email Dr Kerns
If research sponsors must avoid undue inducement in order to avoid the problem of invalidating "free consent," then another question begins to surface: Why would anyone choose to volunteer as a subject in these vaccine studies? The risks involved would seem to provide good reasons for some potential volunteers to decline participation. In addition, general feelings of distrust toward government agencies (who would probably be co-sponsoring such studies) is hardly a peculiarity of Western societies. In the US, the history of ethically questionable medical experimentation, such as the Tuskegee study of untreated syphilis in black men, as well as numerous instances of government insensitivity toward persons of color, has made it exceptionally difficult for vaccine researchers to recruit black volunteers. Researchers in some AIDS Vaccine Evaluation Units around the US, for example, have had a difficult time convincing members of the black community that this time, in this research, for this sexually transmitted disease, the government is going to treat them fairly and ethically. A study of 1160 gay men in Denver, San Francisco and Chicago found that 86 per cent of them had serious misgivings about how much the government could be trusted, or had "a real fear about the government". It would not surprise me to learn that Ugandans, whose recent history has included Idi Amin and a number of other oppressive dictators, have similar feelings of distrust toward government agencies. If Tanzanians, Brazilians and Thais sometimes have similar distrust of government, then whatever would motivate persons to volunteer as subjects in a vaccine trial sponsored by the government, given this potential distrust and these real risks? Are there any good reasons an ordinary citizen might have for offering to volunteer in these trials? Some possible motivations do come to mind.
21.1 Altruism
Altruism is probably the
real motivation for some volunteers. Such volunteers will probably
be very aware of the seriousness of the pandemic and will want
to do something to help out. Perhaps their brother or daughter
died of AIDS in recent months or years, and by volunteering as
a subject in a vaccine study they perhaps feel they can somehow
express their love for him or her, and at the same time try to
do something to help fight the epidemic, and perhaps even benefit
the wider human community. Particularly in phase I trials, in
which subjects need to be seronegative (as is necessary for all
three phases of the trials), and must not be at any significant
degree of risk for becoming infected with HIV (as phase III volunteers
must be), altruism seems so far to be the main motivator. Phase
I studies require only a small number of subjects (approximately
30-80), and it may not be difficult to find this number of persons
who are willing to volunteer, at some risk to themselves, and
for virtually no benefit, just because they want to help out.
But researchers for phase II trials which require a larger number
of subjects, and phase III trials which require thousands, or
tens of thousands, of subjects, may have difficulty finding a
large enough number of people who will volunteer for purely humanitarian
reasons, in spite of the risks and with no particular benefit
to themselves.
So we need to ask what benefits a volunteer might imagine would
accrue to them which could outweigh the risks he or she faces
by joining one of these studies? Some possible perceived benefits
might include the following:
21.2 Money
Money paid to them by researchers
might be a sufficient motivation for some volunteers, but the
amount of that money must be extremely negligible, otherwise it
would violate the undue inducement clauses of the International
Ethical Guidelines. In some communities, in order to protect
against even the appearance of undue inducement, the amount of
money paid to volunteers will need to be very small indeed.
21.3 Medical
care
The promise of medical care
may be an incentive for some, but the extent of that medical care
will need to be extremely minimal, otherwise that too will constitute
undue inducement. It seems clear that the Guidelines proscribe
both money and medical care, except in minimal amounts, as prime
incentives to participate in the research. So lacking these motivators,
are there any other reasons that might incline a person to participate
in such a vaccine study?
21.4 The chance
of protection
One possible incentive for
a volunteer to participate in a vaccine trial is their belief
that they might be lucky, that they could be one of the random
subjects who actually gets the candidate vaccine rather than the
placebo, that the candidate vaccine they get might be a relatively
safe and effective one, and that they could therefore be protected,
to some degree, from getting infected with HIV or contracting
AIDS. Since this may in fact be the motivation of many potential
volunteers, the preliminary education and informing of potential
subjects, before they volunteer, will need to make some important
points very clear:
i) It must be made clear that the "vaccine"
being studied is only possibly an effective vaccine, that
it is not known whether this candidate vaccine will be effective
at all, and that therefore the candidate vaccine should not be
relied on to protect anyone from anything.
ii) It must also be made clear that this study
is a placebo-controlled study, which means that only a certain
percent of subjects will receive the actual candidate vaccine,
and that all other subjects (perhaps 30 - 50 per cent) will receive
only an inert placebo which has no effect of any sort and confers
no protection against anything. (Another question for ethicists
to consider: should potential volunteers also be told the exact
percentage of probability that they will receive the candidate
vaccine or the placebo, so they can calculate their chances?)
iii) It must also be made clear that even if
they do happen to receive the candidate vaccine and even if it
does prove to be effective to some extent, it would still probably
be effective only a certain percent of the time. In other words,
it must be stressed that no vaccine, not even the very best, is
anywhere near 100 per cent effective, and that present HIV candidate
vaccines will probably be very much less effective - perhaps only
30 per cent to 60 per cent effective - than most vaccines already
in existence for other diseases.
iv) Finally, it must be stressed that during
the entire study subjects will be counseled and urged to not
engage in any behaviors that put them at risk of HIV infection.
