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Rethinking vulnerable groups in clinical research

  • M. Finnegan (a1) and B. O’Donoghue (a2)
Abstract

Vulnerable groups are often excluded from clinical research on the basis of scientific, ethical and practical reasons. Although intended to protect vulnerable people and maintain study integrity, exclusion of vulnerable groups from research through use of standard exclusion criteria may not always be necessary and may result in findings that are not generalisable. Achieving a balance between the competing needs to protect vulnerable people and to make progress in our understanding of disorders and their management through research requires a reconsideration of exclusion criteria and consent processes to ensure vulnerable people are appropriately represented in clinical research. Reasons for development of broad exclusion criteria include both concrete barriers and intangible discouraging factors. This paper examines this situation and its consequences, perceived and real barriers to inclusion of vulnerable people in research, and suggests methods for overcoming these barriers and applying thoughtful exclusion criteria.

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Corresponding author
*Address for correspondence: M. Finnegan, Research Department, St Patrick‘s University Hospital, James St Dublin 8, Ireland. (Email: finnegma@tcd.ie)
References
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Adams P, Wongwit W, Pengsaa K, Khusmith S, Fungladda W, Chaiyaphan W, Limphattharacharoen C, Prakobtham S, Kaewkungwal J (2013). Ethical issues in research involving minority populations: the process and outcomes of protocol review by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand. BMC Medical Ethics 14, 33.
Appelbaum PS (2006). Decisional capacity of patients with schizophrenia to consent to research: taking stock. Schizophrenia Bulletin 32, 2225.
Appelbaum PS (2007). Assessment of patients’ competence to consent to treatment. New England Journal of Medicine 357, 18341840.
Appelbaum P, Grisso P, Hill-Fotouhi C (1997). The MacCAT-T: a clinical tool to assess patients’ capacities to make treatment decisions. Psychiatric Services 48, 14151419.
Beauchamp TL, Jennings B, Kinney ED, Levine RJ (2002). Pharmaceutical research involving the homeless. The Journal of Medicine and Philosophy 27, 547564.
Bernabe RD, Van Thiel GJ, Van Delden JJ (2016). What do international ethics guidelines say in terms of the scope of medical research ethics? BMC Medical Ethics 17, 23.
Buxton M, Hanney S, Jones T (2004). Estimating the economic value to societies of the impact of health research: a critical review. Bulletin of the World Health Organization 82, 733739.
Chambers M, Gallagher A, Borschmann R, Gillard S, Turner K, Kantaris X (2014). The experiences of detained mental health service users: issues of dignity in care. BMC Medical Ethics 15, 50.
Charles A, Rid A, Davies H, Draper H (2016). Prisoners as research participants: current practice and attitudes in the UK. Journal of Medical Ethics 42, 246252.
Conus P, Berk M, Cotton S, Kader L, Macneil C, Hasty M, Hallam K, Lambert M, Murphy B, McGorry P (2015). Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: an 8-week randomised controlled trial. European Psychiatry 30, 975982.
Council for International Organizations of Medical Sciences (2007). International Ethical Guidelines for Biomedical Research Involving Human Subjects. CIOMS: Geneva2002. In External Resources Pubmed/Medline (NLM).
Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, Jose E, Agronin M, Davis CS, Nguyen U (2015). Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA 314, 12421254.
da Conceicao PO, Nascimento PP, Mazetto L, Alonso NB, Yacubian EMT, de Araujo Filho GM (2013). Are psychiatric disorders exclusion criteria for video-EEG monitoring and epilepsy surgery in patients with mesial temporal sclerosis? Epilepsy & Behavior 27, 310314.
de Jonghe A, van de Glind EM, van Munster BC, de Rooij SE (2014). Underrepresentation of patients with pre-existing cognitive impairment in pharmaceutical trials on prophylactic or therapeutic treatments for delirium: a systematic review. Journal of Psychosomatic Research 76, 193199.
European Commission (2009). Challenging futures of science in society: emerging trends and cutting-edge issues. Monitoring Activities of Science in Society Expert Group European Commission, Brussels.
European Council (2001). Directive 2001/20/EC Additional protocol to the convention on human rights and biomedicine, concerning biomedical research Regulation (EU), No 536/2014. European Council.
European Parliament, Council of the European Union (2014). Clinical trials on medicinal products for human use. No. 536/2014 OJ L158. European Council.
