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Biomedical research involving human subjects has traditionally been treated as a unique endeavor, presenting special risks and demanding special protections. But in several ways, the regulatory scheme governing human subjects research is counter-intuitively less protective than the labor and employment laws applicable to many workers. This Article relies on analogical and legal reasoning to demonstrate that this should not be the case; in a number of ways, human research subjects ought to be fundamentally recast as human research workers. Like other workers protected under worklaw, biomedical research subjects often have interests that diverge from those in positions of control but little bargaining power for change. Bearing these important similarities in mind, the question becomes whether there is any good reason to treat subjects and protected workers differently as a matter of law. With regard to unrestricted payment, eligibility for a minimum wage, compensation for injury, and rights to engage in concerted activity, the answer is no and human subjects regulations ought to be revised accordingly.

Background: Very few researchers have reported on procedures of recruiting, obtaining informed consent, and compensating participants in health research in the Arabian Gulf Region. Empirical research can inform the debate about whether to adjust these procedures for culturally diverse settings. Our objective was to delineate procedures related to recruiting, obtaining informed consent, and compensating health research participants in the extremely high-density multicultural setting of Qatar., Methods: During a multistage mixed methods project, field observations and qualitative interviews were conducted in a general medicine clinic of a major medical center in Qatar. Participants were chosen based on gender, age, literacy, and preferred language, i.e., Arabic, English, Hindi and Urdu. Qualitative analysis identified themes about recruitment, informed consent, compensation, and other research procedures., Results: A total of 153 individuals were approached and 84 enrolled; the latter showed a diverse age range (18 to 75 years); varied language representation: Arabic (n = 24), English (n = 20), Hindi (n = 20), and Urdu (n = 20); and balanced gender distribution: women (n = 43) and men (n = 41). Primary reasons for 30 declinations included concern about interview length and recording. The study achieved a 74% participation rate. Qualitative analytics revealed key themes about hesitation to participate, decisions about participation with family members as well as discussions with them as "incidental research participants", the informed consent process, privacy and gender rules of the interview environment, reactions to member checking and compensation, and motivation for participating. Vulnerability emerged as a recurring issue throughout the process among a minority of participants., Conclusions: This study from Qatar is the first to provide empirical data on recruitment, informed consent, compensation and other research procedures in a general adult population in the Middle East and Arabian Gulf. This investigation illustrates how potential research participants perceive research participation. Fundamentally, Western ethical research principles were applicable, but required flexibility and culturally informed adaptations.

This paper introduces the term "structural coercion" to underscore the ways in which broader social, economic, and political contexts act upon individuals to compel them to enroll as subjects in clinical research. The paper challenges the adequacy of the concepts of "coercion" and "undue influence" in determining when research participation is voluntary. Acknowledging structural coercion shifts the frame of ethical deliberation away from specific individuals and specific studies to see important patterns in research participation by salient demographic characteristics. The effects of structural coercion manifest themselves in particular research settings, but unlike the conventional form of coercion, it is not rooted in the researcher-participant relationship or linked to particular study protocols. By extracting voluntariness from entrenched conceptions of the researcher-participant dyad, this paper proposes approaches to minimize the effects of structural coercion while creating new ethical imaginaries for review boards and researchers alike.

Payment to recruit research subjects is a common practice but raises ethical concerns relating to the potential for coercion or undue influence. We conducted the first national study of IRB members and human subjects protection professionals to explore attitudes as to whether and why payment of research participants constitutes coercion or undue influence. Upon critical evaluation of the cogency of ethical concerns regarding payment, as reflected in our survey results, we found expansive or inconsistent views about coercion and undue influence that may interfere with valuable research. In particular, respondents appear to believe that coercion and undue influence lie on a continuum; by contrast, we argue that they are wholly distinct: whereas undue influence is a cognitive distortion relating to assessment of risks and benefits, coercion is a threat of harm. Because payment is an offer, rather than a threat, payment is never coercive., (© 2012 John Wiley & Sons Ltd.)

