Speaker 1: Section three of Safeguarding Children Pediatric Medical Countermeasure Research by
Speaker 1: Presidential Commission for the Study of Bioethical Issues. This LibriVox
Speaker 1: recording is in the public domain. Recording by Patrick mcaffee,
Speaker 1: Merritt Island. Chapter two Current Ethical and Regulatory Framework for
Speaker 1: Pediatric Research, Part one. Pediatric research is essential to ensure
Speaker 1: that children have access to therapies that are safe and effective. Quote.
Speaker 1: Children are not just small adults end They vary substantially
Speaker 1: from adults and from other children of different ages in
Speaker 1: the ways they process medicines, respond to interventions, interact with
Speaker 1: their environment, drug effects and toxicities, as well as immune
Speaker 1: responses to vaccines are affected by the rapid growth and
Speaker 1: development in body size, weight, and organ function, as well
Speaker 1: as the metabolic processes that characterize childhood. Children behave differently
Speaker 1: from adults as well. For example, they generally spend more
Speaker 1: time outdoors and put objects in their mouths when they
Speaker 1: are young, increasing their exposure to some environmental contaminants. Given
Speaker 1: these differences, without specific data from pediatric research, health care
Speaker 1: providers often have inadequate information to accurately estimate dosages, formulations,
Speaker 1: and treatment regimens. The pharmaceutical industry historically has had little
Speaker 1: incentive to conduct systematic clinical trials with children, even when
Speaker 1: those trials could have been conducted with minimal risk to
Speaker 1: individual children. US childhood is relatively short and most children
Speaker 1: are healthy. The market for pediatric pharmaceuticals and other medical
Speaker 1: products is small and subdivided by stages of development, often
Speaker 1: making it difficult to enroll adequate numbers of appropriate participants
Speaker 1: necessary for rigorous trials. As of nineteen ninety seven, studies
Speaker 1: showed that up to eighty percent of the drugs used
Speaker 1: by children had never been studied in pediatric populations for safety, dosing,
Speaker 1: or efficacy. Beginning in the late nineteen nineties, out of
Speaker 1: concern for protecting children through research rather than from research,
Speaker 1: Congress passed a series of laws to remedy the paucity
Speaker 1: of pediatric data by creating incentives for ethically sound peddle
Speaker 1: theatric clinical research. This legislation, including the Best Pharmaceuticals for
Speaker 1: Children Act of two thousand two and the Pediatric Research
Speaker 1: Equity Act of two thousand three, provided extended market exclusivity
Speaker 1: for products tested with children, and enabled the US Food
Speaker 1: and Drug Administration FDA to request drug and biologic testing
Speaker 1: with pediatric populations. These incentive programs have spurred pediatric research
Speaker 1: and provided data that contributed to an approximately fifty percent
Speaker 1: reduction in off label use of drugs for children. This
Speaker 1: is a vast improvement from the recent past, although the
Speaker 1: rate of off label use still remains high. Historical research abuses,
Speaker 1: a convergence of research abuses influenced the move toward regulatory
Speaker 1: human subject's research protections, developed in part by the National
Speaker 1: Commission in the nineteen seventies and enacted by the Department
Speaker 1: of Health, Education and Welfare now HHS in the late
Speaker 1: nineteen seventies and early nineteen eighties. Research abuses, including well
Speaker 1: known cases such as Willowbrook, Tuskegee, and the Nazi atrocities,
Speaker 1: were historically important in moving toward regulation. Henry Beecher's publication
Speaker 1: of an article in the New England Journal of Medicine,
Speaker 1: which exposed twenty two cases of human experimentation abuses, also
Speaker 1: motivated human subject's research regulation. Among the cases included in
Speaker 1: Beecher's publication was the Willebrook study, research conducted with institutionalized
Speaker 1: and mentally handicapped children. The current ethical and regulatory framework
Speaker 1: has proven largely capable of protecting children in the face
Speaker 1: of increasing pediatric research, promoting their welfare, and enhancing research quality.
