Conducting Research with Children:

Legal and Ethical Issues

LEONARD H. GLANTZ, J.D.

ABSTRACT
Research with children and mentally disabled individuals raises difficult legal and ethical issues. It is the obligation of
researchers and those who review research to protect both the rights and welfare of research subjects. Ethicists, legal
scholars, and national commissions have examined the circumstances under which it is acceptable to use incompetent
people as research subjects, since they are unable to provide consent for participation. Furthermore, there is an
extensive set of federal rules that govern the use of children as research subjects. Children may be used as research
subjects after a careful weighing of risks and benefits, and as long as they participate in the decision to the extent they
are able to do so. However, research projects that will not provide children with direct benefit, such as some placebo-
controlled trials, raise particularly difficult issues concerning the protection of these subjects. While biomedical research
is an important and socially desirable undertaking, it must proceed only when the rights and welfare of the subjects are
scrupulously protected. J. Am. Acad. Child Ado/esc. Psychiatry, 1996, 35(10):1283-1291. Key Words: research,
children, law, ethics.

Research with human subjects is viewed with mixed future unknown persons if the research is successful.
emotions in the United States. On one hand research If the research is unsuccessful in improving human
is seen as important in that it creates new knowledge, health, then the risks and discomforts that the human
which is viewed as a social good in and of itself. subjects have encountered will not lead to benefit, and
Furthermore, biomedical research is seen as vitally it may be felt that the burdens of being a subject were
important because the knowledge it creates reduces the not outweighed by any benefit. A large and somewhat
burden of disease and injury from which individuals complex system has been established to review research
suffer. This is good not just from an individual perspec- that is conducted with human subjects to try to ensure
tive, but from a societal perspective as well. Indeed, their rights and welfare. Indeed, there is a federal office
our belief in the importance of research is proven by called the Office for Protection from Research Risks
the fact that we have created a large research establish- whose job it is to enforce a comprehensive set of federal
ment that funds and conducts research with human regulations governing human research (US Department
beings. of Health and Human Services, 1991).
On the other hand, research with human subjects While adult subjects are considered in need of protec-
is also viewed with some suspicion. It is an undertaking tion from research risks, the major method for accomp-
that uses human beings as a means to acquiring new lishing this goal is through the doctrine of informed
knowledge. When human subjects are used in this consent. It is believed that once competent adults
way, we may not be acting with their best interests in
are properly informed about the risks, benefits, and
mind. In addition, human subjects encounter risks and
alternatives to their participation in a research project,
discomforts that may not benefit them but will benefit
they can make an autonomous decision about their
participation. But children and mentally disabled per-
Accepted December 29, 1995. sons are considered particularly vulnerable as research
Mr. Glantz is Professor ofHealth Law at the Boston University Schools of subjects for a number of reasons:
Medicine and Public Health.
Reprint requests to Mr. Glantz, Boston University School ofPublic Health,
• They may not be competent to volunteer to partici-
80 E. Concord Street, Boston, MA 02118.
0890-8567/96/3510-1283$03.00/0©1996 by the American Academy pate in a research project and so they will be partici-
of Child and Adolescent Psychiatry. pating either nonvoluntarily or involuntarily.

