This article examines a key ethical concern that has arisen in the work of the international research consortium GenoMEL (http://www.genomel.org) and that has relevance to all genetic research in humans. The question is whether it is ethical to deny research participants the opportunity to receive individualised genetic results obtained from the biological samples they provide. Where those results are of clinical importance, a “respect for persons” requirement would make the offering of those results imperative. However, where those results are of uncertain clinical value, the picture is less clear. This paper argues that researchers may not be ethically obliged to offer such results to their participants, because of competing ethical demands.
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Our burgeoning genetic knowledge is greatly enhancing our understanding of human disease and creating new avenues for prevention and treatment. Recent research has identified genetic variants that predispose some people to malignant melanoma. In certain parts of the world, tests for these variants are offered as part of clinical care, but the general view is that these tests are still primarily a research tool.1
Researchers using tests for known genetic variants that predispose a person to malignant melanoma are faced with a dilemma: should research participants be offered their individual test results? Between groups in the international melanoma research consortium GenoMEL, there is no common practice—approximately half offer individualised results to participants while the other half do not. Intriguingly, where there is more than one group in a particular country, those groups often have conflicting approaches. In the UK, for example, the GenoMEL group in Glasgow offers individualised results, whereas the one in Leeds does not. All GenoMEL groups have local ethical approval for their studies.
So which position is ethically correct? Or are both positions permissible, with the result that the researchers can choose? Alternatively, does it depend on local conditions? First it would seem sensible to consider why any research results need to be offered to research participants in the first place.
WHY OFFER ANY RESULTS AT ALL?
Guidance in general research
The right to self-governance is usually regarded as a core bioethical precept, and as Beauchamp and Childress state, “respect for the autonomous choices of persons runs as deep in common morality as any principle”.2 To make autonomous choices, an individual needs access to information upon which to base their decisions. This “respect for persons” would seem to imply a pro tanto duty (a duty that has some weight but may not be conclusive) to offer research participants any results. For the purposes of this paper, a research “result” is simply regarded as a new piece of information that may relate to a particular individual.
Regardless of whether the results were of any practical use, and as long as there are no factors opposing disclosure, then a desire on the part of the participant to know would be reason enough to tell them their results. Doing so would simply be observing that individual’s autonomous choice. In the UK, the National Health Service’s Research governance framework for health and social care refers to research subjects as participants3 and states that results should typically be fed back to them. This perhaps reflects a concern for treating people as autonomous individuals, not just as the means to obtaining research results. Human participants are essential to the genetic research under question, and their participation could be said to give them a stake in, and a claim to, the results. This claim would be independent of whether the results had any practical import for that individual.
The Research governance framework appears to be in accord with worldwide guidance, such as the International ethical guidelines for biomedical research involving human subjects, issued by the Council for International Organizations of Medical Sciences (CIOMS). CIOMS gives the following guidance (guideline 5, item 7):
That, after the completion of the study, subjects will be informed of the findings of the research in general, and individual subjects will be informed of any finding that relates to their particular health status.4
It would seem that the starting position in most research is that participants should be offered generalised results and quite possibly individualised results. Intriguingly however, in genetic research it is often advocated that only generalised results should be offered unless there are compelling reasons to do otherwise.
Guidance in the literature on feeding back individualised genetic research results
In the previous section I looked at the guidance for research in general. Here I will look at guidance for genetic research, highlighting the difference between the two.
The US National Bioethics Advisory Commission (NBAC) have said that genetic results should be disclosed only when stringent criteria have been met. According to the NBAC, for disclosure to take place the findings have to be “scientifically valid and confirmed” and must have “significant implications for the subject’s health”, and “a course of action or treatment” must be available (Austin, 2002, p590).5 The NBAC’s guidance would seem to be based on a precautionary principle of disclosing results only when you are sure they are valid, relevant and instrumentally useful.
The US Centers for Disease Control and Prevention (CDC) have formed a multidisciplinary team to examine the issue of genetic research with regard to population-based studies. The model consent documents that they have prepared and published reflect a similar policy to NBAC of not disclosing individual genetic research results to participants unless strict conditions are met.6 It is not immediately obvious to the author why both the NBAC and the CDC advise the opposite approach to that normally advocated in research.
