agreement to participate in research: is that a promise?

Agreement to Participate in Research: Is That a Promise?Author(s): Lisa H. NewtonSource: IRB: Ethics and Human Research, Vol. 6, No. 2 (Mar. - Apr., 1984), pp. 7-9Published by: The Hastings CenterStable URL: http://www.jstor.org/stable/3564476 .

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March/April 1984

Agreement to Participate in Research: Is That a Promise? by Lisa H. Newton

Should investigators "be allowed to impose limits on the freedom of subjects to withdraw from participation in research"? Robert J. Levine posed that question in IRB and identified it as "an issue that requires further ethical analysis."1, at p.9 What follows is an at- tempt to begin that analysis, or at least to lay the groundwork for it.

When a prospective subject is ap- proached to see if he would be interested in participating in research, or when a prospective subject answers an advertisement, and approaches an investigator to see if there are still open- ings in a project, the interview aims at an agreement: the prospective subject agrees to participate as a subject in the investigation and the investigator agrees that the research will be carried out as described.

The agreement is sometimes made formal by a signature on a consent form; written or not, the consent is never left out of the preparations to commence the investigation. Whether or not the subject at this point in the process actually conceives of himself as "coadventurer" with the investigator, on a journey into the unknown,2,3,4 that "consent" would surely appear to be a case of promising to be, and to con- tinue to be, part of the research. But then the "freedom" in question is an anomaly in ethics, since it appears that your right to withdraw from a project you said you would undertake is in direct conflict with your ordinary duty to keep your promises. How can we account for such a right? An answer to that question may throw new light on the relationship between investigator and subjects-specifically, upon the limits that the society seems interested in imposing on that relationship.

The first and most crucial distinction is between the obligation to participate in research at all and, having once agreed to participate, the obligation to remain in research. DHHS requires each protocol to include a statement that (1) participation is voluntary; (2) refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled; and (3) the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled (Section 46.116a). (2)

and (3) do not mean the same thing at all, and (1) is ambiguous, encompass- ing both of them, depending on whether the voluntariness of participation is in question before or after the agreement to participate has been made.

Many of the "limits on freedom" that Levine goes on to mention are limits on the freedom to refuse to participate from the beginning. One very stringent limit on the freedom to refuse to participate is that certain ther- apies that alone hold out any hope for a patient (such as human growth hor- mone for dwarfs) are available only to physicians who will use them according to a protocol. If the patient wants treatment, he must participate in research.

McCormicks and others have sug- gested a moral limit on freedom to refuse: your very membership in society imposes a duty to help that society. Accordingly, even children should be allowed, even urged, to participate in research for the good of society. Sim- ilarly, the principle of "gratitude," Ross would argueP at pp.20-22 or j"re- ciprocal obligation," as Levine calls it, may require that a subject who is ben- efiting from an innovative therapy re- pay that benefit by undergoing the inconvenience of the extra tests that serve the ends of research rather than therapy.

Another limitation on freedom to refuse to participate in research arises in the case of children and incompetents who might incidentally benefit from the research. Thus if a child wishes not to participate in research, his objec- tion is binding "unless the interven- tion holds out a prospect of direct benefit ... to the child and is available only in the context of the research.'7

Such considerations constrain subjects-morally, legally, or practi- cally-to participate in research, and constrain them to remain in the research only because withdrawal would return them to original condition, and the constraint would reap- pear in its original force. But these considerations miss the point of the question. Suppose we have a situation where none of the considerations above apply, and the subject, under no constraint at all, freely agrees to participate in research. Doesn't that agreement bind him, quite apart from

any surrounding circumstances, to remain in the protocol until it is com- plete? At the least, does he not have to produce good reasons to release him from his promise?

