Speaker 1: Section four of Safeguarding Children Pediatric Medical Countermeasured 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 McAfee,
Speaker 1: Merritt Island. Chapter two Current Ethical and Radilatory Framework for
Speaker 1: Pediatric Research, Part two. This Bioethics Commission reaffirms its own
Speaker 1: commitment to the principle and practice of democratic deliberation and
Speaker 1: its importance in shaping pediatric research protections, given the dual
Speaker 1: obligations to protect individual research participants and to protect children
Speaker 1: as a class. Enhanced transparency and accountability and extensive community engagement,
Speaker 1: for example, are essential to informing the review and conduct
Speaker 1: of pediatric research by fostering meaningful inclusion of the affected
Speaker 1: communities at all stages of their research process. Community engagement
Speaker 1: constitutes a component of democratic deliberation that researchers can employ
Speaker 1: to incorporate the values of the community into the research process.
Speaker 1: The Bioethics Commission includes in its recommendations appropriate provision for
Speaker 1: community engagement in both pre and post event research. Moreover,
Speaker 1: in all stages of pediatric research, democratic deliberation provides an
Speaker 1: essential means of confirming both that the research is consistent
Speaker 1: with societal and community values, and also that it achieves
Speaker 1: socially valuable and broadly valued goals. Indeed, the Bioethics Commission
Speaker 1: has begun the community engagement process, specifically in the democratic
Speaker 1: deliberation process more generally through its deliberations, and recognized that
Speaker 1: communities are well positioned to contribute to the discussion now
Speaker 1: before any research occurs. The significant test of the social
Speaker 1: value and importance of pediatric research projects, especially when such
Speaker 1: projects subject individual children to some risk for the potential
Speaker 1: benefit of children as a class, is that a broad
Speaker 1: range of citizens and parents, having been informed and given
Speaker 1: the opportunity to comment, value and support those projects. Foundational
Speaker 1: ethical principles provide both clarification and guidance in formulating strong
Speaker 1: safeguards for children, both as individuals and as a group.
Speaker 1: Essential research protections that follow from a principled approach often
Speaker 1: involve appeal to more than one ethical principle. One protection
Speaker 1: central to this report, a commitment to repudiating exploitation provides
Speaker 1: a clear example of such an appeal. The commitment derives
Speaker 1: from the principle of respectful persons and its attendant imperative
Speaker 1: not to treat others as mere means, as well as
Speaker 1: from non maleficence, the duty to do no harm, the
Speaker 1: commitment to avoid exploiting the vulnerable is clearly a matter
Speaker 1: of justice and deliberty. Democracy helps to assure a just
Speaker 1: outcome by promoting dialogue with those who have not yet
Speaker 1: had their chance to voice concerns, thereby protecting against exploitation.
Speaker 1: Continuing in the tradition of the National Commission, this Bioethics
Speaker 1: Commission reaffirmed the view that ethical research is not research
Speaker 1: that strikes the appropriate balance or trade off among fundamental
Speaker 1: social values, but rather quote that all of these principles
Speaker 1: must be taken together as the necessary and sufficient conditions
Speaker 1: for the ethical conduct of research regarding children. Unless research
Speaker 1: can be designed which reflects all four, it cannot be
Speaker 1: called ethical. The recommendations of this report therefore are informed by,
Speaker 1: and seek to satisfy all four fundamental principles of respect
Speaker 1: for persons, beneficence, justice, and democratic deliberation, which are widely
Speaker 1: affirmed by our society and firmly established in the best
Speaker 1: practices of scientific research with human subjects. Current regulations for
Speaker 1: conducting pediatric research, the three Belmont principles and the principle
Speaker 1: of democratic deliberation also informed the National Commission's reasoning and
Speaker 1: rect recommendations for additional regulatory protections for pediatric research participants.