ARGUMENTS FOR TREATING GENETIC RESEARCH DIFFERENTLY
In this section I will present, and reject, a number of arguments that have been used to try to justify different guidance for genetic research.
The results are not really “information”
One argument against disclosing individualised genetic research results is centred on their often preliminary nature. If the results represent the first steps in understanding a particular disease or biological pathway, they might simply have very little meaning on an individual basis. As Glass and colleagues comment,
If respect for persons implies a right to medical information, this cannot include a right to test results that are not “information”. When a test is so preliminary that results are unlikely to affect the individual’s risk assessment, the subject’s autonomy is not furthered by knowing these results.7
First, even if the result does not “affect their risk assessment”, it might still be something the individual would like to know. Second, simply saying that the information has little personal meaning is not, on its own, an argument for denying someone those results. At best, it suggests that no great practical harm is done when results are not fed back (since the information makes no difference to their risk assessment). Further argument is required to justify the claim that results need not be offered to participants, and such arguments will be examined in due course.
The risks of disclosure and insurance
The NBAC and the CDC would seem to be partly basing their positions on avoiding the potential harms incurred by knowing about your genetic constitution. The existence of special or great risks from genetic knowledge are often alluded to by commentators but are rarely quantified. Within the general literature, however, Ashburn and colleagues do mention documented cases of insurance and employment discrimination based on genetic information.8
If people know their genetic test results, they may have an obligation to answer the questions of their potential insurers on the topic. This could then lead to them paying higher premiums than before, or even being refused insurance. But how real is this threat? In the USA, many states have anti-discrimination laws that prevent employers or insurers from requesting genetic test results.9 In the UK, the government and the insurance industry have agreed on a voluntary concordat, namely:
(i) Customers will not be asked to disclose another person’s predictive test results, such as a blood relative’s test.
(ii) Customers will not be asked to disclose any predictive or diagnostic genetic test results acquired as part of clinical research.10
This moratorium on the use of predictive genetic tests has been renewed until 2011, so the situation may change in the future, but there would seem to be no immediate threat to research participants’ obtaining insurance in Britain.
Furthermore, even if there are risks, it can be argued that the participants should be the ones to decide if they want to run those risks by requesting results. Only when there is a significant threat to a participant’s welfare do ethical bodies feel that autonomy can be overridden by beneficent concern, and it would seem doubtful if the risks involved in this case truly warrant such a step.
It is possible that the risks of discrimination and stigmatisation are being overstated and are obscuring the real reasons that researchers do not want to offer results. Feeding back results can be a time-consuming exercise, potentially diverting researchers away from their core activity, research. This issue of resource allocation will be returned to later.
The risk:benefit ratio
Current guidance would seem to suggest that the risks of disclosure are worth taking only when the information is of highly practical, medicinal relevance:
Thus, the decision to use the approach suggested here should be based on an assessment at the outset of the likelihood that research results will generate information that could lead directly to an evidence-based intervention.6
This is a very narrow view of what value research results might have to an individual. To regard information as having value only in terms of its practical usefulness (and only its medical usefulness, at that) seems overly reductionist.
It is possible that participants would make ill-judged decisions based on preliminary research results, or that receiving the results will disturb them psychologically and emotionally. However, these dangers could relate more to whether someone is properly prepared for receiving the results and whether their implications are explained appropriately. Actually receiving the result might not be the problem.
A further concern is that we are only considering the risk:benefit ratio in terms of participant welfare. This is open to the charge of paternalism, because it does not consider the issue of the participant’s autonomy. Unless the potential harms are truly great, it is difficult to see why the autonomy of the participants is being overridden. Where a participant is incompetent to make such a decision, paternalistic protection would be warranted. However, such an individual would presumably be unable to give informed consent to participate in the study in the first place.
Competing ethical principles
It would seem that there is a tension between two core bioethical principles. First, a “respect for persons” requires that individualised research results be offered. Second, a commitment to beneficence (through a risk:benefit analysis) means that in some circumstances results should not be offered.
A choice has to be made. For some this choice seems clear:
If there is a duty to disclose research results that flows from the principle of respect for persons, then why does it matter if there are risks? … We contend that there are no conditions under which an offer of disclosure of research results should not be made.11
For others, “respect for persons” does not trump all, and weighing of the two duties is required:
But the principle of respect for persons is tempered by the principle of beneficence: the decision to disclose test results must involve a consideration of the risks and benefits of disclosure.7
However, even if we accept the second position of weighing relevant factors, it is highly debatable whether the risks associated with the case under discussion are truly significant.
