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Institute of Medicine (US) Committee on Clinical Research Involving Children; Field MJ, Behrman RE, editors. Ethical Conduct of Clinical Research Involving Children. Washington (DC): National Academies Press (US); 2004.

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Ethical Conduct of Clinical Research Involving Children.

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BState Regulation of Medical Research with Children and Adolescents: An Overview and Analysis

Amy T. Campbell, J.D., M.Bioethics

Research with children and adolescents is increasingly recognized as vital to promote the health of our youth, both current and future. The conduct of such research requires access to children and adolescents both to enhance the scientific validity of research with relevance to these populations and, as a matter of justice, to ensure that children and adolescents enjoy the benefits of research.

Children and adolescents are considered -- both in law and in ethics -- "vulnerable" populations deserving special protections. These protections enable society to reach a reasonable balance between protecting the safety of children and adolescents from research risks and promoting their inclusion in studies to benefit them and future generations.

Special federal regulations provide guidance to child and adolescent heath care researchers. One section of these regulations (Subpart A of 45 CFR Part 46 for the U.S. Department of Health and Human Services) provides for basic human subject protections and is known as the “Common Rule” for its application to most research conducted, supported, or otherwise regulated by 17 federal agencies 1. Additional protections (Subpart D of 45 CFR 46), which apply specifically to children, have been adopted by the U.S. Department of Health and Human Services 2, the Food and Drug Administration (FDA) (except for Section 46.408(c), which pertains to the waiver of parental permission), the U.S. Department of Education, the Central Intelligence Agency, and the Social Security Administration. Additional regulations issued by the U.S. Department of Education under the Protection of Pupil Rights Amendment govern social research conducted in school settings or otherwise related to education matters 3 (Table B.1; all tables are located in Addendum B1). The language of the federal regulations is frequently adopted as institutional review board (IRB) policy 4, with a likely result that most research, irrespective of the funding source, is reviewed -- at least as an initial matter -- according to the parameters of the federal guidelines.

TABLE B.1. State Education-Related Provisions for Research with Children and Adolescents (in School Settings) .

TABLE B.1

State Education-Related Provisions for Research with Children and Adolescents (in School Settings) .

Notably, with respect to several issues, the federal research regulations rely on state laws to provide relevant definitions or other elements essential to interpretation and application of the regulations. For example, the regulations define “children” as those persons who have “not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted” (emphasis added) 5. Similarly, “guardian” means “an individual who is authorized under applicable state or local law to consent on behalf of a child to general medical care” 6.

Thus, it is critical that researchers, IRB members, and others engaged in or affected by the research process understand how state laws might affect research with children and adolescents. Relevant inquiries include the following issues: age of majority, emancipation status, the “mature minor” rule and other specific provisions related to age of consent for general medical care, and/or specific conditions (e.g., substance abuse disorders or emotional disturbances).

An overview of state laws related to these issues follows. Also addressed are state laws, regulations, or policies specific to children in state custody (e.g., children in foster care or detention facilities), when such laws, regulations, or policies are available.1 These guidelines are of particular importance in that they apply to those children who likely have unique medical or psychosocial issues distinct from those of the general population of children.2 In light of these particular issues, targeted research is needed to focus on these specific concerns; however, special protections are justifiably attached to vulnerable (“at-risk”) children.3 A brief analysis incorporating relevant case law follows the overview to highlight the ways in which states do -- or do not -- regulate research with these specific populations. Directions for state guidance are also provided.

SUMMARY OF STATE LAWS RELEVANT TO MEDICAL AND BEHAVIORAL RESEARCH WITH CHILDREN AND ADOLESCENTS

Age of Majority

As a first issue, the age of majority in each state is important, as it sets forth the age above which Subpart D of the federal regulations, in addition to any special state protections, do not apply. That is, it is important to know what each state defines as the age of majority, since those who are above the age of majority should not be subject to Subpart D. Most states set the age of majority at 18 years, meaning that -- for legal purposes -- children are those individuals who have not yet reached the age of 18 (Table B.2).4 This is a fairly easy “bright-line” standard of which to be aware. However, for purposes of determining the ability of children -- most likely adolescents -- to assent, and even consent, to research participation, it is important to go beyond these “majority” statutes to focus on other consent-related provisions.

TABLE B.2. Age of Majority.

TABLE B.2

Age of Majority.

It is also worth noting that this is a legal definition and, hence, is not necessarily indicative of the maturity level, decisional capacity, or cognitive abilities of youth. In fact, several commentators call for greater attention to this matter and clarity in the law to accord adolescents greater respect vis-a-vis their decisional capacities and need for confidentiality in medical care and research 8. Furthermore, it is important to recognize that while this sets out a bright-line distinction between legal attainment of “competence” in medical decision making (as an adult), who is or is not a “child” for purposes of federal research regulation references state laws (but not specifically the age of majority) on this matter. The latter, in turn, set forth conditions under which certain “minors” might be able to make medical decisions on their own on the basis of certain life events or in certain medical scenarios. Hence, they might be “minors” according to a brightline test but are not subject to federal research regulations as “children” when state law is applied.

In the sections that follow, which discuss emancipation, the mature minor rule, and minor consent to treatment provisions, it should be emphasized that state laws have relevance in two different ways: the application of the definition of “children” and the waiver of parental permission to medical treatment and in other contexts. That is, certain state laws place a minor outside the definition of children (which would seemingly make Subpart D of the federal regulations inapplicable); other state law provisions support the waiver of parental permission (which would be much more context sensitive and which may or may not reasonably extend to research-related decisions).

Emancipated Minors

As noted earlier, certain life events remove minors from the purview of child or adolescent medical regulation. That is, the age of majority may not be met, but emancipation frees the former “child” from parental custody and control. Typical conditions that states use to establish emancipation are marriage 9, military service 10, or court order 11 (Table B.3).

TABLE B.3. Emancipation Conditions.

TABLE B.3

Emancipation Conditions.

The concept of emancipation arose in common law (court-developed law) and has only more recently been explicitly addressed in statutes.5 The “classical” definition of emancipation under the common law could be summarized thusly: emancipation occurs when a minor voluntarily lives independently of his or her parents (whether by marriage, military service, or the establishment of financial independence), the latter who, in turn, make no attempt at ongoing control or care of their child. In turn, it does not seem to make sense to treat “children” who meet the common-law definition of emancipated minors as being under parental authority 12.

More recently, states have begun to supplant the common law with statutory refinements on the concept, including a focus on a broadened range of emancipation effects, including, for example, an ability to consent to medical treatment 13. However, not every state has an emancipation statute; moreover, some that do continue to apply the concept rather narrowly, for example, to allow certain contract rights 14. Additionally, many statutes list only certain emancipation effects. For example, some statutes establishing criteria and procedures for emancipation explicitly allow for consent to medical care; others do not 15.6

Furthermore, despite early developments in common law from which “emancipation” emerged (i.e., a focus on rights to contract, own property, and retain wages), few state courts have recently addressed the issue with respect to an “expanded” view of the effects of emancipation 16. Thus, unfortunately for the researcher searching for uniformity, the picture is far from clear. For the purposes of this review, however, emancipation, whatever the causal event, is taken to mean that the child becomes an adult in the eyes of the state; that is, all rules governing parental custody or control are severed, which could include parental permission for research participation, to the extent that states follow a broader range of emancipation effects. Moreover, in this appendix, only those individuals considered adults for all purposes under state law are included in the category “emancipated minors.”

Mature Minors

Although emancipation in effect turns the “child” into an “adult” for the purposes of state law, other events may occur as a result of which the child or adolescent may be seen as sufficiently mature to make (certain) health care decisions 17. In turn, the latter falls into two distinct categories: the “mature minor” rule (which is derived from common law and which has specific meaning and scope) and law that allows exceptions to the requirements of parental permission because of the types of services sought or the status of the minor. Moreover, it should be noted that the distinction between emancipation and mature minor status is unfortunately far from clear or uniform, especially as time has progressed and the two concepts have become more intertwined and complex.7

TABLE B.4. Mature Minor Provisions.

TABLE B.4

Mature Minor Provisions.

