, Levinson, E, Roberts, JS, Bhatt, D, Biesecker, B, Blacker, D, Chen, C, Cox, E, Davis, JG, Farrer, L, Griffith, P, Harkins, K, Hiraki, S, Johnson, M, Johnson, S, Juengst, E, Karlawish, J, Le, L, McCarty Wood, E, Obisesan, T, Post, S, Quaid, K, Ravdin, L, Roter, D, Stern, R, Sadovnick, A, Sami, S, Sankar, P, Topol, E, Uhlmann, W, Waterston, L & Wright, L 2015, 'A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease', Alzheimer's and Dementia, vol. 11, no. 10, pp. 1222-1230. https://doi.org/10.1016/j.jalz.2014.10.014
Green, Robert C. ; Christensen, Kurt D. ; Cupples, L. Adrienne ; Relkin, Norman R. ; Whitehouse, Peter J. ; Royal, Charmaine D M ; Obisesan, Thomas O. ; Cook-Deegan, Robert ; Linnenbringer, Erin ; Butson, Melissa Barber ; Fasaye, Grace Ann ; Levinson, Elana ; Roberts, J. Scott ; Bhatt, D. ; Biesecker, B. ; Blacker, D. ; Chen, C. ; Cox, E. ; Davis, J. G. ; Farrer, L. ; Griffith, P. ; Harkins, K. ; Hiraki, S. ; Johnson, M. ; Johnson, S. ; Juengst, E. ; Karlawish, J. ; Le, L. ; McCarty Wood, E. ; Obisesan, T. ; Post, S. ; Quaid, K. ; Ravdin, L. ; Roter, D. ; Stern, R. ; Sadovnick, A. ; Sami, S. ; Sankar, P. ; Topol, E. ; Uhlmann, W. ; Waterston, L. ; Wright, L. / A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease. In: Alzheimer's and Dementia. 2015 ; Vol. 11, No. 10. pp. 1222-1230.
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abstract = "Introduction Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. Methods A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Results Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71{\%} female, 23{\%} African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5{\%} upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. Conclusions These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.",
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T1 - A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease

AU - Green, Robert C.

AU - Christensen, Kurt D.

AU - Cupples, L. Adrienne

AU - Relkin, Norman R.

AU - Whitehouse, Peter J.

AU - Royal, Charmaine D M

AU - Obisesan, Thomas O.

AU - Cook-Deegan, Robert

AU - Linnenbringer, Erin

AU - Butson, Melissa Barber

AU - Fasaye, Grace Ann

AU - Levinson, Elana

AU - Roberts, J. Scott

AU - Bhatt, D.

AU - Biesecker, B.

AU - Blacker, D.

AU - Chen, C.

AU - Cox, E.

AU - Davis, J. G.

AU - Farrer, L.

AU - Griffith, P.

AU - Harkins, K.

AU - Hiraki, S.

AU - Johnson, M.

AU - Johnson, S.

AU - Juengst, E.

AU - Karlawish, J.

AU - Le, L.

AU - McCarty Wood, E.

AU - Obisesan, T.

AU - Post, S.

AU - Quaid, K.

AU - Ravdin, L.

AU - Roter, D.

AU - Stern, R.

AU - Sadovnick, A.

AU - Sami, S.

AU - Sankar, P.

AU - Topol, E.

AU - Uhlmann, W.

AU - Waterston, L.

AU - Wright, L.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Introduction Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. Methods A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Results Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. Conclusions These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.

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