Objective measures of drug use are very important in treatment outcome studies of persons with substance use disorders, but obtaining and interpreting them can be challenging and not always practical. Thus, it is important to determine if, and when, drug-use self-reports are valid. To this end we explored the relationships between urine drug screen results and self-reported substance use among adolescents and young adults with opioid dependence participating in a clinical trial of buprenorphine-naloxone. In this study, 152 individuals seeking treatment for opioid dependence were randomized to a 2-week detoxification with buprenorphine-naloxone (DETOX) or 12weeks of buprenorphine-naloxone (BUP), each with weekly individual and group drug counseling. Urine drug screens and self-reported frequency of drug use were obtained weekly, and patients were paid $5 for completing weekly assessments. At weeks 4, 8, and 12, more extensive assessments were done, and participants were reimbursed $75. Self-report data were dichotomized (positive vs. negative), and for each major drug class we computed the kappa statistic and the sensitivity, specificity, positive predictive value, and negative predictive value of self-report using urine drug screens as the "gold standard". Generalized linear mixed models were used to explore the effect of treatment group assignment, compensation amounts, and participant characteristics on self-report. In general, findings supported the validity of self-reported drug use. However, those in the BUP group were more likely to under-report cocaine and opioid use. Therefore, if used alone, self-report would have magnified the treatment effect of the BUP condition., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Payment of research participants helps to increase recruitment for research studies, but can pose ethical dilemmas. Research ethics committees (RECs) have a centrally important role in guiding this practice, but standardisation of the ethical approval process in Ireland is lacking., Aim: Our aim was to examine REC policies, experiences and concerns with respect to the payment of participants in research projects in Ireland., Method: Postal survey of all RECs in Ireland., Results: Response rate was 62.5% (n=50). 80% of RECs reported not to have any established policy on the payment of research subjects while 20% had refused ethics approval to studies because the investigators proposed to pay research participants. The most commonly cited concerns were the potential for inducement and undermining of voluntary consent., Conclusions: There is considerable variability among RECs on the payment of research participants and a lack of clear consensus guidelines on the subject. The development of standardised guidelines on the payment of research subjects may enhance recruitment of research participants.

The rules for compensation for injury and death in clinical trials have recently been notified. These rules clarify that medical management of all injuries in clinical trials is mandatory and in cases in which injury or death is related to the clinical trial, the subject (or nominee) is entitled to compensation over and above the medical management. They also specify procedures and timelines for reporting serious adverse events. These require simplification. The rules will hopefully make clinical trial safer for subjects and investigators alike. However, they suffer from certain inconsistencies that should be reconsidered. They need to be modified so that they do not damage the industry.

Background: There are a number of practical and ethical issues raised in school-based health research, particularly those related to obtaining consent from parents and assent from children. One approach to developing, strengthening, and supporting appropriate consent and assent processes is through community engagement. To date, much of the literature on community engagement in biomedical research has concentrated on community- or hospital-based research, with little documentation, if any, of community engagement in school-based health research. In this paper we discuss our experiences of consent, assent and community engagement in implementing a large school-based cluster randomized trial in rural Kenya., Methods: Data collected as part of a qualitative study investigating the acceptability of the main trial, focus group discussions with field staff, observations of practice and authors' experiences are used to: 1) highlight the challenges faced in obtaining assent/consent; and 2) strategies taken to try to both protect participant rights (including to refuse and to withdraw) and ensure the success of the trial., Results: Early meetings with national, district and local level stakeholders were important in establishing their co-operation and support for the project. Despite this support, both practical and ethical challenges were encountered during consenting and assenting procedures. Our strategy for addressing these challenges focused on improving communication and understanding of the trial, and maintaining dialogue with all the relevant stakeholders throughout the study period., Conclusions: A range of stakeholders within and beyond schools play a key role in school based health trials. Community entry and information dissemination strategies need careful planning from the outset, and with on-going consultation and feedback mechanisms established in order to identify and address concerns as they arise. We believe our experiences, and the ethical and practical issues and dilemmas encountered, will be of interest for others planning to conduct school-based research in Africa., Trial Registration: National Institute of Health NCT00878007.

Concerns that cash payments to people who inject drugs (PWID) to reimburse research participation will facilitate illicit drug purchases have led some ethical authorities to mandate department store/supermarket vouchers as research reimbursement. To examine the relative efficacy of the two forms of reimbursement in engaging PWID in research, clients of two public opioid substitution therapy clinics were invited to participate in a 20-30 min, anonymous and confidential interview about alcohol consumption on two separate occasions, 4 months apart. Under the crossover design, at Time 1, clients of Clinic 1 were offered $A20 cash as reimbursement, while clients of Clinic 2 were offered an $A20 voucher; at Time 2, the form of reimbursement was reversed. Using clinic records to determine the denominator (number of clients dosed), we found that compared with clients offered a voucher, a significantly higher proportion of clients who were offered cash participated in the survey (58% (139/241) vs 74% (186/252); χ(2)=14.27; p=0.0002). At first participation, respondents most commonly reported planning to purchase food/drinks/groceries (68%), cigarettes (21%) and transport/fuel (11%) with their payments, with those reimbursed in cash more likely to report planning to fund transport/fuel (19% vs 1%; p<.01) and less likely to report planning to purchase food/drinks/groceries (62% vs 76%; p=0.02). Just three out of 155 cash participants reported planning to purchase illicit drugs with their payment. Results demonstrate that modest cash payments enhanced recruitment of this group, an important consideration given the challenges of delineating the parameters of a population defined by illegal activity, seemingly without promoting excessive additional drug use.

