email Dr Kerns
Even the urgency of our global situation,
even the fact that we are in the midst of a serious pandemic in
which the number of new infections every hour is accelerating,
even these urgencies, says the Antithesis position, should not
allow ethical guidelines, especially those relating to informed
consent, to be relaxed. The Nazi doctors certainly felt that the
urgent demands of a major war effort justified taking ethical
shortcuts in their medical experiments with human beings, but
the condemnations of the Nuremberg trials have made that kind
of thinking unacceptable ever since. The Antithesis position insists
that even today's urgencies must not be used as an excuse for
taking ethical shortcuts in human subjects research. "The
life-threatening and infectious nature of HIV/AIDS does not justify
any suspension of the rights of research subjects to informed
consent."
The question one is then left with
is: Will it actually be possible to fully inform all prospective
subjects? The answer to this question will be difficult. Ethics
Review Committees will need to decide how best to apply the principle
of informed consent in developing nations. That the principle
of requiring informed consent from each individual research subject
does and should apply, virtually all ethicists (including those
from developing nations) do seem to believe. Given this reality,
we must now face questions about how best to implement the principle
in cultures where it did not originate.
The principle of informed consent is articulated in Guideline #1 of The International Ethical Guidelines for Biomedical Research Involving Human Subjects.
For all biomedical research involving human subjects, the investigator must obtain the informed consent of the prospective subject or, in the case of an individual who is not capable of giving informed consent, the proxy consent of a properly authorized representative.
The astute reader will already have noticed the caveat, "in
the case of the individual who is not capable of giving informed
consent". In medical ethics discussions in the past five
decades, this phrase has been primarily applied to individual
clinical patients who are a) too young to give legal consent,
or b) are comatose (or virtually comatose), or c) are judged to
be in some way "non compos mentis," perhaps due to mental
retardation, advanced age or some mentally incapacitating disease
process (either physical or psychological). The thinking has been
that for an individual who is not "competent" to give
consent, the "proxy consent" of someone who represents
the patient, and who is authorized to express the wishes of the
patient, will be accepted in his or her stead. As far as I know,
the principle of proxy consent has been applied almost exclusively
in clinical situations.
The application of the proxy consent
principle to subjects in biomedical research has been much less
common. Where it has been applied to research, it has been in
situations that are a mix of therapy and research where, for example,
a non-competent patient could be given access to an experimental
drug or procedure which also has potential therapeutic value.
The purposes to be served in using the experimental drug or procedure
are twofold: there is both a therapeutic purpose for the potential
benefit of that individual patient, and there is a research related
purpose in which we want to know more about that drug or procedure.
In dual purpose situations of this nature, proxy consent has been
used. Very rarely have any pure research situations resorted to
the proxy consent principle.
The "Commentary on Guideline #1" in The International Ethical Guidelines contains a paragraph which may be applicable to this question of proxy consent. It deserves to be quoted at length:
When the research design involves no more than minimal risk - that is, risk that is no more likely and not greater than that attached to routine medical or psychological examination - and it is not practicable to obtain informed consent from each subject (for example, where the research involves only excerpting data from subjects' records) the ethical review committee may waive some or all of the elements of informed consent. Investigators should never initiate research involving human subjects without obtaining each subject's informed consent, unless they have received explicit approval to do so from an ethical review committee.
This commentary emphasizes the importance,
in all human subjects research, of obtaining each individual subject's
informed consent. Two exceptions are allowed. (I have flagged
both with italics.) The first exception applies only when two
conditions are both present: a) when there is minimal risk, and
b) when it is not practicable to obtain informed consent from
each subject. In phase III HIV vaccine trials in developing nations,
the second condition may well apply, that is, it may be very difficult
to obtain informed consent from each subject. The first condition,
however, that the experiment involve only minimal risk clearly
does not apply, as we have seen above in chapter 11, on Real Risks.
Might the other exception, namely, receiving explicit approval from an ethics review committee to dispense with "obtaining each subject's informed consent" apply to such trials? That is unknown right now, but if it did happen, it would require:
a) that research sponsors provide to the Ethics Review Committee
a list of solid reasons why it would be ethically acceptable to
dispense with informed consent from each subject; and
b) that sponsors also suggest alternate procedures which would
provide support for the autonomy of individual subjects and would
protect vulnerable subjects, since these are two of the main goals
of the informed consent principle.
Having heard these reasons and alternate
procedures, the Ethics Review Committee would then deliberate,
make its decision, and the decision, presumably, would be final.
In any case, and by whatever method research sponsors choose to obtain the informed consent of subjects, that such consent will be necessary in HIV vaccine trials is absolutely clear. Informed consent is required by virtually all codes of medical conduct written and promulgated, both nationally and internationally, since Nuremberg. The requirement is also part of international law and is even included in the United Nations International Covenant on Civil and Political Rights, promulgated in 1966 and adopted by the UN General Assembly in 1974. Specifically, article 7 of the covenant reads:
No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment. In particular, no one shall be subjected without his free consent to medical or scientific experimentation.
It is the ERC's responsibility to
ensure that the requirement for getting individual informed consent
from each subject is adequately met by the research sponsors.
It is probably not likely that the
review committee would take measures to oversee the actual ongoing
research to insure that ethical standards were being followed,
but the committee will probably require annual review of the protocols
to determine compliance with ERC requirements. Then if reasons
for suspicion developed, the committee would certainly be able
to withdraw its approval of the protocol and could in the future
require stringent, on-site oversight procedures to insure compliance.
There have actually already been
allegations of serious ethical misconduct in the performance of
early HIV vaccine trials. There have been accusations of intentionally
initiating vaccine trials in developing nations where there were
as yet no provisions for ethical review of research, in hopes
of having less strict oversight over research. There have been
allegations of trying untested HIV vaccines on small children
who are too young to know what is happening to them. There have
been charges of withholding data about the deaths of vaccinated
subjects from published reports of vaccine experiments in order
to make the results look better than they actually were. There
have been charges of surreptitious alteration of government patent
documents to cover up possible misconduct. These are all only
allegations, of course, and may well prove to have no validity
at all. After all, anyone can make any allegations. But if such
allegations were found to have some merit, an ERC would almost
certainly withdraw approval from the involved protocols, and this
would doubtless have the effect of terminating all funding for
the project. The research would then be out of business until
it could be shown that the protocol was back in formal compliance
with all ethical requirements.