Speaker 1: The Department of Health and Human Services HHS and later
Speaker 1: FDA adopted the National Commission's recommendations almost verbatim, and the
Speaker 1: regulations subsequently promulgated concerning research with children remain largely the
Speaker 1: same today, comprising Subpart D of HHS Regulations at forty
Speaker 1: five CFR Part forty six and FDA Regulations at twenty
Speaker 1: one CFR Part fifty. The language of these two sets
Speaker 1: of regulations is substantively identical. Although Subpart D makes up
Speaker 1: part of these agencies Human Subjects Protections Regulations, it is
Speaker 1: separate from and supplementary to iois Subpart A, referred to
Speaker 1: as the Common Rule, which governs research with adults. Sub
Speaker 1: Part D specifies stringent protections for children in addition to
Speaker 1: those provided in the Common Rule. The key impetus for
Speaker 1: a separate regulatory subpart addressing additional protections for child participants
Speaker 1: in research was the recognition that while adults can consent
Speaker 1: to assume research risks, children cannot. More specific to the
Speaker 1: content of this report. Adults can consent to participate in
Speaker 1: research from which they will accrue no benefit for themselves
Speaker 1: but that benefits others. By contrast, children cannot participate in
Speaker 1: research that poses higher risks than those of daily life,
Speaker 1: except in circumstances where research offers the prospect of benefit
Speaker 1: to participants themselves or to those with the same condition.
Speaker 1: For the most part, protections for pediatric research participants are
Speaker 1: well defined and well implemented. The regulations include special protections
Speaker 1: for wards of the state, delineate requirements for parental permission
Speaker 1: and child assent, and provide criteria for rbs to use
Speaker 1: in reviewing research depending on its level of risk and
Speaker 1: potential benefit. Local IRBs can review and approve research with
Speaker 1: children that one does not involve greater than minimal risk,
Speaker 1: two involves greater than minimal risk but presents the prospect
Speaker 1: of direct benefit to individual participants, or three involves a
Speaker 1: minor increase over minimal risk and no prospect of direct
Speaker 1: benefit to individual research participants, but is likely to yield
Speaker 1: generalizable knowledge about the children's disorder or condition. Local IRBs
Speaker 1: are not permitted to approve research outside of these categories,
Speaker 1: but quote research not otherwise approvable, which presents an opportunity
Speaker 1: to understand, prevent, or alleviate a serious problem affecting the
Speaker 1: health or welfare of children end quote. Generally, higher risk
Speaker 1: non therapeutic research can nonetheless be approved by the Secretary
Speaker 1: of HHS in consultation with a panel of national experts.
Speaker 1: This report refers to such national level expert review by
Speaker 1: its HHS Provision number forty five CFR Section forty six
Speaker 1: point four zero seven, Section four zero seven, which is
Speaker 1: a common convention in ethics discourse on this subject. Equivalent
Speaker 1: substantive requirements are found in FDA Regulations at twenty one CFR,
Speaker 1: Section fifty point five four. Whether the review is conducted
Speaker 1: by the HHS Office for Human Research Protection OHRP FDA,
Speaker 1: or both, the ethical requirements are essentially the same across
Speaker 1: both sets of regulations. The regulations governing these review mechanisms
Speaker 1: are included in Table two point one. Table two point
Speaker 1: one Regulations governing Review of Pediatric Human Subjects Research Protocols.
Speaker 1: Local IRB review mechanisms minimal risk. HHS will conduct or
Speaker 1: fund research in which the IRB finds that no greater
Speaker 1: than minimal risk to children is presented only if THERB
Speaker 1: finds that adequate provisions are made for soliciting assent of
Speaker 1: the children and the permission of their parents or guardians
Speaker 1: as set forth in section forty six point four zero eight.
Speaker 1: Prospect of direct benefit to the individual participant. HS will
Speaker 1: conduct for fund research in which the IRB finds that
Speaker 1: more than minimal risk to children presented by an intervention
Speaker 1: or procedure that holds out the prospect of direct benefit
Speaker 1: for the individual subject, or by a monitoring procedure that
Speaker 1: is likely to contribute to the subjects well being only
Speaker 1: if the IRB finds that a the risk is justified
Speaker 1: by the anticipated benefit to the subjects, b the relation
Speaker 1: of the anticipated benefit to the risk is at least
Speaker 1: as favorable to the subjects as that presented by available
Speaker 1: alternative approaches, and adequate provisions are made for soliciting the
Speaker 1: assent of the children and permission of their parents or
Speaker 1: guardians as set forth in section forty six point four
Speaker 1: zero eight, likely to yield generalizable knowledge about participants condition
Speaker 1: and only minor increase over minimal risk. HHS will conduct
Speaker 1: or fund research in which the IRB finds that more
Speaker 1: than minimal risk to children is presented by an intervention
Speaker 1: or procedure that does not hold out the prospect of
Speaker 1: direct benefit for the individual subject, or by a monitoring
Speaker 1: procedure which is not likely to contribute to the well
Speaker 1: being of the subject. Only if the IRB finds that
Speaker 1: a the risk represents a minor increase over minimal risk.