Purpose: Studies have shown an association between socioeconomic status (SES) and quality of oncology care, but less is known about the impact of patient SES on clinical trial participation., Patients and Methods: We assessed clinical trial participation patterns according to important SES (income, education) and demographic factors in a large sample of patients surveyed via an Internet-based treatment decision tool. Logistic regression, conditioning on type of cancer, was used. Attitudes toward clinical trials were assessed using prespecified items about treatment, treatment tolerability, convenience, and cost., Results: From 2007 to 2011, 5,499 patients were successfully surveyed. Forty percent discussed clinical trials with their physician, 45% of discussions led to physician offers of clinical trial participation, and 51% of offers led to clinical trial participation. The overall clinical trial participation rate was 9%. In univariate models, older patients (P = .002) and patients with lower income (P = .001) and education (P = .02) were less likely to participate in clinical trials. In a multivariable model, income remained a statistically significant predictor of clinical trial participation (odds ratio, 0.73; 95% CI, 0.57 to 0.94; P = .01). Even in patients age ≥ 65 years, who have universal access to Medicare, lower income predicted lower trial participation. Cost concerns were much more evident among lower-income patients (P < .001)., Conclusion: Lower-income patients were less likely to participate in clinical trials, even when considering age group. A better understanding of why income is a barrier may help identify ways to make clinical trials better available to all patients and would increase the generalizability of clinical trial results across all income levels.

What I call 'the standard view' claims that IRBs should not regard financial payment as a benefit to subjects for the purpose of risk/benefit assessment. Although the standard view is universally accepted, there is little defense of that view in the canonical documents of research ethics or the scholarly literature. This paper claims that insofar as IRBs should be concerned with the interests and autonomy of research subjects, they should reject the standard view and adopt 'the incorporation view.' The incorporation view is more consistent with the underlying soft-paternalist justification for risk-benefit assessment and demonstrates respect for the autonomy of prospective subjects. Adoption of the standard view precludes protocols that advance the interests of subjects, investigators, and society. After considering several objections to the argument, I consider several arguments for the standard view that do not appeal to the interests and autonomy of research subjects., (Published 2011. This article is a US Government work and is in the public domain in the USA.)

Background: Stroke is one of the most disabling neurological conditions. Clinical research is vital for expanding knowledge of treatment effectiveness among stroke patients. However, evidence begins to accumulate that stroke patients who take part in research represent only a small proportion of all stroke patients. Research participants may also differ from the broader patient population in ways that could potentially distort treatment effects reported in therapeutic trials. The aims of this study were to estimate the proportion of stroke patients who take part in clinical research studies and to compare demographic and clinical profiles of research participants and non-participants., Methods: 5,235 consecutive patients admitted to the Stroke Care Unit of the Royal Melbourne Hospital, Melbourne, Australia, for stroke or transient ischaemic attack between January 2004 and December 2011 were studied. The study used cross-sectional design. Information was collected on patients' demographic and socio-economic characteristics, risk factors, and comorbidities. Associations between research participation and patient characteristics were initially assessed using χ(2) or Mann-Whitney tests, followed by a multivariable logistic regression analysis. The logistic regression analysis was carried out using generalised estimating equations approach, to account for patient readmissions during the study period., Results: 558 Stroke Care Unit patients (10.7%) took part in at least one of the 33 clinical research studies during the study period. Transfer from another hospital (OR = 0.35, 95% CI 0.22-0.55), worse premorbid function (OR = 0.61, 95% CI 0.54-0.70), being single (OR = 0.61, 95% CI 0.44-0.84) or widowed (OR = 0.77, 95% CI 0.60-0.99), non-English language (OR = 0.67, 95% CI 0.53-0.85), high socio-economic status (OR = 0.74, 95% CI 0.59-0.93), residence outside Melbourne (OR = 0.75, 95% CI 0.60-0.95), weekend admission (OR = 0.78, 95% CI 0.64-0.94), and a history of atrial fibrillation (OR = 0.79, 95% CI 0.63-0.99) were associated with lower odds of research participation. A history of hypertension (OR = 1.50, 95% CI 1.08-2.07) and current smoking (OR = 1.23, 95% CI 1.01-1.50) on the other hand were associated with higher odds of research participation., Conclusions: The results of this study indicate that stroke patients who take part in clinical research do not represent 'typical' patient admitted to a stroke unit. The imbalance of prognostic factors between stroke participants and non-participants has serious implications for interpretation of research findings reported in stroke literature. This study provides insights into clinical, demographic, and socio-economic characteristics of stroke patients that could potentially be targeted to enhance generalizability of stroke research studies. Given the imbalance of prognostic factors between research participants and non-participants, future studies need to examine differences in stroke outcomes of these groups of patients., (Copyright © 2013 S. Karger AG, Basel.)

