Skip to main content

Advertisement

SpringerLink
Log in

Decisional Capacity for Informed Consent in Males and Females with Fragile X Syndrome

  • Original Paper
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Although informed consent is critical for all research, there is increased ethical responsibility as individuals with intellectual or developmental disabilities (IDD) become the focus of more clinical trials. This study examined decisional capacity for informed consent to clinical trials in individuals with fragile X syndrome (FXS). Participants were 152 adolescents and adults (80 males, 72 females) with FXS who completed a measure of decisional capacity and a comprehensive battery of neurocognitive and psychiatric measures. Females outperformed males on all aspects of decisional capacity. The ability to understand aspects of the clinical trial had the strongest association with the ability to appreciate and reason about the decision. Scaffolding improved understanding, suggesting researchers can take steps to improve decisional capacity and the informed consent process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Appelbaum, P. S. (2007). Assessment of patients’ competence to consent to treatment. New England Journal of Medicine, 357(18), 1834–1840.

    PubMed  Google Scholar 

  • Appelbaum, P. S., & Grisso, T. (2001). The MacArthur Competence Assessment Tool for clinical research (MacCAT-CR). Sarasota, FL: Professional Resource Press.

    Google Scholar 

  • Appelbaum, P. S., & Lidz, C. (2008). The therapeutic misconception. In E. J. Emanuel, C. Grady, R. A. Crouch, R. K. Lie, F. G. Miller & D. Wendler. (Eds.), The Oxford textbook of clinical research ethics. New York: Oxford University Press.

    Google Scholar 

  • Bear, M. F., Huber, K. M., & Warren, S. T. (2004). The mGluR theory of fragile X mental retardation. Trends in Neurosciences, 27(7), 370–377.

    PubMed  Google Scholar 

  • Becker, H., Roberts, G., Morrison, J., & Silver, J. (2004). Recruiting people with disabilities as research participants: Challenges and strategies to address them. Mental Retardation, 42(6), 471–475.

    PubMed  Google Scholar 

  • Bruininks, R. H., Woodcock, R. W., Weatherman, R. F., & Hill, B. K. (1996). Scales of independent behavior—Revised comprehensive manual. Itasca, IL: Riverside Publishing.

    Google Scholar 

  • Burket, J. A., Herndon, A. L., Winebarger, E. E., Jacome, L. F., & Deutsch, S. I. (2011). Complex effects of mGluR5 antagonism on sociability and stereotypic behaviors in mice: Possible implications for the pharmacotherapy of autism spectrum disorders. Brain Research Bulletin, 86(3–4), 152–158.

    PubMed  Google Scholar 

  • Cameron, L., & Murphy, J. (2007). Obtaining consent to participate in research: The issues involved in including people with a range of learning and communication disabilities. British Journal of Learning Disabilities, 35(2), 113–120.

    Google Scholar 

  • Carey, E., & Griffiths, C. (2017). Recruitment and consent of adults with intellectual disabilities in a classic grounded theory research study: Ethical and methodological considerations. Disability & Society, 32(2), 193–212.

    Google Scholar 

  • Cea, C. D., & Fisher, C. B. (2003). Health care decision-making by adults with mental retardation. Mental Retardation, 41, 78–87.

    PubMed  Google Scholar 

  • Cleaver, S., Ouellette-Kuntz, H., & Sakar, A. (2010). Participation in intellectual disability research: A review of 20 years of studies. Journal of Intellectual Disability Research, 54(3), 187–193.

    PubMed  Google Scholar 

  • Dalton, A. J., & McVilly, K. R. (2004). Ethics guidelines for international, multicenter research involving people with intellectual disabilities. Journal of Policy and Practice in Intellectual Disabilities, 1(2), 57–70.

    Google Scholar 

  • de Vrij, F. M., Levenga, J., van der Linde, H. C., et al. (2008). Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiology Disease, 31(1), 127–132.

    Google Scholar 

  • Delis, D. C., Kaplan, E., & Kramer, J. H. (2001). Delis–Kaplan executive function system™. San Antonio, TX: The Psychological Corporation.

    Google Scholar 

  • Department of Health. (2014). The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. The Journal of the American College of Dentists, 81(3), 4.

    Google Scholar 

  • Dunn, L. B., Nowrangi, M. A., Palmer, B. W., Jeste, D. V., & Saks, E. R. (2006). Assessing decisional capacity for clinical research or treatment: A review of instruments. The American Journal of Psychiatry, 163, 1323–1334.

    PubMed  Google Scholar 

  • Dye, L., Hare, D. J., & Hendy, S. (2007). Capacity of people with intellectual disabilities to consent to take part in a research study. Journal of Applied Research in Intellectual Disabilities, 20(2), 168–174.