General lay audiences often confuse the concepts of emancipation and maturity; for legal purposes, however, they are not the same. For the purposes of this appendix, and in accord with the general sentiments from common law, “mature minors” are typically defined as children who are seen as “sufficiently” mature (a subjective decision, made on a case-by-case basis) with the capacity to understand the risks and consequences of certain decisions and, hence, who have the ability to make those decisions, including, at times, decisions relating to medical treatment (Table B.4).8 The historical development of the “mature minor” doctrine in common law supports a distinction from emancipation, inasmuch as the former doctrine is of more recent vintage conferring more context-sensitive consent rights in children, for example, to consent to certain medical treatments.9

Age of Consent for Medical Care

Some youth, who are still technically “minors” under state law, are allowed to consent to general medical treatment under specific state statutory provisions 19. For example, several states allow minors to make medical decisions when they hold sufficient capacity to understand the nature of the treatment 20. A few states have set age limits younger than 18 years at which they allow minors to provide general consent for health care, such as 14 years (Alabama) 21, 15 years (California, Oregon) 22, and 16 years (South Carolina) 23. Other states (e.g., Colorado, Indiana, and Maine) allow earlier consent to health care or treatment on the basis of certain events that indicate that the minor has sufficient decisional capacity, such as living separately and apart from the parents 24. It is worth noting again, however, that statutes delineating conditions of sufficient decisional capacity should be distinguished from “emancipation” status. Emancipation represents a “legal” transition to adulthood in the eyes of the state, whereas decisional maturity represents a context-specific ability to consent in certain instances.10

Age of Consent Under Certain Circumstances

In addition, all states explicitly authorize minors to provide consent to health care when the decisions are related to certain disorders or types of care. That is, for purposes of consenting to specific health care services, these minors may be explicitly allowed -- ”by statute -- consent authority 25. It is important to note, however, that this does not mean that such minors cannot consent in other situations; rather, for public policy reasons, states have, at times, chosen to specifically address minors' decisional capacity in certain situations to promote health-seeking behavior 26.11 Examples include consent for mental health treatment, substance abuse treatment, treatment for human immunodeficiency virus (HIV) infection or acquired immune deficiency sydrome (AIDS), testing or treatment for sexually transmitted diseases (STDs), and family planning services (Table B.5).

TABLE B.5. Minor Consent for Certain Conditions/Disorders.

TABLE B.5

Minor Consent for Certain Conditions/Disorders.

These conditions, in essence, allow individuals who are technically minors to make their own health care decisions under specific conditions. At issue, however, is the extent to which treatment-related consent, whether in general medical settings or for specific conditions, translates to the research setting.

Research-Specific Legislation

Few states have any regulations that apply specifically to research with children and adolescents 27. Moreover, those statutes that address research with youth do so only under confined circumstances 28. Thus, although federal regulations reference state law, state law -- as specifically applied in the research setting -- is a relative vacuum in terms of the regulation of research with children and adolescents.

This uncertainty and frequent silence on the matter leaves researchers and IRBs in a position to make a best guess as to whether state laws related to treatment also apply to research, although there are good reasons to believe that they do apply, at least in certain situations 29. Arguments have been put forward that such laws should apply, at least to the extent that research relates to specific conditions for which consent to treatment laws apply, for example, mental health and STDs 30. For example, if a study sought to investigate the behavioral mechanisms at play in adolescents' decisions to seek out treatment for an STD, a state that allows adolescents to consent to treatment for an STD should also allow for consent to research in connection with that STD. The argument might proceed that the legislative intent behind consent to treatment -- to promote individual and public health while preserving confidentiality -- should similarly apply to research.

Moreover, it is important to note that where the law is silent on the issue (e.g., the applicability of treatment consent by minors to research consent), silence does not imply impermissibility. In fact, it could be argued that actions are permissible unless they are specifically restricted by the courts or legislative actions 31.

As a general principle, however, judicial development of the common law is not arrested by piece-meal legislative adoption of specific statutory exceptions to a general common law rule. One of the great attributes of Anglo-American common law has been the flexibility demonstrated by the case by case judicial development of the principles and rules of the common law to adapt to the emerging conditions of society; this flexibility permits the law to remain relevant and reasonable, preventing “mindless obedience to a precept that can confound the search for truth and foster an attitude of contempt” 32.

Alternatively, of course, it should be noted that there is an important distinction between research and treatment. The former seeks to build generalizable knowledge without a focus on individual benefit, whereas the latter focuses on individual well-being. Accordingly, inasmuch as their intents vary, so too might the legal protections for children and adolescents attached to research versus treatment justifiably vary. Federal regulations also note that “assent,” the child's “affirmative agreement to participate in research,” is required when IRBs determine that children are capable of such, thus leaving much to the IRB's discretion 33. This imprecision in federal regulations has not been addressed by the states 34.

Finally, it is also worth clarifying the distinction between emancipation and mature minor status, a distinction not always clearly made in state law.12 In general, emancipation (in this appendix) confers broader “adult” status to youth in all aspects of their lives, whereas the attainment of “mature minor” status is more narrowly construed in terms of the sort of health care consent authority that it confers. These differences might similarly affect the reach of regulations on research with minors, or at least the requirements to consent to research. “Emancipated minors,” to whose lives events have conferred -- in the eyes of the state -- legal adulthood, should be able to consent to research as adults.13 “Mature minors,” on the other hand, are likely more limited in what they can and cannot consent to in treatment and in research.

Unfortunately, there is thus a great deal of uncertainty as to the extent of state regulations and the applicability of existing state regulations with respect to medical research with children and adolescents. Perhaps this should be unsurprising given the particularly recent nature of calls to enhance the base of research with populations of this age 35. Whatever the case, states have for the most part seen fit to follow federal regulations in this area to date 36. Whether the increasing demands for research with children and adolescents, coupled with advances in understanding of child and especially adolescent capacity and maturity, will affect states' perceived need for further regulation remains to be seen. However, it would not be surprising if the conduct of more research in the absence of clear authority led to litigation, not unlike that witnessed in Maryland 37. Before the discussion turns to case law, however, it is also important to touch upon a certain subset of the child and adolescent population: children in state custody.

Research-Specific Regulations: Children Under State Custody

Of special concern to researchers and policy makers are regulations pertaining to children in state custody, for example, children in foster care, juvenile delinquents, and wards of the state. These children fall under state control under the doctrine of parens patriae, the concept that the states assume a “parental” role to protect children when biological parents are not able to do so, such as in instances of child neglect or abuse or when children enter the juvenile detention system.

As the primary “authority” figure for these children, the state therefore typically assumes a custodial role for children that may extend to health care decision-making. The federal child-specific regulations contain a section explicitly addressing research with “wards of the state” 38. Research with such children is permissible only if it relates to their status as wards or if it is conducted in settings in which a majority of the children involved as subjects are not wards 39. Examples of the former might include research specifically related to issues facing children in foster care subsequent to child abuse; the latter might pertain to school-based research in which wards of the state are in a minority.

The federal regulations further require that special advocates -- not state-appointed guardians -- be appointed for each child 40. These regulations are in addition to the more general federal regulations, which require IRBs to weigh the risks and benefits of any studies with any child populations, to ensure that IRBs do not allow high-risk (greater than a “minor increase over minimal risk”) studies unless they have a prospect of directly benefiting the participants. Of interest is the extent to which states expand on federal guidance, inasmuch as they are the custodians primarily concerned with the welfare of children.

A further distinction is whether parental ties have been terminated, that is, if the child is simply in temporary custody of the state (state as custodian) or if the child is in a permanent out-of-home placement (state as legal guardian) because parental rights were terminated. If ties are not terminated, states likely defer to the authority of the parents over their child's medical care, especially if the treatment is considered optional. If the state deems treatment to be necessary, however, and the parent refuses permission, the state could override the decision and provide its own authorization for treatment pursuant to parental neglect or abuse laws 41. (This appendix refers generally to parental permission according to federal regulatory language, but some of the statutes and court decisions refer to parental consent, and that language is retained when individual statutes or court decisions are cited.)

The general tendency, however, is to defer to parental rights and, to the extent possible, involve parents in decision making when it is feasible and in the best interest of the child, as well as in keeping with constitutional law around parental rights 42. It is likely that research participation decisions would follow a similar process, although deference to parental authority is even more likely unless the research is deemed of direct benefit and minimal risk.

A review of state law, regulation, and case law related to this research suggests that little formal guidance is available. To clarify this, commissioners of each state's child welfare or social services department were recently contacted for further information on state and local policies or other guidance related to research with children under state custody. On the basis of the feedback received, it appears that there is little guidance in this area beyond federal research regulations or state consent to treatment laws that generally apply to children and adolescents (Table B.6). In fact, there seems to be a general lack of familiarity with and training in research issues generally, and research ethics specifically, among state agency personnel.

TABLE B.6. Regulation of Research with Children and Adolescents in State Custody: Responses from Child Welfare or Social Services Personnel.

TABLE B.6

Regulation of Research with Children and Adolescents in State Custody: Responses from Child Welfare or Social Services Personnel.

Applicable policies, when such policies exist, tend to track federal regulations on research with children generally. They also typically apply different standards to research with various levels of risk and to research conducted by agency employees (e.g., state or local department of social services case workers) compared with the standards that they apply to research conducted by external researchers 43. Other states choose not to apply special rules, relying on federal regulations and IRB review by relevant institutions (presumably, the home institutions of external researchers) 44.

Moreover, when policies do exist, they often restrict the research methods used with these populations -- such as research with pharmaceuticals or the use of placebos -- inasmuch as the “in-custody” child and adolescent population is seen as particularly vulnerable 45. The extent to which these policies -- or the general lack thereof -- affect research with children under state custody is an important empirical question deserving further study. (See Addendum B2 for a discussion of two hypothetical studies proposing to perform research with children in state custody and how states might approach such proposals.)