For paediatric medicine to advance, research must be conducted specifically with children. Concern about poor recruitment has led to debate about payments to child research participants. Although concerns about undue influence by such 'compensation' have been expressed, it is useful to determine whether children can relate the time and inconvenience associated with participation to the value of payment offered. This study explores children's ability to determine fair remuneration for research participation, and reviews payments to children participating in research. Forty children were interviewed before outpatient visits at two London Hospitals: Great Ormond Street Children's Hospital and the Whittington Hospital District General Hospital. Children were asked to value their involvement in two hypothetical research scenarios - the first an 'additional blood sample', the second also involving daily oral oil capsules taken for a fortnight before further venesection. Background knowledge about familiarity with money, and experience with hospitalisation was assessed. The mean valuation of involvement in the second scenario (£13.18) was higher than in the first (£2.84) (p<0.001). This higher valuation persisted when children were categorised into groups 'aged 12+' and 'below 12'. Those undergoing a blood test on the day placed a higher valuation on participation in the second scenario (£10.43, £21.67, p=0.044). These children aged 8-16 demonstrated the capacity to discern a fair valuation for participation in medical research. The monetary sums are influenced by the time and inconvenience involved in the research, and by the extent of recent experience with hospital procedures. The authors review current ethical thinking regarding payments to child research participants and suggest that a fair wage model might be an ethically acceptable way to increase participation of children in research.

Slow or insufficient enrollment in clinical research and a high demand for research participants raises questions about the need for and use of incentives to participate, including payment. Much of the available literature on payment to research participants focuses on ethical concerns, and rarely addresses guidelines, benchmarks, or formulas to assist investigators to assign or evaluate appropriate payment for individuals who take part in clinical research trials and procedures. Using four years of data collected about the inconvenience units assigned by intramural investigators to selected clinical research procedures conducted at the National Institutes of Health (NIH) Clinical Center, this study provides payment benchmarks for commonly performed procedures. Results were obtained from data collected on 36,273 incidents of payment made for procedures to research participants from August 2004 to August 2008. Analysis of the inconvenience units value assigned to specific procedures suggests that despite a wide distribution and frequent outliers, a convergence in practice around the center of distribution for most procedures does exist. As one of the first published studies reporting data reflecting payment amount for specific clinical research procedures, these data can guide investigators and institutional review boards as they establish and review an appropriate amount of payment to offer research participants. Our data may be useful in promoting payment standards for procedures, thereby complementing proposals or guidelines that advise payment calculations according to time and procedures., (Published by Elsevier Inc.)

Unlabelled: Increasingly, US-sponsored research is carried out in developing countries, but how US Institutional Review Boards (IRBs) approach the challenges they then face is unclear., Methods: I conducted in-depth interviews of about 2 hours each, with 46 IRB chairs, directors, administrators and members. I contacted the leadership of 60 IRBs in the United States (US) (every fourth one in the list of the top 240 institutions by National Institutes of Health (NIH) funding), and interviewed IRB leaders from 34 (55%)., Results: US IRBs face ethical and logistical challenges in interpreting and applying principles and regulations in developing countries, given economic and health disparities, and limited contextual knowledge. These IRBs perceive wide variations in developing world IRBs/RECs' quality, resources and training; and health systems in some countries may have long-standing practices of corruption. These US IRBs often know little of local contexts, regulations and standards of care, and struggle with understandings of other cultures' differing views of autonomy, and risks and benefits of daily life. US IRBs thus face difficult decisions, including how to interpret principles, how much to pay subjects and how much sustainability to require from researchers. IRB responses and solutions include trying to maintain higher standards for developing world research, obtain cultural expertise, build IRB infrastructure abroad, communicate with foreign IRBs, and 'negotiate' for maximum benefits for participants and fearing 'worst-case scenarios'., Conclusions: US and foreign IRBs confront a series of tensions and dilemmas in reviewing developing world research. These data have important implications for increased education of IRBs/RECs and researchers in the US and abroad, and for research and practice., (© 2012 Blackwell Publishing Ltd.)