Eynan R, Bergmans Y, Antony J, Cutcliffe JR, Harder HG, Ambreen M, Balderson K, Links PS (2014). The effects of suicide ideation assessments on urges to self-harm and suicide. Crisis 35, 123–131.
Fertig E, Fureman BE, Bergey GK, Brodie MA, Hesdorffer DC, Hirtz D, Kossoff EH, LaFrance WC, Versavel M, French J (2014). Inclusion and exclusion criteria for epilepsy clinical trials – recommendations from the April 30, 2011 NINDS workshop. Epilepsy Research 108, 825832.
Førde R, Norvoll R, Hem MH, Pedersen R (2016). Next of kin’s experiences of involvement during involuntary hospitalisation and coercion. BMC Medical Ethics 17, 76.
Freedman B, Fuks A, Weijer C (1992). Demarcating research and treatment. Clinical Research 40, 653660.
Frew PM, Saint-Victor DS, Isaacs MB, Kim S, Swamy GK, Sheffield JS, Edwards KM, Villafana T, Kamagate O, Ault K (2014). Recruitment and retention of pregnant women into clinical research trials: an overview of challenges, facilitators, and best practices. Clinical Infectious Diseases 59, S400S407.
Fry C, Dwyer R (2001). For love or money? An exploratory study of why injecting drug users participate in research. Addiction 96, 13191325.
Gurrera RJ, Karel MJ, Azar AR, Moye J (2007). Agreement between instruments for rating treatment decisional capacity. The American Journal of Geriatric Psychiatry 15, 168173.
Gysels M, Shipman C, Higginson IJ (2008). Is the qualitative research interview an acceptable medium for research with palliative care patients and carers? BMC Medical Ethics 9, 7.
Hall S, Longhurst S, Higginson IJ (2009). Challenges to conducting research with older people living in nursing homes. BMC Geriatrics 9, 38.
Head MG, Walker SL, Nalabanda A, Bostock J, Cassell JA (2015). Researching scabies outbreaks among people in residential care and lacking capacity to consent: a case study. Public Health Ethics, Published online 16 April 2015. doi:10.1093/phe/phv011.
Hietanen P, Aro AR, Holli K, Absetz P (2000). Information and communication in the context of a clinical trial. European Journal of Cancer 36, 20962104.
Humphreys K (2014). A review of the impact of exclusion criteria on the generalizability of schizophrenia treatment research. Clinical Schizophrenia & Related Psychoses 20, 125.
Humphreys K, Weisner C (2000). Use of exclusion criteria in selecting research subjects and its effect on the generalizability of alcohol treatment outcome studies. American Journal of Psychiatry 157, 588594.
Irish Council for Bioethics (2004). Guidance on Operational Procedures for Research Ethics Committees, The Irish Council for Bioethics Academy House, 19 Dawson St, Dublin 2. (http://health.gov.ie/wp-content/uploads/2014/07/Operational_Procedures1.pdf). Accessed 11 November 2017.
Kipnis K (2001). Vulnerability in research subjects: a bioethical taxonomy. In: Report on Ethical and Policy Issues in Research Involving Human Participants 2, Commissioned Papers and Staff Analysis, National Bioethics Advisory Commission, Online Ethics Center for Engineering 6/15/2006 OEC. (http://www.onlineethics.org/Topics/RespResearch/ResResources/nbacindex/33959/hkipnis.aspx). Accessed 11 November 2017.
Kirino S, Suzuki T, Takeuchi H, Mimura M, Uchida H (2017). Representativeness of clinical PET study participants with schizophrenia: a systematic review. Journal of Psychiatric Research 88, 72–79.
Kleiderman E, Avard D, Black L, Diaz Z, Rousseau C, Knoppers BM (2012). Recruiting terminally ill patients into non-therapeutic oncology studies: views of health professionals. BMC Medical Ethics 13, 33.
Kost RG, Lee LM, Yessis J, Wesley RA, Henderson DK, Coller BS (2013). Assessing participant-centered outcomes to improve clinical research. The New England Journal of Medicine 369, 2179.
Lecouturier J, Rodgers H, Ford GA, Rapley T, Stobbart L, Louw SJ, Murtagh MJ (2008). Clinical research without consent in adults in the emergency setting: a review of patient and public views. BMC Medical Ethics 9, 9.