Speaker 1: B The intervention or procedure presents experiences to subjects that
Speaker 1: are reasonably commensurate with those inherent in their actual or
Speaker 1: expected medical, dental, psychological, social, or educational situations. C The
Speaker 1: intervention or procedure is likely to yield generalizable knowledge about
Speaker 1: the subject's disorder or condition, which is of vital importance
Speaker 1: for the understanding or amelioration of the subject's disorder or condition.
Speaker 1: And d Adequate provisions are made for soliciting assent of
Speaker 1: the children and permission of their parents or guardians, as
Speaker 1: set forth in Section forty six point four zero eight
Speaker 1: National Level Review mechanisms greater than minimal risk with no
Speaker 1: prospect of direct benefit to individual participants or those participants' condition,
Speaker 1: HHS will conduct or fund research that the IRB does
Speaker 1: not believe meets the requirements of Section forty six point
Speaker 1: point four zero four, Section forty six point four zero
Speaker 1: five or Section forty six point four zero six only
Speaker 1: if a the IRB finds that the research presents a
Speaker 1: reasonable opportunity to further the understanding, prevention, or alleviation of
Speaker 1: a serious problem affecting the health or welfare of children,
Speaker 1: and b the Secretary, after consultation with a panel of
Speaker 1: experts impertinent disciplines for example, science, medicine, education, ethics, law,
Speaker 1: and following opportunity for public review and comment, has determined
Speaker 1: either one that the research in fact satisfies the conditions
Speaker 1: of Section forty six point four zero four, Section forty
Speaker 1: six point four zero five or Section forty six point
Speaker 1: four zero six, as applicable, or two the following one,
Speaker 1: the research presents a reasonable opportunity to further the understanding, prevention,
Speaker 1: or alleviation of a serious problem affecting the health or
Speaker 1: welfare of children. Two, the research will be conducted in
Speaker 1: accordance with sound ethical principles, and three adequate provisions are
Speaker 1: made for soliciting the ascent of children and the permission
Speaker 1: of their parents or guardians, as set forth in Section
Speaker 1: forty six point four zero eight. Note in the case
Speaker 1: of review by FDA. Under section fifty point five to four,
Speaker 1: the Commissioner of Food and Drugs convenes the expert panel
Speaker 1: and makes the final determination, which is forwarded to the
Speaker 1: HHS Secretary for concurrent review. Under sections forty six point
Speaker 1: four zero seven and fifty point five four, the Secretary
Speaker 1: makes the final determine end of Table two point one.
Speaker 1: This report references research regulated by Section four zero seven
Speaker 1: as research with healthy children that poses more than minimal
Speaker 1: risk with no prospect of direct benefit. The Bioethics Commission
Speaker 1: recognized and considered in its work the full range of
Speaker 1: research that is encompassed by Section four zero seven, including
Speaker 1: one research with healthy children that poses greater than minimal
Speaker 1: risk and that offers no prospect of direct benefit, two
Speaker 1: research with children affected by a disease or condition that
Speaker 1: poses more than minimal risk and does not yield information
Speaker 1: of vital importance about their disease or condition, and three
Speaker 1: research with children affected by a disease or condition that
Speaker 1: poses greater than a minor increase over minimal risk pediatric
Speaker 1: research subject to local IRB approval. The National Commission's most
Speaker 1: straightforward recommendations addressed research that poses only minimal risk codified
Speaker 1: in section four zero four, or that offers the prospect
Speaker 1: of direct benefit to participants codified in section four zero five.
Speaker 1: More complicated, but still ethically tractable was research posing greater
Speaker 1: than minimal risk but likely to yield generalizable knowledge about
Speaker 1: the participant's condition, codified in section four zero six. Research
Speaker 1: that is greater than minimal risk with no prospect of
Speaker 1: direct benefit to subjects or benefit to others with their
Speaker 1: condition was considered decidedly more controversial and ethically problematic section
Speaker 1: four zero four minimal risk research. Making its recommendation on
Speaker 1: minimal risk research, the National commissionized that quote the scope
Speaker 1: of parental responsibility includes the right to choose activities and
Speaker 1: to define a manner of life for their children end quote.
Speaker 1: Finding that quote many experiences which parents generally allow to
Speaker 1: their children are somewhat risky and cannot be said without
Speaker 1: forcing the case to involve particular benefits end quote, the
Speaker 1: National Commission considered it uncontroversial that parents should have the
Speaker 1: opportunity to enroll their children in research where the risks
Speaker 1: quote are equivalent to normal risks of childhood end quote.