The DHHS requirement says it does not, and he does not, and the question is, why not? Levine suggests that the requirement "derives from the as- sumption that the subject is always doing something for the good of others; such supererogatory acts are gen- erally not considered obligatory." Joining the research to begin with, agreeing to participate, may have been such a work of charity. But keep- ing a promise is by no means a work of supererogation; indeed, it is a strict obligation. And promises have most binding force precisely where other constraints are absent. If I am strongly motivated by prudence to perform an act, it is unnecessary (even hypocriti- cal) to promise to perform it; if I have to do something, it is quite beside the point to promise it (I do not promise to pay my taxes every year). A promise creates an obligation that was not there before, bring about an "ought" where before there was only "is."8 at p.177; 9, at p.43: 10

A more likely cue comes from the regulations themselves, pinning the right to withdraw on "voluntariness." The rationale for permitting subjects to withdraw from research at any time is very simple: only voluntary participation in research is permissible, according to the Nuremberg Code and the Declaration of Helsinki. The patient who wants to withdraw is, with regard to voluntariness, in the same position as the patient who does not want to join to begin with-participation after that point would not be voluntary. The provision that a subject can withdraw, without prejudice to his relationship with the institution or deprivation of any rights he would otherwise enjoy, underscores this par- allel: as physician and hospital have no right to exercise coercion, or ad- duce coercive circumstances, to influence the prospective subject to join, so they have no right to hold out the prospect of deprivations to influence the current subjects to stay in. The effect of this interpretation of the regulation is to deny that a promise to participate makes any moral differ- ence in the situation; the subject's autonomy-the voluntariness of his par-

Lisa Newton is Professor of Philosophy at Fairfield Universitv.

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8

I~II~3 ticipation-is the only factor that has

any weight.

Is Autonomy Absolute?

This argument amounts to making the principle of autonomy absolute-so absolute that it cannot be limited by even an autonomous decision on the part of the subject. The ultimate in "respect" for this absolute "autonomy" was, perhaps, providing artificial heart recipient Barney Clark with his own key to the machine that sustained the circulation of his blood. Thus Dr. Clark could, at any time, by turning off the machine, and his own circulation, "withdraw" from the research. I see nothing wrong with the key, as ensur- ing that the disedifying spectacle of "Whose Life Is It, Anyway?" will not be repeated-the physically helpless patient pleading with physicians to turn off the "life-sustaining" equipment that he himself cannot reach. But that precaution has to do with refusal of treatment, not withdrawal from research. What can be said about the "right to withdraw" as part of respect for autonomy? For starters, what can be said about autonomy as an absolute?

The question does not appear for the first time in the field of human subjects research. It emerged primarily as an issue in political philosophy: If we truly respect individual autonomy, then what kind of government can possibly be legitimate? An argument that real respect for autonomy renders all government illegitimate was presented more than a decade ago by Robert Paul Wolff, in a work aptly titled In Defense of Anarchism. The Defense argued, in short, that if we have a right, indeed a moral duty, of self-determination (autonomy), then we have no right to bind ourselves to obey any rule, ruler, law, or state in advance of deliberating upon the desirability of the specific acts or omissions that will be required of us. If, confronted with the expecta- tion that we will act, forebear, or undergo in certain ways (because a law binding on us so requires, or because we are under contract so to do), we now determine that it would not be best so to do, forebear, or undergo-if our conscience instructs us otherwise- then we are morally obligated to act as we presently see fit. External struc- tures, even those we lent our agreement to in the past, cannot prevail over our autonomous judgment as to what is right for us right now. Wolff's simple and logical argument amounts to no more than taking autonomy very seriously. In the process, unfortunately,

he makes all government impossible, hence its terminus in anarchism.

The response to Wolff is that part of "autonomy" is the right to make a binding commitment-the right to make a promise, sign a contract, or join a community in formation (by a document like, say, the Mayflower Compact), by which act you explicitly limit your own right to determine, by yourself and on the instant, what you shall do."11 If you cannot make a binding commitment-if your every agreement for the future is subject to abrogation by you unpredictably, at any moment-yours is a state of sub- jection, or servitude, rather than autonomy. Being subject to your own future whim is, just as the ancients told us, as oppressive as being subject to the most arbitrary of earthly ty- rants. The common feature of both kinds of servitude is the servant's in- ability to predict or control his own future; he must wait, passively and helplessly, for a command that he will not be at liberty to disobey. As the op- posite of servitude, freedom or autonomy must admit of such control. But then, freedom entails the ability to make a commitment that you are not free to abrogate, i.e., to make a promise. The right, or duty, to maintain one's own autonomy entails the duty to keep promises.