Background: There is general consensus internationally that unfair distribution of the benefits of research is exploitative and should be avoided or reduced. However, what constitutes fair benefits, and the exact nature of the benefits and their mode of provision can be strongly contested. Empirical studies have the potential to contribute viewpoints and experiences to debates and guidelines, but few have been conducted. We conducted a study to support the development of guidelines on benefits and payments for studies conducted by the KEMRI-Wellcome Trust programme in Kilifi, Kenya., Methods: Following an initial broad based survey of cash, health services and other items being offered during research by all programme studies (n = 38 studies), interviews were held with research managers (n = 9), and with research staff involved in 8 purposively selected case studies (n = 30 interviewees). Interviews explored how these 'benefits' were selected and communicated, experiences with their administration, and recommendations for future guidelines. Data fed into a consultative workshop attended by 48 research staff and health managers, which was facilitated by an external ethicist., Findings: The most commonly provided benefits were medical care (for example free care, and strengthened quality of care), and lunch or snacks. Most cash given to participants was reimbursement of transport costs (for example to meet appointments or facilitate use of services when unexpectedly sick), but these payments were often described by research participants as benefits. Challenges included: tensions within households and communities resulting from lack of clarity and agreement on who is eligible for benefits; suspicion regarding motivation for their provision; and confusion caused by differences between studies in types and levels of benefits., Conclusions: Research staff differed in their views on how benefits should be approached. Echoing elements of international benefit sharing and ancillary care debates, some research staff saw research as based on goodwill and partnership, and aimed to avoid costs to participants and a commercial relationship; while others sought to maximise participant benefits given the relative wealth of the institution and the multiple community needs. An emerging middle position was to strengthen collateral or indirect medical benefits to communities through collaborations with the Ministry of Health to support sustainability.

Background: A safe and efficacious vaccine may be the most efficient and cost-effective strategy for controlling the hepatitis C virus (HCV) epidemic among people who inject drugs (PWID) and several candidates are in development. However, little is known about the factors that influence willingness to participate (WTP) in candidate HCV vaccine trials among this group., Methods: HCV seronegative PWID recruited between 2008 and 2010 as part of a prospective observational cohort study in Sydney, Australia were asked whether they would be willing to participate in a future candidate hepatitis C vaccine trial and to provide reasons to explain their decision., Results: Of 113 participants, 74% indicated WTP, 15% were unwilling to participate and 11% reported WTP that was contingent on vaccine characteristics and trial design issues. The most commonly reported motivator for hypothetical trial participation was altruism, followed by potential health benefits, financial remuneration, and knowledge gain. Barriers to hypothetical participation included fears about possible harms to health, such as concerns about vaccine safety, side effects, and acquiring HCV from the vaccine; other barriers included mistrust of biomedical research and time constraints., Conclusions: These results may be useful in designing strategies to enhance HCV vaccine trial recruitment and retention and have ethical implications for developing informed consent processes and standards of care., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Attrition in studies of substance use disorder treatment is problematic, potentially introducing bias into data analysis., Objectives: This study aimed to determine the effect of participant compensation amounts on rates of missing data and observed rates of drug use., Methods: We performed a secondary analysis of a clinical trial of buprenorphine/naloxone among 152 treatment-seeking opioid-dependent subjects aged 15-21 during participation in a randomized trial. Subjects were randomized to a 2-week detoxification with buprenorphine/naloxone (DETOX; N = 78) or 12 weeks buprenorphine/naloxone (BUP; N = 74). Participants were compensated $5 for weekly urine drug screens and self-reported drug use information and $75 for more extensive assessments at weeks 4, 8, and 12., Results: Though BUP assignment decreased the likelihood of missing data, there were significantly less missing data at 4, 8, and 12 weeks than other weeks, and the effect of compensation on the probability of urine screens being positive was more pronounced in DETOX subjects., Conclusion: These findings suggest that variations in the amount of compensation for completing assessments can differentially affect outcome measurements, depending on treatment group assignment., Scientific Significance: Adequate financial compensation may minimize bias when treatment condition is associated with differential dropout and may be a cost-effective way to reduce attrition. Moreover, active users may be more likely than non-active users to drop out if compensation is inadequate, especially in control groups or in groups who are not receiving active treatment.