Li RH, Wacholtz MC, Barnes M, Boggs L, Callery-D’Amico S, Davis A, Digilova A, Forster D, Heffernan K, Luthin M (2016). Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees. Journal of Medical Ethics 42, 229234.
Locock L, Smith L (2011). Personal experiences of taking part in clinical trials – a qualitative study. Patient Education and Counseling 84, 303309.
Maas AI, Steyerberg EW, Marmarou A, McHugh GS, Lingsma HF, Butcher I, Lu J, Weir J, Roozenbeek B, Murray GD (2010). IMPACT recommendations for improving the design and analysis of clinical trials in moderate to severe traumatic brain injury. Neurotherapeutics 7, 127134.
Marson DC, Ingram KK, Cody HA, Harrell LE (1995). Assessing the competency of patients with Alzheimer’s disease under different legal standards: a prototype instrument. Archives of Neurology 52, 949954.
McDonald K, Kidney C, Patka M (2013). ‘You need to let your voice be heard’: research participants’ views on research. Journal of Intellectual Disability Research 57, 216225.
Mental Capacity Act (2005). c.9, Part 1, s 30-34 (http://www.legislation.gov.uk/ukpga/2005/9/section/30). Accessed 11 November 2017.
Misra S, Socherman R, Hauser P, Ganzini L (2008). Appreciation of research information in patients with bipolar disorder. Bipolar Disorders 10, 635646.
Moore A, Donnelly A (2015). The job of ‘ethics committees’. Journal of Medical Ethics, Published Online 13 November 2015. doi: 10.1136/medethics-2015-102688.
Moore LW, Miller M (1999). Initiating research with doubly vulnerable populations. Journal of Advanced Nursing 30, 10341040.
Morán-Sánchez I, Luna A, Sánchez-Muñoz M, Aguilera-Alcaraz B, Pérez-Cárceles MD (2016). Decision-making capacity for research participation among addicted people: a cross-sectional study. BMC Medical Ethics 17, 3.
National Institute for Health and Care Excellence (2011). Service user experience in adult mental health: improving the experience of care for people using adult NHS mental health services: Clinical guideline [CG136]: Research Recommendations.
National Institute for Health and Care Excellence (2015). Violence and aggression: short-term management in mental health, health and community settings: NICE guideline [NG10]: Research Recommendations.
Newman E, Walker EA, Gefland A (1999). Assessing the ethical costs and benefits of trauma-focused research. General Hospital Psychiatry 21, 187196.
Office of the Minister for Children and Youth Affairs. (2010). Ethical Review and Children’s Research in Ireland. The National Children’s Strategy Research Series. The Stationery Office: Dublin.
Oireachtas (2013). Assisted Decision Making (Capacity) Bill. (http://www.oireachtas.ie/documents/bills28/bills/2013/8313/b8313d.pdf).
Oireachtas (2015). Assisted Decision-Making (Capacity) Act (Ireland), Houses of the Oireachtas, Dublin, 2015. (https://www.oireachtas.ie/documents/bills28/acts/2015/a6415.pdf). Accessed 11 November 2017.
Olsen DP, Mahrenholz D (2000). IRB-identified ethical issues in nursing research. Journal of Professional Nursing 16, 140148.
Pentz RD, Flamm AL, Sugarman J, Cohen MZ, Daniel Ayers G, Herbst RS, Abbruzzese JL (2002). Study of the media’s potential influence on prospective research participants’ understanding of and motivations for participation in a high-profile phase I trial. Journal of Clinical Oncology 20, 37853791.
Porteri C, Petrini C (2015). Research involving subjects with Alzheimer’s disease in Italy: the possible role of family members. BMC Medical Ethics 16, 12.
Reijula E, Halkoaho A, Pietilä A-M, Selander T, Kälviäinen R, Keränen T (2015). Therapeutic misconception correlates with willingness to participate in clinical drug trials among patients with epilepsy; need for better counseling. Epilepsy & Behavior 48, 2934.
Roberts LW (1998). The ethical basis of psychiatric research: conceptual issues and empirical findings. Comprehensive Psychiatry 39, 99110.
Roberts LW, Roberts B (1999). Psychiatric research ethics: an overview of evolving guidelines and current ethical dilemmas in the study of mental illness. Biological Psychiatry 46, 10251038.