Speaker 1: Medical countermeasure MCM. Research, however, presents unique ethical challenges to
Speaker 1: the existing regulatory framework. This chapter provides an overview of
Speaker 1: the ethical and regulatory framework for pediatric research. It begins
Speaker 1: with an overview of the ethical principles that form the
Speaker 1: foundation of current federal regulations governing pediatric lias research, and
Speaker 1: concludes with a discussion of how those fundamental principles animated
Speaker 1: the development and adoption of pediatric research protections. Ethical underpinnings
Speaker 1: guiding principles. A core set of ethical principles provides the
Speaker 1: foundation for pediatric research protections, reflecting a consensus on the
Speaker 1: ethical conduct of human subjects research. These ethical principles are
Speaker 1: drawn from the National Commission for the Protection of Human
Speaker 1: Subjects of Biomedical and Behavioral Researches, the National Commissions, Belmont
Speaker 1: Report and furthered by democratic deliberation which the National Commission
Speaker 1: and subsequent commissions practiced in their work, and this Bioethics
Speaker 1: Commission explicitly adds as a critical principle for publicly accountable
Speaker 1: decision making in research involving children. The National Commission emphasized
Speaker 1: the importance of including children in research to interrupt what
Speaker 1: had become a long history of untested and harmful pediatric innovations.
Speaker 1: The National Commission recognized that, in addition to protecting children
Speaker 1: from research risks, society ought to protect children through research.
Speaker 1: This need to ensure the safety of children was grounded
Speaker 1: in respect for persons and the inability of children to
Speaker 1: consent to research related risks. The National Commission's report clarified
Speaker 1: what became the United States Central tenet of pediatric research.
Speaker 1: Pediatric research generally should be allowed only when such research
Speaker 1: exposes children to minimal risk. Minimal risk research entails a
Speaker 1: level of risk in which the degree and likelihood of
Speaker 1: harm is no greater than that faced by a healthy
Speaker 1: child in daily life or at a routine physical or
Speaker 1: psychological examination. Research risk can be greater than minimal only
Speaker 1: when the research offers the prospect of direct benefit to
Speaker 1: participants themselves, or if a minor increase above minimal risk,
Speaker 1: when research offers the prospect of benefit to others with
Speaker 1: the same condition, except in extraordinary circumstances, asking children to
Speaker 1: take on greater risk in research when they do not
Speaker 1: stand to benefit directly pushes the bounds of ethical acceptability
Speaker 1: because children do not have the legal or ethical capacity
Speaker 1: to consent, and society has a duty to protect children
Speaker 1: from risk of harm to which they cannot consent. This
Speaker 1: view is widely shared, affirmed in leading international guidance documents,
Speaker 1: and reflected in US law. It continues to serve as
Speaker 1: the first principle of ethically sound pediatric research around the
Speaker 1: world today. Development of the central tenet of pediatric research.
Speaker 1: The four ethical principles that guided the Bioethics Commission's discussion
Speaker 1: of pediatric research protections are respect for persons, benefit and
Speaker 1: justice as outlined in the Belmont Report, and democratic deliberation,
Speaker 1: which was implicit both in the way the National Commission
Speaker 1: carried out its work and also in its recommendations regarding
Speaker 1: the process of reviewing and approving pediatric research. Respect for
Speaker 1: persons the Belmont Report delineates the principle of respect for persons,
Speaker 1: which recognizes persons as autonomous and capable of deliberating about
Speaker 1: their personal goals, considering their own choices and opinions, and
Speaker 1: determining their own lives. Respect for persons also establishes quote
Speaker 1: that persons with diminished autonomy, including children, are entitled to protection.
Speaker 1: Some commentators believe that the obligation of protection in the
Speaker 1: Belmont Report is really a matter of beneficence. However, disregard
Speaker 1: for the well being of children also reflects a lack
Speaker 1: of respect owed to them as young persons. This respect
Speaker 1: derives in part from the fact that children have and
Speaker 1: will further develop personal values and goals, as well as
Speaker 1: the capacity for self determination to strive and fulfill them.