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GLANTZ

• The person consenting to a child's participation may But not all research was so benign. The germ theory
have a variety of motives for providing such consent was tested by intentionally infecting both adults and
and, therefore, may not be solely or primarily con- children with diseases. The health officer at a Hawaiian
cerned about protecting the child's best interests, leprosarium injected six girls under his care with the
This may be particularly true of parents who are "virus of syphilis." Dr. Henry Heiman, a New York
overwhelmed by the physical and psychological bur- physician, was not embarrassed to report that he was
dens that a child's illness brings to bear on the parent able to successfully produce gonorrhea in a 4-year-old
and the family. "idiot with chronic epilepsy" as well as in a 16-
• Children who are institutionalized are more removed year-old boy who was also an "idiot" (Lederer and
from the "ideal" protective parent. Grodin, 1994).
• Histoty indicates that children and mentally disabled The invention of the x-ray prompted much research
people have been abused and exploited as research in children and adults. Physicians used x-rays to study
subjects. the normal development of children and adults. In
1896, Dr. Arthur Wentworth published a paper de-
scribing spinal taps he performed on 29 children at
History
Children's Hospital in Boston to determine whether
Those who do research with children today have the procedure was harmful. He determined they were
inherited the legacy of researchers who have come safe. But Philadelphia physician John Roberts, noting
before them. Understanding this history provides a that these procedures were with "no therapeutic indica-
context for understanding the current rules that govern tions for the operation" and for "purely and avowedly
research with children. Many of the great medical experimental" reasons, labeled Wentworth's use of these
advances that have been made used children as research procedures "human vivisection." Roberts argued that
subjects. The first test of immunization used children using children in this fashion without gaining the
and slaves as subjects. Jenner vaccinated his I-year-old permission of the children's mothers intensified public
son with cowpox to see whether it would confer fear of hospitals, especiallyamong the poor. Wentworth
immunity to smallpox. In 1802 Jenner's vaccine was resigned his post at the Harvard Medical School but
tested on 48 children living in an almshouse who were the controversy did not abate. At the turn of the
then challenged with smallpox to determine whether century there were proposals made in several states to
they were immune from the disease (Lederer and outlaw research on children, the insane, and pregnant
Grodin, 1994). women. In 1941, Francis Payton Rous, editor of the
In the 1900s an increased interest in child welfare JournalofExperimental Medicine, rejected a manuscript
was coupled with an increased desire to learn more from a physician and wrote to the author: "the inocula-
about the physical aspects of children. In the first tion of a 12 month old infant with herpes ... was an
decade of the century Alfred Hess, a respected pediatri- abuse of power, an infringement of the rights of an
cian, became the medical director of the Hebrew Infant individual, and not excusable because the illness which
Asylum in New York. He believed that conducting followed had implications for science. The statement
research in an asylum was ideal because it approximated that a child was 'offered as a volunted-whatever that
those "conditions which are insisted on in considering may mean-does not palliate the action" (Lederer and
the course of experimental infection among laboratory Grodin, 1994). This statement represents an important
animals, but which can rarely be controlled in a study turning point in the discussion of research with chil-
of infection in man." There were studies in institutions dren. It is one of the first statements to acknowledge
that were clearly beneficial to the children-subjects. In that children themselves have rights as individuals and
1915 the US Public Health Service discovered that that the thought that one could be "offered as a
the incidence of pellagra in children living in orphan- volunteer" was a contradiction in terms. Recent revela-
ages could be reduced by providing the orphanages tions indicate that at about this same time, mentally
with fresh milk, vegetables, and eggs. Happily, these disabled adults and children were unknowingly being
experiments were replicated throughout the South exposed to radiation in a variety of forms (Allen, 1994;
(Lederer and Grodin, 1994). Kong, 1994).

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 RESEARCH WITH CHILDREN: LAW AND ETHICS

