The Baltimore Campus perceives another way to interpret the Court=s holding, however, in which the holding is considered in light of the context of the opinion as a whole. 4 This interpretation deems the holding to forbid parental consent for a child=s participation in genuinely risky research without anticipated direct benefit to the subjects, but to allow parental consent in other types of pediatric research authorized by the federal regulations cited approvingly by the Court in its opinion. Although the second way of interpreting the holding is reasonable, that is cold comfort to researchers who read what the Court has written and worry about State tort liability if they proceed with their research. An authoritative and unambiguous clarification of the Court=s holding is needed to preserve ethically conducted research that is vital to the promotion of children=s health.

       ARGUMENT

  THE COURT SHOULD CONFIRM THAT ITS HOLDING ALLOWS PARENTAL CONSENT FOR A CHILD=S PARTICIPATION IN RESEARCH AUTHORIZED BY FEDERAL REGULATION.

I.          THE HOLDING IS CONSISTENT WITH THE FEDERAL REGULATION OF ADIRECT BENEFIT@ RESEARCH.

The first issue is the meaning and scope of the Court=s conclusion that Aa parent ... cannot consent to the participation of a child ... in nontherapeutic research ....@ The Court=s use of this term is understandable, for it was the term used by the appellants in presenting the issue to the Court when they sought review of the trial court=s dismissal of their claims. Slip op. at 14. Nevertheless, the use of the term, like the use of its counterpart, Atherapeutic research,@ creates uncertainty. The very term Atherapeutic research@ is inherently troublesome, for it combines conceptually distinct elements of medicine. On the one hand, therapeutics, the science and art of healing, calls for a clinician=s single-minded attention to the medical needs of the patient, with adjustments made to a course of therapy depending upon the patient=s reaction and progress. On the other hand, biomedical research, by definition, is primarily designed not to heal individuals but to acquire scientific knowledge.[5] In research, matters like access to a drug being tested and dosage rates are based on a predetermined protocol, not the individual needs of the subjects.

  Nevertheless, from the perspective of a subject for whom conventional therapy is nonexistent or unavailing, participation in research might be the best, or even the only, hope for medical benefit. The same may be true of preventative measures, like a vaccine, intended to protect against a disorder for which a child is at risk. That is why the federal regulations imposing protections for children involved as subjects for research, 45 C.F.R. Part 46, Subpart D, contain a provision authorizing children to become subjects in research involving an Aintervention or procedure that holds out the prospect of direct benefit for the individual subject.@ 45 C.F.R. '46.405. The Court=s explanation, early in its opinion, of the difference between therapeutic and nontherapeutic research likewise identifies the element of potential direct benefit as the key point of distinction:

  At least to the extent that commercial profit motives are not implicated, therapeutic research=s purpose is to directly help or aid a patient who is suffering from a health condition the objectives of the research are designed to address ─ hopefully by the alleviation, or potential alleviation, of the health condition.

  Nontherapeutic research generally utilizes subjects who are not known to have the condition the objectives of the research are designed to address, and/or is not designed to directly benefit the subject utilized in the research, but, rather, is designed to achieve beneficial results for the public at large (or, under some circumstances, for profit).

Slip op. at 1, note 2.

In the Court=s formulation, therapeutic research has four characteristics, none of which was said by the Court to be true of the lead abatement study at issue in the case. First, the research subjects are Apatients,@ in the sense that they are Asuffering from a health condition.@ Second, the research is Adesigned to address@ the health condition from which the subjects are suffering. Third, if the goal of the research is achieved, those who participate will be Adirectly help[ed]@ because they will receive alleviation of the underlying disease process or its symptoms. Fourth, this direct help need not be certain, but the researchers and the parents must have a reasonable basis to be Ahopeful@ about the Aalleviation, or potential alleviation, of the health condition.@ The Court left open to parents the judgment that participation in this kind of research might be in their child=s best interest, considering the child=s medical condition, the availability or effectiveness of alternative approaches to management of the child=s disorder, the nature of the potential benefits that could be derived from research participation, and the nature and degree of the research-related risks.

Although the Court=s language differs from that in the pertinent section of the federal regulations, the central concepts are the same. Under 45 C.F.R. '46.405, the Department of Health and Human Services Awill conduct and fund research in which the IRB finds that more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is likely to contribute to the subject=s well-being ....@ In addition, the IRB may approve this category of pediatric research only if it finds that:  

(a)       the risk is justified by the anticipated benefits to the subjects;

  (b)       the relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches; and

  (c)       adequate provisions are made for soliciting the assent of the children and permission of their parents or guardians ....@

  All four elements present in the Court=s characterization of therapeutic research are reflected in this regulation as well. First, the regulation assumes that the subjects either have or are threatened by a medical disorder, for otherwise there would be no point to the requirement that the IRB consider Aavailable alternative approaches.@ Second, Aanticipated benefit to the subjects@ must be integral to the research design. Third, the research must present a Aprospect of direct benefit@ ─ that is, a benefit related to the subject=s actual or threatened condition that derives from the research intervention or procedure. Benefits to society in the form of increased scientific knowledge, or even indirect benefits to the subjects like the possibility that some other disorder might be detected because of the close monitoring associated with the research, are by themselves insufficient to satisfy the requirement of a prospect of direct benefit. Fourth, both the IRB and the parents must have a reasoned basis for anticipating benefits to the children that justify the risk, but there need only be a Aprospect@ of such benefit, not a certainty.