Context: Federal regulations mandate independent review and approval by an "institutional review board" (IRB) before studies that involve human research subjects may begin. Although many researchers strongly support the need for IRB review, they also contend that it is burdensome when it imposes costs that do not add to the protections afforded to research participants and that this burden threatens the viability of research. The U.S. Department of Health and Human Services recently announced its intention to reform the regulations governing IRB review., Methods: We used a search of the PubMed database, supplemented by a bibliographic review, to identify all existing primary data on the costs of IRB review. "Costs" were broadly defined to include both expenditures of time or money and constraints imposed on the scope of the research. Burdensome costs were limited to those that did not contribute to greater protections for the participants., Findings: Evidence from a total of fifty-two studies shows that IRBs operate at different levels of efficiency; that waiting to obtain IRB approval has, in some instances, delayed project initiation; that IRBs presented with identical protocols sometimes asked for different and even competing revisions; and that some decisions made (and positions held) by IRBs are not in accord with federal policy guidance., Conclusions: While the evidence is sufficient to conclude that there is burden associated with IRB review, it is too limited to allow for valid estimates of its magnitude or to serve as the basis for formulating policies on IRB reform. The single exception is multicenter research, for which we found that review by several local IRBs is likely to be burdensome. No mechanism currently exists at the national level to gather systematic evidence on the intersection between research and IRB review. This gap is of concern in light of the changing nature of research and the increasingly important role that research is envisioned to play in improving the overall quality of health care., (© 2011 Milbank Memorial Fund.)

Health researchers working in low-resource settings often encounter serious unmet health needs among participants. What is the nature and extent of researchers' obligations to respond to such needs? Competing accounts have been proposed, but there is no independent standard by which to assess them or to guide future inquiry. I propose an independent standard and demonstrate its use. In conclusion I recommend two areas of focus for future inquiry: what makes an account of researchers' obligations reasonable from the standpoint of both participants and researchers and how general duties of rescue apply to researchers' resource-allocation decision making in low-resource settings.

Both international and federal regulations exist to ensure that scientists perform research on human subjects in an environment free of coercion and in which the benefits of the research are commensurate with the risks involved. Ensuring that these conditions hold is difficult, and perhaps even more so when protocols include the issue of monetary compensation of research subjects. The morality of paying human research subjects has been hotly debated for over 40 years, and the grounds for this debate have ranged from discussion of legal rights, economic rights, philosophical principles of vulnerability and altruism to bioethical concepts of consent, best-interest determination, and justice theory. However, the thought surrounding these issues has evolved over time, and the way we think about the role of the human research subject today is markedly different than the way we thought in the past. Society first thought of the research subject as an altruist, necessarily giving of his time to benefit society as a whole. As time progressed, many suggested that the subject should not need to sacrifice himself for research: if something goes wrong, someone should compensate the subject for injuries. The concept of redress evolved into a system in which subjects were offered money as an inducement to participate in research, sometimes merely to offset the monetary costs of participation, but sometimes even to mitigate the risks of the study. This article examines ethical and legal conversations regarding compensation from the 1960s through today, examining theories of the ethics of compensation both comparatively and critically. In conclusion, we put forward an ethical framework for treating paid research subjects, with an attempt to use this framework as a means of resolving some of the more difficult problems with paying human subjects in research., (© 2011 American Society of Law, Medicine & Ethics, Inc.)

Offering cash payments to research subjects is a common recruiting method, but this practice continues to be controversial because of its potential to compromise the protection of human subjects. Federal regulations and guidelines currently allow researchers to pay subjects for participation, but they say very little about how much researchers can pay their subjects. This paper argues that the federal regulations and guidelines should implement a standard payment formula. It argues for a wage payment model, and critically examines three candidates for a base wage: the nonfarm production wage, the FLSA minimum wage, and a living wage. After showing that the nonfarm production wage is too high to satisfy ethical criteria, and the minimum wage is too low, this paper concludes that the wage payment model with a base wage equivalent to a living wage is the best candidate for a standard payment formula in human subjects research., (© 2011 American Society of Law, Medicine & Ethics, Inc.)

Offering cash payments to research subjects is a common recruiting method but there is significant debate about whether and in what amount such payments are appropriate. This paper is concerned with exploitation and whether there should be a lower limit on the amount researchers can pay their subjects. When subjects participate in research as a way to make money, fairness requires that researchers pay them a fair wage. This call for the establishment of a lower limit meets resistance in two places: (1) denial that the payments offered by researchers are wages for participation; and (2) concern about undue inducement. This paper critically examines these arguments for and against a lower limit. It shows that the need for a lower limit cannot be avoided by adopting a non-wage payment model and that concerns about undue inducement are unjustified in all trials except those that present greater than minimal risk. This analysis suggests the following compromise position: there should be an unconditional lower limit on payment amounts so that researchers cannot offer less than a fair wage, and when researchers cannot satisfy this limit because fairness requires a problematically large payment, then researchers should offer no payment at all., (© 2009 Blackwell Publishing Ltd.)