Speaker 1: Respect for persons requires that research participants with full decision
Speaker 1: making capacity be given the information and the opportunity to
Speaker 1: consent voluntarily and knowingly to what will happen to them
Speaker 1: as a result of their participation. This imperative is often
Speaker 1: viewed as deriving from the human capacity for reason and
Speaker 1: self determination. Human beings are generally capable of setting their
Speaker 1: own ends in accordance with their values and priorities in
Speaker 1: rationally pursuing these ends. Treating others in a way that
Speaker 1: disregards their human capacity for rationality and self determination constitutes
Speaker 1: disrespect for those persons. And when we use people only
Speaker 1: to pursue the ends or interests of others, in other words,
Speaker 1: using them as mere means we fail to respect their
Speaker 1: human dignity. Coercive uses of research participants, as in the
Speaker 1: Nazi medical atrocities, provide the most obvious instances of the
Speaker 1: impermissible treatment of participants as means only. Coercion of adult
Speaker 1: participants in research is a violation of a participant's autonomy.
Speaker 1: The rational ability to direct the course of one's own
Speaker 1: life to treat people merely as means to exploit them
Speaker 1: or use them only to further the interests of others
Speaker 1: is not the same as treating people both as means
Speaker 1: and as ends in themselves. Ethical human subjects research illustrates
Speaker 1: this distinction. Participation in research that offers a prospect of
Speaker 1: direct benefit might prove useful to others while simultaneously advancing
Speaker 1: the interests of individual research participants. In other instances of
Speaker 1: scientifically and ethically sound research, adult research participants are well
Speaker 1: informed and willing to bear personal risks with no expectation
Speaker 1: of return, in order to benefit others. In these cases,
Speaker 1: transparency about risks and benefits allows individuals to make their
Speaker 1: own assessment of whether research participation comports with their personal
Speaker 1: values and pursuits. Accordingly, adults who provide their informed consent
Speaker 1: to participate in otherwise scientifically sound and necessary research are
Speaker 1: not treated only as means, but also as ends in themselves.
Speaker 1: Ethical safeguards in pediatric research informed by respect for persons.
Speaker 1: Research with children differs from that with adults because children
Speaker 1: cannot consent in the relevant sense. They are substantially lacking
Speaker 1: in the developed capacities necessary for adequately informed, in voluntary
Speaker 1: decision making, making them a vulnerable population. Although this incapacity
Speaker 1: is most often attributed to their level of cognitive development,
Speaker 1: the vulnerability of children can derive from multiple sources, such
Speaker 1: as expectations of deference to adult authority, lack of independent
Speaker 1: resources for autonomous decision making, and long standing institutionalized relationships
Speaker 1: of adult authority and power. For this reason, extra protections
Speaker 1: are warranted to ensure that children are not placed at
Speaker 1: excessive risk for the benefit of others. These additional safeguards
Speaker 1: include parental permission meaning full child assent, and limits on
Speaker 1: the degree of permissible research related risk. Applied ethics in
Speaker 1: pediatric research, paternalism constitutes those actions that restrict the freedom
Speaker 1: of others on the grounds that those actions are the
Speaker 1: best way to promote or protect their interests. In the
Speaker 1: case of children. Such restrictions are not only justified because
Speaker 1: children cannot identify and pursue their own interests, but because
Speaker 1: quote such restrictions on a child's freedom guarantee his autonomy
Speaker 1: in either or both of two ways. These restrictions protect
Speaker 1: the child from harm that would limit his freedom in
Speaker 1: the future, being seriously injured or a lack of education,
Speaker 1: or These restrictions are what we think the child will
Speaker 1: later agree to, what he will later see as something
Speaker 1: he would do in his own interest. Parental permission. Parental
Speaker 1: permission requires that parents act on their child's behalf, operating
Speaker 1: on their understanding of what is in their child's best
Speaker 1: or essential interests. With this in mind, parents might allow
Speaker 1: a child to participate in research that offers a prospect
Speaker 1: of direct benefit, precisely because enrollment appears to promote the
Speaker 1: child's interests. In the context of research that poses no
Speaker 1: substantial risk to a child's health or well being but
Speaker 1: offers no prospect of direct benefit, some parents will compare
Speaker 1: short term risks and benefits. For these parents, research that
Speaker 1: provides no direct benefit might be out of the question.
