ReviewEthical and regulatory considerations in HIV prevention studies employing respondent-driven sampling☆,☆☆
Introduction
Respondent-driven sampling (RDS) is a chain-referral strategy for recruiting populations at risk for infection with HIV, initially used with injection drug users (IDUs) (Heckathorn, 1997, Semaan et al., 2002). RDS is predicated on the recognition that peers are better than outreach workers, study investigators, and staff members in referring members from social networks for enrolment in studies (Heckathorn, 1997). Based on this recognition, RDS uses the practice of participant-driven recruitment and offers remuneration to participants who refer their peers to study sites (Heckathorn, 1997, Heckathorn, 2002). When studies using RDS offer HIV testing or collect serostatus data through behavioural surveys, investigators might learn about discordant partnerships of which participants are unaware. No official guidance exists on remuneration for participant-driven recruitment or on investigators’ responsibilities for notifying participants of their discordant partnerships. However, these practices can be guided by ethical principles, regulations protecting study participants, and data reported in the scientific literature.
Our purpose is to review the ethical principles and relevant regulations to guide investigators using RDS in the practices associated with remuneration for participant-driven recruitment and with investigators’ responsibilities for notifying participants of their discordant partnerships. We focus on studies that have used RDS to recruit IDUs in the United States (U.S.) during 1995–2006 and review the literature for studies with IDUs, and the implications of the relevant ethical literature and federal regulations. We highlight how our review relates to studies conducted in countries other than the U.S., to populations at risk for HIV infection, including those who are at risk because of heterosexual activities, same-sex behaviour, or drug use, and to studies conducted for research as well as surveillance. We conclude with a checklist of ethics-relevant and regulatory-related variables that, where feasible, should be reported from studies using RDS.
We ground our discussion in the ethical principles of respect for persons, beneficence, and justice (The national commission for the protection of human subjects of biomedical and behavioural research, 1978). Application of these principles has been challenged on the basis that the principle of respect for persons relies on a superficial view of choice, that the principle of beneficence relies on a simple assessment of benefits and risks that cannot accommodate the various benefits and harms made by research participants, and that the principle of justice conflates the harms of exploitation with those of disrespect for persons (Simmerling, Schwegler, Sieber, & Lindgren, 2007). Despite these challenges, the ethical principles remain codified in the U.S. federal regulations for protection of study participants at 45 CFR Part 46 (Office of Protection from Research Risk, 1991). The principles are also codified in international regulations and policies (Council for International Organizations of Medical Sciences, 2003, Joint United Nations Program on AIDS, 2000, National Bioethics Advisory Commission, 2003, Nuffield Council on Bioethics, 2005, World Medical Association, 2000).
Scientific advantages of RDS are illustrated by its contribution to sampling IDUs. Because IDUs are a hidden population, and because recruiting representative samples are important for drawing reliable and valid conclusions, RDS is useful in HIV studies. First, it is difficult to construct sampling frames that list names of IDUs for use in recruiting probability samples (Kish, 1991). Second, IDUs do not seek healthcare regularly, and many of them do not live in traditional dwellings, so they may not be represented in public data sets (Kalton, 1993). Door-to-door surveys, telephone surveys, and facility-based surveys tend to underestimate the number of IDUs, exclude them from their samples, or include biased samples (Catania, Gibson, Chitwood, & Coates, 1990; Gagnon et al., 1989). Although IDU samples recruited from venues or institutions may be more representative than household or general-population samples, they exclude IDUs who do not access these facilities. For example, drug treatment facility samples tend to include older IDUs with longer drug use histories. Third, obtaining traditional probability samples of IDUs is expensive, time-consuming, and resource intensive (Laumann, Michael, Gagnon, & Michaels, 1994; Sudman, Sirken, & Cowan, 1988). Fourth, because HIV research necessitates collection of data about illegal drug use and intimate sexual behaviours, developing rapport with IDUs through community-based relationships and participant-driven sampling is necessary to obtain valid responses and high response rates (Magnani, Sabin, Saidel, & Heckathorn, 2005). Finally, RDS allows investigators to overcome many of the sampling biases observed in other methods of chain-referral sampling (Heckathorn, 2002, Salganik, 2006). Thus, for scientific and practical reasons, RDS is often considered superior to other IDU recruitment methods. The resulting samples include IDUs who might not have been included using venue-based, street outreach, or advertising approaches.
