Emergency Medical Research
In recent years, patients brought into emergency rooms and trauma centers
have had increasingly better prognoses. New drugs, devices and treatment
protocols have made it possible to save the lives of many patients who
formerly would have died. These new approaches to treating emergency medical
cases have been developed, as are all new medical treatments, under programs
of rigorous experimental testing. Doing research in the emergency situation,
however, poses some unique and serious problems for the protection of human
subjects. Among these are the time constraints imposed by emergency
treatment, the question of who may consent on the behalf of an incapacitated
patient, the possibly coercive nature of life-or-death situations in soliciting
consent, and contradictions in federal and state regulations.
Time Constraints
Emergency measures by definition are applied immediately. Scientific evidence
suggests that such promising investigational drugs as polyethylene glycol
conjugated super oxide dismutase (PEG-SOD) for head injury must be used
within a few hours of the injury to mitigate possible brain damage. This
small treatment window severely restricts the ability of the researcher
to obtain a legally acceptable surrogate consent in time for the treatment
to be effectively applied. For some emergency procedures, such as
the use of new resuscitation devices applied prior to arrival at the hospital,
the treatment window may be measured in minutes. In these situations it
is very rare to have any person within reach who can consent on the patient's
behalf. The only alternatives seem to be to make exceptions to informed
consent requirements or to forego doing research in these situations.
Who May Consent?
Surrogate consents by next-of-kin or others are much more stringently controlled
when research is involved than when emergency treatment only is rendered.
For treatment, a competent adult family member who demonstrates concern
in and is willing to be involved with the patient's treatment may consent
on behalf of the patient. By federal regulation, proxy consents to
research can be given by "legally authorized representatives". Under
the Illinois Health Care Surrogate Act, permission for clinical care, and
by extension consent for clinical research with a potential to help the
patient may be given by relatives, guardians or close friends according
to a hierarchy of relationships. If a close family member or legally
authorized representative cannot be located within the window of opportunity
for administering an experimental treatment, however, neither law gives
the physician-investigator any recourse.
The Imperative of the Life-or-Death
Situation
Imagine you are a parent whose child has suffered an accident and is severely
head-injured. When a researcher asks your permission to enroll the child
in a randomized protocol it may seem to imply that the experimental treatment
is your only hope to save your child's life. Even though the researcher
presents all the contingencies (including the chance that your child will
actually receive a placebo), under the circumstances, will you be able
to weigh your choices rationally and give a truly informed choice?
Some critics of research in emergency situations suggest that it is
not possible to fully and effectively inform the next-of-kin about research
in life-or-death situations. This is especially true because in many
emergency cases there is no effective alternative treatment available.
Further, the person giving consent may not be aware that experimental drugs
and devices can be used in life-threatening situations under an emergency
drug request without enrollment into a randomized trial.
The Politics of Emergency Medical
Research
The inability of research policies to keep up with the reality of emergency
medical research has had political repercussions. In March of 1994,
a staff report prepared for the U.S. House Subcommittee on Regulation,
Business Opportunities & Technology described this legal and ethical
quandary. In a strongly-worded critique of research policy and practices,
the report said:
"Head trauma, cardiac arrest or intoxicated human subjects
in need of emergency care often are incapable of informed consent and,
in many instances, have no available next-of-kin to speak for them.
When these emergency patients arrive at the hospital and look like good
research subjects, they become, in essence, an unconscious orphan left
on the emergency room door step"
The report detailed findings of nine apparent violations of patients'
rights that it uncovered in IRB-approved research, such as these, later
recounted in national news reports:
"Repeated laboratory tests, including blood and cerebral
spinal fluid collections...
Accident victims that survive initial head trauma and receive experimental
drugs must have multiple tests performed on them to see whether the experimental
drugs work. Some of these patients did not receive the experimental
drug at all but a placebo. Next-of-kin were neither (1) informed that tests
were being conducted, nor (2) given the resulting choice that their relative
would receive a placebo (as part of a randomized trial) or a potentially
life-saving drug."
"...using children without consent, even though the product
may injure their bones and vital organs and was labeled for adult use.
"One IRB permitted cardiac resuscitation research on children as young
as eight years old, even though the device was designed for adult use (18
or older). The government's astonishment was apparent in its original belief
that this was a typographical error. It was not. The experiments were associated
with patients' deaths."
The staff report acknowledged that the conflicting federal regulations
have in the past left IRB's without clear guideposts on how to determine
what constitutes adequate consent in emergency situations:
"Federal regulations require medical researchers to obtain
informed consent before they conduct any research on human beings.
Emergency room research makes that difficult, though not impossible. Federal
regulations provide for exceptions to informed consent requirements...The
definition of what constitutes a valid exception is not clear."
Exceptions to Informed Consent
The issues discussed above lead inevitably to the question of how one might
ethically proceed with research in emergency situations without prior informed
consent. The use of human subjects in medical research is governed by two
sets of federal regulations: those of the Department of Health and Human
Services (DHHS) and those of the Food and Drug Administration (FDA).
Any institution which receives research funding from DHHS, or which maintains
a Multiple Project Assurance with DHHS Office of Protection from Research
Risks must comply with the DHHS regulations regarding protection of human
subjects. Any protocol testing an investigational new drug or device
is governed by the regulations of the FDA. Both agencies have criteria
for when exceptions may be made to the requirement for informed consent.
Historically, the DHHS conditions were more restrictive than the
FDA's, requiring, among other limitations, that the risk be minimal, with
minimal risk defined as that comparable to the risks of every day living.
In most emergency medical research the risks cannot be judged minimal by
this standard.
The FDA, in contrast, prescribed a set of procedures under which physicians
who wished to enroll a patient in emergency medical research could do so
provided that he/she documented that the patient's life was in danger,
that there was no proven effective treatment for the condition, and that
attempts to reach family members had been made and failed.
In research institutions bound by both sets of regulations, many IRB's
were faced with evaluating protocols which might be acceptable to the FDA
but not to DHHS. As a result, a number of research protocols were
put on hold until the rules could be clarified.
NEW RULE FOR WAIVER OF CONSENT IN EMERGENCY
RESEARCH
In September 1995 the Food and Drug Administration issued a proposed rule
to "harmonize" the regulations of the FDA and the DHHS. This rule,
with some significant amendments, was adopted in October of 1996. In general,
the new rule adopts most of the FDA waiver of consent formulation, but
also adds a component of community notification and review.
Community notification arises because we do not know in advance who
will be affected by a medical emergency. Obtaining prior consent from specific
patients is impossible. Therefore the new rule will require that the whole
potential community of research subjects be notified and participate in
review. It also will require oversight by an independent data monitoring
and safety board. The new requirements for community consultation
and public disclosure represent expanded community participation in research
oversight. The ways in which these mandates are carried out may over the
long term alter the relationship between researchers and potential research
subjects.
The controversy over the ethics of emergency medical research continues
as well, with some commentators comparing the new rule to the experimentation
carried out in Nazi Germany. These critics point out that the right
of a patient to voluntarily consent to be a research subject is one of
the linchpins of current ethical thought about human research.
This criticism does not recognize that there have always been research
situations in which informed consent may be waived. Nor does it seem
to take into account the very restrictive situations under which this new
rule allows waiver of consent, nor that the rule can only be applied in
research on life-threatening conditions for which there is no proven alternative
treatment. As of this writing, it remains an open question how one
can ethically investigate new emergency medical treatments.
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See Also:
OPRR/OHRP
Reports: Consent in Emergency Medical Research
The
Belmont Report
45
CFR PART 46 Protection of Human Subjects
Guidelines
for Investigators
Bureau Multiple Project Assurance
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