Abstract
Patients participate in clinical trials for a variety of reasons, the first of which is often the prospect of direct health benefits for themselves. Healthy volunteers, by definition, cannot expect such benefits. In resource-limited settings, healthy volunteers are most often poor people with low literacy levels who might not understand the risks they may be taking and are in no position to refuse financial incentives . For many of them, participation in clinical trials is a critical source of income. An added complication is that some participants covertly enrol in several studies simultaneously, in order to increase their income. This exposes the volunteers to medical risks (e.g. drug-drug interactions), and also potentially biases study data . Our recommendations are that specific efforts are made to ensure proper informed consent of this vulnerable population and that compulsory national databases be established to ensure that healthy volunteers do not participate simultaneously in several studies.
You have full access to this open access chapter, Download chapter PDF
Similar content being viewed by others
Keywords
Area of Risk of Exploitation
In high-income countries, healthy volunteers are sometimes university students with a good literacy level and reasonable living standards. In resource-limited settings however (including in high income countries) , healthy volunteers are most often poor people with low literacy levels who may not understand the risks and are in no position to refuse financial incentives . For many of them, participation in clinical trials is a critical source of income. As a result, even though they might sign informed consent documentation, they are a highly vulnerable group that deserves the “specifically considered protection” recommended by the World Medical Association’s Declaration of Helsinki :
Some groups and individuals are particularly vulnerable and may have an increased likelihood of being wronged or of incurring additional harm .
All vulnerable groups and individuals should receive specifically considered protection (WMA 2013: art. 19).
The Problem
Informal discussions and a literature review conducted by the authors of this case study have revealed little professional interest in or attention to ethical considerations regarding healthy volunteers from low-income settings. There is very little data published on the number of clinical studies using such volunteers, making it difficult to assess the scope of the issue. While most first-in-human (phase I) clinical trials seem to be performed in high-income countries to ensure the quality of these critical studies, a very large number of studies in healthy volunteers are performed in low- and middle-income countries (LMICs) (Ravinetto 2015:3), particularly bioavailability and bioequivalence studies needed to compare originator and generic medicines.
Clinical studies using healthy volunteers are performed by international as well as local companies, often through contract research organizations (CROs) . One of the few papers available on healthy volunteers in LMICs shows how CROs in India resort to “middlemen” to recruit poor participants, who have no understanding of what the studies are about and who sometimes participate in studies without informing their families. They basically “chose to participate in the trials due to insufficient income and unstable jobs” (Krishna and Prasad 2014).
Resource-poor settings are not limited to the LMICs. A few papers describe the situation of healthy volunteers in the US who have become “professional volunteers” and for whom study participation is a way to earn a living (Edelblute and Fisher 2015; Eliott and Abadie 2008). One can assume that many of the ethical issues related to US “professional volunteers” are highly relevant to their counterparts in LMICs. Many have developed tactics to conceal their involvement in several studies at the same time and have become experts at manipulating screening tests for enrolment in clinical trials, for instance by concealing their participation in concomitant studies, medical conditions, concomitant medications or substance abuse (Edelblute and Fisher 2015; Devine et al. 2013). These concealments expose the volunteers to medical risks (e.g. drug-drug interactions) and also potentially bias study data , for instance in terms of safety or pharmacokinetic profiles of the tested drugs (Eliott and Abadie 2008).
The Way Forward
We believe that specific efforts should be expanded to ensure that healthy volunteers are able to understand the key features of the studies (Phase I, II and III) they are offered to participate in, and are therefore able to provide genuine informed consent . This could be done by ensuring that documents are specifically designed for a population with low scientific literacy levels. Establishing compulsory national databases for healthy volunteers appears to be the best way to avoid some of the risks related with participation in multiple studies, detailed above (Devine et al. 2013; Resnik and McCann 2015). Some countries (e.g. France and Morocco) have set up or are in the process of setting up national healthy volunteers’ databases to ensure that a given individual’s involvement in clinical trials is recorded, that sufficient “wash-out periods” between trials are respected and that payments made to volunteers are tracked so as not to exceed certain levels.
Setting up national databases will require changes in countries’ legislation that can only result from the mobilization of key stakeholders, including pharmaceutical companies . In addition to logistical issues that will have to be solved for such systems to be effective, ethical concerns related to confidentiality and data protection issues will have to be addressed. The EU-based pharma industry should support initiatives to ensure that this neglected, highly vulnerable population benefits from the best possible safeguards.
References
Devine EG, Waters ME, Putnam M, Surprise C, O’Malley K, Richambault C, Fishman RL, Knapp CM, Patterson EH, Sarid-Segal O, Streeter C, Colanari L, Ciraulo DA (2013) Concealment and fabrication by experienced research subjects. Clinical Trials 10(6):935–948
Edelblute HB, Fisher JA (2015) The recruitment of normal healthy volunteers: a review of the literature on the use of financial incentives. Journal of Empirical Research on Human Research Ethics 10(1):65–75
Eliott C, Abadie R (2008) Exploiting a research underclass in phase 1 clinical trials. New England Journal of Medicine 358(22):2316–2317
Krishna S, Prasad NP (2014) Ethical issues in recruitment of “healthy volunteers”: study of a clinical research organisation in Hyderabad. Indian Journal of Medical Ethics 11(4):228–232
Ravinetto R (2015) Methodological and ethical challenges in non-commercial North-South collaborative clinical trials. Acta Biomedica Lovaniensia 692. KU Leuven, Antwerp
Resnik DB, McCann DJ (2015) Deception by research participants. New England Journal of Medicine 373(13):1192–1193
WMA (2013) WMA Declaration of Helsinki: Ethical principles for medical research involving human subjects. World Medical Association. http://jamanetwork.com/journals/jama/fullarticle/1760318
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Open Access This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.
The images or other third party material in this chapter are included in the chapter’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Copyright information
© 2018 The Author(s)
About this chapter
Cite this chapter
Leisinger, K.M., Schmitt, K.M., Bompart, F. (2018). Healthy Volunteers in Clinical Studies. In: Schroeder, D., Cook, J., Hirsch, F., Fenet, S., Muthuswamy, V. (eds) Ethics Dumping. SpringerBriefs in Research and Innovation Governance. Springer, Cham. https://doi.org/10.1007/978-3-319-64731-9_8
Download citation
DOI: https://doi.org/10.1007/978-3-319-64731-9_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-64730-2
Online ISBN: 978-3-319-64731-9
eBook Packages: Religion and PhilosophyPhilosophy and Religion (R0)