Operationally, RDS uses a highly structured referral process referred to as participant-driven recruitment (PDR). Studies that use RDS depend on participants to nominate and refer or recruit their peers for study participation. Referral quotas limit the number of recruits a recruiter can invite to the study, and limit remuneration for recruitment. Recruiters receive a pre-determined number of coupons, each with a unique serial number, to refer people they know and who are likely to meet the study's eligibility criteria. Recruiters give the coupons to potential recruits who agree to consider participation and to bring their coupon to study staff. Recruiters can invite friends, acquaintances, sex partners, or drug-injection partners to participate in the study. Staff members explain the study to the recruits, screen them, and (if they are eligible) invite them to participate in the study. The consent process is designed to ensure that recruits do not feel pressured by the recruiter. If recruits choose to enrol, the recruiters are reimbursed for their time and effort. Both recruiters and enroled recruits receive remuneration for study participation.
In terms of the recruitment process, RDS and snowball sampling operate somewhat similarly. Both methods begin with a set of recruiters who are chosen by study staff in a non-random fashion. The initial recruiters, referred to as seeds, recruit the first “wave,” who in turn recruits the second wave, who then recruits the third wave, and so forth, until the sampling goal is reached. Thus, the sample grows wave by wave, similar to the way a snowball increases in size as it rolls down a hill (Heckathorn, 2002). In RDS, the number of waves needed to obtain a representative sample of the target population is usually calculated in advance of recruitment. Four to six waves are recommended to produce a sample that is independent of the initial seeds (Heckathorn, 2002). The relationship between recruiters and recruits is documented in the coupon-management system to assess the participant-driven recruitment process and selection biases. In contrast to snowball sampling, RDS offers participants a higher level of privacy and confidentiality because recruited peers choose whether they would like to come to the study site or not. In snowball sampling, enroled participants often give investigators the name of their peers who wait on investigators to find them.
RDS differs from snowball sampling statistically in that RDS is based on a mathematical model of the network-recruitment process that functions like a corrective lens, controlling the distorting effects that network structure exerts on the sampling process (Heckathorn, 2007). In this way, RDS provides information on relative inclusion probabilities, from which unbiased estimates of population characteristics are calculated. If mathematical model assumptions are satisfied, RDS yields population estimates that are asymptotically unbiased (Heckathorn, 2007, Salganik, 2006).
The assumptions of the mathematical model influence the recruitment process. First, long recruitment chains eliminate bias related to the selection of the seeds. Thus, a distinctive feature of RDS is two interrelated means of cultivating long chains achieved by enhancing participants’ motivation to recruit their peers, and by using recruitment quotas (generally set at three recruits per recruiter). Thus, achieving any given sample size will require a substantial number of waves. Recruitment quotas are consequential from an ethical and regulatory perspective because they limit the amount of money any recruiter can receive; hence, precluding problems arising from excessive payments. Remuneration for participant-driven recruitment is a key aspect of RDS and is not contingent on the target population.
A second constraint on the sampling process is the need to document who recruited whom. As Galton recognized when he formulated the homophily principle, friends tend to resemble one another in race, ethnicity, education, income, religion, and other attributes (Galton, 1874). In studies of IDUs, homophily also includes drug preference and HIV status (Heckathorn, 2002, Heckathorn et al., 2002). Mathematical modelling controls for the non-random recruitment bias by quantitatively assessing the degree to which recruiters’ and recruits’ characteristics are correlated. Thus, network data are collected on network relationships and characteristics to assess homophily and to permit the calculation of selection probabilities and population estimates (Heckathorn, 1997, Heckathorn, 2002). Fortunately, information on potential network size (number of acquaintances, friends, or partners who qualify for participation) does not pose privacy-related constraints. Investigators use the data on network size to control for differential network size and to assess the reach of the recruitment process. Investigators use the information on the relationship between recruiters and recruits (e.g. sex partner, spouse, drug-injection partner, relative, friend, acquaintance, stranger, or other) to control for differences between participants, weight the sample, and produce probability estimates. The implication of requiring documentation of the recruiter–recruit relationships and characteristics is that when HIV information is obtained study investigators will also gather information on discordant partnerships.
In many other network-based studies, investigators can destroy the linking code and de-identify the data after the social network has been mapped and sampling weights have been calculated. Data analysis can then be carried out using de-identified data (Klovdahl, 2005, Margolis, 2000). However, this option may not be ethically justifiable or permissible by institutional review boards (IRBs) or ethics review committees (ERCs) for studies that use RDS if investigators had access to information on discordant partnerships during the study period. Thus, deciding on how to disclose information on discordant partnerships to participants is important because this information is clinically relevant to their health.