Speaker 1: Other parents might be willing to take on risk for
Speaker 1: themselves but reluctant to subject their child to any research
Speaker 1: risk without the prospect of direct benefit, not knowing what
Speaker 1: the child will think upon reaching adulthood about having been
Speaker 1: subjected to risk for the benefit of others without their consent,
Speaker 1: and still other parents will give greater weight to the
Speaker 1: study's incremental contribution to long term scientific or societal endeavors,
Speaker 1: which might eventually result in medical progress that helps their
Speaker 1: child or the child's potential offspring, as well as other children. Alternatively,
Speaker 1: parents might enroll their children in react that poses no
Speaker 1: substantial risk to their health or well being to teach
Speaker 1: them a moral lesson about the value of service to others.
Speaker 1: Parents of older children might wish to give effect to
Speaker 1: their developing autonomy by including them in projects to which
Speaker 1: they assent and which they might later endorse as consistent
Speaker 1: with their own ethical perspective and interests. Meaningful child assent.
Speaker 1: While children are not fully autonomous, they nevertheless have varying
Speaker 1: capacities to make informed self regarding choices and express their
Speaker 1: preferences regarding how they will be treated. Children's partial autonomy
Speaker 1: affords them a developmentally appropriate ability to participate in decisions
Speaker 1: regarding their involvement in research. Out of respect for this
Speaker 1: developing ability of children, their assent should be solicited if possible,
Speaker 1: and their descent respected if applicable. Obtaining the meaningful ascent
Speaker 1: of a capable child is one component of respecting that
Speaker 1: child as a person. It must not be interpreted, however,
Speaker 1: either as informed consent or as a substitute for parental permission.
Speaker 1: Parental permission is absolutely necessary to informed participation in conjunction
Speaker 1: with meaningful child assent. The fact that children have a
Speaker 1: developing capacity for autonomy lends significance to a child's meaningful
Speaker 1: assent or dissent, and also establishes a need to protect
Speaker 1: this capacity for self determination. The principle of respect for
Speaker 1: persons permits only those research protocols that preserve and sustain
Speaker 1: the full development of a child's autonomy, such that the
Speaker 1: current and future aspirations of some children are never unduly
Speaker 1: compromised merely for the sake of benefiting others. This is
Speaker 1: accomplished in important part by the final form of protection
Speaker 1: discussed here, which limits the degree of risk to which
Speaker 1: children can be exposed in research, limiting the degree of
Speaker 1: research related risk, placing strict limits on the level of
Speaker 1: risk acceptable in pediatric research is a third and critically
Speaker 1: important way to protect children. In light of their incomplete
Speaker 1: autonomy and their inability to consent. Child research participants will
Speaker 1: one day grow up and reflect on whether they would
Speaker 1: have consented to participate in the research had they been capable.
Speaker 1: While parents may exercise legitimate discretion when granting permission for
Speaker 1: their children to enroll in research, there is no way
Speaker 1: to know whether all participants, once adults, will endorse the
Speaker 1: decision retrospectively, even if they provided meaningful assent as children.
Speaker 1: To reduce the possibility that some participants will look back
Speaker 1: and think they were unethically used by their parents or researchers,
Speaker 1: protections should be in place to ensure that participants who
Speaker 1: reflect on their past research participation will be likely to
Speaker 1: endorse the ways in which they were protected, if not
Speaker 1: their own participation. On this view, mass participants might later
Speaker 1: reflect that even if they would not have consented to participate,
Speaker 1: protections were in place that prevented them from being harmed.
Speaker 1: Risk limits are essential to combat the potential for exploitation
Speaker 1: of both children and adults. However unintended, such exploitation may
Speaker 1: be because children cannot make an autonomous decision to participate
Speaker 1: in research. From an ethical and legal perspective, great care
Speaker 1: must be taken to ensure that research risks are rigorously limited.