Consequently, because of the substantive similarity between the Court=s concept of therapeutic research and the category of direct benefit research in the federal regulations, the Court should clarify and confirm that its holding does not bar a parent from consenting to a child=s participation in research that an IRB has approved under 45 C.F.R. '46.405. [6] In particular, the Court should confirm that parents may give consent to a child=s participation in the clinical trial of a drug or vaccine, even if the trial, as would be commonplace, has a placebo control arm, so long as there is no adequate standard or preventative therapy for the child=s disorder and the possible benefit from receiving the experimental drug or vaccine justifies the risk of participation, including the risk that the child might be randomized to the placebo arm.[7]

II.        THE HOLDING IS CONSISTENT WITH THE FEDERAL REGULATION OF AMINIMAL RISK@ OR AMINOR INCREASE OVER MINIMAL RISK@ RESEARCH.

  The second half of the Court=s holding, denying parental authority if nontherapeutic research presents Aany risk of injury or damage to the health of the subject,@ also requires clarification. The Appellee and other amici correctly point out that few if any research protocols entail no risk whatever. Even a simple questionnaire, for example, depending on its subject matter, might pose the slight risk of temporarily upsetting a child. On the facts of the case as presented to the Court, however, the health risk, far from being a matter of transient discomfort, was a very serious and long-term one: the risk of lead poisoning.

  When the Court began its discussion of parental authority to consent to a child=s participation in research, it framed the issue as Awhether a parent can consent to the participation of her or his child in a nontherapeutic health-related study that is known to be potentially hazardous to the health of the child ...@ Slip op. at 79 (emphasis added). AWhat right does a parent have,@ the Court asked, Ato knowingly expose a child not in need of therapy to health risks or otherwise knowingly place the child in danger, even if it can be argued it is for the greater good?@ Id. A page later, the Court stated, Ait is not in the best interest of a specific child, in a nontherapeutic research project, to be placed in a research environment, which might possibly be, or which proves to be, hazardous to the health of the child.@ Slip op. at 80 (emphasis added). The Court further observed that it is Anot in the 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.@ Id. (emphasis added). These passages refer to significant risks, not minimal ones.

  Given this context, the Court should clarify that its later reference in the holding to Aany risk@ is not intended to ignore the nature or degree of risk associated with research participation. Rather, the holding should be expressly limited to those risks that, in nature and degree, could constitute a genuine hazard to the health of a child.

  Under 46 C.F.R. '46.404, an IRB may approve pediatric research that presents Ano greater than minimal risk to children ....@^[8] If research entails only minimal risk under the federal regulations, it would not constitute the kind of hazard to a child=s health that the Court was concerned about. The Court=s harsh reaction to the risks assumed by the subjects in the lead abatement study, as perceived by the Court, was not focused on the drawing of blood itself, clearly only a minimal risk procedure, but rather on the children=s exposure to lead dust over the course of the research, which the blood testing was to measure. Accordingly, the Court should confirm that its holding does not bar parental consent to a child=s participation in minimal risk research under 45 C.F.R. '46.404.[ 9]

The Court should also clarify the relationship of its holding to another category of pediatric research recognized under the federal regulations: research involving a minor increment of risk beyond minimal and no prospect of direct benefit to the subjects but aimed at increasing knowledge about the subject=s disorder or condition. Under 46 C.F.R. '46.406, for a protocol within this category of research to be approved, the IRB must find that:

(a)       the risk represents a minor increase over minimal risk;

    (b)       the intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations;

  (c)       the intervention or procedure is likely to yield generalizable knowledge about the subjects= disorder or condition which is of vital importance for the understanding or amelioration of the subjects= disorder or condition; and

d)       adequate provisions are made for soliciting assent of the children and permission of their parents or guardians ....  

The Court should clarify its holding so as not to foreclose the possibility that parents might permissibly deem it in the best interest of their child to participate in research authorized by an IRB under 45 C.F.R '46.406, albeit this type of research is nontherapeutic. This judgment about best interest might be made, for example, if the incremental risk is truly slight, if the research procedure is already known from clinical treatment of the child=s disorder to be well-tolerated, and if the knowledge to be gained might lead to a breakthrough in understanding the child=s disease that could, in turn, open the door to future effective therapy. In short, the Court should clarify that its holding about nontherapeutic research does not extend to situations not considered in the case and far removed from the facts that gave rise to the holding. 10

CONCLUSION  

The University of Maryland, Baltimore urges the Court to grant the motion for reconsideration in order to clarify its holding along the lines described in this brief. The Court should ensure that Maryland law governing parental authority to consent to a child=s research participation harmonizes with and does not circumscribe the categories of permissible research under the federal regulation of pediatric research.