CASE LAW

Case Example

Researchers at a prominent institute affiliated with an academic medical center propose to study the effects of various types of lead abatement on a group of already affected and at-risk children from an urban inner-city environment. The rental properties in the community at issue will be classified into five groups: the members of the first three groups live in homes experiencing various levels of lead abatement (“intervention” groups), and the members of the last two groups are the controls (the members of one control group live in homes that were previously fully abated and the members of the other control group live in homes built without lead paint). Landlords will be recruited, and those who agree to offer their properties for participation in the research will be encouraged, if not required, to rent to tenants with young children. Research investigators will also assist landlords to take advantage of loan programs supporting abatement.

The study would last 2 years, over which time the researchers would measure and compare the short- and long-term effects of the various abatement methods to reduce lead levels in dust and children's blood. The stated purpose is to see if the less expensive means of lead abatement adequately protect the children's health. That is, the hope is that children's health is safeguarded, while the availability of low-rent housing in inner cities is maintained.

Parents who permit their child's participation would be informed immediately if their child's blood level was elevated; lead levels in the dust would also be provided periodically. Lead Registry Surveillance statistics released in 1999 show that although the number of children with elevated blood lead levels (EBLs) and lead poisoning declined during the latter part of the 1990s, the levels were disproportionately concentrated in the study site (urban region). Significantly, although 6.3 percent of children tested statewide had EBLs and 0.9 percent had lead poisoning, the proportions at the study site (urban area) were 16.7 and 2.6 percent, respectively 46. Furthermore, the researchers estimated that the chosen study site targeted children in the highest risk communities for EBLs and lead poisoning 47. Additionally, an annual state report supports claims that during the years leading up to the study (when the study was designed), up to 95 percent of the homes in the study site had lead hazards 48.

The academic medical center's IRB approves the study, and with funding from the Environmental Protection Agency and state agencies, the research proceeds. After the study ends, two families sue the research institute for negligence, alleging untimely notice of EBLs, placing their children at unnecessary risk, in addition to a failure to meet standards of adequate parental informed permission.

The case proceeds to trial, with the lower court agreeing with the defendant that no legal duty exists between the researcher and the subject (summary judgment). The case is appealed and is taken to before the state's highest (appellate) court. How might it respond to the facts of this case?

Illustrative States

Maryland

Few cases directly address state treatment of research with children and adolescents. Perhaps the most compelling and recent case is that described in the “case example” above, which highlights the facts of a recent Maryland case, Grimes v. Kennedy Krieger Institute, Inc. 49. In its decision on this case, the Court of Appeals of Maryland (the state's highest court) decided that a “legal duty normally exists between researcher and subject,” by virtue of the “special relationship” between them and arising out of contract law (the “contract” being the informed consent and permission form signed by the parents, who received compensation for their child's participation) 50. Finding that a duty could exist, the case was remanded to the trial court for a factual determination whether a duty did in fact exist in this case, whether that duty was breached, and if such breach was the proximate cause of damages (standard requirements of action in negligence) 51.

Of particular note was the court's decision to go beyond the issue of negligence to find that, under state law, parental authority to permit their children to participate in research does not extend to nontherapeutic research that carries with it the risk of harm to the health of the child 52.14 In so deciding, the court referenced the history of abuse in research: from Nazi experiments (e.g., typhus experiments with concentration camp inmates) to the Tuskegee study (syphilis studies) and the Jewish Chronic Disease Hospital Study (cancer study without consent) 53. The court was particularly troubled by the economically disadvantaged condition of the children and families in this case 54. As the court stated:

The determination of whether a duty exists under Maryland law is the ultimate function of various policy considerations as adopted by the Legislature, or, if it has not spoken, as it has not in respect to this situation, by Maryland courts. We do not feel that it serves proper public policy concerns to permit children to be placed in situations of potential harm, during nontherapeutic procedures, even if parents, or other surrogates, consent 55.

That is, the court interpreted Maryland law as not allowing parental consent (permission) for greater than minimal risk, “nontherapeutic” research in the first instance (e.g., when a “reasonable parent” would not allow such) 56. Similarly, research was found to be impermissible without valid informed consent 57.

The merits of this decision are beyond the scope of this paper. However, its ramifications are important for future researchers in Maryland and to the extent that it has received national scrutiny across the country. The case has received much press, especially in research, research subject advocate, and legal circles, which quite likely will translate to related case and state law developments 58. It will be interesting to see if other courts, in Maryland and beyond, follow the appellate court's lead and further delineate those conditions under which research with children, including at-risk, sick, or healthy children, is permissible 59. It will also be interesting to see how states respond to challenges to define “risk,” ”therapeutic,” and “nontherapeutic,” as well as the limits of “assent” and parental “permission” in relation to research with youth.

As noted in the preceding sections, state legislatures and executive agencies have, to date, had little to say about research in general and even less about research with children and adolescents. This case might serve to create ferment in state legislative bodies and within child-serving agencies to craft policies, guidelines, and even statutes to address research issues. Of note, however, is the fact that as of this writing (August 2003), the Maryland legislature has not passed legislation specifically responding to concerns raised by the Grimes decision. After the initial Court of Appeals decision, many believed that Johns Hopkins University and the University of Maryland would push for legislation to address the extent or limits of parental authority to permit research with their children, and a legislative committee hearing was scheduled to talk about what was seen as the crippling effect of the decision on research involving children.

However, after a subsequent clarification by the court in its denial of the Kennedy Krieger Institute's motion for reconsideration (in which it clarified its intent as to the meaning of “any risk” as per the bounds of parental authority), the universities backed off, deciding that the ruling would not dramatically alter their respective research portfolios 60. The legislative committee hearing was conducted in October 2001, but its focus shifted from the Grimes case to the “regulatory gap” created by the limits of federal regulation and the unregulated status of non-federally funded, non-FDA research. To address this, a bill was enacted in 2002 61. Interestingly, however, no further legislative attention has been paid to the issues in the Grimes case itself 62.

On the basis of case-specific inactivity in the state legislature to date, how might Maryland trial courts respond? The Court of Appeals remanded the Grimes case back to the trial court for a decision as to the factual merits of claims of liability (by the researchers) and damages. In addition, the court also stated that a determination of “therapeutic” versus “nontherapeutic” research was for factual development on remand.

By “any risk,” we meant in original decision any articulable risk beyond the minimal kind of risk that is inherent in any endeavor. The context of the statement was a non-therapeutic study that promises no medical benefit to the child whatever, so that any balance between risk and benefit is necessarily negative. As we indicated, the determination of whether the study in question offered some benefit, and therefore could be regarded as therapeutic in nature, or involved more than minimal risk is open for further factual development on remand 63.

The lower court's decision is still pending. What is less an issue for the specific parties, but a big issue for future researchers, is the appellate court's decision to extend its holding to the bounds of the consent (permission) authority of parents on behalf of their children. This legal holding is not before the trial court. Thus, the lower court is left to decide if -- in this instance -- the research was therapeutic or not, was minimal or not, or was conducted with “at-risk” or healthy children.

Although it is likely that the case will be settled, if it proceeds to trial, the lower court could conclude that the research in this matter is “nontherapeutic” (i.e., there is insufficient evidence in the record that the researchers contemplated medically benefiting the “healthy” child subjects). Given the strong language of the high court's decision, such an approach would not be out of the question. Inasmuch as the appellate court's decision provided a litany of reasons -- in quite dramatic language -- for protecting children from overzealousness in research, researchers might now be a bit more hesitant when proposing studies with children in Maryland, especially when the children come from disadvantaged backgrounds, the risks are uncertain, and the notion of “benefits” is a stretch.

The relative silence thus far should not be seen as a defeat for those who would seize upon the arguments used by the Maryland Court of Appeals; rather, it might well be the quiet before the storm. The case continues to be discussed in research meetings and is still cited by research subject advocates 64. Thus, the issues raised by the court are still “in the air” and might very well surface in other decisions and on the agendas of other states' legislatures. What might such cases look like in other states, based on their statutory and case law climates to date?

New York

Apply the same facts in the case example cited above to New York: where might its courts fall? New York is generally a conservative state with respect to research with “vulnerable subjects,” especially with persons with mental impairments.15 New York law generally designates parents or guardians as “legally authorized representatives” able to consent to (provide permission for) research with their minor children 66; however, for persons residing in mental health treatment facilities, agencies take over decision-making authority. Furthermore, New York has in place an active mental health legal advocate structure that affects treatment decisions with mentally and developmentally challenged individuals, which also likely translates to research settings.

New York is also the only other known state, beyond Maryland, to address nontherapeutic research with vulnerable populations. In T.D. v. New York State Office of Mental Health 67, New York's trial court ruled that the state's Office of Mental Health (OMH) overstepped its bounds by issuing regulations pertinent to research with persons incapable of giving consent, including children. On appeal, the Appellate Division, First Department, affirmed this decision, but also went on to discuss constitutional and common law defects in the OMH regulations 68. Of specific concern were regulations for consent to greater-than-minimal-risk nontherapeutic (or only possibly therapeutic) research with children and adults unable to give or withhold consent. Of note, the appellate level court went beyond the scope of the earlier ruling to condemn this research, much like the Grimes court did.