Speaker 1: In particular because research is in part always justified on
Speaker 1: the basis of potential benefit to others, but not necessarily
Speaker 1: to the children who are subject to risks as research subjects,
Speaker 1: special efforts must be made to sure that children are
Speaker 1: not exploited by permitting greater research risks to children when
Speaker 1: society stands to benefit in greater measure. The imposition of
Speaker 1: a rigorous risk ceiling ensures that, no matter how great
Speaker 1: the potential benefit, child research participants are not exposed to
Speaker 1: a disrespectful and exploitative level of risk for the interests
Speaker 1: of others in society. Another reason why it is important
Speaker 1: to limit the research risks to which children are subjected
Speaker 1: is that the state does not have the same broad
Speaker 1: latitude as parents to make risk laden decisions on behalf
Speaker 1: of children. There are public obligations to limit both the
Speaker 1: outer bounds of parental authority so as to prevent negligence,
Speaker 1: and the outer bounds of govern mental authority over children
Speaker 1: so as to prevent the exploitation of individual children. For
Speaker 1: public purposes. One way in which the government defines the
Speaker 1: outer bounds of its own authority over individual children and
Speaker 1: respects the future autonomy of children is by limiting the
Speaker 1: levels of research risk that parents may be asked to
Speaker 1: accept for their children, especially when that research is above
Speaker 1: minimal risk and does not directly benefit the child. These
Speaker 1: risk limits are one of the core protections that children receive,
Speaker 1: both out of respect for their dignity as persons and
Speaker 1: to help ensure that they will be able to exercise
Speaker 1: their own autonomy as adults. Interpreting the scope of respect
Speaker 1: for persons, given that children are all under clearly delineated
Speaker 1: circumstances to participate in research without the prospect of direct benefit,
Speaker 1: current regulations implicitly reject one particularly restrictive interpretation of the
Speaker 1: principle of respect for persons see Current Regulations for Conducting
Speaker 1: Pediatric Research, Chapter two. Under this most restrictive interpretation, due
Speaker 1: to their incapacity to consent, the principle of respect for
Speaker 1: persons would prohibit all research with children, including even minimal
Speaker 1: risk research that offers no prospect of direct benefit. Strong
Speaker 1: consensus in the field of bioethics, including the judgment reflected
Speaker 1: in the National Commission's position, regards this understanding as overly restrictive.
Speaker 1: An alternative, widely accepted interpretation of respectful persons allows for
Speaker 1: the participation of children in research that offers no prospect
Speaker 1: of direct benefit under certain carefully defined circumstances, even if
Speaker 1: the research imposes more than minimal risk on pediatric participants,
Speaker 1: stopping short of posing any substantial risk to the fundamental
Speaker 1: health or wellbeing of the research participants. On this widely
Speaker 1: accepted interpretation, research without the prospect of direct benefit is
Speaker 1: permissible if it imposes no greater than minimal risk, a
Speaker 1: level of risk comparable to the risks that healthy children
Speaker 1: living in a safe environment routinely encounter in everyday life
Speaker 1: or during a routine medical examination, and under certain limited circumstances,
Speaker 1: a slightly higher but still very limited level of risk
Speaker 1: which poses no substantial risk to the participant's health or
Speaker 1: well being. The widely accepted interpretation of the principle of
Speaker 1: respect for persons should be endorsed on the grounds that
Speaker 1: research protections can help to ensure respect for children by
Speaker 1: safeguarding their current capacities, guaranteeing their future autonomy by ensuring
Speaker 1: they are not treated as mere means and by not
Speaker 1: subjecting them to undue risk. In addition, this more inclusive
Speaker 1: interpretation receives support from other relevant moral principles. The principle
Speaker 1: of beneficence, further addressed in the next section, calls upon
Speaker 1: society and the research community to advance biomedical knowledge in
Speaker 1: the interest of the public's welfare. The importance of beneficence
Speaker 1: in the context of pediatric biomedical research councils against the
Speaker 1: most restrictive interpretation of respect for persons and in favor
Speaker 1: of the widely accepted approach to pediatric ethics as reflected
Speaker 1: in the national commissions, recommendations and current regulations. All pediatric
Speaker 1: research must satisfy the ethical principle of respect for persons.
Speaker 1: This Bioethics Commission articulated a set of conditions under which
Speaker 1: pediatric research without the prospect of direct benefit fully respects
Speaker 1: and ethically protects children as individuals and as a group
Speaker 1: see pre event studies posing no more than a minor
Speaker 1: increase over minimal risk approvable under section four seven, Chapter three.
