On-line version ISSN 2078-5135
SAMJ, S. Afr. med. j. vol.98 n.2 Cape Town Feb. 2008
L J BurgessI; N SulzerII; S EmanuelIII
IMB BCh, MMed (ChemPath), PhD (ChemPath), Postgrad Diploma in International Research Ethics; TREAD Research/Cardiology Unit, Department of Internal Medicine, Tygerberg Hospital and Stellenbosch University, Parow, W Cape
IIBSc Med Hons, MSc Med; TREAD Research/Cardiology Unit, Department of Internal Medicine, Tygerberg Hospital and Stellenbosch University, Parow, W Cape
IIIMB ChB; TREAD Research/Cardiology Unit, Department of Internal Medicine, Tygerberg Hospital and Stellenbosch University, Parow, W Cape
To the Editor: The remuneration of patients in clinical trials is controversial because money may influence their decision to participate. When the amount becomes irresistible, it represents undue inducement and may persuade patients to participate in a clinical trial or resist discontinuation against their better judgement, which can potentially compromise the informed consent process and the scientific validity of the trial.1 This is particularly relevant in South Africa, where the potential to exploit vulnerable communities readily exists.2
The task of creating guidelines to assist the clinical trial industry in deciding what remuneration, if any, trial patients should receive is fraught with complexities. Regulatory authorities provide general recommendations cautioning against undue inducement, but no guidance on when money is not due, or how much money constitutes undue inducement.1 The Council for International Organisations of Medical Sciences (CIOMS) gives the most comprehensive guideline, stating that ' ... subjects may be paid for inconvenience and time spent and should be reimbursed for expenses incurred, in connection with their participation in research'.1,3 South Africa's Medicines Control Council (MCC) stipulates that all Phase II - IV clinical trial participants receive R150 per study visit - which has been much criticised by the local research community.
Our study aimed to (i) document the opinions of trial participants regarding remuneration in clinical trials, and (ii) clarify the amount of money that would represent an undue inducement to a South African clinical trial patient.
The study was conducted by TREAD Research, a clinical trial unit located within Tygerberg Hospital, Parow. Patients attending the unit between January 2005 and May 2006 were approached to participate. The study was approved by Stellenbosch University's Ethics Committee. Consenting patients completed an anonymous validated questionnaire in their home language. Patients were assigned a random consecutive number, and no identifying data were recorded on the questionnaire. Patients were asked to provide basic demographic data, level of completed school education, current occupation, monthly earnings, health care system used (state or private) and method of transport to the study visits. Patients were also asked questions regarding their remuneration and for what purpose they used it. Data were entered into a spreadsheet programme by an independent data capturer. All data were analysed by means of Statistica Software Version 7.0 (© StatSoft, Inc., USA).
A total of 250 patients completed the questionnaire. The mean (±SD) age of subjects was 56.3 ±10.9 years. The majority of the respondents were Afrikaans (71.7%). There were 118 male subjects (47.0%) and 132 female subjects (52.6%). Unemployed respondents comprised 66.5%, with only 31.5% registering a paying job. The median (lower; upper quartile) monthly family income was R1 800 (R740; R5 200). Of the respondents, 34.0% had completed grade 12 (Matric), 40.6% received after school training, and 12.4% had a university education. Sixty-four per cent were solely dependent on the public heath care system, 15.1% had private health care, and 18.7% made use of both public and private heath care. Modes of transport to the clinic were private car (60.7%), taxi (25.6%), train (7.2%) and bus (6.5%).
Seventy-four per cent of trial participants felt that they should receive payment for their clinic visits, yet 93.6% indicated that they would still participate in a clinical trial if they received no payment. Ninety-four per cent indicated that they would not hide details regarding their medical history in order to participate in a trial. The amount of R150 would not tempt 90.0% of participants to withhold information about their true state of health in order to participate in a study. Ninety-one per cent indicated that payment was not used by the investigator as encouragement to participate in a clinical trial.
Regarding why they felt they should be paid for participating in a clinical trial, 72.9% responded that payment should be made to cover travel expenses, 13.9% that it was an incentive to participate, and 13.1% that it covered time spent (Fig. 1). Regarding their use of the remuneration, 88.8% of subjects reported using it for travel expenses, 7.2% for nothing specific, and 6.4% for necessities (Fig. 2).