Although the court focused on non-federally funded research with children and adults residing in state-run mental health facilities, the court's language appears to go far beyond this specific population to include all human subjects of questionable capacity, whose interests should be protected even at the expense of some research 69. With respect to children, the court took issue with the fact that persons other than parents or guardians could provide consent (permission) for participation of children in “greater than minimal risk nontherapeutic research” 70. Furthermore, the court did not simply condemn allowing nonparents to make decisions; the court also addressed the limits of parental authority, in ways similar to the Grimes decision.

We are not dealing here with parental choice among reasonable treatment alternatives, but with a decision to subject the child to nontherapeutic treatments and procedures that may cause harmful permanent or fatal side effects. It follows therefore that a parent or guardian, let alone another adult who may be a member of the child's family, may not consent to have a child submit to painful and/or potentially life-threatening research procedures that hold no prospect of benefit for the child and that may have the same result as a denial of necessary medical treatment 71.

The court was not moved by federal regulations that might allow such research, instead setting forth a standard for New York's approach to research with minors of certain categories of risk and benefit. And, as in Grimes, the court was critical of the IRB's discretion in applying research protection 72.

Finally, of import for research with children under state custody, the court also critiqued the IRB's discretion in allowing waiver of parental consent (permission) when the latter is not a “reasonable requirement to protect the patients (for example, abused and neglected children)” 73. The court's argument clarifies that consent (permission) authority for these subjects lies with the local commissioner of health (as in the treatment context) 74. Moreover, it is also noteworthy for specifically referencing treatment-related law in a research case. That is, pursuant to the court's reasoning, this decision might provide support for an argument that treatment statutes, at least insofar as they address who can consent (provide permission) on behalf of minors, could also apply in research milieus 75.

Taken together with the Grimes case, these arguments point toward a highly “restrictive” environment on the continuum of permissibility of research with children and adolescents as regulated by the states, at least insofar as research exceeds minimal-risk standards without the prospect for direct benefit. Each court interpreted state law as restricting the ability to do nontherapeutic, greater-than-minimal-risk research with children. Furthermore, each did so by explicitly acknowledging the need for state protection, notwithstanding federal regulations or cases in which such regulations do not apply (non-federally funded research), especially when such research is tied to commercial interests 76.

Each decision also provides convenient language to support claims that research with a child that is not clearly minimal risk or therapeutic is best avoided -- ethically and legally. In addition, each decision inserts the necessity for judicial review into the research process. “Science cannot be permitted to be the sole judge of the appropriateness of such research methods on human subjects, especially in respect to children” 77. States with particularly activist courts might also subject researchers to judicial interpretations of permissible research and the limits thereof.

However, what about states without similar case laws dealing with research with vulnerable subjects? It is worth noting that most states do not have a body of state law on this issue, especially in relation to children and adolescents. Therefore, the general trend among state court decisions vis-a-vis medical treatment for children and adolescents might have some bearing on the issue, at least to the extent that they provide useful arguments -- and possible comfort levels -- for researchers.

Massachusetts

Consider, for example, Massachusetts, a state with recent case law addressing minors' ability to consent to or refuse medical treatment. In a noteworthy case, the Appeals Court of Massachusetts held that a 17-year-old female patient should have been able to voice her own interests in deciding against a blood transfusion, “where she apparently had the testimonial capacity to answer questions. Only after evaluating this evidence in light of her maturity could the judge properly determine her best interests” 78.

The court so held the decision on the basis of “well-settled” state law that would apply a three-part balancing test for treatment decisions with unemancipated minors: the child's best interests, the parents' interests, and the state's interests 79. Moreover, the best interests criteria parallel those used in substituted judgment cases, which would include the “patient's expressed preferences, if any” 80. The court also noted that the state's legislature affirmed considering a minor's “maturity” in relation to enunciating her own interests by enacting law to allow an abortion without parental consent (permission) if the judge deems the minor “mature enough to make an informed decision” 81. The court indicates that, at least in certain situations and with “minors” of a certain age or maturity level, the typical “best-interests” standard applied to treatment decisions should also include reference to what the minor him- or herself thinks.

Tennessee

The Tennessee Supreme Court has also recognized the common law “mature minor exception” by adopting the “Rule of Sevens” 82. This common law rule of capacity holds that (1) a minor under the age of 7 years lacks capacity; (2) a minor between 7 and 14 years of age is presumed not to have capacity, but that assumption can be rebutted (the burden is on the minor arguing that he or she has capacity); and (3) a minor aged 14 years and over is presumed to have capacity (the burden is on the one arguing against capacity) 83. It further held that the mature minor exception is part of Tennessee's common law to be applied on a case-by-case basis (i.e., not a bright-line test) and that such consent by a minor, when validly given (as it was in this case), freed the physician complying with such consent (again, in this case) from battery charges 84.16

Summary

Of course, there is no explicit reason to believe that reasoning similar to that described above would apply to a decision whether or not to allow a minor to consent to participation in a research protocol. In fact, it should be noted that many cases upholding a minor's consent based on “maturity” did so when the minor was near 18 years of age. Thus, for younger children, for decisions related to riskier research, and with stronger parental disagreement, there may be a less permissive attitude toward minor consent 85. Nor is there reason to believe that nontherapeutic research would not fall to a similar fate as in New York and Maryland, wherein no matter the willingness to agree to research participation -- by the parent or the minor -- some research might be invalid per se. Yet, for states where there is greater silence or “leniency” as to research in state courts or legislatures and where strong case law exists to promote mature minor treatment decision making, the same principles could arguably extend to research decisions, at least inasmuch as research specifically relates to areas in which minor consent is allowed, for example, for STD treatment 86.

FUTURE DIRECTIONS: UNIFORM STATE GUIDELINES AND NATIONAL DISCUSSION

In sum, where do the review and analysis presented above leave the research community? On the basis of a review of state law -- statutory and case law -- on this point (research with children and adolescents), there is little to go by in terms of the permissibility of and limits of such research. Moreover, even where case law does exist, arguments exist to preclude research with certain minors in certain situations, particularly if such children are deemed to be especially vulnerable (e.g., impoverished or suffering from emotional disturbances).

This is not to say that research will not or may not proceed. Rather, researchers are wise to review state law in the myriad of places where it might be found (e.g., health, public welfare, education, corrections, and social services codes). They should also judge the climates of their local and state courts and legislatures to determine the legal stance likely to be adopted in relation to research with children that goes beyond minimal risk and that is quite likely of no direct benefit. Researchers might also be well advised to seek agency approval for research with children in or at risk of being under state custody and also to develop research protocols with greater community input, particularly those members of the community from which subjects or families are likely to be drawn 87.

States, too, could respond to this uncertain climate by clarifying the bounds of what is and is not permissible in research with children and adolescents, while doing so in accord with laws that increasingly recognize “mature” status for certain medical decisions. States might be wise to do so proactively rather than wait for the “hard case” that could lead to “bad law.”

A possible and advisable approach would be for a national body representing state governments, for example, the National Governors Association or the National Conference of State Legislatures, to convene a national group of key stakeholders and experts to develop state guidelines for research with children and adolescents. As state-based guidelines and not national law, the purpose would not be to mandate compliance by states or researchers within those states. Given the nascent nature of state regulation in this area in general, it seems premature to develop a model law.

However, the process of developing national guidelines might serve to foster a broader dialogue about the limits that society accepts for research with children and adolescents. In this fashion, guidelines could be used to develop a consensus on “best practices” in research with children and adolescents. In addition, their development might influence the research agenda itself, to promote additional studies that would support the empirical basis behind the guidelines, as well as an empirical base that could influence later revisions to the guidelines 88. So, too, would it invite greater stakeholder input into the process of setting limits, inclusive of not only researchers and state officials but also potential subjects, families, advocacy groups, and representatives of groups or institutions affected by the variety of situations or locations in which such research might take place (e.g., schools). Although states have generally chosen, when they do address the issue, to track federal regulations, especially when describing the risk-benefit calculations for IRB reviews, federal regulations only extend to federally funded research; furthermore, they leave much to IRB discretion. These are areas where state-level dialogue could be especially beneficial.

Perhaps nothing will come of the recent court actions in New York and Maryland; in fact, as of this writing, the Maryland legislature declined to specifically address the facts of the Grimes case. Yet, as the impetus behind research with children and adolescents builds 89 and an increasingly vigilant and media-savvy subject advocate network grows 90, it seems likely that litigation could ensue. So, too, might litigation be prompted by new privacy regulations as applied in research settings 91. In consideration of such regulations, might it be wise for states to address this issue proactively to clarify the landscape out of an ethical sense of obligation, a legal sense of duty, and a pragmatic response to the growing media “buzz”? Additionally, might it also be wise for states to set forth guidance more uniformly and to learn from each other's experiences, in recognition of the growing “multistate” nature of research? Such guidance could, for example, address more precisely what is meant by “emancipated minor” and “mature minor” on the one hand and “greater than minimal risk” and “nontherapeutic research” on the other 92.