From the 1950s through the 1970s, a research team base of scientific knowledge. The problem with the
at the Willowbrook state school systematically infected researchers was not that they were evil, but rather that
mentally retarded children with strains of hepatitis. they were zealous.
This was a signal event in the discussion of research
The Creation of Research Rules
with children and the mentally disabled. Believing that
virtually all children would contract the disease in any The evil researchers were found in Nazi Germany,
event because of the conditions at the institution, the where many distinguished physicians engaged in hor-
investigators infected children to study the natural rendous experiments to further the interests of the
course of the disease as well as some other matters. Third Reich. At the end of the war they were tried
The research team provided a specially equipped and as the criminals they were, and seven were hanged.
staffed unit where the children would be protected Out of this experience came the Nuremberg Code, a
from other diseases in the institution. There was a set of universal principles designed to govern the use of
waiting list for admission to the institution, but parents humans as research subjects (Annas and Grodin, 1992).
who consented to have their children participate in There are 10 principles stated in the Code. The
the study were assured more rapid admission to a first says, "the voluntary consent of the human subject
special unit. There was a substantial outcry over the is absolutely essential." This raises an important issue
Willowbrook experiments because children were inten- for those who do research with children or mentally
tionally afflicted with a serious illness, parents who disabled people: they often cannot give their consent.
were desperate for some kind of care for their mentally If they are to participate as human subjects they must
disabled children were exploited, and the wretched be "volunteered." How to get around this ethical
conditions in which mentally disabled children were problem has been the subject of much controversy. It is
housed were being used as an excuse to intentionally worth noting that the promulgation of the Nuremberg
make them sick. The legal authority of parents to Code seems to have had little impact in the United
"volunteer" their children for such research was chal- States after World War II, as much research continued
lenged. As one critic of this research project noted, no to be done that would apparently violate its provisions.
attempt was made to enlist the institution's adult Both the radiation experiments referred to earlier and
personnel, which included 600 ward attendants who the Willowbrook experiments would seem to fall into
were also exposed to hepatitis, to participate in the this category, as would the now infamous Tuskegee
research, and nothing was said about attempts to con- syphilis experiment (Jones, 1981).
trol or defeat the epidemic at Willowbrook "by more In 1974, the then Department of Health, Education
ordinary, if more costly and less experimental, proce- and Welfare promulgated regulations designed to pro-
dures.... If this had been an orphanage for normal tect human subjects. Also in that year Congress estab-
children or a floor of private patients, instead of a lished the National Commission for the Protection of
school for mentally defective children, one wonders Human Subjects of Biomedical and Behavioral Re-
whether the doctors would so readily have accepted search. Among its charges was to make recommenda-
the hepatitis as a 'natural' occurrence and even as an tions about research with children and research with
opportunity for study" (Ramsey, 1970, p. 49). institutionalized mentally disabled people. During the
It is against this background that we need to view deliberations it became clear. that no one thought it
the concern that children and mentally disabled people was a good idea to ban research with children-with
need some type of special protection in the research the exception of one kind of research. Paul Ramsey,
context. Being a child or being mentally disabled has the well-respected theologian, argued that any research
historically been associated with questionable treatment that did not have the potential to directly benefit the
at the hands of researchers. Being both a child and child-subject could not ethically be performed if it
mentally disabled has been associated with particular subjected the child to the risk of harm. In his words,
vulnerability for maltreatment. Furthermore, the people From consent as a canon of loyalty in medical pracrice ir follows
who conducted these projects over the years, including that children, who cannot give a mature and informed consent,
or adult incompetents, should not be made the subjects of medical
the researchers in the Tuskegee Syphilis Study, all experimentation unless, other remedies having failed to relieve their
thought that they were doing good by increasing our grave illness, it is reasonable to believe that the administration of