This line of reasoning suggests a very different starting point for our reflections on the right of subjects to withdraw from protocols. Why should we guarantee that they will suffer not at all if they decide to withdraw? Did they not promise to help the research? And doesn't that promise bind them, as the investigators' promises bind them? Let us turn the question around. Since the regulations clearly affirm a right to withdraw regardless of voluntary undertaking to participate (i.e., freely given informed consent), the undertaking clearly was not binding. And since it is of the nature of promises to bind, the undertaking was therefore not a promise. As the right to withdraw applies to all cases of research, it follows that there is, by law, no such thing as a promise to participate as a subject in research.

Turning the question around in this way leaves us room to maneuver; in- stead of asking, "Why should subjects not be morally bound by the promises they make?", which has no answer, we can now ask, "Why might it be in the public interest to prohibit promises to participate in biomedical or behav- ioral research as a subject?" That question at least permits explorations in the direction of an answer.

Four Possible Reasons for Prohibiting Promises

Four possibilities worth exploring follow.

1. Such promises should be prohib- ited because, in the nature of research, the subject cannot know what he is getting into, hence what he is promising, and such "promises" are invalid.

This argument calls our attention to the obvious that research is a voyage into the unknown. (If we knew what the results would be, there would be no point to carrying on the investigation.) The subject's agreement to participate can therefore not be construed as an agreement to stay through an entire course of the research as conceived by the investigator (which is itself subject to change as new circumstances rise); at most, it must be construed only as an agreement to undergo the procedures immediately foreseeable, after which the promise must be renewed for the next procedures. (Analogy: A Roman legionnaire did not swear to fight for Rome for the duration of his term in the army. He swore only to follow a particular commander on a particular campaign, and the oath had to be renewed for each new set of battles.)

2. Such promises should be prohib- ited because the people on whom we do research are in many cases eligible for that research only because they are in some condition that renders all their promises sus- pect.

This argument applies in all cases where the subjects are children, very sick, debilitated, deranged, or just very dependent on the care provided by the institution in which the research is carried on. They may not (in the last four cases) be legally "incompetent," but their autonomy is diminished, and they are more than ordinarily vulnerable. So we do not hold them to promises made to the staff of the institution, if they later regret having made them.

3. Such promises should be prohib- ited because, in the nature of research, the unusual burdens placed on the subject may be more than he can bear.

Granted that the investigators have an obligation to separate from the protocol those subjects who are suffering, it is the better part of safety to leave the separation decision in the hands of the one who is doing the suffering. This argument applies not only in the expected cases, where new cancer thera- pies produce unendurable nausea or



March/April 1984

untried drugs turn out to cause severe pain. It would also apply in long-term projects, where the "mere inconvenience" of returning to a hospital at set intervals for tests turns into a major burden if the subject is forced by circumstances to change employment, move to another city, etc. It is difficult to think of examples, but that, of course, is the point of the reservation: since we cannot tell in advance what suffering will be involved in any particular project, we must leave the suf- ferer free to withdraw at any time.

Possibilities (1), (2), and (3) describe promise-limiting situations that are by no means unique to research. (1) de- scribes an epistemological situation (radical uncertainty) where we would hesitate to ask for, or accept, promises from anyone; (2) specifies a set of per- sons from whom we would hesitate to accept promises no matter how clear and certain the situation; (3) posits a set of post-promise circumstances where we would ordinarily release anyone from a promise, unless the release would cause much more suffering for the subject or for other people. An argument in favor of the present "right to withdraw" from research could take the form of a claim, that all cases of research with human subjects fall into one of those categories, and that many fall into more than one. Therefore there can be no "promises" to participate in research. But is this claim correct? If not, a fourth possibility arises:

4. In Ihose cases where the course of the research is reasonably foreseeable, where the subject is a healthy volunteer, and where no undue burdens materialize, the agreement to participate in research is a promise, and no regulation should be interpreted in such a way as to deny it.