Speaker 1: By treating the int of child participants as a paramount concern,
Speaker 1: pediatric research without the prospect of direct benefit, can respect
Speaker 1: and uphold the humanity of participants and refuse to view
Speaker 1: them as objects merely serving the ends of science or society,
Speaker 1: provided that the research risks are strictly limited and parental
Speaker 1: permission and meaningful child assent are obtained. This generally entails
Speaker 1: permitting research that involves no more than minimal risk, but
Speaker 1: under certain strictly limited circumstances, permitting a slightly higher than
Speaker 1: minimal but still very limited level of risk, provided that
Speaker 1: the protocol poses no substantial risk to the children's health
Speaker 1: or well being Beneficence. Beneficence, as described in the Bellport,
Speaker 1: is the obligation to undertake efforts to secure the well
Speaker 1: being of others. In pediatric research, the duty to safeguard
Speaker 1: participants by protecting them from harm and undue risk of
Speaker 1: harm is particularly salient because children have reduced autonomy and
Speaker 1: cannot legally consent, making them a vulnerable population. Beneficence requires
Speaker 1: that special safeguards be employed to protect vulnerable populations, for example,
Speaker 1: the requirement of minimal risk or prospect of direct benefit
Speaker 1: for most pediatric research. This principle provides additional support for
Speaker 1: the conclusion that some proposed pediatric trials impose excessive risks
Speaker 1: too high to ask parents to consider having their children
Speaker 1: bear These studies would involve potential harm that would threaten
Speaker 1: the basic health or well being of children, who, as
Speaker 1: research participants, would not stand to directly benefit or be
Speaker 1: able to offer their own informed consent. The Belmont Report
Speaker 1: includes under beneficence the corollary principle of non maleficence or
Speaker 1: do no harm, an obligation not to cause deliberate harm
Speaker 1: to others. This obligation to minimize the risk of harm
Speaker 1: from research, especially for children, in view of their inability
Speaker 1: to consent, provides an additional principled foundation for a firm
Speaker 1: limit to acceptable research risks. Notably, however, there might be
Speaker 1: cases in which, in order to avoid harm, research is
Speaker 1: needed to discover what is harmful. Similarly, to discover what
Speaker 1: is beneficial might at times require exposing some persons to
Speaker 1: the risk of harm. As stated by the National Commission. Quote,
Speaker 1: the problem posed by these imperatives is to decide when
Speaker 1: it is justifiable to seek certain benefits despite the risks involved,
Speaker 1: and when the benefits should be foregone because of the
Speaker 1: risks end quote. Beneficence is directed not only at individual
Speaker 1: research participants, but also toward the broader public seeking to
Speaker 1: benefit society as a whole. The Belmont Report acknowledged this,
Speaker 1: stating quote, the obligations of beneficence affect both individual investigators
Speaker 1: and society at large because they extend both to particular
Speaker 1: research projects and to the entire enterprise of research. In
Speaker 1: the case of scientific research in general, members of the
Speaker 1: larger society are obliged to recognize the longer term benefits
Speaker 1: and risks that may result from the improvement of knowledge
Speaker 1: and from the development of novel medical, psychotherapeutic, and social procedures.
Speaker 1: End quote. Those who deliberate and consider whether research should
Speaker 1: proceed ought to take into account the duty quote of
Speaker 1: a society and its government to promote individual activities and
Speaker 1: institutional practices, including scientific and biomedical research, that have great
Speaker 1: potential to improve the public's well being end quote. Beneficence
Speaker 1: guides the risk benefit assessment in research. While risk indicates
Speaker 1: possible harm, benefit refers to the anticipated game means resulting
Speaker 1: from the research. The Belmont Report offered five considerations for
Speaker 1: assessing risk benefit justification in research with all human participants.