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a drug yet untested or insufficiently tested on human beings, or even though courts have allowed the removal of a
the performance of an untried operation, may further the patient's
kidney from a healthy child for transplantation into a
own recovery [emphasis in original] (Ramsey, 1970, p. 11).
sick sibling, it would be extremely unlikely that a court
Ramsey essentially argues that the first principle of would permit the removal of a healthy kidney from a
the Nuremberg Code should be taken seriously: the child so that it could be provided to a researcher
consent of the individual is absolutely essential, at least (Glantz, 1994).
where there is risk and no benefit to the subject. In There is a spectrum of activities that researcher-
fact, this is the type of research at which the Nuremberg physicians engage in that runs from pure research in
Code is probably directed: the research at the concentra- which the sole goal is the creation of new knowledge,
tion camps was in no way designed to provide any of to pure clinical activities in which the sole goal is
the subjects with any benefit. When one is dealing patient benefit. Pure research is the most suspect activity
with pure research (in which the onlygoal is the creation and pure therapy is the least suspect. This is largely
of new knowledge), it is correct to say that one cannot due to the issues just discussed. But it is also because
subject a person to a risk of harm for the benefit of in a pure therapeutic relationship physicians owe their
others without that person's consent. When individuals only allegiance to their patients , whereas in pure re-
consent to being subjects in research that cannot benefit search the researchers' allegiance is primarily to the
them directly, they are acting altruistically, giving a creation of knowledge. As a result, the protection of
gift to the rest of us. By definition altruistic acts and the human subject has to come from somewhere other
gifts must be voluntarily made by the giver. To use than the investigator.
people in pure research without their consent, ethicists The federal rules for the protection of human sub-
would argue, treats a person like an object, like a jects, especially the additional protections accorded to
laboratory animal, as a means to an end, and therefore children, recognizes this spectrum. The more research
devalues and dehumanizes the person. As a result, it resembles clinical care the less it is regulated, and the
is argued that researchers cannot conduct, and parents more it looks like pure research the more it is regulated.
cannot consent to, research that cannot benefit the Indeed the current federal rules are quite a bit more
child but may harm the child. Parents as guardians of lenient than earlier proposed rules. For example, the
their children are only authorized to act in their child's first federal proposal dealing with children as research
best interests. How can participation in this type of subjects, issued in 1973, required proposed research
research meet that test? with children to go through two committees, an
But this does not mean that parents cannot take "agency ethical review board," which would review
some chances with their children's health, even when the overall acceptability of the proposed research, and
the benefits seem indirect, or the benefits are psycholog- a "protection committee," which would oversee the
ical or even social. If this were not the case, then conduct of the research-for example, it would monitor
parents could not consent to their child's participation the subject's continuing willingness to participate in
in high school football, an activity that involves a the research and determine the reasonableness of the
substantial risk of harm. Furthermore, we know that parent's consent (US Department of Health, Education
there are times when parents may consent to the and Welfare, 1973). These proposed rules also prohib-
physical invasion of one child for the benefit of another ited research on any child who was involuntarily
child. For example, courts have permitted a kidney to confined in an institutional setting, or with any child
be removed from a healthy child for the purpose of 7 years ofage or older who did not consent to participa-
transplantation into a sick sibling (Hart v Brown, tion. The current federal rules are much more lenient
1972). But here the benefit to another in the family and provide a good deal of leeway for investigators
is very direct and the psychological benefit to the and institutional review boards (lRBs).
healthy child also seems direct. But even in such cases
The Current Federal Regulations
the courts have required some kind of review of the
parents' consent; parental consent alone has not been In the current rules the term "children" is defined
sufficient to authorize such an invasion of a healthy as "persons who have not attained the legal age for
child's body primarily for the benefit of another. And consent to treatments or procedures involved in the

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 RESEARCH WITH CHILDREN: LAW AND ETHICS

research" under the laws of the jurisdiction in which understanding or ameliorating the subject's disease or
the research is to be conducted (US Department of condition; and the subject's assent is obtained. Both
Health and Human Services, 46.402(a), 1991). Thus, parents must ordinarily give permission. This is a
the federal rules do not adopt a uniform definition of utilitarian approach to research that cannot directly
the term "children" bur rather defer to the state laws benefit the child. It allows for the use of children in
in which the research is being conducted. Although such research if the knowledge derived from the research
in general children become adults at the age of 18, is very important and the risks are small. Still, there
states have rules that allow children consent to some is a strong argument that this type of research is
medical procedures, and in such situations they would ethically questionable since it permits nonconsenting
not be considered "children" for purposes of the federal subjects who cannot benefit from their participation
regulations. For example, in Massachusetts 16-year- in the research to be placed at risk for the sole purpose
olds can voluntary admit themselves to mental hospitals of acquiring new knowledge.
for treatment. They would therefore not be "children" Category 4: Research not otherwise approvable which
in regard to research about voluntary admissions to presents an opportunity to understand, prevent, oralleviate
mental hospitals as far as the federal research regulations a seriousproblem affecting thehealth orwelfare ofchildren.
are concerned. Rather, they would be covered under This would include research that would present more
the more general research protection rules that apply than a minimal risk of harm to children with no
to competent adults. benefit to the individual child. For this research to be
The current federal regulations on research adopt approved, the Secretary of Health and Human Services
the sliding-scale approach to participation of children must consult with a panel of experts and give the
in research which was proposed by the National Com- public an opportunity to review and comment on the
mission. Essentially, the rules create four categories of proposal. There is no indication that this has ever
research with children (US Department of Health and been done.
Human Services, 46.404-46.407, 1991): These rules depend to a large extent on determining
Category 1: Research not involvinggreater than mini- that there is only minimal risk to children or a minor
mal risk. Such research is permissible as long as adequate increase over minimal risk. The term "minimal risk"
provisions are made for obtaining the permission of is defined as a risk that is not greater than those "already
the parent and the child's assent. encountered in daily life or during the performance of
Category 2: Research involvinggreater than minimal routine physical or psychological examinations or tests"
risk but presenting the prospect of direct benefit to the (US Department of Health and Human Services,
individual subject. To approve this type of research the 46.102(1), 1991). On the surface this appears to be a
IRB must find that the risk is justified by the anticipated reasonably protective standard, but it is actually a
benefit to the subject and that the risk-benefit ratio is standard without much content. Minors, especially
at least as favorable to the subject as alternative ap- adolescents, encounter quite substantial risks in every-
proaches. Again, a parent's permission and the child's day life. In fact, it is probably fair to say that as a
assent are required. This is likely to be the category into group adolescents encounter more risks on an average
which the majority of psychopharmacological research day than adults. If taken literally, this standard would
with children falls today. permit research in which adolescents were asked to
Category 3: Research involvinggreater than minimal have sex without using condoms because we know this
riskand noprospect ofdirect benefit to individualsubjects, is a risk that adolescents "encounter in daily life."
but likely to yield generalizable knowledge about the Even more difficult, in category 3 research, one needs
subject's condition. This category of research is approv- to figure our what is meant by a minor increase over
able only if the IRB finds the risk represents a "minor minimal risk.
increase" over minimal risk; the research procedures Because of the vagueness of the rules, they need to
are "reasonably commensurate with the subject's actual be viewed less as rules and more as concepts. We may
or expected medical, dental, psychological social or not be able to define minimal risk, but we know what
educational situation"; the intervention is likely to those words are trying to accomplish. A risk of everyday
yield generalizable knowledge of "vital importance" in life for a child may include not wearing a bicycle

