How Researchers Define Vulnerable Populations in HIV/AIDS Clinical Trials

Abstract

In this study, we interviewed researchers, asking them to define vulnerable populations in HIV/AIDS clinical trials, and provide feedback on the federal regulations for three vulnerable populations. Interview data informed a conceptual framework, and were content analyzed to identify acceptability or disagreement with the regulations. Beginning with several characteristics of vulnerable enrollees identified by researchers, the conceptual framework illustrates possible scenarios of how enrollees could be considered vulnerable in clinical research. Content analysis identified barriers affecting HIV/AIDS researchers' ability to conduct clinical trials with pregnant women, prisoners, and children, for which the regulations specify additional protections. This study challenges current thinking about federal regulations' group-based approach to defining vulnerable populations.

The concept of ‘vulnerability’ in research ethics: an in-depth analysis of policies and guidelines

“…National Statement, TCPS2, Common Rule)Vulnerable because: • Historically considered vulnerable and “have, at times, been treated unfairly and inequitably in research, or have been excluded from research opportunities” a ([35], p. 8) • Explanation unclear [18, 33]Vulnerable to: • Coercion or undue influence [38] Certain ethnic, racial minority, or ethnocultural groups (CIOMS, ICH GCP, TCPS2, Belmont Report)Vulnerable because: • Historically considered vulnerable and “have, at times, been treated unfairly and inequitably in research, or have been excluded from research opportunities” a ([35], p. 8) • May continually be sought as research subjects due to ready availability and administrative convenience; have a dependent status and, frequently, compromised capacity for free consent; are easy to manipulate as a result of their illness or socioeconomic condition b [37] • Explanation unclear [29, 33] Patients in emergency settings, prospective participants for emergency research (CIOMS, Clinical Trials Regulation, ICH GCP, TCPS2)Vulnerable because: • Their incapacity to make decisions creates vulnerable circumstances [35] • No explanation [32] • Explanation unclear [29, 33] Subordinate members of hierarchies or relationships c (CIOMS, ICH GCP, Aus. National Statement)Vulnerable because: • Voluntary consent may be compromised by expectations of benefit or repercussions from superiors [29, 33] • Pre-existing relationships may compromise the voluntariness of consent because they typically involve unequal status, where one party has influence or authority over the other [34]Vulnerable to: • Being over-researched [29, 34] Economically disadvantaged persons (Belmont Report, Common Rule)Vulnerable because: • Dependent status, impaired capacity to consent, easy to manipulate as a result of their illness [37]Vulnerable to: • Coercion or undue influence [38] Homeless persons (CIOMS, ICH GCP) • Explanation unclear [29, 33] Institutionalized persons (TCPS2, Belmont Report)Vulnerable because: • Historically considered vulnerable and “have, at times, been treated unfairly and inequitably in research, or have been excluded from research opportunities” a ([35], p. 8) • Their ability to fully safeguard their own interests in research may be limited, and their situation may compromise the voluntariness of consent in other ways [35] • May continually be sought as research subjects due to ready availability and administrative convenience; have a dependent status and, frequently, compromised capacity for free consent; are easy to manipulate as a result of their illness or socioeconomic condition b [37] Nomads (CIOMS, ICH GCP) • Explanat...…”

“…National Statement, TCPS2, Common Rule)Vulnerable because: • Limited freedom or capacity to consent [29, 35] • Vulnerability arising from developmental stage [35] • No explanation [31, 32] • Explanation unclear [34]Vulnerable to: • Coercion or undue influence [38] Persons with mental illness or mental health problems (Clinical Trials Regulation, Aus. National Statement, TCPS2, UK Research Governance Framework)Vulnerable because: • Historically considered vulnerable and “have, at times,  been treated unfairly and inequitably in research, or  have been excluded from research opportunities” a ([35], p. 8) • Unclear [32, 36]Vulnerable to: • Various forms of discomfort and stress [34] Elderly persons (CIOMS, Clinical Trials Regulation, TCPS2)Vulnerable because: • Likely to acquire “vulnerability-defining” traits (e.g., institutionalization, dementia) ([29], p. 65] • Historically considered a group in vulnerable circumstances “have, at times, been treated unfairly and inequitably in research, or have been excluded from research opportunities” a ([35], p. 8) • No explanation [32] Persons with limited (or no) freedom or capacity to consent (CIOMS, Clinical Trials Regulation, ICH GCP)Vulnerable because: • Relatively (or absolutely) incapable of protecting their own interests [29] • No explanation [32] • Explanation unclear [33]Vulnerable to: • Exploitation for financial gain by guardians [29] Pregnant or breastfeeding women (Clinical Trials Regulation, Common Rule)Vulnerable to: • Coercion or undue influence [38] • No explanation [32] Adults with learning difficulties (UK Research Governance Framework) • No explanation [36] Handicapped persons (Common Rule) • No explanation [38] Mentally disabled persons (Common Rule)Vulnerable to: • Coercion or undue influence [38] Persons who have serious, potentially disabling or life-threatening diseases (CIOMS)Vulnerable because: • May be treated with drugs or other therapies with unproven safety and efficacy [29] Very sick persons (Belmont Report)Vulnerable because: • May continually be sought as research subjects due to ready availability and administrative convenience; have a dependent status and, frequently, compromised capacity for free consent; are easy to manipulate as a result of their illness or socioeconomic condition b [37] People suffering from multiple chronic conditions (Clinical Trials Regulation) • No explanation [32]…”

“…Empirical evidence has shown that an understanding of vulnerability in the context of research cannot be assumed to be universal – in a study with Russian and Romanian research ethics trainees, Loue and Loff [36] found that, at the initiation of their training, their existing understanding of vulnerability varied considerably from conceptualisations in the international guidelines. A study by Sengupta et al [37] gathered researchers’ perspectives on vulnerability in HIV/AIDS clinical trials and on the Common Rule guidance related to vulnerability and found that researchers assessed vulnerability in relation to situational factors that can render participants vulnerable, and that they emphasised the need to assess vulnerability on a case-by-case basis (i.e. rather than relying on a group-based strategy).…”

II. The Research Ethics Involving Vulnerable Groups

“…The case of HIV/AIDS includes individuals and population groups with a wide range of vulnerability characteristics, such as belonging to racial/ethnic minorities, being women, having different sexual preferences, being sexual workers, and/or using drugs 21 . However, vulnerability as a group arises from the risk of social stigmatization and issues related to employment and insurance that the subjects may face if their status is revealed.…”

“…The problem of overweight and obesity due to its complexity requires multidimensional solutions. It may be challenging to justify intervening in the lives of some individuals or groups in the interest of achieving better health outcomes for the whole population 21 , since unintended effects of research studies and programs, such as stigmatization and discrimination, are not uncommon 23 .…”