Speaker 1: One brutal or inhumane treatment of human subjects is never
Speaker 1: morally justified. Two Risks should be reduced to those necessary
Speaker 1: to achieve the research objective. Risk can perhaps never be
Speaker 1: entirely eliminated, but it can often be reduced by careful
Speaker 1: attention to alternative procedures. Three. When research involves significant risk
Speaker 1: of serious impairment, review committees should be extraordinarily insistent on
Speaker 1: the justification of the risk, looking usually to the likelihood
Speaker 1: of benefit to the subject, or, in some rare cases,
Speaker 1: to the manifest voluntariness of the participation. Four. When vulnerable
Speaker 1: populations are involved in research, the appropriateness of involving them
Speaker 1: should itself be demonstrated. A number of variables go into
Speaker 1: such judgments, including the nature and degree of risk, the
Speaker 1: condition of the particular population involved, and the nature and
Speaker 1: level of the anticipated benefits. Five Relevant risks and benefits
Speaker 1: must be thoroughly arrayed in the informed consent process. Two
Speaker 1: of these considerations are especially applicable to the question before
Speaker 1: the Bioethics Commission. Two reducing risk to that necessary to
Speaker 1: achieve the research objective and to the lowest possible level
Speaker 1: by considering alternative approaches. And four justifying the appropriateness of
Speaker 1: including vulnerable populations in this case children. Non maleficence, which
Speaker 1: requires us to reduce research risks as far as possible,
Speaker 1: becomes especially salient when research is planned with children who
Speaker 1: cannot consent to assume risks on the behalf of others.
Speaker 1: Beneficence and non maleficence, similar to respect for children as persons,
Speaker 1: obligate us to ensure that research risks be necessary and minimized,
Speaker 1: and to employ alternative approaches that might avoid exposing children
Speaker 1: to risk, for example, using computer and animal models or
Speaker 1: adult participants who can consent to assume risk on behalf
Speaker 1: of others. Moreover, risks should be shown to be minimal
Speaker 1: in the youngest adults through testing them before proceeding with
Speaker 1: the oldest children. Further, non maleficence toward child research participants
Speaker 1: and beneficence towards participants and towards society as a whole
Speaker 1: must be jointly considered in determining an acceptable level of risk.
Speaker 1: In general, research related risks that are greater than minimal
Speaker 1: are ethically permissible only if there is a prospect of
Speaker 1: direct benefit for the child participants, or there is the
Speaker 1: prospect of benefit to the class of children from which
Speaker 1: the participants are drawn justice. The principle of justice reflects
Speaker 1: the National Commission's commitment to fairness in distribution, or what
Speaker 1: is deserved. Ethical distribution of research and benefits generally prevents
Speaker 1: the possibility of asking participants and families to consider bearing
Speaker 1: too heavy a burden on behalf of society. More specifically,
Speaker 1: in the conduct of research, justice requires that research participants
Speaker 1: not be denied a benefit to which they are entitled,
Speaker 1: and that no individual participant be burdened with undue risk
Speaker 1: of harm or hardship. These obligations can be met by
Speaker 1: ensuring that all research participants are treated equitably, for instance,
Speaker 1: by allocating research burdens and benefits according to ethically justifiable
Speaker 1: criteria in the case of research with children. Moreover, justice
Speaker 1: in combination with respect for persons, beneficence and non maleficence,
Speaker 1: requires that children should not bear more risk than absolutely
Speaker 1: necessary during research, and that risks children undertake during research
Speaker 1: may be assumed only in order to address research questions
Speaker 1: that can only be addressed with children. For example, children
Speaker 1: should not be asked to bear research risks solely to
Speaker 1: benefit adults. Just distribution of research risks applies not only
Speaker 1: to the design and conduct of research, but also to
Speaker 1: subject selection, even when they are treated equitably once enrolled
Speaker 1: in research, Children and families might be selected unjustly if
Speaker 1: they are chosen from certain subgroups of the population that
Speaker 1: are already excessively burdened by conditions of socioeconomic disadvantage, that
Speaker 1: have made uncommon sacrifices in the course of public service,
Speaker 1: or that have been subject to repeated recruitment for research.
Speaker 1: Enrollment reviewers and researchers must ensure that all necessary safeguards
Speaker 1: are in place to avoid exploiting participants when enrolling those
Speaker 1: who might be vulnerable based on their age, clinical status, marginalization,
Speaker 1: economic deprivation, or similarly relevant factors. Justice justice requires that
Speaker 1: similar cases be treated similarly, So to does justice require
Speaker 1: that we be alert to significant differences. Researchers therefore must
Speaker 1: be cognizant of the potential for exploitation, the ability to
Speaker 1: take unfair advantage of participant vulnerability. The principle of justice requires,
Speaker 1: as noted by the National cos Mission, that researchers adapt
Speaker 1: their practices to treat cases that differ in morally relevant
Speaker 1: respects differently, for example, modifying consent or recruitment practices in
Speaker 1: order to equalize protection from harm for all participants once
Speaker 1: research has concluded. Justice requires equitable distribution of benefits that
Speaker 1: emerge from successful research endeavors. Just distribution takes into account
Speaker 1: not only such factors as who participated in the research,
Speaker 1: but also ensures that children are not excluded from receiving
Speaker 1: benefits on the basis of poverty or other marginalizing factors.