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GLANTZ

helmet, but it is unlikely that an IRB would (or should) rules state that the parents give permzsszon and the
vote to approve a research protocol in which children child gives assent. Neither is accorded the full power
are sent to ride in traffic without helmets to compare to consent. The ideal the rules strive for is that both
their morbidity with children who do wear helmets. the parent and the child need to agree that the child
So, although the terms may be hard to define, the may participate in a research project as a condition to
concept of minimizing risk is one that researchers and such participation.
research reviewers know they need to attend to. The most important right that children have, how-
For the most part, children's "rights" under these ever, is the right to be protected from harm and
rules have not been addressed. Rather the focus has exploitation by adults. It is the requirement that the
been on safeguarding the welfare of children. Very child's welfare always comes first. Although it might
often discussions of research focus on informed consent, sound strange, it is the right to be treated paternalis-
which is a very important concept, as alluded to earlier. tically. While paternalism is a dirty word when it
Also, as mentioned above, in the draft rules, children comes to the treatment of competent adults, those
older than 6 years of age had to give their consent to who are not competent or who are not adults need
participate in research. The adopted rules provide: and deserve protection. It is for this reason that the
... The IRB shall determine that adequate provisions are made focus on research ethics and regulation should be on
for soliciting the assent of children, when in the judgment of the the acceptability of the research being proposed. It
IRB children are capable of providing assent. In determining
whether children are capable of assenting, the IRB shall take into
should not matter whether a parent or child consents
account the ages, maturity, and psychological state of the children to having the child's eyes infected with gonorrhea. The
involved (US Department of Health and Human Services, problem with that research was not the lack of informed
46.408(a), 1991). consent. Consent to an unacceptable act does not make
Even if a child is deemed capable of providing assent, the act acceptable. It is therefore absolutely essential
if the IRB determines that the proposed intervention for researchers and research reviewers to look closely
"holds out a prospect of direct benefit that is important at the ethics of the research they are proposing before
to the health or well-being of the children and is even thinking of presenting it to a subject for consent.
available only in the context of research," the assent The most important considerations in looking at the
of the child is not necessary. The Committee on ethics of a research intervention is the magnitude of
Bioethics of the American Academy of Pediatrics (AAP) the potential harm, the significance of the knowledge
has recently published a statement that encourages to be learned, the likelihood that the research will
physicians to obtain the assent of children in practice produce such knowledge, and the methods chosen to
settings (AAP Committee on Bioethics, 1995). As an minimize the potential harm to the subjects.
example, it states that physicians should seek the assent
Application to Pediatric Psychopharmacology
of a third grader for whom psychotropic medication
is being prescribed to treat an attention deficit disorder. An example of the obligation to protect subjects
Certainly older minors, who can understand the nature from harm in the context of psychopharmacology
of the research and what it entails, should be able to research is discussed in an article by Dr. Jay Katz, who
decide whether or not they wish to participate in a is a psychiatrist on the faculty of Yale University Law
research project. Research on the capacity of minors School and the leading scholar in the area of the
to make decisions supports this notion (Weithorn and ethics of research with human beings (Katz, 1993).
Scherer, 1994). The law increasingly recognizes that An experiment was designed to determine whether
older adolescents have the capacity to make important better predictions could be made about which schizo-
decisions. This is why mature minor women have a phrenic patients could be safely withdrawn from anti-
constitutional right to make abortion decisions without psychotic medications. This is obviously an important
parental involvement (Bellotti v Baird, 1979). It is issue. In the first phase, lasting 24 weeks, subjects were
interesting to note that the rules on participation of randomized into two groups. For the first 12 weeks half
minors as research subjects start with the assumption received a standardized dose of 12.5 mg of fluphenazine
that neither the parent nor the child has the full (Prolixins') and the other half received a placebo. In
authority to consent to research participation. The the second 12 weeks the injections given to the subjects