Of this study population, 64.1% depended solely on the state health care system. Only 34.0% had completed grade 12, and 66.5% were unemployed. Despite these facts, most respondents (93.6%) indicated that they would still participate in a clinical trial if they received no payment.
The most common reasons for our patients participating in clinical trials included contributing to scientific understanding, learning about their condition, achieving a sense of belonging, and having access to services that they would otherwise be unable to afford (Burgess et al., unpublished data). In addition, 80% of respondents did not think clinical trial participation was an easy way to obtain money.
Our study revealed that trial participants believed that they should receive remuneration to compensate for travel expenses and time spent (Fig. 1). The majority of respondents used the remuneration to cover transport costs (Fig. 2). This echoes the CIOMS guidelines.3
Blanket compensation, such as that mandated by the MCC, is contentious in light of these findings as it does not consider the complexities of the clinical trial setting. These include the phase and design of the study, disease under study, study subject and the fact that money means different things to different people. A phase I study, where healthy volunteers often undergo repeated phlebotomy and exposure to highly experimental treatments, cannot be compared with a phase IV post-marketing study. A patient suffering from a life-threatening condition may make health decisions based on different criteria to the otherwise well patient with mild seasonal asthma. In making decisions on matters of health, wealthy employed participants with medical insurance are unlikely to use the same criteria as poorly educated, unemployed participants, who are reliant on state health care. Finally, although many may agree that money represents an inducement, it is not clear what amount of money constitutes undue inducement.1
How the MCC reached their decision that trial participants receive R150 per study visit is unclear. However, it is necesssary to contextualise this amount of money to understand what it means to a trial participant in this country. The average study visit takes approximately 2 hours, which effectively means that clinical trial patients receive R75 per hour for their participation. However, the average South African salary is currently R51 per hour.4 The median (first, third quartile) hourly income of these study participants was R10.23 (R4.10, R29.54).
These figures highlight the potential for undue inducement. Most guidelines simply caution against 'undue inducement' but do not describe when or how much money constitutes undue inducement. The Belmont Report states that '... undue influence occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance'.5 The majority of respondents in the present study indicated that they would not hide details regarding their medical history to qualify for a trial, and that the amount of R150 would not tempt them to withhold information about their true state of health. Furthermore, according to these respondents, investigators did not use payment to encourage trial participation.
These results therefore suggest that R150 does not constitute an undue inducement as it does not compromise participants' integrity or freedom of choice and ability to give voluntary consent. However, in the South African context of an average hourly salary of R51, the amount of R150 may be considered an '. excessive and unwarranted reward', as cautioned against.5 We also found that the majority of trial participants were of the opinion that remuneration should be provided for travel expenses and time spent at the study visit. This contradicts the concept of a blanket compensation rate for trial participation and also questions for what purpose patients in this country are remunerated.
Generalisations regarding trial reimbursement for clinical trial participation are clearly impossible. This study indicates that remuneration should be calculated individually for travel expenses and time. Instead of stipulating their generalised and ostensibly unjustifiable remuneration fee, the regulatory authority could offer a written policy guideline advocating the purpose and intention of clinical trial remuneration. Clinical trialists could then customise this policy on an individualised, per patient basis. The challenge remains to find a remuneration figure which is not excessive and thereby does not constitute undue inducement, while at the same time protecting against exploitation of vulnerable communities who are involved in clinical research in this country.
1. Moodley K, Myer L. Participant remuneration for research - how much is enough? S Afr Med J 2003; 93(9): 677-678. [ Links ]
2. Guidelines on Ethics for Medical Research: General principles. 4th ed. Cape Town: Medical Research Council of South Africa, 2002. [ Links ]
3. International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva: Council for International Organizations of Medical Sciences, 1993. [ Links ]
4. Tommey D. Earning under R10 000 makes you average. Johannesburg: IOL, 11 April 2007. http://www.iol.co.za/index.php?set_id=1&click_id=594&art_id=vn20070411114033187C499458 (accessed 30 July 2007). [ Links ]
5. The Belmont Report. Bethesda, Maryland, USA: The National Commission for the Protection of Human Subjects of Research, 1979. [ Links ]
L J Burgess