Ethical considerations and regulatory requirements regarding remuneration for participant-driven recruitment and for informing participants of their discordant partnerships are relevant to all studies employing RDS. These topics gain importance as use of RDS gains momentum. Since information on RDS first appeared (Heckathorn, 1997, Heckathorn, 2002), and since its initial application to recruit IDUs (Broadhead et al., 1998, Heckathorn et al., 2002), researchers have used RDS for its practical and statistical advantages to recruit other populations at risk for HIV infection. RDS has been employed for research and surveillance purposes in the U.S. and more than 30 other countries (Frost et al., 2006, Heckathorn et al., 2007, Platt et al., 2006, Simic et al., 2006, Stormer et al., 2006; Yeka, Maibani-Michie, Prybylski, & Colby, 2006). For example, RDS was used in the U.S. to recruit heroin and cocaine users (Broadhead et al., 1998, Heckathorn et al., 2002), MDMA (ecstasy) users (Wang et al., 2005), transgender persons (Clements-Nolle, Marx, Guzman, & Katz, 2001), and MSM (Ramirez-Valles, Heckathorn, Vazquez, Diaz, & Campbell, 2005). Our review and example of studies that used RDS with IDUs in the U.S. show that the confluence of the ethical and regulatory considerations and the scientific literature can help contribute to the development of evidence-based ethics (Halpern, 2005).
With expanding worldwide use of RDS, knowledge of relevant guidelines and regulations is increasingly important. For example, the U.S. federal regulations require all U.S. federally funded research to be reviewed by an IRB. When U.S. federally funded research is conducted outside the U.S., the regulations require that the research protocols be reviewed in both the U.S. and the host country. Studies conducted outside the U.S. should follow the regulations and codes of the host country and relevant literature (Akabayashi & Slingsby, 2006; Hearnshaw, 2004; Rivera, Borasky, Rice, Carayon, & Wong, 2007). Additionally, societal factors can influence the ethics of studies that use RDS. In the case of drug users, these factors include mistrust of authorities, density of networks, mobility of drug users, interaction between IDUs and other populations, female-to-male ratio of drug users, stigma, partner violence, and cultural expectations about privacy, confidentiality, and disclosure of HIV discordant results (Des Jarlais & Semaan, 2005; Klein, 2001; Paxton, 2002, Semaan and Leinhos, 2007; Warszawski & Meyer, 2002).
During the past decade, controversies have emerged over the applicability of regulatory and ethical considerations of resource-rich countries, particularly those of the U.S., to resource-limited countries (Weijer & Anderson, 2001). Subsequently, different ethical frameworks and benchmarks were published on how to resolve such controversies in clinical research, which can be useful for behavioural research, including for remuneration for participant-driven recruitment and for investigators’ responsibilities for informing participants of their discordant partnerships. The benchmarks include those that relate to social value, scientific validity, fair selection of study population, favourable risk-benefit ratio, independent review, informed consent, and respect for recruited participants and study communities (Emanuel, Wendler, Killen, & Grady, 2004; Fitzgerald, Wasunna, & Pape, 2003).
Epidemiologic and intervention studies are classified as research for regulatory purposes, and are subject to specific regulations and policies. Conversely, surveillance activities abide by different policies that pertain to public health activities (Centers for Disease Control and Prevention, 1999, Snider and Stroup, 1997). More recently, several calls have been made to reconsider the policies of surveillance activities (Fairchild, 2005, World Health Organization, 2004). This emphasises the need to inform participants of the purpose of surveillance activities and to share relevant test results with them. More specifically, the calls question the ethics of the practical and economic reasons that have traditionally been used to argue against notification of HIV test results in surveillance activities (Fairchild & Bayer, 2004; World Bank Group, 2002). Project staff training and sufficient resources can increase the feasibility of notification, but are not always available, in which case alternative strategies for notification might be warranted.
Because of the safeguards in studies involving RDS, remuneration for time and cost for participant-driven recruitment is generally accepted as non-coercive, does not cause undue inducement, is not excessive, and does not compromise the voluntariness necessary for informed consent. Coercion typically occurs when the threat of a specific harm compels a person to act in a manner that they would not otherwise choose (Hawkins & Emanuel, 2005). It can be argued that there is some risk for coercion in studies involving RDS if recruiters intimidate recruits to join the study. Undue influence is defined as an offer that leads people to use poor judgment and assume substantial risks of harm that compromise their welfare (Emanuel, 2004, Wilkinson and Moore, 1997). Undue influence could occur when recruiters overzealously encourage their peers to consider study participation while thinking more of their own remuneration than the welfare of their peers. Another important question is whether remuneration payments for participant-driven recruitment pose any risk of harm that is beyond what the participants experience in the course of their daily lives.