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 RESEARCH WITH CHILDREN: LAW AND ETHICS

were reversed. In the next phase all "clinically appro- researchers caused subjects to become sick? Finally,
priate" patients were to receive no drug. Criteria for how effective are the current regulations at protecting
relapse included high scores on test measures for con- human subjects? This study was approved by an IRB.
ceptual disorganization and unusual thought content, If this were a study that involved minor children,
but also included high scores on scales of bizarre the answers to these questions would be particularly
behavior, self-neglect, hostility, and suicidality. It ap- difficult to determine. It is unlikely, for example, that
pears that the investigators were willing to tolerate parents have the authority to consent to having their
severe recurrences in symptomatology. One of the children made sick.
justifications the researchers provide in their protocol Indeed the authority of parents to consent to some
for the drug withdrawal is that many patients had of the techniques that are considered important in
been requesting drug withdrawal for months. But Dr. conducting psychophamacological research needs closer
Katz points out that therapists who believe that patients examination. The controversy surrounding the use of
need such drugs try to impress on patients the need placebo-controlled studies has recently resurfaced.
to take them or to encourage resumption as soon as Rothman and Michels recently argued that the use of
any symptoms recur. In this case all patients were placebo-controlled studies is usually unethical (Roth-
withdrawn from the drugs that were effectively control- man and Michels, 1994). One of the studies they cite
ling their symptoms. Relapse in this study was not an as an example of what they believe to be the unethical
unfortunate consequence of treatment, but an integral use of placebos involved a study in which half of the
aspect of the research design. Katz avers that this is seriously depressed patients received a placebo even
particularly problematic because of the controversy though the investigators acknowledged that effective
over whether relapse leads to additional and at times antidepressant compounds were available. They argue
irreversible injury. The consent form informed prospec- that ethics require every patient to receive "either the
tive subjects that "the purpose of this study is to take best available treatment or a new treatment thought
people like me off medication in a way that will give to be as good or better" (p, 397). Needless to say,
the most information about medication, its effects on their position was met with considerable disapproval
me, on others and the way the brain works." The (Letters to the Editor, 1995). The argument for the
purpose was not stated to be the study of the recurrence use of placebos with adult subjects is that as long as
of symptoms after drug withdrawal. This study began adults are fully informed of the risks they take when
in the early 1980s. In the consent form of July 1988 consenting to participate in such a research project,
it stated that the subject may become worse. But at and as long as the risks are not unduly serious, then
that time it was known that 88% of the subjects had an adult should be able to consent to such risks for
suffered a relapse. The consent form also stated that altruistic purposes. For example, an adult should be
"my condition may improve, worsen or remain un- able to consent to the risk of not taking antihypertensive
changed." Although these outcomes are listed as equally medication for 8 weeks as long as proper provisions
likely possibilities, they obviously were not. Few sub- are made for monitoring that subject's condition to
jects were likely to improve or remain the same. reduce the risk of harm. This is a much more difficult
The question this research protocol presents involves problem when it comes to children or others who are
the adequacy of the consent process. It would appear not competent to give their consent. Assume a child
that the researchers were less than candid with their with attention-deficit hyperactivity disorder whose con-
potential subjects. But the next question is, should this dition iswell controlled with currently available medica-
research have been done in this fashion? Why did it tions. A research project is proposed to try to prove
go on for so many years? What was the minimum that a different drug is just as effective. May a child
number of subjects needed to get scientifically sound be put at risk of being withdrawn from a known
information? Is it appropriate for doctors to encourage effective treatment to be put on an inert substance or
their patients to stop taking effective medication? How a medication of unknown efficacy? If a parent is to act
much do patient-subjects need to deteriorate before in the child's "best interest" when making a surrogate
the needed information on relapse is acquired? How decision, how could that test be met in such a circum-
different is this from a Willowbrook-type case wherein stance? And while adults can act altruistically when