It is likely that separate guidance would be needed for research with children and adolescents generally and research with children under state custody specifically, as the latter sit in unique circumstances in relation to the state's protection and oversight of their care. Yet, whether the guidelines address one, two, or even three situations (e.g., a third situation applying to “sensitive” research, such as studies related to sexual promiscuity among adolescents), it is arguably better to provide clarifying guidance before the research endeavor with children develops a force of its own or breaks down in the face of a few unfortunate research endeavors or before research guidelines split between guidelines for government-funded research and guidelines for industry-funded research. The future of the state response is unclear. The future, however, likely includes more, not less, research with children and adolescents and, hence, will raise more research-related issues, concerns that states could begin to address now in a systematic and empirically testable fashion.

ACKNOWLEDGMENTS

This review and analysis was funded by the Institute of Medicine. I wish to acknowledge the assistance of the Family Violence Clinic at the State University of New York at Buffalo School of Law, in particular, Shannon O'Keefe, clinic student, and Catherine Cerulli, faculty member. Thanks also to Abigail English and numerous child welfare representatives for sharing their ideas and resources. Finally, I owe a special thanks to Angela Roddey Holder for reviewing this paper and, most importantly, for her ongoing support and mentorship.

ADDENDUM B1

Hypothetical Research Studies with Children in State Custody: How Might States Respond?

The following hypothetical research protocols, followed by hypothetical state responses to the regulation of such (based on inquiries made of researchers and regulators in a number of states), may serve to highlight the myriad of approaches applied to research studies involving youth in state custody. They were developed in consultation with researchers focused on the foster care population and were circulated to researchers whose work touches upon these issues in numerous states, as well as representatives of state child welfare departments (or the relevant agencies who regulate such research) for feedback. The comments below are not those of a single respondent; rather, they illustrate the collective wisdom of the respondents; that is, researchers and regulators.

Scenario 1: Behavioral Study

Faculty at a state university's Center for Research in Child and Adolescent Health (the Center) wish to add to their colleagues' work in documenting risk factors for adolescents in foster care. An earlier study from the Center found that adolescents in foster care often have multiple psychosocial and mental health problems that place them at risk for early sexual experiences and HIV infection. The researchers wish to identify such risk factors at early stages to better prevent such later effects. Thus, they propose to target preteens (children ages 9 to 12) in foster care and collect information about substance abuse, sexual activity, maltreatment, and suicidal intent to identify discernible interrelationships among factors that might contribute to early sexual experiences and other HIV-related behaviors (e.g., use of needles to inject illegal drugs). This prospective study will involve 400 youth ages 9 to 12 in foster care. At the onset of the project, children will be given a battery of psychiatric, social, and adaptive functioning measures to gauge mental health risk and protective factors. They will then be monitored for 5 years to identify patterns of behavior. Children will be drawn from multiple sites in four different states.

Was your (foster care/child welfare) office confronted with this situation, or if a similar proposal was brought before it, did it/might it permit these children to participate in the study? Please explain.

More regulatory or restrictive state Obviously, the most restrictive stance would be to bar such research with children in state custody outright. Beyond that, however, there could likely be “exceptions” to the ban (e.g., for “special cause”) or a slightly more permissive stance with tight control via departmental regulation.

For example, State A (say) has its own Research Review Board that reviews all requests for conducting research with its client population (by providing access to confidential records or data or direct access to the clients). Its review criteria track those provided for in federal regulations; however, special attention is paid to the “vulnerability” of its subject population, and more invasive research methods (including surveys with highly sensitive information) are scrutinized closely. Informed consent is required: the presumption is in favor of seeking parental consent for children, unless parental rights have been terminated, even though the Department has legal authority for approving “ordinary medical care” for children in its custody. If parental rights are not terminated and if parents are not causing harm to their children, their objection to research will bar their child's participation. Additional review and reconsent are required if there are any changes in the protocol; similarly, reconsent is required if the custodial status of the child changes (e.g., the child is placed with a new foster parent).

Or consider State B, in which requests for direct access to child clients is subject to court approval. It is further stipulated that the caseworker for each child must consent on the child's behalf, as well as obtain the child's assent.

Less regulatory or restrictive state Falling closer to the less restrictive end of the continuum, State C allows research, including access to confidential data and direct client access, if the research protocol is approved by the researcher's own IRB. The researcher must sign a confidentiality agreement and agree not to include personally identifying information in subsequent research reports. Consent for client participation is generally given by the Department of Children & Families (DCF) acting as the custodian for the children. Although the Department's regulations focus on confidentiality, it is expected that research that targets the needs of children in state custody and the needs of the DCF and also that DCF's resources (e.g., staff) will not be stretched in complying with research.

Scenario 2: Research Tied to Clinical Needs

In the early years of HIV infection, there was no treatment for the disease. Many babies who were born infected were placed in foster care because their mothers were too sick to care for them, and most mothers died before the babies' first birthday. When zidovudine (AZT) began to be tested in studies with adults, many pediatric HIV physicians wanted to do clinical trials with HIV-infected children, including these babies, since nothing else was available to save their lives.

Was your (foster care/child welfare) office confronted with this situation, or if a similar proposal was brought before it, did it/might it permit these children to participate in the study? Please explain.

More regulatory or restrictive state States A and B, which were slightly more permissive of noninvasive research, prohibit medical or pharmaceutical experimentation and thus choose to bar this research. As this is far beyond what they consider “ordinary care and treatment” for pediatric populations, they are that much more cautious about enrolling children under their custody, who face their own host of vulnerabilities.

Less regulatory or restrictive state State C is also highly concerned by this hypothetical research and would require ample showing of cause or medical justification for the treatment methods contained within the protocol; that is, there must be some physician documentation that the testing is being conducted with all pediatric populations, not simply those in foster care, and that it is medically warranted and not purely an experiment without some data backing AZT's use. Furthermore, the children's prognoses must be sufficiently poor as to balance the risks of the research. Close monitoring by the host institution's IRB is also expected. Consent will be required by each caseworker, who will act somewhat like an ombudsperson for his or her clients.

Overall Comments: Conducting Research in a State of Flux

Based on a query of noted researchers in the field, as well as a sampling of the opinions of regulators from select (larger) states, it seems that the more likely approach to the inclusion of wards of the state in research cannot be depicted as either black or white (i.e., as routinely permissive or routinely negative), but rather resembles shades of gray. That is, researchers likely face a continuum of permissibility, based on the county or local atmosphere, the population involved (including age), the risks inherent in the study, whether the study has a medically indicated or therapeutic” connection (e.g., treatment, say, with a new anti-HIV medication for youth is available only within the context of research protocol) or seems more purely research based or experimental, etc. As the research risks increase (e.g., in the AZT study described above), it is more likely that the research will be prohibited or at the very least subjected to much greater regulatory scrutiny and monitoring, whereas survey research and the like might be approached more favorably, with fewer restrictions. Children who are wards of the state (e.g., in juvenile detention facilities or psychiatric institutions) are more likely to be excluded from participation than children in physical custody of the state (e.g., foster care).

The lack of black-and-white approaches is not necessarily a problem; in fact, it likely represents the best course given the need for individualization of studies to match individual or local community needs. Such flexibility is also in keeping with the federal government's emphasis on local review, notably, through the IRB structure. However, this results in a situation of uncertainty for researchers, who are advised to build rapport with local regulators and routinely confer with these regulators -- as well as ethics and legal counsel -- to ensure that a proper balance is maintained between research needs and the protection of vulnerable children and adolescents.

Footnotes

1

U.S. Department of Health and Human Services. Protection of Human Subjects in Research. Washington, D.C.: U.S. Government Printing Office, 1991 (codified at 45 CFR Part 46). The regulations and a list of all agencies adopting the Subpart A (the Common Rule) may be found at http://ohrp​.osophs.dhhs​.gov/humansubjects/guidance/45cfr46​.htm (accessed May 6, 2004).

2

45 CFR 46, Subpart D.

3

34 CFR Part 97 (Protection of Human Subjects) and Part 98 (Student Rights in Research, Experimental Programs, and Testing). The Protection of Pupil Rights Amendment (PPRA), codified at 34 CFR Part 98, requires schools and contractors that receive funding from the U.S. Department of Education to obtain written parental consent before minor students are required to participate in any U.S. Department of Education-funded survey, analysis, or evaluation that reveals certain information, including mental and psychological problems potentially embarrassing to the student and his or her family; sexual behavior and attitudes; and illegal, antisocial, self-incriminating, and demeaning behavior. PPRA also seeks to ensure that parents can review such surveys, analyses, or evaluations before their minor child's participation. Subsequent legislation (No Child Left Behind Act) required that schools must provide directory information to military recruiters upon request and allowed parents to refuse their child's participation in certain additional information collection activities. More information is available on the U.S. Department of Education's website. Available at: http://www​.ed.gov/offices​/OII/fpco/ppra/index.html (accessed August 28, 2003) and http://www​.ed.gov/policy​/gen/guid/fpco/ppra/parents.html (accessed May 6, 2004).

4

See, e.g., Standard Operating Procedures. Guidance on the Inclusion of Children in Research, Johns Hopkins University Committee on Human Research (which explains four categories of risk under “additional protections” for child subjects with reference to federal regulations). Available at: http://www​.jhsph.edu​/chr/Childrens_guidelines.pdf (accessed June 24, 2003); Informed Consent Guide for the Institutional Review Board of the University of Southern California Health Sciences Campus, November 2, 1999 (which provides informed-consent requirements based on DHHS and FDA regulations, including the consent and assent procedures for research with children). Available at: http://ccnt​.hsc.usc.edu/irb/irb.html (accessed June 23, 2003).

