American Journal of Law & Medicine

Research with children.(Law, Medicine and Socially Responsible Research)

I. INTRODUCTION

In the United States we have very mixed feelings about research with human subjects.(1) The Nuremberg Code (the Code), which provides a foundation for the protection of human subjects, was written by American judges in the context of trying Nazi doctors who committed atrocious acts of human experimentation on concentration camp inmates.(2) The Code provides ten common-sense guidelines controlling research.(3) For example, a researcher may not conduct research on human subjects without that subject's informed consent,(4) or if there is an a priori reason to believe that the research will cause death or disabling injury to the subject.(5) What is remarkable about the creation of the Code is that it was thought to be necessary to document and impose the most fundamental moral principles on researchers.(6) The Code demonstrates a remarkable suspicion of research with human subjects and those who perform such research.(7) Of course, given the context in which the Code was written, these suspicions were more than justified.(8) But since the Code was written, other abuses of human subjects have come to light.(9) The most notorious is the Tuskegee syphilis research in which black men were not treated for their disease so the researchers could follow the natural course of syphilis in black males.(10) Not only was their informed consent not acquired, they were lied to about the reasons for procedures that were conducted on them for research purposes and they suffered numerous other indignities and injuries at the hands of the researchers.(11) Recent disclosures demonstrate that post-1945 radiation research was conducted on nonconsenting human subjects in the United States.(12) This history causes suspicion of research with human subjects.(13)

On the other hand, research with human subjects has also led to remarkable health benefits.(14) The advent of new treatment modalities is largely dependent on the use of human subjects to determine their safety and effectiveness. The creation of antibiotics, vaccines, medical devices and other beneficial modalities all result from research with human subjects.(15) The mixed feelings we have about research with human subjects are described in the title of a 1975 National Academy of Sciences report entitled Experiments and Research with Humans: Values in Conflict.(16)

This conflict in values is even more pronounced when the research subjects are children.(17) Children have been particularly subjected to abuses by researchers(18) and "those who do research with children today have inherited the legacy of researchers who have come before them."(19) Recognizing this history provides a context for understanding the current rules that govern research with children. Susan Lederer and Michael Grodin have well documented many of the abuses of research with children.(20) Most of the following historical information comes from their work. The first tests of immunization were performed on slaves and children.(21) Edward Jenner vaccinated his one-year-old son with cowpox to see if it offered immunity to smallpox.(22) His next subject was an eight-year-old child who was challenged with an inoculation of smallpox material in order to determine if the inoculation was effective.(23) In 1802, Jenner's vaccine was tested on forty-eight children living in an almshouse.(24) All the children were challenged with smallpox to see if they were effectively immunized.(25)

Following the exploitation of children as laborers in the Industrial Revolution, the 1900s saw an increased interest in child welfare along with an increased desire to learn more about children's health problems.(26) In the first decade of the 1900s, Alfred Hess, a respected pediatrician, became the medical director of the Hebrew Infant Asylum in New York.(27) He noted that conducting research in an asylum was ideal because it approximated those "conditions which are insisted on in considering the course of experimental infection among laboratory animals, but which can rarely be controlled in a study of infection in man."(28)

The germ theory was tested by intentionally infecting both adults and children with diseases.(29) The health officer at a Hawaiian leprosarium injected six girls under his care with the syphilis virus.(30) Dr. Henry Heiman reported that he was able to successfully produce gonorrhea in a four-year-old "idiot" with chronic epilepsy as well as in a sixteen-year-old male "idiot."(31)

The invention of the x-ray prompted much research in children and adults.(32) Physicians used x-rays to study the normal development of children and adults, including the fetus in utero.(33)

In 1896, Dr. Arthur Wentworth published a paper describing spinal taps he performed on twenty-nine children at Children's Hospital in Boston to determine if the procedure was harmful.(34) He determined they were safe.(35) However, John Roberts, a Philadelphia physician, noting that these procedures were with "no therapeutic indications for the operation" and for "purely and avowedly experimental" reasons, labeled Wentworth's use of these procedures "human vivisection."(36)

In 1941, Francis Payton Rous, editor of the Journal of Experimental Medicine, rejected a manuscript from a physician and wrote to the author, "the inoculation of a twelve month old infant with herpes ... was an abuse of power, an infringement of the rights of an individual, and not excusable because the illness which followed had implications for science."(37) The fact that "a child was `offered as a volunteer'--whatever that may mean--does not palliate the action."(38) This statement represents an important turning point in the discussion of research with children. It is one of the first statements to acknowledge that children themselves have rights as individuals and that the thought that one could be "offered as a volunteer" was a contradiction in terms.