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they volunteer to stop taking their drugs through was never adopted is not clear. In a letter explaining
random selection, children who are "volunteered" by the Department of Health and Human Services' lack
their parents are not themselves acting voluntarily. of action in this area, then Assistant Secretary for
This is not to say that children can never be stopped Health Edward Brandt wrote, "It would be unwise to
from taking the drugs they are currently taking. For promulgate final regulations in this highly controversial
example, when a child is taking a drug that has serious and difficult area in view of the degree of divergence of
side effects, research designed to lower the dose or to opinion about solutions to ethical and legal problems"
remove the need for a potentially toxic drug altogether (Brandt, 1983). There continues to be interest in the
would be beneficial for the child. To stop a current question of whether the mentally disabled need special
medication and start another medication that, based protections. In the past, however, it was believed that
on sound scientific reasoning, is likely to be as effective these special protections might be needed because of
but have fewer side effects is not the same as stopping the institutionalization of people with mental disorders.
an effective medication and starting one that is known However, today the locale of treatments has changed
to be ineffective. dramatically. This raises difficult questions about how
The AAP has recently taken the position that "Pla- one would define the class of people who would come
cebo or untreated observational control groups can be under such regulations. But the controversy does con-
used in pediatric studies if their use does not place tinue. Recently a judge in New York ruled that patients
children at increased risk" (AAP Committee on Drugs, in psychiatric institutions cannot be given experimental
1995, p. 294). Circumstances in which the AAP com- drugs unless they give their own consent. In doing
mittee says that placebos may be ethically employed this, the judge specifically struck down regulations of
under this guideline include the following: the state office of mental health that authorized family
or friends to provide such consent on behalf of incom-
1. When there is no commonly accepted therapy for
petent persons (Fein, 1995).
the condition and the agent under study is the first
While the conduct of research with children who
one that may modify the course of the disease
suffer from mental disorders raises difficult ethical
process;
questions, not doing such research also raises important
2. When the commonly used therapy for the condition
questions. Do we not have some obligation to try to
is of questionable efficacy;
alleviate suffering and disability? Do we not need to
3. When the commonly used therapy for the condition
use scientific methods to distinguish between what is
carries with it a high frequency of undesirable side
truly effective and what is only folklore? A review of
effects and the risks may be significantly greater
the 1991 Physicians'Desk Reference showed that 81%
than the benefits;
of listed drugs excluded children. In 1992, of the 19
4. When the placebo is used to identify incidence and
new molecular entities with potential use in children,
severity of undesirable side effects produced by
79% were not labeled for use in children (AAP Com-
adding a new treatment to an established regimen; or
mittee on Drugs, 1995). The issue is not whether to
5. When the disease process is characterized by fre-
do research with children as subjects. The issue is
quent, spontaneous exacerbations and remissions
how to conduct such research in a manner that best
and the efficacy of the therapy has not been demon-
demonstrates respect and caring for the subjects of
strated (AAP Committee on Drugs, 1995).
such research.
It is worth noting that the only proposed federal
regulations that were never finally promulgated were
the regulations to provide additional protections to REFERENCES
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