In short, in the absence of circumstances that would ordinarily (in situations other than human subjects research) excuse from promises or negate their existence, the promise exists and obligates, in human subjects research as elsewhere. The investigator in such cases may be obliged by law to inform the subject that he will not be penal- ized by deprivation of other rights if he arbitrarily withdraws from the protocol. But he is under no obligation, le- gal or moral, to tell the subject that it is "all right" to withdraw in the absence of good reason.

Research is not carried on for fun, for free, or (only) for the enhancement of the reputation of the investigator. It holds out the prospect of real increase in knowledge in an area of importance

It might be more useful, in future reformulations of the DHHS requirements, to assume that the relationship between investigator and subject is a normal contractual one, binding on both sides, hence to be taken very seriously on both sides, and go on to specify the circumstances that shall be taken to negate or cancel that mutual commitment.

to future physicians and patients-if it does not, no IRB should have approved it in the first place. Human, financial, and other resources have been commit- ted to it. When a subject withdraws, the research is necessarily rendered less significant and reliable, and the benefits expected from it are rendered less certain. Other people, in short, are going to be hurt, if only indirectly, by that withdrawal.

Why does the law, then, appear not to take this constraint into account? There are two possible answers. The first is that those who drafted the regulations, and the recommendations that lie behind them, honestly thought that all consent to participate in research was so flawed, or likely to be invali- dated by unforeseeable burdens, that it would be the better part of policy not to allow that consent to be read as a promise under any circumstances. The other possibility is that those who drafted the law intended specifically to place all control of the relationship between subject and investigator firmly in the hands of the subject, even to the point of encouraging the subject to think of his commitments, like those of a divine-right monarch, as retractable at whim. The motivation for such as- signment of control might well be a felt need to correct for the abuses of control exercised by investigators in earlier research;12 at pp. 51-53 the result would surely be to render research more un- certain and difficult for the investigator, hence to cut down on the amount of research being done and ensure that what was done was of such significance to make it worthwhile to persevere through such difficulty.

Given the predictable nature of much human subjects research, and the other safeguards in place, the time for this sort of limitation may be past. Further, as Jay Katz has pointed out,'3 provision for a right to withdraw at any time may seriously damage the

process of securing consent: the subject reasons that he "isn't really promising anything" and consents without full information, the investigator reasons that the subject can leave the project anyway, anytime he finds it unpleas- ant, so he need not be told everything that might happen.

It might be more useful, in future re-

.formulations of the DHHS require-

ments, to assume that the relationship between investigator and subject is a normal contractual one, binding on both sides, hence to be taken very seriously on both sides, and go on to specify the circumstances that shall be taken to negate or cancel that mutual commitment.

REFERENCES 'Levine, R.J. What should subjects be told

about withdrawing from a protocol? IRB: A Review of Human Subjects Research 3 (No. 9):9-10, November, 1981.

2Ramsey, P.: The Patient as Person. New Haven: Yale University Press, 1970.

3Jonas, H.: Philosophical reflections on experi- menting with human subjects. In: Experi- mentation with Human Subjects, pp. 1-31, ed. by P.A. Freund, George Braziller, New York, 1970.

4Katz, J.: Experimentation with Human Beings. New York, Russell Sage, 1972.

SMcCormick, R.A. Proxy consent in the experimentation situation. Perspectives in Biology and Medicine 18:2-20, 1974.

6W.D. Ross, The Right and the Good, Oxford: Ox- ford University Press, 1930.

7National Commission for the Protection of Human Subjects of Biomedical and Behav- ioral Research: Research Involving Children: Report and Recommendations, DHEW Publi- cation No. (OS) 77-0004, Washington, 1977, Recommendation 7B.

8Searle, J.R. Speech Acts. London: Cambridge University Press, 1969.

9Searle, J.R. How to derive an 'ought' from an 'is.' Philosophical Review 73:43-58, 1964.

'toPerkins, L.H. Natural law in contemporary analytic philosophy. Amer. J. Jurisprudence 17:111-119, Spring, 1972.

"Perkins, L.H. On reconciling autonomy and authority; a response to Wolff. Ethics 82:114-123, January, 1972.

12Levine, R.J. Ethics and Regulation of Clinical Research Baltimore: Urban and Schwarzen- burg, 1981.

'3Katz, J. personal communication.

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agreement to participate in research: is that a promise?

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