The difference between research and clinical care
The CDC group also based their recommendation on the difference between research and clinical care. They contend that obligating researchers to provide results could confuse the role of the researcher with that of a physician. It is true that physicians are typically seen as having to act solely in the best interests of their patients, while a researcher is at least partially working in the interests of future patients.
Ethics committees are often insistent that research documents, such as information sheets, are very clear that the participant is taking part in research. Also, consent forms typically state that declining to take part will not affect a person’s clinical care. The concern is that potential participants are not misled into thinking research is actually clinical care, or that they must consent to the research so as to receive treatment. Making a distinction between clinicians and researchers prevents conflicts of interest and ensures that people understand the voluntary nature of taking part in research.
However, clinicians often have to balance their obligation to a particular patient against their obligations to other patients, their employer and their professional body. So it is not entirely clear why having to balance their duties, as both a researcher and a clinician, are so different. Indeed, many researchers are also clinicians, and while this might cause tensions, few advocate that no clinicians should ever divide their loyalties by acting as researchers as well. These tensions might well be more intense with clinical trials and the use of experimental therapies. In such circumstances, randomising treatments is probably the best way for the researcher to determine which one is the best, or has the least side effects. To clinicians, however, the treatment to give is the one that will most benefit their individual patient, given the existing evidence available. Still, with the research currently under discussion, the split between researcher and clinician does not seem so relevant. It is difficult to see how taking part in the research would compromise existing care and treatment.
A wider point is that the split between research and clinical care is not generally considered a bar to the general policy of offering results to research participants. If it is contended that this split prevents the disclosure of genetic test results, it should be asked why it does not stop the feedback of individual results for all medical research. All of the arguments considered so far do not support treating genetic research differently from other forms of research.
The argument that research results may not be as reliable as clinical results
One objection to offering any individualised research results is that such results are less dependable than clinical results, but this is not necessarily a fatal objection.
Richards and colleagues12 highlight the difference between research and clinical care in the feedback of individualised results to women taking part in a genetic epidemiological study of breast cancer. They draw attention to the fact that methods and standards of mutation detection in research differ from those in the clinical environment, and in their study, “positive” mutation results were not always confirmed in clinical follow-up.12 This was potentially a very stressful and confusing situation for those individuals. Those authors seem to suggest that participants are not overly concerned with receiving individualised research results, but this could well be mistaken.
Richards and colleagues also point out that by consenting to take part in the study the women were potentially agreeing to a predictive genetic test, and it was questionable whether they really understood this at the outset. They may have thought it was simply about increasing knowledge about breast cancer, as opposed to discovering the degree of risk within their family in comparison with other families. The offer of a genetic test is typically accompanied by genetic counselling to support a person through such a process. It is not clear why the researchers did not foresee this requirement at the beginning of the study.
In conclusion, Richards and colleagues say that individualised results should be offered only in very specific circumstances and that “the importance and salience of issues for research participants may not be the same as for all those who contribute to these debates from a more theoretical standpoint”.12 However, the difficulties they identify—erroneous research results and a lack of participants’ understanding of what they were consenting to—are more indications of their failings as researchers. To obviate these problems by not offering results would seem to be ignoring the real issues. The fact that research results are, by their very nature, preliminary and less reliable than clinical results can also be conveyed to the participants who want feedback.
USING INFORMED CONSENT
So in what way could researchers ethically decline to offer individualised genetic research results? A possible answer to this question is often advanced in the guise of informed consent. The contention is that by informing the participants that they will not receive a test result (and only taking their consent on that basis), the researchers meet their ethical obligations. In effect, by consenting to the study the participant absolves the researcher of the duty of feeding back results.
I would contend that informed consent is being used here as a way of limiting, as opposed to observing, a participant’s rights. Informed consent, properly understood, is addressed to observing the “respect for persons” requirement, not a defence for the researcher against later claims of wrongdoing. This misconception might well be common: in one survey of surgical patients, 80% thought the consent form was “a protection for the physician”.13 Simply saying that the participant was informed about condition X does not, in itself, make X acceptable. However, the possible role of informed consent will be returned to later.