5

45 CFR 46.402(a) (emphasis added).

6

45 CFR 46.402(e).

1

A separate project conducted under the auspices of the University of Rochester Medical Center is also pending. That project will survey IRBs at major academic medical centers in each state for further input as to state and local policies, guidance, etc., related to research with children and adolescents. Results from that study will be analyzed and published at a later date in a separate report.

2

In fact, statistics indicate that children in foster care often end up in out-of-home placements because of parental neglect and/or abuse, substance abuse, the disproportionate impact of poverty, human immunodeficiency virus infection/AIDS, and similar problems 7.

7

Taussig HN. 2002. Risk behaviors in maltreated youth placed in foster care: a longitudinal study of protective and vulnerability factors. Child Abuse & Neglect 26:1179-1199 (study examining protective and vulnerability factors in foster care youth); Child Welfare League of America. National Fact Sheet 2003: Making Children a National Priority. Available at: http://www​.cwla.org/advocacy​/nationalfactsheet03.htm (accessed October 23, 2003) (citing evidence that children whose families do not receive appropriate treatment for alcohol and other drug abuse are more likely to end up in foster care, remain in foster care longer, and reenter foster care once they have returned home than are children whose families do receive treatment).

3

These protections are typically state specific and are often not formalized in policy but, rather, are handled on a case-by-case basis and are dependent on a variety of factors, such as the risks-benefits of the study, the age ranges of the children, the presence or availability of parents, and treatment alternatives outside of research.

4

State statutes, administrative regulations, case law, and other written policies were identified through searches of Lexis/Nexis (a legal database) and were affirmed through reference to ClinLaw (a Thompson Publishing Group-sponsored database containing information on clinical laws) and the advice of other experts. As this is a complicated area of the law, a great deal of it exists at an “informal” (less “explicit”) level, and as adolescent maturity is an everchanging concept, this review and the accompanying tables are not meant to be relied upon as exhaustive studies of the law; rather, they offer insights into the myriad of ways in which states may approach -- or choose not to approach -- these issues.

8

English A. 1995. Guidelines for adolescent health research: legal perspectives. Journal of Adolescent Health 17:277-286; Santelli J, et al. 2003. Guidelines for adolescent health research. A position paper for the Society of Adolescent Medicine. Journal of Adolescent Health 33(5):396-409; Hartman RG. 2002. Coming of age: devising legislation for adolescent medical decision-making. American Journal of Law and Medicine 28:409-453; Broome ME, Stieglitz KA. 1992. The consent process and children. Research in Nursing & Health 15:147-152.

9

See, e.g., Ariz. Rev. Stat. Ann. 44-132.

10

See, e.g., Ind. Code Ann. 16-36-1-3; Maine Rev. Stat. Ann. Tit. 15, 3506A.

11

See, e.g., Calif. Fam. Code 7002(c), 7120-7122; N.C. Gen. Stat. 7B-3500.

5

Of note, this early impetus to define emancipation was driven by the desire to allow minors to enter contracts and own property and to relieve emancipated minors from the duty to turn over their wages to their parents.

12

See, e.g., Connecticut Office of Legislative Research (OLR) Research Report 2002-R-0008 (emancipation of minors under common law). Note also that emancipation likely also released parents from debts arising from their children's decisions. See, e.g., Support of Minors and Emancipation, State of Michigan, 37th Circuit Court, Family Division Justice Center, April 2000; Conn. Gen. Stat. Sec. 46b-150(d)(a) (emancipation order allows minor to “consent to mental, dental, or psychiatric care, without parental consent, knowledge, or liability” (emphasis added); W.Va. Code 49-7-27 (parents or custodians of emancipated minor not obligated to provide care of financial support); Wy. Stat. 14-1-202(a)(iii) (emancipation terminates parental tort liability for minor).

13

Conn. Gen. Stat. Sec. 46b-150(d)(a).

14

Md. Code Ann., Est. & Tr. Art. 13, sec. 503(c) (a minor 15 or older may contract for annuities or life insurance for self).

15

For explicitly including right to make health care decisions among legal effects of emancipation, see Calif. Family Code sec. 7050(e)(1) (effects of emancipation include minor's capacity to “consent to medical, dental, or psychiatric care, without parental consent, knowledge, or liability”); Conn. Title 46B, Ch. 815t sec. 46b-150d(a) (emancipated minor may “consent to medical, dental, or psychiatric care, without parental consent, knowledge, or liability”). But see, e.g., Md. Code Ann., Est. & Tr. Art. 13 sec. 503(a) (a married minor may buy/sell property if spouse of age); Md. Code Ann., Est. & Tr. Art. 13 sec. 503(c) (at age 15 an individual may contract for insurance); Md. Code Ann., Est. & Tr. Art. 13 sec. 503(b) (a minor in the military can enter real estate transactions); N.C. Gen. Stat. 7B-3507 (final decree of emancipation gives the minor or petitioner the “same right to make contracts and conveyances, to sue and to be sued, and to transact business as if the petitioner were an adult”).

6

This does not imply that consent to other issues is barred; rather, it simply means that legislative action has only explicitly addressed certain situations that it finds imperative.

16

A. Campbell, personal communication (with Abigail English, JD, Director, Center for Adolescent Health & The Law), August 5, 2003.

17

See, e.g., W.Va. Code 16-30-3(o) (which defines a “mature minor” as “a person less than eighteen years of age who has been determined by a qualified physician, a qualified psychologist or an advanced nurse practitioner to have the capacity to make health care decisions).

7

Compare Tables B.3 and B.4 for areas of overlap.

8

As commented upon by the American Law Institute, a prominent legal authority, in its Restatement (Second) of Torts, a minor's consent should be effective if he or she is “capable of appreciating the nature, extent and probable consequences of the conduct consented to e.g., medical treatment,” even if parental consent is “not obtained or is expressly refused” 18.

18

Restatement (Second) of Torts, sec. 892A, cmt.b (1979).

9

This distinction (i.e., event versus context-sensitive maturity and the setting in which the decision is made) is followed in this paper.

19

But cf. Novak v. Cobb County-Kennestone Hospital Authority, 849 F.Supp 1559 (N.D. Ga. 1994), aff'd 74 F.3d 1173 (11th Cir. 1996) (which declined to recognize mature minor exception pursuant to O.C.G.A. sec. 31-9-7).

20

See, e.g., Id. Code 39-4302; Ark. Stat. Ann. 20-13-104, 20-9-106, 20-9-60; Miss. Code Ann. 41-41-3.

21

Ala. Code 22-8-4.

22

Calif. Family Code 6922 (applies only to minors age 15 years or older who are living apart from their parents and managing their own affairs); Oregon Rev. Stat. 109.640.

23

S.C.C.A. 20-7-280 (for health services other than operations, unless the operation is deemed essential to the health and the life of child).

24

See, e.g., Colo. Rev. Stat. 13-22-103; Ind. Code Ann. 16-36-1-3; 22 Maine Rev. Stat. 1503.

10

Again, however, it should be emphasized that the concept of “emancipation” in states is far from clear. For the purposes of this appendix, emancipation is seen as a transition to adulthood in state law, but researchers would need to consult experts in their own states for guidance on the bounds of emancipation in the respective states.

25

See, e.g., Va. Code Ann. 54-2969.

26

For further discussion of the extent and limits of minor medical decision-making, see Stenger RL. 1999/2000. Exclusive or concurrent competence to make medical decisions for adolescents in the United States and United Kingdom. Journal of Law and Health 14(209):208-241.

11

Again, this does not mean that other areas of consent are prohibited; instead, they exist in the “gray zone” of prudent (“reasonable”) responses to the facts of a given case.

27

Santelli J, et al. 2003. Guidelines for adolescent health research: a position paper for the Society of Adolescent Medicine. Journal of Adolescent Health 33(5):396-409.

28

See, e.g., 25 Tex. Admin. Code 405.409 (which requires minor's assent for research of mental health patients); 25 Tex. Admin. Code 414.758 (special conditions for greater-than-minimal-risk research and research with minors); 25 Tex. Admin. Code 414.754 (which provides special rules for research with persons involuntarily committed to Texas Department of Mental Health and Mental Retardation facilities); Va. Code Ann. 32.1-162.16, 32.1-162.18, 32.1-162.19, 12 Va. Admin. Code 5-20-10, 5-20-100, 35-180-10 (research connected with Department of Health and Department of Mental Health facilities must adhere to special requirements for nontherapeutic, greater-than-minimal-risk research); V.C.A. 32.1-16.16 (in which nontherapeutic research is defined as having no reasonable expectation of direct benefit to the physical or mental condition of the subject); Calif. H&S Code 24178 (A.B. 2328, signed September 11, 2002, as Chap. 477, which allows for surrogate consent to research in certain situations); Calif. H&S Code 111530 (which requires parental/guardian consent and minor assent if the child is age 7 years or older for experimental use of drugs with minors); 15 Calif. Code Regs. 1454 (which provides specific rules for clinical research with juveniles in the state corrections system); Del. HSS Policy Memo No. 55 (July 1992) (clients served by Delaware Health & Social Services may not be research subjects unless the Human Subjects Review Board approves the research and the research is compatible with DHHS federal regulations); D.C.C. 21-2047 (the guardian of an incapacitated person may not consent to experimental treatment or research); D.C. Code 6-1969 (a parent or guardian may act as a legally appointed representative (LAR) for experimental research with mentally retarded individuals); Ohio Admin. Code 5122-28-05 (which considers a parent or guardian of a minor to be the LAR for research subject to the authority of the Department of Mental Health); Ohio Admin. Code 5122-28-05(A)(4) (consent age of 18 for research subject to Department of Mental Health regulation); Code of Maine Regs. 14-193-001(XI); 14-142-001(XI) (for children receiving services from Bureau of Children with Special Needs, clinical research laws require full written informed consent, assent by minors over age 12, approval of clinical director for off-label use of FDA-approved drug, Research and Experimental Review Board review, and compliance with federal DHHS regulations; a special review process is required if research with minors presents greater than minimal risk).

