In defence of participants buying their way onto drug trials

By Angela Ballantyne and Mike King

Donor-funded research is research funded by private donors in exchange for research-related benefits, such as trial participation or access to the trial intervention. An example of this is the oncolytic virus trial for neuroendocrine cancer at Uppsala University, for which Alexander Masters procured £2 million in funding from a private donor. The donor, who died before the trial began, has had the oncolytic virus named after him.

Clinical research is a public good, which provides the evidence base for clinical interventions. Populations who are excluded from research are disadvantaged by the lack of evidence to inform their care. This can include being undertreated, missing out on innovative therapies, and struggling to advocate for public funding for ‘unproven’ treatment. These issues raise empirical questions about how clinical research is resourced, and ethical questions about how funding resources are distributed.

In the paper we consider three different research funding models where the trial is financed by private donors.

  1. The first model is the plutocratic proposal. This is based on Masters and Nutt’s 2017 Journal of Medical Ethics paper (and earlier article by Masters) describing a model where a donor funds phase I or phase IIa clinical trial of a promising intervention and in exchange receives access (for themselves or a nominee) to the experimental intervention. Masters and Nutt propose that the donors’ interaction with the researchers would be facilitated and mediated by a matching agency to reduce the risk of coercion and/or undue influence.
  2. The second model is a variation on the plutocratic proposal and we call this play to try. Here a private donor funds a trial and in return they (or their nominee) receive access to the experimental intervention through a compassionate use exemption. The funder is not enrolled as a trial participant and the relationship between funder and the researchers is direct.
  3. The third variation we call pay to play and has been previously discussed in the bioethics literature. This model involves research participants paying a fee for enrolment in the trial. For example, research conducted in private allied health facilities is often restricted to those who can pay to purchase the clinical services (e.g., sleep clinics, physiotherapy, weight management). Some new stem cell trials are restricted to patients who can pay.

Prima facie, these models are attractive as they provide novel funding options for medical research. Despite this attraction, their prohibition has been called for on both ethical and scientific grounds.  First, private donors may be especially vulnerable to the ‘therapeutic misconception’, which could invalidate consent. Second, such research might wrongfully exploit the donor by failing to deliver sufficient benefit (many drugs do not pass phase I testing) in return for their significant financial contribution. Third, it is unfair for patients to be able to buy access to clinical trials. Fourth, patients who fund trials may attempt to influence aspects of the study design, such as eligibility criteria, use of placebos and randomization, in ways that corrupt the scientific method.

In our paper we have specific responses to each of these concerns. However, our main argument is that that none of them are exceptional or specific to donor-funded research. Nearly half of all global research is funded by for-profit companies and concerns about conflicts of interest, skewing of the research agenda, and potential undue influence on study design can arise here as well. This is bread-and-butter work for Institutional Review Boards/Research Ethics Committees.  Reviewers should reject studies if they are not confident that the study has been designed so as to deliver scientifically valid results, or if there is unacceptable risk of therapeutic misconception, or invalid informed consent. Just like standard research, some donor-funded research may fall below the acceptable standard owing to these issues. However there is no reason to think that all would or that the risks of these faults are so much greater in donor-funded research that such studies should be ineligible to apply for Institutional Review Boards/Research Ethics Committees consideration and approval.

We share the concerns of previous critics that some specific examples of pay-to-play research appear to lack both scientific integrity and risk wrongfully exploiting the desperation of very sick patients. In particular there is growing concern about the proliferation of under-regulated stem cell clinics which sell access to experimental therapies. While many are advocating for tighter regulation of these clinics, the new “Right to Try” law, signed by US President Donald Trump in May 2018, may have the opposite effect because it gives gravely ill patients new rights to access experimental treatments. So there are legitimate concerns and important debates for bioethicists, regulators and researchers to have about private funding models.

But our approach in this paper is to measure donor-funded research proposals against broadly accepted minimal standards of research ethics.  This standard is appropriate because it ensures consistency with how we review and assess other models of clinical research. Our concern is that previous critiques have, it seems, assessed donor-funding against aspirational research ethics standards and thus outright rejected such models. We argue this is inconsistent and unfair. If we were to prohibit outright all research where there is a significant risk of therapeutic misconception, the research prioritised diseases that occur in wealthy people, or there was a moderate risk of private interests seeking to alter study design to suit their purposes – a lot more than donor-funded research would be rejected.

The consistency we argue for is not only fair, but also beneficent. Ethical regulation of research should be both. Socially valuable and scientifically robust research is a public good, and expanding the funding options for this should be pursued.

Paper: Donor-funded research: permissible, not perfect

Authors: Mike King1 and Angela Ballantyne1 2

Affiliations:

1 Bioethics Centre, University of Otago, Dunedin, New Zealand

2 Department of Primary Health Care and General Practice, University of Otago, New Zealand

Competing interests: None declared.

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