There is concern that research reimbursements to adolescents may increase substance use. However, these concerns have not been examined empirically. Participants were 70 adolescents (13-19 years) with at least one non-nicotine substance use disorder (SUD) enrolled in a 12-week clinical trial of atomoxetine/placebo for attention/deficit-hyperactivity disorder (ADHD). Adolescent participants received cash reimbursement after each study visit (maximum possible = $425 over 12 weeks). Participants reported each week how they spent the previous reimbursement. Results were tallied, and correlates of spending a payment on substances were examined. Results showed that 26 of 70 subjects reported spending at least one research payment on alcohol or drugs, and 25 of 70 subjects reported spending at least one payment on tobacco. Comparing those who did and did not spend a research payment on alcohol/drugs, those who did had more frequent baseline alcohol/drug use but did not differ in demographics (age, gender) or other clinical characteristics (ADHD severity, diagnosis of conduct disorder, number of SUD diagnoses, number of treatment sessions attended, or pre/post-change in number of days used substances in the past 28 days). Comparing those who did and did not spend a payment on tobacco, those who did were slightly older and had more frequent baseline tobacco use. In conclusion, a significant proportion of subjects used at least a portion of one research payment to buy alcohol, drugs or tobacco. However, there was little indication that research payments increased substance use., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The principle that payment to participants should not be undue or coercive is the consensus of international and national guidelines and ethical debates; however, what this means in practice is unclear. This study determined the attitudes and practices of IRB chairpersons and investigators regarding participant payment. One thousand six hundred investigators and 1900 IRB chairpersons received an invitation to participate in a web-based survey. Four hundred and fifty-five investigators (28.3%) and 395 IRB chairpersons (18.6%) responded. The survey was designed to gather considerations that govern payment determination and practical application of these considerations in hypothetical case studies. The survey asked best answer, multiple choice, and open text questions. Short hypothetical case scenarios where presented, and participants were asked to rate factors in the study that might impact payment and then determine their recommended payment. A predictive model was developed for each case to determine factors which affected payment. Although compensation was the primary reason given to justify payment by both investigators and IRB chairpersons, the cases suggested that, in practice, payment is often guided by incentive, as shown by the impact of anticipated difficulty recruiting, inconvenience, and risk in determining payment. Payment models varied by type of study. Ranges for recommended payments by both groups for different types of procedures and studies are presented.

Although compensation for expenses to participants in research projects is considered important and the primary reason for paying, there is no evidence to support that investigators and IRB members actually calculate participant cost. Payment recommendations for six hypothetical studies were obtained from a national survey of IRB chairpersons (N = 353) and investigators (N = 495). Survey respondents also recommended payment for specific study procedures. We calculated participant cost for the six hypothetical cases both by procedures and by time involvement. A large percentage recommended only token payments for survey, registry, and medical record review studies. Most chose payment for pharmaceutical studies but the recommended payment did not compensate for calculated costs. Results suggest that compensation and reimbursement as the primary reasons for paying research participants may not match actual practice.

The acceleration of the market globalisation process over the last three decades has internationalised clinical research and influenced both the way in which it is funded and the development and application of research practices. In addition, in recent years international multicentre randomised clinical trials have become the model par excellence for research on new medicines. The neoliberal model of globalisation has induced a decline in state power, both with regard to establishing national research for health priorities and to influencing the development of adequate ethical guidelines to protect human beings that participate in multinational research. In this respect, poor and low-income countries, which lack sustainable control and review systems to deal with the ethical and methodological challenges of complex studies conducted by researchers from affluent countries and funded by large multinational pharmaceutical companies, are particularly vulnerable. The aim of the present paper is to explore critically some of the actual and possible ethical pitfalls of globalisation of clinical research and propose mechanisms for turning transnational clinical research into a more cooperative and fairer enterprise.