29

This link was made in a prominent report issued by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which recommended allowing minor consent to research when the research is conducted in or relates to the types of care to which minors can consent in the treatment context. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1977. Report and Recommendations: Research Involving Children. DHEW publication (OS) 77-0004. Washington, D.C.: U.S. Government Printing Office.

30

See, e.g., English A. 1995. Guidelines for adolescent health research: legal perspectives. Journal of Adolescent Health 17:277-286; Nelson RM. 2001. Nontherapeutic research minimal risk, and the Kennedy Krieger Lead Abatement Study. IRB: Ethics & Human Research 23(6):7-11.

31

See, e.g., Cohen v. Bolduc, No. SJC-08544 (Mass. 01/11/2002) (“We conclude that, absent an express limitation by the principal in the health care proxy itself, the proxy statute does not prevent an agent from making that treatment decision, provided the principal does not object.”). Available at: http://caselaw​.lp.findlaw​.com/scripts/getcase​.pl?court=ma&vol=sjcslip​/8554&invol=1.

32

Cardwell v. Bechtol, 724 S.W. 2d 739, 743-4 (Tenn. 1987) (citations omitted). The Cardwell case is preeminent among recent cases in its clear enunciation of the origins of and reasoning behind the “mature minor” exception, as well as its explanation, cited here, of the flexibility of the law in adapting to changing conditions and the openness to a context-sensitive interpretation of actions in the absence of specific relevant legislative enactments. For a further discussion of Cardwell, see text accompanying notes 82-84, infra. Complicating matters, however, states may choose to remove this flexibility in interpretation in the face of silence by explicitly superseding common law through statutory means. See, e.g., N.C. Gen. Stat. 7B-3509 (which supersedes the common law of emancipation, other than by marriage).

33

45 CFR 46.402(b).

34

For useful suggestions for developing guidance to clarify “assent” and “consent” in research with children, see Broome ME, Stieglitz KA. 1992. The consent process and children. Research in Nursing & Health 15:147-152. See also American Academy of Pediatrics. 1995. Informed consent, parental permission, and assent in pediatric patients. Pediatrics 95:314-317; Wendler D, Shah S. 2003. Should children decide whether they are enrolled in nonbeneficial research? American Journal of Bioethics 3(4):1-7 (which argues that the “assent” threshold should be set at age 14 and that a “dissent” requirement should also be adopted for nonbeneficial research).

12

See discussion infra, pp. 323-325.

13

This still leaves the question, however, of how a researcher or IRB should reach the conclusion that a minor is emancipated. Arguably, at a minimum, minors who satisfy the common law criteria for emancipation or who have been emancipated by a court should be considered emancipated.

35

See, e.g., National Institutes of Health (NIH) Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects, released March 6, 1998. Available at: http://grants1​.nih.gov​/grants/guide/notice-files/not98-024​.html (accessed June 23, 2003) (for grant proposals received by NIH after October 1, 1998, the website sets forth policy and guidelines for inclusion of children (defined as youth up to age 21) to encourage NIH-supported research with children); Best Pharmaceuticals for Children Act, January 4, 2002 (P.L. 107-109) (which extends the pediatric exclusivity provision of the Food and Drug Administration Modernization Act of 1997 (P.L. 105-115), which sunset on January 1, 2002, through 2007; note that the exclusivity provision provides marketing incentives to manufacturers that conduct drug studies with children by extending patent protection for 6 months in return for such studies); Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological Products in Pediatric Patients (FDA Pediatric Rule), 21 CFR sec. 201, 312, 314, 601, 63 FR 66632, December 2, 1998 (which requires manufacturers of certain products to provide sufficient data and information to support directions for pediatric use for the claimed indications). Note that the Pediatric Rule was struck down in October 2002 by a federal court as exceeding FDA's statutory authority (Association of American Physicians and Surgeons, Inc. v. United States Food and Drug Administration, Civil Action No. 02-02898 (Dist. Ct. D.C., October 17, 2002); however, DHHS worked with Congress to pass similar federal legislation requiring pharmaceutical companies to conduct clinical drug trials with children (see Bush Administration will Seek New Legislation for Mandatory Pediatric Drug Testing, DHHS Press Release, December 16, 2002. Available at: http://www​.hhs.gov/news​/press/2002pres/20021216c.html (accessed June 23, 2003)). The Pediatric Research Equity Act of 2003 was signed into law on December 5, 2003.

36

See, e.g., Md. Health-General Article Cod. Ann. Sec. 13-2001 et seq. (2002).

37

Grimes v. Kennedy Krieger Institute, Inc., 366 Md. 29, 782 A.2d 807 (2001) (hereinafter Grimes); see also Mastroianni A, Kahn JP. 2002. Risk and responsibility: ethics, Grimes v. Kennedy Krieger, and public health research involving children. American Journal of Public Health.92(7):1073-1076.

38

45 CFR 46.409.

39

45 CFR 46.409(a).

40

45 CFR 46.409(b).

41

A. Campbell, personal communication (with Mary Jane Davis, Asst. General Counsel, Tennessee Department of Children's Services), July 21, 2003. Tennessee's Department of Children's Services is currently revising its informed-consent policy to clarify this presumption of parental consent authority. TN DCS Policy 20.24, eff. 02/01/00, rev'd. 05/09/03 (draft copy on file with author).

42

Pierce v. Society of Sisters, 268 U.S. 510 (1925) (which upholds the liberty interest of parents to direct upbringing and education of children); Parham v. J.R., 442 U.S. 584 (1979) (which states that parents' liberty interests in raising children extends to decisions over whether to institutionalize children with mental illness, although parental discretion is not absolute). It is also worth noting that in the Parham decision, the U.S. Supreme Court determined that there did not need to be a separate process for initial admission decisions for inpatient commitment of children for children who were wards of the state (versus children whose natural parents sought admission). In so holding, the Court stated that, “Since the state agency having custody and control of the child in loco parentis has a duty to consider the best interests of the child with respect to a decision on commitment to a mental hospital, the State may constitutionally allow that custodial agency to speak for the child, subject, of course, to the restrictions governing natural parents” (Parham, 442 U.S. 584, 619).

43

See, e.g., Utah Department of Human Services IRB. Procedures & Instructions for Researchers. Department of Human Services Resource Manual, eff. February 24, 2003 (copy on file with author).

44

A. Campbell, personal communication (with Dr. Page B. Walley, Commissioner, Alabama Department of Children's Affairs), June 16, 2003.

45

See, e.g., Utah Department of Human Services IRB. Procedures & Instructions for Researchers. Department of Human Services Resource Manual, eff. February 24, 2003; State of Tennessee Department of Children's Services. Research Proposals. Administrative Policies & Procedures: 6.1, eff. February 1, 2000, rev'd. November 1, 2001 (copy on file with author).

46

Maryland Department of the Environment. Lead Poisoning Prevention Program. Childhood Blood Lead Surveillance in Maryland. 1999 Annual Report. Released February, 2001. Available at: http://www​.mde.state​.md.us/assets/document​/LeadCoordination/leadreport99.pdf (accessed August 11 2003.

47

Maryland Department of Health and Mental Hygiene. Community and Public Health Administration. Center for Maternal and Child Health. Childhood Lead Screening Program. Targeting Plan for Areas at Risk for Childhood Lead Poisoning. May 2000. Available at: http://www​.fha.state​.md.us/och/html/stp.html (accessed August 11, 2003).

48

Maryland Department of the Environment. Annual Report 2000, p. 53. Available at: http://www​.mde.state​.md.us/assets/document​/AboutMDE/annualreport.pdf (accessed August 11, 2003).

49

Grimes at 807.

50

Grimes at 818, 819, 842.

51

Id. at 819.

52

For interesting discussions of the merits and the ramifications of the decision, see Kopelman LM. 2002. Pediatric research regulations under legal scrutiny: Grimes narrows their interpretation. Journal of Law, Medicine & Ethics;30:38-49; Glantz LH. 2002. Nontherapeutic research with children: Grimes v. Kennedy Krieger Institute. American Journal of Public Health 92(7):1070-1073.

