Introduction

According to paragraph 30 of the Declaration of Helsinki, after a clinical trial has ended, "the best proven prophylactic, diagnostic and therapeutic methods identified by the study" should be made available to the participants. This controversial requirement raises many ethical and practical issues and has provoked much discussion. In a review of this debate, Brian Greenwood and William Hausdorff discussed the extent of researchers' and sponsors' obligations to publish and disseminate results, provide treatment to people who become infected during participation in vaccine trials, and ensure that the clinical trial has a sustainable impact on the health system of the host community. [1] They covered many practical issues but had insufficient space to explore the ethical arguments in much depth. This article complements theirs by setting out some of these arguments in more detail.

The debate about researchers' responsibilities is heavily influenced by the relationship between autonomy, business interests, and social justice. Autonomy refers to an individual's power to make decisions that affect his or her person and welfare, and the corresponding right to have such autonomy recognised and respected. Social justice concerns equity within or between societies, and the extent to which members of societies are equally valued and have equal moral and civil status.

Some commentators argue that the obligations of researchers are shaped by only their interests, those of their sponsors, and the autonomy of individual research participants. They suggest that if a participant thinks that an offer to take part in research is rational, then it is not for the World Medical Association or some ethicist to interfere — even to improve the terms of participation. Others think that the grim inequalities between the world's poor and rich societies require researchers and sponsors to do whatever they can to reduce this gap - even where this might seem to pose extreme demands that should fall partly or entirely on other institutions.

At issue in these perspectives and debates, then, is fairness — both in terms of distributive justice (fair allocation of resources) and responsibility (fair allocation of duties and rights to take action).

Position one: researchers' obligations are minimal

In the minimal obligation position, those conducting a clinical trial are required to provide a specified treatment only for the duration of that trial. Of course, they must carry out the trial as effectively as possible, in accordance with international guidelines on consent, risk/benefit ratios, and so on. But the only true obligations they incur are those concerned with honesty, beneficence (doing good), non-maleficence (avoiding harm), and respect for autonomy. Importantly, as long as researchers and sponsors don't withhold any normally available effective treatment, they can be thought of as dealing fairly with trial participants.

Any higher standard of care that the researchers or sponsors are able to provide is supererogatory: that is, morally praiseworthy, but not obligatory. In fact, such acts may actually conflict with other duties. For instance, a trustee of public money is obliged to use that money only for the purpose for which it was intended — in this case, to further research. Similarly, a recipient of a private contract or charitable grant has a duty to use that money according to contractual stipulations.

More generally, it could be argued that since there is a strong public interest in promoting research, diverting money away from that goal and towards healthcare is unacceptable. Decisions about how to allocate money between research and healthcare are important, but they are for the funder of the health system or host government to make, not the researcher.

Decisions about priorities in funding (how much to spend on treatment, development, or research) should not be arbitrarily reversed or altered at the whim of any or every researcher. They are morally significant, and can be made well or badly, rightly or wrongly. But it is the sponsor and host of research funds and development aid who "own", and are morally responsible for, these decisions and their consequences, not the researcher. In many cases we need also to take account of the responsibility of patients for their own health, and voters for the governments they elect.

In theory, a researcher could ask for additional funding within their research bid to cover long-term follow-up healthcare. But he or she may lose out to others who put in cheaper bids that cover only direct research costs. If these lower cost bidders were being unethical, then this "economic" argument would not be important.

However, there are two arguments here. The first is based on the concept of non-obviousness — namely that it is not obvious that trying to make a bid as cheap as possible is morally wrong. For there is no obvious level of support that is the obligatory minimum, and failure to know what that minimum is cannot therefore be morally culpable. By driving costs down, researchers and sponsors take a moral risk (of failing to provide the morally obligatory minimum); but it is an unknown risk.

Second, there is an argument derived from opportunity cost: the more expensive a bid, the more opportunities to develop other beneficial interventions are excluded. On that basis, in terms of beneficial future outcomes, it is essential to make bids as cheap as possible to maximise the efficiency with which research funds are allocated.

Furthermore, researchers are scientists, not healthcare non-governmental organisations (NGOs) or development specialists (although they may be working alongside such experts). Their use of money for healthcare may well be misguided or ad hoc. It would be better for them to do what they do well, as cost-effectively as possible. Thus, trying to act as a combined research and healthcare operation is misguided.

Finally, as well as attempting to answer the question of obligation by specifying the duties of the researcher and the limits on those duties (the deontological approach), we can look at the issue in terms of outcomes (the consequentialist approach). It can be argued that a clinical trial that is prohibitively expensive will not be carried out, and that it is better to have a well conducted, short, cheap trial than none at all, since this option maximises total welfare. Furthermore, even in such situations the research participants receive — for the duration of the trial — better treatment than normal; in other words, they derive a direct benefit from participation, if only for a limited time. [2]

Position two: researchers' obligations are maximal

The argument for this position is much simpler than the preceding one. It is rooted in the observation that trial participants contribute significantly to researchers' objectives, and that (commercial) sponsors make a lot of money from the results of successful research. Participants, therefore, at least on the face of it, have a right to share in the benefits of such research. [3] Second, they assume a number of risks by participating, for which they deserve to be compensated. Third, by enrolling participants in a trial, the researcher has taken on a burden of 'duty of care' for those participants, which cannot be cancelled unilaterally.