In one of the initial research projects designed to determine if phenylalanine accumulations caused phenylketonuria (PKU), a metabolic disorder that causes mental retardation, the researchers first put a two-year-old girl with PKU on a diet low in phenylalinine.(39) A gradual improvement resulted over a few months.(40) Due to the importance of establishing the role of phenylalinine in this condition, the researchers decided to add phenayalinine to the child's special diet without telling the child's mother so that any change could be noted by her without bias.(41) The mother reported a definite deterioration; within a few days, she reported that her daughter lost all the ground that had been gained in the past ten months.(42) This was then repeated with the same child.(43) From the 1950s through the 1970s, a research team at the Willowbrook State School systematically infected mentally retarded children with strains of hepatitis.(44) This was a signal event in the discussion of research with children and the mentally disabled. Believing that virtually all children would contract the disease in any event because of the conditions at the institution, the investigators infected children to study the natural course of the disease as well as some other matters.(45) The research team provided a specially equipped and staffed unit where the children would be protected from other diseases in the institution.(46) There was a waiting list for admission to the institution and parents who consented to have their children participate in the study were assured more rapid admission to the school.(47) There was a substantial outcry over the Willowbrook experiments.(48) Essentially, children were intentionally afflicted with a serious illness; parents who were desperate for some kind of care for their mentally disabled children were seen to be exploited; the wretched conditions in which mentally disabled children were housed were used as an excuse to make them sick intentionally, and the legal authority of parents to "volunteer" their children for such research was challenged.(49)

Other examples could be given here but are not necessary. It is clear that children have been misused as research subjects and the very fact that they were children would seem to have made them more likely to be abused as research subjects.(50)

Concern about these past abuses have led to the adoption of federal regulations that are specifically designed to protect children when they are enrolled as research subjects.(51) Indeed, a New York court which limited the use of children and mentally disabled individuals as research subjects began its opinion by stating:

The mere mention of experimental medical research on incapacitated human

beings--the mentally ill, the profoundly retarded, and minor children summons

up visceral reactions with recollections of the brutal Nazi experimentation

with helpless subjects of concentration camps, and elicits shudders of

revulsion when parallels are suggested. Even without the planned brutality,

we have had deplorable instances of over-reaching medical research in this

country.(52)

On the other hand, at about the same time that the New York courts questioned research with incompetent subjects, federal policy was being adopted that would increase research with children. The U.S. Food and Drug Administration (FDA) has become increasingly concerned about the lack of labeling indications for drugs that are used to treat children.(53) Large numbers of drugs that are regularly used for the treatment of children have not been specifically approved for such use and the pharmaceutical manufacturers have not conducted research designed to determine the safety and effectiveness of such drugs in children.(54) The FDA points out that, "many of the drugs and biological products most widely used in pediatric patients carry disclaimers stating that safety and effectiveness in pediatric patients have not been established."(55) To remedy this problem, the FDA has proposed regulations that would require drug manufacturers to test new drugs on children, thereby increasing the number of children who will be human subjects.(56)

Similarly, the National Institutes of Health (NIH) recently adopted a policy and guidelines that essentially require researchers to include children as research subjects or to explain why they have decided not to include children as research subjects.(57)

We can see in these contrasting judicial and regulatory approaches to research with children the conflicting social policies being discussed: the need for useful scientific and medical information about children and the need to protect vulnerable populations from misuse as research subjects.