AN ALTERNATIVE ARGUMENT FOR NOT OFFERING INDIVIDUALISED RESULTS
The arguments reported so far against offering feedback are flawed, but the question remains as to whether there are more powerful reasons for declining to offer the feedback of individualised results. In my opinion there is another, more powerful, argument, which can be applied to both general research and genetic research.
If we accept that researchers have a duty to offer individualised results, it is still possible that this duty may be outweighed by other factors. Researchers could argue that their time and resources are limited and that they should best employ them to address important research questions. The offering of results, which at best are of only abstract interest to participants, may justifiably have a low priority. Enabling individualised feedback may well entail achieving clinical certification of the research laboratory and the provision of trained genetic counsellors, and such measures are very resource intensive. A researcher could well argue that it is unethical to commit such resources when they could be used for a higher priority.
Ravitsky and Wilfond state the argument thus:
Finally, justice requires balancing participants’ preferences against considerations of prioritizing resource utilization to maximize the benefits of research to society.14
To use limited resources on a lower rather than a higher ethical priority would seem intuitively wrong. Researchers seem to shy away from stating this argument explicitly but it is, I would suggest, the strongest available to them. This is doubly unfortunate, because when combined with some of the justifications presented previously, it makes a much stronger case for declining to feed back results. For example, the argument based on the limited personal usefulness of the information was found to be unconvincing when considered in isolation, but when combined with consideration of the costs of feeding that information back, it becomes much stronger.
THE CORRECT USE OF INFORMED CONSENT
These justifications could sensibly be combined with informed consent, but this approach requires a greater appreciation of what is actually being asked of the participant.
The consent process should acknowledge the participant’s general right to information about their health, while asking them to waive that right in this particular circumstance. This is rather different from simply informing a participant that a result will not be forthcoming. Study information sheets should explain the “cost” of offering individualised results, and how such feedback will limit what the researchers could otherwise achieve.
THE POSSIBLE FUTURE UTILITY OF RESULTS
If results can enhance treatment and care, there is an ethical imperative to offer feedback. I have argued that where the results are not particularly informative either course may be acceptable. However, if the decision is made not to offer individualised results, there is a potential complication due to the very nature of biomedical research. Such research is not always of immediate benefit to anyone, but its ultimate aim is to be beneficial at some time in the future. Therefore, there is always the possibility that the research will actually produce results that can enhance treatment and care at some point in the future (such that, if the research was starting afresh, results would be offered to participants). In those circumstances, the participants’ consent has been sought and given on the basis that they will never receive a result, and yet now there is an ethical obligation to offer them those results.
There are a number of strategies that could address this problem, and different groups within GenoMEL do indeed use different methods. It might be felt that promising to give individualised feedback, if and when results achieve clinical significance, is preferable, but this amounts to an open-ended commitment that might not be sustainable. I would contend that the best approach is to tell all participants, by means of generalised feedback, that a particular test has now reached clinical significance and that they should consider seeking testing via a clinical geneticist. This method observes the clinician/researcher division and ensures that results are given by those best trained to do so. This would certainly seem the most effective use of the researchers’ resources, and it also addresses any concerns about research testing being less rigorous than clinical testing.
Offering individualised feedback would seem a pro tanto obligation based on the notion of “respect for persons”. Where those results have clear clinical use, or relevance to life decisions, this is a very strong obligation. For example, the results of research into single gene disorders will often be of huge personal relevance and suggest offering feedback. However, in other circumstances (such as the GenoMEL situation), this obligation or duty may be outweighed by other factors. If researchers believe it is outweighed, then they should be clear about what those factors are and they should communicate them to potential research participants. This approach can be applied to other forms of research than genetic investigations.
This work is based on my dissertation for a MA in Healthcare Ethics at the University of Leeds. Particular thanks must go to my dissertation supervisor, Rob Lawlor, for his insightful comments and advice. Also, without the support of GenoMEL and its researchers this work would not have been possible. However, this work represents my own views, not those of GenoMEL as a whole. Finally I must thank the peer reviewers for their comments.
Competing interests: None.
Funding: The author is employed by the coordinator of GenoMEL, the University of Leeds, as a project manager.
Provenance and peer review: Not commissioned; externally peer reviewed.