This argument leads to the conclusion that researchers (and sponsors) have certain responsibilities to research participants that extend beyond the research period. These responsibilities are created by virtue of the fact that researchers have entered into a relationship with the research participants and the host community that cannot simply be waved away because it is inconvenient.

However, many of the trials conducted in the developing world test treatments for, or vaccinations against, chronic diseases. This situation poses specific problems: it is hard to create a need for a treatment — by making it available in a clinical trial — without also creating the opportunity for the patient to use that treatment for as long as it is needed. Obtaining informed consent does not release researchers from moral responsibilities. An ancient, but now defunct, principle of law held that free citizens could freely contract between each other, and, provided that the nature of the contract was not actually criminal, the state could not interfere, nor release either party from the contract without the other party's consent. This is the doctrine of "freedom of contract". Yet even in the heyday of this doctrine, freedom of contract was not normally regarded as diminishing the professional responsibilities of doctors for their patients. [4,5]

Even if we were to set high standards for what participants deserve after a trial ends, questions remain. For example, when would provision of treatment tail off? Would the offer of these long-term benefits prevent invited participants from considering the actual risks of a trial seriously enough? And would this offer to a lucky few heighten the injustice to the unlucky many who cannot take part in the trial? These questions are not intended to prove that these obligations, merely because they can appear unclear or "unrealistic", do not exist. Rather, they are challenges to researchers and funders to find institutions and approaches that would deliver fair provision of resources and develop communities' capacity to become self-sustaining and take over responsibility for the newly created healthcare needs. Thus, the argument is in fact that having created a relationship, it falls to the researchers to bring it to a satisfactory conclusion, rather than to walk away.

Towards a more nuanced response

It is clear that neither of these positions satisfactorily answers the question of what obligations researchers and sponsors owe participants after a trial is over. Rather, aspects of both approaches should be incorporated, while considering the main constraints that should shape any solution: rationality, limited responsibility, and non-exploitation.

Rationality
Any solution must be rationally justifiable (an arbitrary compromise is not defensible). In particular, it must take account of the situation in developing countries: scarce resources, intense medical need, and competing alternatives for investment and research focus.

Limited responsibility
Some moral philosophers have suggested that there are no rational limits to our responsibility for the welfare of people less fortunate than ourselves. In other words, there is no point at which one can say: I won't do what morality requires me to do, because that would make me worse off than I think I deserve to be. Most philosophers, however, recognise that this position is unrealistic, and that morality must reflect our psychological motivations to act, which includes recognising that there are limits to what you can reasonably expect from individuals, and that these limits include our limited motivations to help others. One approach to this quandary is to look to institutions and democracy to make decisions that are accountable to public reason and argument. Through building institutions that make decisions in a fair way, we make fairness in distribution possible. And while we cannot constrain individuals, we can design institutions that act in a way that individuals know is right and fair, and distribute the burden between individuals in a way that respects our psychological limitations.

Non-exploitation
Aside from the important question of resource allocation, a major issue in determining obligation is respect for research participants and the needs of their communities. This is captured by the constraint of non-exploitation, which ensures, among other things, that people's needs are not regarded as unimportant merely because of who or where they are, or their position on one side or another of a power imbalance.

Conclusion

Debates continue about the duties of researchers and sponsors to provide care after a clinical trial is over. Although the positions described here each have their merits, a problem-solving strategy based around the ethical constraints outlined is likely to yield greater progress than a polarised approach.

At its May 2004 Council Meeting, the World Medical Association (WMA) decided to leave paragraph 30 of the Declaration of Helsinki unaltered, but added a note of clarification:

The WMA hereby reaffirms its position that it is necessary during the study planning process to identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements or other care must be described in the study protocol so the ethical review committee may consider such arrangements during its review. [6]

This amendment essentially does no more than push the issue back to individual researchers, requiring them to plan, and to state and justify their plan, for access to treatment when the trial is over. However, the emphasis is on ensuring that at least some access is assured, suggesting that the ethical consensus is nearer the second position than the first. But, as Greenwood and Hausdorff noted, [1] the practical specifics of what this "clarified" paragraph actually requires can remain obscure. Nonetheless, work on the ethical status of different research objectives has produced sophisticated and persuasive solutions to the problem of how researchers ought to allocate their attention to problems, which if anything is a harder intellectual problem. [7] Two things are clear: the paragraph 30 requirement remains the binding ethical norm, albeit one whose interpretation may be flexible. And meeting this requirement will need much more explicit collaboration between researchers, funders, hosts, and health systems, if this part of the Declaration is to be more than simply "aspirational". [8]

Richard Ashcroft is Head of the Medical Ethics Unit and Reader in Biomedical Ethics, Imperial College, London, United Kingdom. 

Further reading

World Medical Association. Declaration of Helsinki (revised). Paragraph 30. http://www.wma.net/e/policy/b3.htm (2004).

Murphy LB. Moral Demands in Nonideal Theory. New York: Oxford University Press, 2000.

Unger P. Living High and Letting Die: Our Illusion of Innocence. Oxford: Oxford University Press, 1996.

Daniels N, Sabin J. Setting Limits Fairly: Can We Learn to Share Medical Resources? Oxford: Oxford University Press, 2002.

Pogge TW. World Poverty and Human Rights: Cosmopolitan Responsibilities and Reforms. Oxford: Blackwell, 2002.

Wertheimer A. Exploitation. Princeton: Princeton UP, 1999