    Google Scholar 

  • Dye, L., Hendy, S., Hare, D. J., & Burton, M. (2004). Capacity to consent to participate in research—A recontextualization. British Journal of Learning Disabilities, 32(3), 144–150.

    Google Scholar 

  • Esbensen, A. J., Rojahn, J., Aman, M. G., & Ruedrich, S. (2003). Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. Journal of Autism and Developmental Disorders, 33, 617–629.

    PubMed  Google Scholar 

  • Fisher, C. B. (2003). Goodness-of-fit ethic for informed consent to research involving adults with mental retardation and developmental disabilities. Developmental Disabilities Research Review, 9(1), 27–31.

    Google Scholar 

  • Fisher, C. B., Cea, C. D., Davidson, P. W., & Fried, A. L. (2006). Capacity of persons with mental retardation to consent to participate in randomized clinical trials. American Journal of Psychiatry, 163(10), 1813–1820.

    PubMed  Google Scholar 

  • Freedman, R. I. (2001). Ethical challenges in the conduct of research involving persons with mental retardation. Mental Retardation, 39(2), 130–141.

    PubMed  Google Scholar 

  • Goldsmith, L., Skirton, H., & Webb, C. (2008). Informed consent to healthcare interventions in people with learning disabilities—An integrative review. Journal of Advanced Nursing, 64(6), 549–563.

    PubMed  Google Scholar 

  • Grisso, T., & Appelbaum, P. S. (1998). Assessing competence to consent to treatment: A guide for physicians and other health professionals. Oxford: Oxford University Press.

    Google Scholar 

  • Grisso, T., & Appelbaum, P. S. (2006). Appreciating anorexia: Decisional capacity and the role of values. Philosophy, Psychiatry, & Psychology, 13(4), 293–297.

    Google Scholar 

  • Iacono, T., & Murray, V. (2003). Issues of informed consent in conducting medical research involving people with intellectual disability. Journal of Applied Research in Intellectual Disabilities, 16(1), 41–51.

    Google Scholar 

  • Jønch, A. E., & Jacquemont, S. (2017). Reflections on clinical trials in Fragile X Syndrome. In Fragile X syndrome (pp. 419–441).

  • Loesch, D. Z., Huggins, R. M., & Hagerman, R. J. (2004). Phenotypic variation and FMRP levels in fragile X. Mental Retardation and Developmental Disabilities Research Reviews, 10(1), 31–41.

    PubMed  Google Scholar 

  • Lord, C., Rutter, M., Dilavore, P. C., Risi, S., Gotham, K., & Bishop, S. L. (2012). Autism diagnostic observation schedule (2nd ed.). Los Angeles, CA: Western Psychological Services.

    Google Scholar 

  • McDonald, K. E. (2012). We want respect”: Adults with intellectual and developmental disabilities address respect in research. American Journal on Intellectual and Developmental Disabilities, 117(4), 263–274.

    PubMed  Google Scholar 

  • McDonald, K. E., & Kidney, C. A. (2012). What is right? Ethics in intellectual disabilities research. Journal of Policy and Practice in Intellectual Disabilities, 9(1), 27–39.

    Google Scholar 

  • McDonald, K. E., Kidney, C. A., & Patka, M. (2013). ‘You need to let your voice be heard’: Research participants’ views on research. Journal of Intellectual Disability Research, 57(3), 216–225.

    PubMed  Google Scholar 

  • Michalon, A., Sidorov, M., Ballard, T. M., et al. (2012). Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron, 74(1), 49–56.

    PubMed  Google Scholar 

  • Mitty, E. L. (2012). Decision-making and dementia. In Try this: Best practices in nursing care to older adults with dementia (D, 9).

  • Nugent, A. C., Miller, F. G., Henter, I. D., & Zarate, C. A. (2017). The ethics of clinical trials research in severe mood disorders. Bioethics, 31(6), 443–453.

    PubMed  PubMed Central  Google Scholar 

  • Palmer, B. W., Harmell, A. L., Pinto, L. L., Dunn, L. B., Kim, S. Y., Golshan, S., & Jeste, D. V. (2017). Determinants of capacity to consent to research on Alzheimer’s disease. Clinical Gerontologist, 40(1), 24–34.

    PubMed  Google Scholar 

  • Peisah, C., Sorinmade, O. A., Mitchell, L., & Hertogh, C. M. (2013). Decisional capacity: Toward an inclusionary approach. International Psychogeriatrics, 25(10), 1571–1579.

    PubMed  PubMed Central  Google Scholar 

  • Powers, L., Dinerstein, R., & Holmes, S. 2005. Self-advocacy, self-determination, social freedom, and opportunity. In National goals and research for people with intellectual and developmental disabilities (pp. 257–287).

  • Roid, G. H. (2003). Stanford Binet intelligence scales (SB5) (5th ed.). Itasca, IL: Riverside Publishing.