Rogers B (1990). Ethics and research. AAOHN Journal 38, 581585.
Rose D, Russo J, Wykes T (2013). Taking part in a pharmacogenetic clinical trial: assessment of trial participants understanding of information disclosed during the informed consent process. BMC Medical Ethics 14, 34.
Sanci LA, Sawyer SM, Weller PJ, Bond LM, Patton GC (2004). Youth health research ethics: time for a mature-minor clause? Medical Journal of Australia 180, 336338.
Schneider LS, Olin JT, Lyness SA, Chui HC (1997). Eligibility of Alzheimer’s disease clinic patients for clinical trials. Journal of the American Geriatrics Society 45, 923928.
Schwenzer KJ (2008). Protecting vulnerable subjects in clinical research: children, pregnant women, prisoners, and employees. Respiratory Care 53, 13421349.
Shepherd V (2016). Research involving adults lacking capacity to consent: the impact of research regulation on ‘evidence biased’ medicine. BMC Medical Ethics 17, 55.
Sigman GS, O’Connor C (1991). Exploration for physicians of the mature minor doctrine. The Journal of Pediatrics 119, 520525.
Staphorst MS, Hunfeld JA, van de Vathorst S (2017). Are positive experiences of children in non-therapeutic research justifiable research benefits? Journal of Medical Ethics 43, 530534.
Sutton LB, Erlen JA, Glad JM, Siminoff LA (2003). Recruiting vulnerable populations for research: revisiting the ethical issues. Journal of Professional Nursing 19, 106112.
Ulrich CM, Wallen GR, Grady C (2002). Research vulnerability and patient advocacy: balance-seeking perspectives for the clinical nurse scientist? Nursing Research 51, 71.
UyBico SJ, Pavel S, Gross CP (2007). Recruiting vulnerable populations into research: a systematic review of recruitment interventions. Journal of General Internal Medicine 22, 852863.
Vallely A, Lees S, Shagi C, Kasindi S, Soteli S, Kavit N, Vallely L, McCormack S, Pool R, Hayes RJ (2010). How informed is consent in vulnerable populations? Experience using a continuous consent process during the MDP301 vaginal microbicide trial in Mwanza, Tanzania. BMC Medical Ethics 11, 10.
van Lent M, Rongen GA, Out HJ (2014). Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review. BMC Medical Ethics 15, 83.
Van Spall HG, Toren A, Kiss A, Fowler RA (2007). Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 297, 12331240.
Verástegui EL (2006). Consenting of the vulnerable: the informed consent procedure in advanced cancer patients in Mexico. BMC Medical Ethics 7, 13.
Wang S-B, Wang Y-Y, Ungvari GS, Ng CH, Wu R-R, Wang J, Xiang Y-T (2016). The MacArthur Competence Assessment Tools for assessing decision-making capacity in schizophrenia: a meta-analysis. Schizophrenia Research 183, 56–63.
Welch MJ, Lally R, Miller JE, Pittman S, Brodsky L, Caplan AL, Uhlenbrauck G, Louzao DM, Fischer JH, Wilfond B (2015). The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials. Clinical Trials 12, 503–510.
Willison DJ, Steeves V, Charles C, Schwartz L, Ranford J, Agarwal G, Cheng J, Thabane L (2009). Consent for use of personal information for health research: do people with potentially stigmatizing health conditions and the general public differ in their opinions? BMC Medical Ethics 10, 10.
Woolfall K, Frith L, Gamble C, Young B (2013). How experience makes a difference: practitioners’ views on the use of deferred consent in paediatric and neonatal emergency care trials. BMC Medical Ethics 14, 45.
World Medical Association (2001). World Medical Association, Declaration of Helsinki: Ethical principles for medical research involving human subjects. Bulletin of the World Health Organization 79, 373.
Yamal J-M, Robertson CS, Rubin ML, Benoit JS, Hannay HJ, Tilley BC (2014). Enrollment of racially/ethnically diverse participants in traumatic brain injury trials: effect of availability of exception from informed consent. Clinical Trials 11, 187194.
Yanos PT, Stanley BS, Greene CS (2009). Research risk for persons with psychiatric disorders: a decisional framework to meet the ethical challenge. Psychiatric Services 60, 374–383.
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