14

Instead of referring to nontherapeutic research, many refer to research that does not present the prospect of direct benefit, as explained in Chapter 1.

53

Grimes at 816-817.

54

Id. at note 6.

55

Id. at 850.

56

Nelson RM. 2001. Nontherapeutic research minimal risk, and the Kennedy Krieger Lead Abatement Study. IRB: Ethics & Human Research23(6):7-11, 8-9.

57

Grimes at 853 (“not in best interest of any healthy child to be intentionally put in a nontherapeutic situation where his or her health may be impaired, in order to test methods that may ultimately benefit all children”).

58

See, e.g. Alliance for Human Protection. A landmark decision by Maryland's highest court; Infomail. August, 20, 2001. Available at: http://www​.researchprotection​.org/infomail/0801/20.html (accessed June 20, 2003).

59

Kopelman LM. 2002. Pediatric research regulations under legal scrutiny: Grimes narrows their interpretation. Journal of Law, Medicine & Ethics,30:38-49; Nelson RM. 2001. Nontherapeutic research minimal risk, and the Kennedy Krieger Lead Abatement Study. IRB: Ethics & Human Research 23(6):7-11.

60

See, e.g., University of Maryland Baltimore County IRB. Requirements for Research Involving Children. Updated March 11, 2002. Available at: http://www​.umbc.edu/irb/Children.htm (accessed June 21, 2003).

61

Md. Health-General Code Ann. Sec. 13-2001 et seq. (2002).

62

A. Campbell, personal communication (with Jack Schwartz, Assistant Attorney General, State of Maryland), June 20, 2003.

63

Grimes at 862.

64

See, e.g., Sharav VH. 2003. Children in clinical research: a conflict of moral values. The American Journal of Bioethics 3(1):1-81. Available at: http://www​.bioethics​.net/journal/infocus/pdf/sharav.pdf (accessed February 25, 2004).

15

Query whether this stems from a prime example of research abuse within its own borders: the Willowbrook scandal 65. It stands to reason that states which have experienced the ill effects, including bad press, of research cases are more likely to respond with protective statutory and common law approaches.

65

For more information on the Willowbrook scandal, see Bonita L. Weddle, Mental Health in New York State, 1945-1998: An Historical Overview. New York State Archives: New York. Available at: http://www​.archives.nysed​.gov/includes/g​/researchroom/c_rr_health_mh_hist.html (accessed June 23, 2003).

66

NY Cons. Law Services Pub Health sec. 2442.

67

T.D. v. N.Y. State Office of Mental Health, 165 Misc. 2d 62, 626 N.Y.S.2d 1015 (1995).

68

T.D. v. N.Y. State Office of Mental Health, 228 A.D.2d 95 (1996) (hereinafter T.D.).

69

Id. at 100.

70

Id. at 123.

71

Id. at 124.

72

Id. at 120; see also Grimes at 817.

73

T.D. at 124-5, citing NYCRR 527.10(e)(3)(iii).

74

See, however, 45 CFR 46.408(c) (which allows the waiver of parental permission if it is not a reasonable requirement for the subjects involved, e.g., abused and neglected children). This federal regulation allows for protection of minors by waiving parental consent, so long as another mechanism is in place for their protection and it is in accord with state and local law. The New York court suggests--at least for studies with abused or neglected children that are not federally funded and that are nontherapeutic and present greater than minimal risk--local commissioners of health are the appropriate, and necessary, consenting authorities; surrogate consent or a waiver of “guardian” consent is not appropriate. T.D. at 124-125.

75

The court argues that the OMH regulations' surrogate consent provisions are unacceptable for greater-than-minimal-risk nontherapeutic research in light of earlier treatment-related holdings and the state's interest in child health and welfare as parens patriae, suggesting such research may lead to the same result at “denial of necessary medical treatment” (Id. at 124).

76

See, e.g., Grimes at 840 and T.D. at 127.

77

Grimes at 855; see also T.D. at 122-123 (need for notice and judicial review).

78

In re the Matter of Rena, 705 N.E.2d 1155, 1157 (Mass. App. Ct. 1999). See also In re E.G., 549 N.E.2d 322 (Ill. 1989) (Jehovah's Witness case in which the Illinois Supreme Court applied substituted judgment standard to see whether a minor was sufficiently mature to make informed decision); In re Swan, 569 A.2d 1202 (Maine 1990) (the state's highest court holds that evidence of the wishes of a minor with the capacity to weigh risks and benefits in refusing life-sustaining treatment is an important factor). But c.f. In re Application of Long Island Jewish Medical Ctr., 557 N.Y.S.2d 239 (Sup. Ct. 1990) (the court orders a transfusion for a 17-year old over his objection under the parens patriae doctrine, without consideration of “mature minor” framework, another example of New York's conservative approach).

79

In re Rena at 1156-1157.

80

Id. at 1157.

81

Id. at note 2, citing Mass. G.L. c. 112, sec. 12S.

82

Cardwell v. Bechtol, 724 S.W. 2d 739 (Tenn. 1987).

83

Id. at 745.

84

Id. at 749 (“for the jury to determine whether the minor has the capacity to consent to and appreciate the nature, the risks, and the consequences of the medical treatment involved”). In this case, the court ruled that the minor, a female 5 months shy of 18 years of age, had the capacity and maturity to consent to treatment for a herniated disk.

16

See further discussion of the “mature minor” doctrine infra, pp. 324-326.

85

See Stenger RL. 1999/2000. Exclusive or concurrent competence to make medical decisions for adolescents in the United States and United Kingdom. Journal of Law and Health 14(209):208-241.

86

National Commission for the Protection of Human Subjects of Biomedical Research. 1977. Research Involving Children: Report and Recommendations. DHEW publication (OS) 77-0044. Washington, D.C.: U.S. Government Printing Office, (which suggests that adolescents' legal ability under state law to consent to certain medical treatments without need for parental permission, indicative of adolescent capacity, should extend to research context for same conditions). See also, Santelli J, et al. 2003. Guidelines for adolescent health research: a position paper for the Society of Adolescent Medicine. Journal of Adolescent Health 33(5): 396-409.

87

Mastroianni A, Kahn JP. 2002. Risk and responsibility: ethics, Grimes v. Kennedy Krieger, and public health research involving children. American Journal of Public Health 92(7):1073-1076; Rogers AS, D'Angelo L, Futterman D. 1994. Guidelines for adolescent participation in research: current realities and possible resolutions. IRB: Ethics & Human Research 16(4):1-6, 3-4; Santelli J, et al. 2003. Guidelines for adolescent health research: a position paper for the Society of Adolescent Medicine. Journal of Adolescent Health 33(5): 396-409.

88

See Hartman RG. 2002. Coming of age: devising legislation for adolescent medical decision-making. American Journal of Law and Medicine 28:409-453. For examples of studies that might benefit the policy-making community, see Bernhardt BA, et al. 2003. Parents' and children's attitudes toward the enrollment of minors in genetic susceptibility research: implications for informed consent. American Journal of Medical Genetics 116A:315-323 (which assesses parents' and children's reactions to disease susceptibility research and perceptions of risks and benefits of participating); Oleschnowicz JQ, et al. 2002. Assent observed: children's involvement in leukemia treatment and research discussions. Pediatrics 109:806-814 (which examines the role of older children in discussing recent diagnosis of leukemia and treatment options including enrollment in a randomized, clinical trial); Rogers AS, Schwartz DF, Weissman G, English A. 1999. A case study in adolescent participation in clinical research: eleven clinical sites, one common protocol, and eleven IRBs. IRB: Ethics & Human Research 21(1):6-10 (which investigates decision-making by IRBs with respect to one common study protocol recruiting minor adolescents for HIV/STD study).

89

See, e.g., Brown K.2003. The medication merry-go-round. Science 299:1646-1649; Meadows M. 2003. Drug research and children. FDA Consumer Magazine January-February. Available at: http://www​.fda.gov/fdac​/features/2003/103_drugs.html (accessed March 24, 2003).

90

See, e.g., The Alliance for Human Research Protection (AHRP). Its listserv and website increasingly draw attention to research with children, especially pharmaceutical research; for example, see the recent alert to recent developments in the United Kingdom where the British government disapproved a license for Seroxat (Paxil) for use by children and adolescents based on adverse events in recent clinical trials. GlascoSmithKline sic PAXIL Warning Letter to Health Care Professionals. AHRP News Alert, June 19, 2003. Available at: http://www​.ahrp.org/infomail/0603/19​.html (accessed June 23, 2003).

91

45 CFR Parts 160 and 164 (Standards for Privacy of Individually Identifiable Health Information, implementing requirements set forth in the Health Insurance Portability and Accountability Act of 1996).

92

For a state example of the latter, see Va. Code Ann. 32.1-162.16 (which defines “nontherapeutic research” as that which holds “no reasonable prospect of direct benefit to the physical or mental condition of the human subject.”). A point to illuminate: Does “direct benefit” mean benefit to the subject's well-being generally or only specifically to that condition or disorder under investigation?

Copyright © 2004, National Academy of Sciences.
Bookshelf ID: NBK25556

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