In other words, pre-study educators will have a strong obligation
to make it clear that subjects would be foolish to rely on whatever
they receive in this study to protect them from HIV infection.
Nevertheless, in spite of such pre-trial counseling and informing,
some potential subjects may feel that a very small chance of some
small degree of protection is better than no chance at all. These
potential subjects may be planning to continue their risky behaviors,
and may therefore see participation in a vaccine study as an opportunity
to increase their chances for survival, even if by only a small
percentage. These subjects, of course, are the very ones who,
because they will feel safer, may even increase their risk
behaviors, and thereby worsen their chances of infection, and
possibly even worsen the spread of the epidemic. Nevertheless,
unrealistic and unwise as their thinking may be in this matter,
the possibility of getting protected may well be some subjects'
motivation for participating in the trials.
21.5 Other motives
Other motives to participate
may include a desire to be seen as a good community member, or
a desire to think of oneself as forwarding the aims of scientific
research, or even a desire to do one more good act (by being a
research subject) despite continuing to participate in risky behaviors.
Some persons may volunteer simply because they were told to do
so by a boss, a spouse, a partner, a community leader, or military
officer. They may have even been threatened, and hence forced
to volunteer. Others may volunteer because of having experienced
a great deal of social pressure to volunteer. The consent of these
"volunteers," of course, would thus have been coerced,
and therefore ethically invalid, but the coercion may be completely
invisible to (that is, hidden from) those who are conducting the
trial.
Some form of "easy out" should probably be offered to
all prospective subjects just to avoid this possible eventuality.
For example, when a local blood center has a blood drive seeking
voluntary donations of blood, a certain office group or boss may
decide that the whole office staff should go together and donate
blood. If one person in the office is HIV+, and hence should not
donate any blood, but is afraid to disclose that fact to his or
her coworkers, that person may feel forced to go along with the
group and donate his or her blood anyhow, just to protect their
privacy. Fortunately, blood banks have provided an "easy
out" just for persons in situations like this. When a person
is filling out his or her donor card, there is a little box at
the bottom of the card that says "Do not use this blood for
any purposes." If you check that box (you need not give any
explanation, and they will not ask for any), then they will not
use your blood; they will throw it away. They will, however, go
through all the motions of drawing your blood just as they are
drawing everyone else's blood, and you will have given the full
appearance of having participated in the office blood drive, thus
protecting your confidentiality. To all appearances, you donated
blood just as everyone else did.
It may be wise to provide an "easy out" of this same
sort for any volunteers who might need it. They would then be
able to avoid actual participation in the trial, but would be
able to give the impression that they had volunteered to participate.
It seems that some of the potential motivations reviewed above are probably not well thought out, and hence might not be sufficient motivation to sustain a subject throughout the whole course of a study. Other motivations, such as altruism, may not motivate a large enough number of subjects. Research sponsors will doubtless want to have it clear in their own minds what sorts of reasons would motivate subjects to participate in their protocols. In some communities, finding volunteers for the studies may require a certain amount of active marketing. If that turns out to be the case, another whole set of ethical considerations will need to be discussed and implemented concerning the methods and procedures for carrying out such marketing and advertising.
21.6 Quitting
Volunteers will remember
that they have been told clearly and directly by research sponsors
that they can drop out of the study at any time they wish, without
incurring any cost or penalty. Whatever motivation they may have
for participating, therefore, will have to be enough of a motivation
to sustain them throughout the long months and years that the
trial lasts. It is no small inconvenience to researchers when
subjects choose to quit the study, since research sponsors will
have invested a good amount of time, effort, and financial resources
in each volunteer. When one volunteer quits it may mean having
to recruit another, with all the time and cost that would entail,
and, if a large number of subjects quit the trial, it may even
mean a consequent postponement of the trial's termination date.
Trial sponsors will not want to have subjects quitting the study.
But on the other hand, subjects must be made aware that they are
allowed to quit at any time they wish for any reason at all (or
even for no reason).
I have been told of some vaccine research protocols that asked
volunteers to sign a "commitment form" when they join
the study. This practice seems to me to be designed for the benefit
of the research sponsors rather than for the benefit of the research
subjects. I have privately wondered how ERCs that reviewed those
protocols might have justified the requirement for subjects to
sign a commitment form, in light of the requirement that each
volunteer be made fully aware that they can quit the study at
any time for any reason.
Having considered these possible motivations for why some persons might choose to join and stay in a vaccine study, we could now find ourselves wondering whether these motivations will be sufficient, either for the subjects or for the sponsors. We will not know the answer to this question, despite some recent studies that try to assess the future motivations and behaviors of certain groups, until recruitment programs for the trials actually begin.