Speaker 1: Democratic deliberation. Democratic deliberation is a process that seeks to
Speaker 1: clarify and articulate factual and ethical issues at the core
Speaker 1: of a debate, to create consensus whenever possible, and to
Speaker 1: map the terrain of disagreements in a respectful way when
Speaker 1: agreement is not immediately attainable, by encouraging reciprocity, respectful persons, transparency, publicity,
Speaker 1: and accountability. This principle embraces inclusion of community members, individuals
Speaker 1: and their representatives in meaningful and active participation in an
Speaker 1: ongoing public exchange of ideas in research. Democratic deliberation is manifest,
Speaker 1: for example, in community engagement and in various aspects of
Speaker 1: institutional research review and approval. The National Commission valued the
Speaker 1: principle of democratic deliberation and honored it both in its
Speaker 1: approach as well as its recommendations. While studying the matter
Speaker 1: of research protections for child participants in the nineteen seventies,
Speaker 1: the National Commission took extensive measures to involve experts, advocates,
Speaker 1: parents and other stakeholders. The National Commission invited representatives of
Speaker 1: professional societies, federal agencies, public interest groups, parents, and other
Speaker 1: members of the public to present their views at public hearings.
Speaker 1: In addition to creating an open forum for interested individuals
Speaker 1: and parties to present their views, the National Commission actively
Speaker 1: convened a National Minority Conference on Human Experimentation to represent
Speaker 1: the views of those who might not otherwise be adequately represented.
Speaker 1: The Commission reviewed papers and surveyed existing pediatric research practices
Speaker 1: to inform its public deliberations and develop recommendations for pediatric research.
Speaker 1: This inclusive approach to its deliberations was evident not only
Speaker 1: in the National Commission's process, but also in the content
Speaker 1: of its report, Research Involving Children, which lays out its
Speaker 1: argument through chapters devoted to each level of its inquiry.
Speaker 1: These chapters include the various surveys to characterize contemporary research,
Speaker 1: review and consent practices, views presented by stakeholders, and discourse
Speaker 1: by psychology, law and ethics experts of the day. One
Speaker 1: recommendation in particular, demonstrates the importance of democratic deliberation to
Speaker 1: the National Commission, not only in its own work, but
Speaker 1: also in the ongoing review and approval of research with children.
Speaker 1: Although all pediatric research requires review by an Institutional Review
Speaker 1: Board RB, a form of democratic deliberation, the National Commission
Speaker 1: recommended that research involving greater than minimal risk with no
Speaker 1: prospect of direct benefit to healthy children should only be
Speaker 1: approved effort an opportunity for extensive public comment and open deliberation.
Speaker 1: Because the National Commission considered this category of research approvable
Speaker 1: only in extraordinary circumstances and as a matter of social exigency,
Speaker 1: it considered solicit visiting the input of citizens essential both
Speaker 1: to inform and legitimate the work. Accordingly, the National Commission
Speaker 1: recommended that research in this category could only be considered
Speaker 1: for approval by the Secretary of the responsible Agency after
Speaker 1: consultation with a panel of experts and opportunity for public comment,
Speaker 1: observing the principles at stake one the obligation to protect
Speaker 1: the community or come to the aid of those within it,
Speaker 1: and two the prohibition against unethically using persons who cannot
Speaker 1: consent at considerable risk to their well being for the
Speaker 1: common good. The National Commission stated, quote, these principles are
Speaker 1: of such moment, and their observance so big to adjust
Speaker 1: in humane society, that any debate about their application should
Speaker 1: be held at the most public level of discourse. End
Speaker 1: end of Chapter two. Current Ethical and Regulatory Framework for
Speaker 1: Pediatric Research, Part one. Recording by Patrick mccaffee, Merritt Island,