Speaker 1: The National Commission recommended and the regulations allow an IRB
Speaker 1: to approve minimal risk research that provides for parental permission
Speaker 1: and meaningful assent from child participants, as well as standard
Speaker 1: pediatric research safeguards such as risk minimization, privacy and confidentiality protections,
Speaker 1: and equitable subject selection. The National Commission defined risk as
Speaker 1: quote the probability and magnitude of physical or psychological harm
Speaker 1: that is normally encountered in the daily lives or in
Speaker 1: the routine medical or psychological examination of healthy children. End
Speaker 1: As implemented. Protections for minimal risk research have been subject
Speaker 1: to ongoing debate, mostly focused on the regulatory definition of
Speaker 1: minimal risk, which omits the National Commission's reference to healthy children.
Speaker 1: While disagreement remains as to whether the standard is intended
Speaker 1: to be objective or subjective, several national committees studying the
Speaker 1: matter have concluded that minimal risk should be interpreted as
Speaker 1: the degree of risk in encountered in the daily life
Speaker 1: of a healthy child living in a safe environment, or
Speaker 1: the risk to which a healthy child is exposed during
Speaker 1: a routine examination. The Bioethics Commission accepted this shared understanding
Speaker 1: section four zero five. Research presenting the prospect of direct
Speaker 1: benefit in considering research that presents greater than minimal risk
Speaker 1: but also the prospect of direct benefit to research participants.
Speaker 1: The National Commission concluded that risk might be justified by
Speaker 1: avoidance of greater harm or provision of important anticipated benefit.
Speaker 1: Any risk entailed in research, however, can be justified only
Speaker 1: by the potential direct benefits to the individual child participant
Speaker 1: that are associated with the intervention itself, not by ancillary
Speaker 1: benefits such as a medical examination. The risk benefit ratio
Speaker 1: of the experimental intervention must be at least as good
Speaker 1: as that of available alternatives. The relevant regulatory language closely
Speaker 1: reflects that of the National Commission, stating that an RB
Speaker 1: may approve a protocol if it finds that the risk
Speaker 1: is greater than minimal, but that the research holds the
Speaker 1: prospect of direct benefit to the individual, either through the
Speaker 1: intervention or through quote a monitoring procedure that is likely
Speaker 1: to contribute to the subject's well being end quote. Beneficial
Speaker 1: monitoring procedures might include, for example, obtaining samples of blood
Speaker 1: or spinal fluid in order to determine that drug levels
Speaker 1: are safe and effective. A reviewing IRB must also find
Speaker 1: that a quote the risk is justified by the anticipated
Speaker 1: benefit to the subject end quote B. The risk benefit
Speaker 1: ratio is at least as good as existing alternatives, and
Speaker 1: see all relevant parental permission and meaningful child assent provisions
Speaker 1: are observed. There is ongoing debate over the extent to
Speaker 1: which benefit should include non medical benefits, but in practice
Speaker 1: the scope is most often limited to medical benefits associated
Speaker 1: with the intervention being studied Section four zero six more
Speaker 1: than minimal risk without the prospect of direct benefit, but
Speaker 1: likely to yield knowledge about the participant's condition. The National
Speaker 1: Commission recognized that some valuable research involving children will inevitably
Speaker 1: present greater than minimal risk with no prospect of direct
Speaker 1: benefit to the individual participants. Prohibiting this type of research completely,
Speaker 1: as initially supported by some members of the National Commission,
Speaker 1: might have come at too great a cost, sacrificing research
Speaker 1: of critical importance to child welfare in order to avoid
Speaker 1: only a minor increased risk. In developing its recommendations for
Speaker 1: approval of a limited class of research entailing greater than
Speaker 1: minimal risk and no prospect of direct benefit, the National
Speaker 1: Commission kept in mind the proposition that parents are routinely
Speaker 1: allowed to authorize their child's involvement in activities such as skiing,
Speaker 1: where risk is greater than minimal and the potential for
Speaker 1: benefit is debatable. Given that information, the National Commission recommended
Speaker 1: that pediatric research with no prospect of direct benefit in
Speaker 1: presenting no more than a minor increase over minimal risk
Speaker 1: could be ethically permissible and allowed by regulation if the
Speaker 1: knowledge likely to be generated by the research was of
Speaker 1: vital importance to understand or ameliorate a pediatric disorder or condition. Specifically,
Speaker 1: in light of reports that valuable diagnostic, therapeutic and preventive
Speaker 1: measures have been discovered in research that entails risk that quote,
Speaker 1: while minor, would be considered more than minimal end quote.