Because of these concerns, studies that use RDS adopt several safeguards to protect participants and ensure that coercion or undue influence does not impair the voluntary decision of potential enrolees to participate in a study or their assessment of the risks and benefits of participation. The safeguards include giving recruiters a maximum of three coupons to minimize the recruiters’ influence on the study sample, and to limit the emergence of quasi-professional recruiters (Heckathorn et al., 2002). Recruits’ informed consent is obtained by study staff. Remuneration for participant-driven recruitment is modest, even for those who recruit the maximum of three recruits. Furthermore, investigators do not mention payments in recruitment advertisements or coupons. As additional safeguards, recruiters have to meet with study staff to learn if their potential recruits were enroled in the study. Once study staff validates recruitment information in the coupon management system, recruiters are remunerated for their efforts. Only recruiters are allowed to redeem their non-transferable coupons for participant-driven recruitment. Investigators can choose to conduct interviews with potential participants about the recruitment process to assess relevant concerns. If the risk of harm from recruitment or participation is identified during the interview process, study staff can choose to withhold recruitment or remuneration.
Remuneration for participant-driven recruitment is different from finders’ fees. Finders’ fees, which were used for remunerating physicians for recruiting their patients into clinical studies, are disallowed by IRBs because they might have influenced the judgment of health care providers about the appropriateness of research participation for their patients (Lemmens & Miller, 2003). Recruiters and recruits in studies that use RDS do not share a clinical or consulting relationship; thus, they do not have a financial or professional conflict of interest. Studies that have used RDS with IDUs in the U.S. have been behavioural studies that evaluated prevention interventions or collected behavioural surveillance data, and have not offered medical treatment (Abdul-Quader, Heckathorn, Sabin, & Saidel, 2006; Gallagher, Denning, Allen, Nakashima, & Sullivan, 2007; Lansky et al., 2007). Behavioural surveillance activities and prevention research studies are usually classified as minimal-risk, in which the probability and magnitude of harm or discomfort associated with participation is not greater than those ordinarily encountered in daily life; or during the performance of routine physical or psychological examinations (Office of Protection from Research Risk, 1991).
Section snippets
Methods
We identified U.S.-based HIV prevention and control studies, conducted during 1995–2006, that had used RDS with IDUs who injected heroin, cocaine, or both. We searched two electronic databases (Pubmed and OVID Medline), used their ‘find related’ function to find relevant articles, and conducted manual searches of reference lists. Because the regulations for research are likely to differ by country, we focused our review on studies conducted in the U.S. to allow for linking the scientific
Characteristics of studies and participants
We located and reviewed all the articles employing RDS with IDUs in the U.S. Our strategy provided us with eight articles describing four studies (two studies were described in more than one article) (Abdul-Quader, Heckathorn, McKnight, et al., 2006; Broadhead, Heckathorn, Grund, Stern, & Anthony, 1995; Broadhead et al., 1998, Des Jarlais et al., 2007, Heckathorn et al., 2002, Hughes, 1999, McKnight et al., 2006, Robinson et al., 2006) (Table 1). Two earlier studies, published during 1995–2002,
Discussion
Our review of the scientific literature sheds light on the ethical and regulatory considerations for remuneration for participant-driven recruitment and informing participants recruited in this manner of their HIV-discordant partnerships.
Conclusion
Our review is meant to enhance the commitment to ethical research of studies that use RDS. As investigators, IRBs, and ERCs develop a deeper understanding of the ethical considerations and regulatory requirements that affect studies involving RDS, they can cultivate a dialogue through which they can learn about each other's perspective. Soliciting the input of local populations is very important in developing an informed consent process, including consent forms that meet relevant expectations
Acknowledgment
The authors would like to acknowledge the insightful comments of Dr. Charles Heilig of the Centers for Disease Control and Prevention, Atlanta, GA, and of Mr. Scott Burris of Temple University, Philadelphia, PA, on an earlier version of this paper. Dr. Des Jarlais’ effort on this paper was supported by grants R01 DA 03574 and P30 DA 11041 from the National Institutes of Health.
The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the
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Cited by (0)
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An earlier version of this paper was presented at the XV International AIDS conference, Bangkok, Thailand, 15 July 2004 and at the U.S. National HIV Prevention Conference, Atlanta, GA, 4 December 2007.
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The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.