    Google Scholar 

  • Rutter, M., Bailey, A., & Lord, C. (2003). Social communication questionnaire. Los Angeles, CA: Western Psychological Services.

    Google Scholar 

  • Sansone, S. M., Schneider, A., Bickel, E., Berry-Kravis, E., Prescott, C., & Hessl, D. (2014). Improving IQ measurement in intellectual disabilities using true deviation from population norms. Journal of Neurodevelopmental Disorders, 16, 1–14.

    Google Scholar 

  • Sheslow, D., & Adams, W. (2003). Wide range assessment of memory and learning (2nd ed.). Lutz, FL: Psychological Assessment Resources, Inc.

    Google Scholar 

  • Shogren, K. A., Wehmeyer, M. L., Uyanik, H., & Heidrich, M. (2017). Development of the Supported Decision Making Inventory System. Intellectual and Developmental Disabilities, 55(6), 432–439.

    PubMed  Google Scholar 

  • Tam, N. T., Huy, N. T., Thoa, L. T. B., Long, N. P., Trang, N. T. H., Hirayama, K., & Karbwang, J. (2015). Participants’ understanding of informed consent in clinical trials over three decades: Systematic review and meta-analysis. Bulletin of the World Health Organization, 93, 186–198H.

    PubMed  PubMed Central  Google Scholar 

  • Thomas, A. M., Bui, N., Perkins, J. R., Yuva-Paylor, L. A., & Paylor, R. (2012). Group I metabotropic glutamate receptor antagonists alter select behaviors in a mouse model for fragile X syndrome. Psychopharmacology, 219(1), 47–58.

    PubMed  Google Scholar 

  • Walmsley, J. (2001). Normalisation, emancipatory research and inclusive research in learning disability. Disability & Society, 16(2), 187–205.

    Google Scholar 

  • Wang, S. B., Wang, Y. Y., Ungvari, G. S., Ng, C. H., Wu, R. R., Wang, J. & Xiang, Y. T. (2017a). The MacArthur Competence Assessment Tools for assessing decision-making capacity in schizophrenia: A meta-analysis. Schizophrenia Research 183, 56–63.

    PubMed  Google Scholar 

  • Wang, Y. Y., Wang, S. B., Ungvari, G. S., Yu, X., Ng, C. H., & Xiang, Y. T. (2017b). The assessment of decision-making competence in patients with depression using the MacArthur competence assessment tools: A systematic review. Perspectives in Psychiatric Care. 54, 206–211

    PubMed  Google Scholar 

  • Woodcock, R. W., McGrew, K. S., & Mather, N. (2001, 2007). Woodcock Johnson III tests of achievement. Rolling Meadows, IL: Riverside Publishing.

  • Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005). Suppression of two major Fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology, 49(7), 1053–1066.

    PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to all of the individuals with FXS and their caregivers who participated in this study.

Funding

This study was funded by a grant from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (R01HD071987-01A1). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health.

Author information

Author notes

  1. Adrienne Villagomez

    Present address: Children’s Hospital Colorado, Anschutz Medical Campus, 13123 East 16th Avenue, Aurora, CO, 80045, USA

  2. Kylee Miller

    Present address: Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA

Authors and Affiliations

  1. RTI International, 3040 E. Cornwallis Road, P.O. Box 12194, Research Triangle Park, NC, 27709, USA

    Anne C. Wheeler, Amanda Wylie, Melissa Raspa, Anne Edwards & Donald B. Bailey Jr.

  2. Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, 101 Renee Lynne Court, Carrboro, NC, 27714, USA

    Adrienne Villagomez, Kylee Miller & Margaret DeRamus

  3. Vagelos College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 122, New York, NY, 10032, USA

    Paul S. Appelbaum

Authors
  1. Anne C. Wheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amanda Wylie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa Raspa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adrienne Villagomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kylee Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne Edwards
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Margaret DeRamus
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paul S. Appelbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Donald B. Bailey Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ACW contributed to the design of the study, oversaw data collection, and drafted the majority of the manuscript; AW provided all statistical analysis; MR contributed to the design and leadership of the study; AV, KM, AE, and MD collected a majority of the data and contributed to the oversight of the study; PSA provided expert consultation on the use of the MacCAT-CR; DBB conceptualized the study and provided leadership and oversight. All authors approved of the final version of the manuscript.

Corresponding author

Correspondence to Anne C. Wheeler.

Ethics declarations

Conflict of interest

None of the authors have any conflict of interests to declare.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent and/or assent were obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wheeler, A.C., Wylie, A., Raspa, M. et al. Decisional Capacity for Informed Consent in Males and Females with Fragile X Syndrome. J Autism Dev Disord 50, 1725–1747 (2020). https://doi.org/10.1007/s10803-019-03930-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-019-03930-4

Keywords

Search

Navigation