II. PROTECTION OF CHILDREN

Children are particularly vulnerable as research subjects for numerous reasons. First, they may not be competent to volunteer to participate in a research project and so they will be participating either nonvoluntarily or involuntarily.(58) Second, the person giving consent for the child's participation may have ulterior motives that go against the best interests of the child, especially considering the psychological effects an illness can have on a family.(59) Furthermore, parents may be offered incentives for their child's participation that may influence their decisions to allow their child to participate.(60) Third, the person proposing the research may have motives for conducting the research that are unrelated to, or even conflict with, the particular subject's welfare.(61) Fourth, if the children are institutionalized or otherwise in state care, they are removed from the "ideal" protective parent.(62) Fifth, the legal authority of parents or guardians to "volunteer" their children to participate as research subjects is unclear.(63) Last, there may be subgroups of children, such as terminally ill children or children with rare conditions, that may place them at special risk.(64)

III. MAY PARENTS CONSENT TO THEIR CHILD'S PARTICIPATION IN RESEARCH?

Parents have broad authority to make decisions about their children. Indeed the ability of the state to interfere with parental authority over their children is subject to constitutional constraints.(65) When parents act in a manner that arguably furthers the interest of their children, their judgments are not subject to state scrutiny or limitation.(66) Alternatively, parents are not obligated to act in the objective best interests of their children. They are not required to send their children to the best schools available or to provide them with the best food, shelter or medical care they can afford. Rather, parents must meet a standard of adequacy, not excellence. Parents may make idiosyncratic decisions for their children for personal or religious reasons. For example, Amish parents have been found to have the constitutional right to keep their children from attending high school, although non-Amish parents may not do so, even though the public consensus, represented by a legislative enactment, is that such schooling is beneficial to children.(67) A parent who refuses to consent to the repair of his teenage son's harelip and cleft palate may lawfully do so even though the consensus of medical opinion is that the child would benefit from the procedure.(68) Similarly, a New York court held that a parent may use "alternative therapies" to treat a child suffering from cancer as long as one licensed physician supports that decision, even when the vast majority of medical opinion was that the child would more likely survive with standard medical therapies.(69) Absent an almost certain death from lack of medical treatment, parents have almost unlimited authority to make medical decisions on behalf of their minor children.(70) The foundation for this rule is the socially accepted notion that parents should be able to decide what activities or experiences are desirable or beneficial for their child. The child is not a creature of the state and the state should not interfere with the private parent-child relationship except in exceptional circumstances.(71)

The scope of parental authority becomes more questionable when the parent is agreeing to a risky intervention or activity that cannot possibly benefit the child. Clearly, parents may agree to a child's participation in activities that may prove harmful to the child, particularly when the child also volunteers to participate in those activities. For example, adolescents, with their parents' approval, may participate in sports, such as high school football, that may lead to serious injuries. Both social and physical benefits are derived from participation in organized sports, even where there is a risk of harm. The balancing of the risks and benefits is usually considered a matter for the parent and the child, not the state.(72)

However, there have been instances where the authority of a parent or guardian to consent to nonbeneficial intrusions into a child's or ward's body have been questioned. In the early history of organ transplantation, in a number of instances it was proposed that a kidney be transplanted from one identical twin to another.(73) Physicians and hospitals refused to rely on parental consent for the removal of an organ from a healthy child because it was unclear that parents had the authority to consent to a surgical procedure that had some risk, that left the child in a somewhat worse physical condition as a result of the procedure and that was not for the child's benefit.(74)

The first of these cases arose in 1957 in Massachusetts when a kidney transplant was proposed between nineteen-year-old identical twins (who were considered minors at that time).(75) Although both the parents and the children consented to the procedures, the physicians refused to operate because of the uncertainty of the validity of parental consent for the removal of the kidney from the healthy child.(76) A declaratory judgment was sought from a single justice of the Massachusetts Supreme Judicial Court.(77) Expert psychiatric testimony was offered, which stated that the death of the sick twin would have grave emotional impact on the healthy twin.(78) As a result, the court was able to find that the operation was "necessary for the continued good health" of the healthy twin and therefore removing the kidney from the healthy twin would result in "conferring a benefit upon" him.(79) The same court used the justification of "psychological benefit" to authorize kidney transplants between two sets of fourteen year old twins in subsequent cases,(80) Notably, in each of these cases the court also found that the children understood the risks and consequences of the procedures and gave their consent free of pressure or coercion.(81) Thus, where both "competent" children and their parents consented to a procedure that conferred "psychological benefit" at the cost of what was seen as a relatively small risk, courts authorized the procedure.(82) Nowhere did the courts intimate that parents alone could volunteer uncomprehending children for organ donation.(83)

In later cases, courts permitted the removal of kidneys from individuals who were clearly incapable of giving their own consent. …

Log in to your account to read this article – and millions more.