The main goal of early phase trials is to gain knowledge about the clinical suitability of novel compounds, without pursuing specific therapeutic purposes. Healthy volunteers usually represent the ideal model for conducting phase I clinical trials, in order to investigate pharmacokinetics and pharmacodynamics as well as to document safety and tolerability without interference by concomitant pathological conditions. The increasing cost of novel drug development, in conjunction with ethical considerations, has fostered a new procedure for first-in-man trials, designated as "phase 0," which is conducted very early on a limited number of healthy volunteers who are exposed to low drug levels. The present review discusses issues concerning the enrollment of healthy volunteers in the early phase of drug development from different points of view, with some focus on the Italian experience. From the ethical standpoint, much discussion revolves around payments to healthy volunteers. Most authors agree that an adequate remuneration must be provided to healthy subjects, while avoiding coercion and excessive psychological pressure. Pending the lack of international and national guidelines, our center for clinical drug experimentation has implemented an operative procedure to estimate payments for healthy volunteers based on specific items, including restriction, time spent, discomfort, and risk. Other unresolved issues about the recruitment of healthy volunteers are represented by the lack of international consensus on the definition of healthy status and the need for guidelines about advertisement on clinical trials addressed to potential participants.

ABSTRACT Can it be wrong to conduct medical research on human subjects even with their informed consent and even when the transaction between the subjects and researchers is expected to be mutually beneficial? This question is especially pressing today in light of the rise of a semi-professional class of 'guinea pigs'- human research subjects that sell researchers a right of access to their bodies in exchange for money. Can these exchanges be morally problematic even when they are consensual and mutually beneficial? I argue that there are two general kinds of concern one can have about such transactions - concerns about the nature of what is sold and concerns about the conditions in which the selling occurs. The former involves worries about degradation and the possible wrongness of selling a right of access to one's body. These worries, I argue, are not very serious. The latter involves worries about coercion, exploitation, and undue influence - about how, by virtue of their ignorance, impulsiveness, or desperation, guinea pigs can be taken advantage of by medical researchers. These worries are quite serious but I argue that, at least in cases where the exchange between guinea pigs and researchers is consensual and mutually beneficial, they do not raise insurmountable moral problems.

Here I inquire into the status of the rules promulgated in the canonical pronouncements on human subjects research, such as the Declaration of Helsinki and the Belmont Report. The question is whether they are ethical rules or rules of policy. An ethical rule is supposed to accurately reflect the ethical fact (the fact that the action the rule prescribes is ethically obligatory), whereas rules of policy are implemented to achieve a goal. We should be skeptical, I argue, that the actions prescribed by the rules are ethically obligatory, and consequently we should focus our attention on how to craft the rules so as to promote the legitimate goals of human subjects research. Unfortunately, this cannot be done without evidence about the likely effects of various candidate policies-evidence we currently lack. Therefore, we should take the rules as mere starting points, subject to revision as the evidence comes in.

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open-ended, in-depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research stakeholders, the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment. While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical-legal framework and research policies, and, for further research.

Background: Research involving minors has been the subject of much ethical debate. The growing number of longitudinal, pediatric studies that involve genetic research present even more complex challenges to ensure appropriate protection of children and families as research participants. Long-term studies with a genetic component involve collection, retention and use of biological samples and personal information over many years. Cohort studies may be established to study specific conditions (e.g. autism, asthma) or may have a broad aim to research a range of factors that influence the health and development of children. Studies are increasingly intended to serve as research platforms by providing access to data and biological samples to researchers over many years.This study examines how six birth cohort studies in North America and Europe that involve genetic research handle key ethical, legal and social (ELS) issues: recruitment, especially parental authority to include a child in research; initial parental consent and subsequent assent and/or consent from the maturing child; withdrawal; confidentiality and sample/data protection; handling sensitive information; and disclosure of results., Methods: Semi-structured telephone interviews were carried out in 2008/09 with investigators involved in six birth cohort studies in Canada, Denmark, England, France, the Netherlands and the United States. Interviewees self-identified as being knowledgeable about ELS aspects of the study. Interviews were conducted in English., Results: The studies vary in breadth of initial consent, but none adopt a blanket consent for future use of samples/data. Ethics review of new studies is a common requirement. Studies that follow children past early childhood recognise a need to seek assent/consent as the child matures. All studies limit access to identifiable data and advise participants of the right to withdraw. The clearest differences among studies concern handling of sensitive information and return of results. In all studies, signs of child abuse require reports to authorities, but this disclosure duty is not always stated in consent materials. Studies vary in whether they will return to participants results of routine tests/measures, but none inform participants about findings with unknown clinical significance., Conclusions: Analysis of how cohort studies in various jurisdictions handle key ELS issues provides informative data for comparison and contrast. Consideration of these and other examples and further scholarly exploration of ELS issues provides insight on how best to address these aspects in ways that respect the well-being of participants, especially children who become research subjects at the start of their lives.