Speaker 1: The National Commission recommended that local IRBs could approve research
Speaker 1: that meets the following conditions. One quote, the risk involved
Speaker 1: must be only a minor increment beyond minimal end quote.
Speaker 1: Two quote, the procedures to be used must be reasonably
Speaker 1: commensurate with similar to those with which prospective subjects have
Speaker 1: had experience end quote, and three quote, the research must
Speaker 1: be likely to yield generalizable knowledge important for the understanding
Speaker 1: or amelioration of the subject's specific disorder or condition. Research
Speaker 1: that meets these specifications may be approved because the minor
Speaker 1: additional increment of risk to participants is acceptable in light
Speaker 1: of the quote foreseeable benefit in the future to an
Speaker 1: identifiable class of children quote. In making its recommendation, the
Speaker 1: National Commission emphasized that quote minor increase over minimal risk
Speaker 1: in quote is only a narrow expansion, and that any
Speaker 1: protocol submitted under this provision should quote pose no significant
Speaker 1: threat to the child's health or well being. HHS and
Speaker 1: FDA adopted the National Commission's recommendation. Taken together, the three
Speaker 1: categories of research that can be approved by a local
Speaker 1: IRB constitute the majority of pediatric research approved and conducted
Speaker 1: in the United States. Where a protocol does not fall
Speaker 1: into one of these approvable categories, it is generally adminded
Speaker 1: so that it conforms to local review requirements, or else
Speaker 1: it is denied approval. Only rarely is such a protocol
Speaker 1: elevated for national level review under section four zero seven
Speaker 1: see Pediatric Research requiring National level review, higher risk and
Speaker 1: no prospect of direct benefit, Chapter two. These regulatory provisions
Speaker 1: for local IRB review place strict, ethically sound limits on
Speaker 1: the degree of risk to which children can be exposed
Speaker 1: in research, and from the time they have been in place,
Speaker 1: they have permitted and indeed fostered research lead to interventions
Speaker 1: for the most common childhood illnesses and conditions, pediatric research
Speaker 1: requiring national level review higher risk and no prospect of
Speaker 1: a direct benefit to healthy participants Section four zero seven.
Speaker 1: Although the National Commission created a mechanism for local approval
Speaker 1: of greater than minimal risk research with children affected by
Speaker 1: a disorder or condition, it did not develop a set
Speaker 1: of criteria for local IRBs to approve higher risk research
Speaker 1: with healthy children, or research where the risk is greater
Speaker 1: than a minor increase over minimal risk. This latter type
Speaker 1: of research was reserved for evaluation and approval by a
Speaker 1: national panel of experts in the Secretary of HHS, later
Speaker 1: codified as Section four zero seven. The National Commission struggled
Speaker 1: with the idea of involving children in such research with
Speaker 1: no prospect of direct benefit to the individual child participant,
Speaker 1: but recognized that there might be extraordinary circumstances in which
Speaker 1: the dangers to children as a class or the community
Speaker 1: as a whole that would result from excluding children from
Speaker 1: research would be so great that they might require society
Speaker 1: reluctantly to accept a higher level of research risk. For instance,
Speaker 1: in the event of a pending epidemic that could be
Speaker 1: stemmed by testing a novel vaccine with children. The circumstances
Speaker 1: might require this reluctant acceptance of levels of risk otherwise
Speaker 1: unacceptable in pediatric research, for example, higher risks involved in
Speaker 1: determining dosing specifications for particular age groups. Acknowledging that every
Speaker 1: such situation would involve different considerations that could not be
Speaker 1: precisely resolved in the abstract, the National Commission concluded that
Speaker 1: it would be preferable to debate the matter in an
Speaker 1: actual situation, where the quote real issues and the likely
Speaker 1: cost of any solution can be more clearly discerned end quote.
Speaker 1: In providing the opportunity for considered debate in light of
Speaker 1: more specific circumstances, the National Commission went a step further,
Speaker 1: calling for public input as well, stating that the moral
Speaker 1: obligation to protect the community to the extent ethically and
Speaker 1: practically possible, and the prohibition against using unconsenting persons at
Speaker 1: considerable risk to their well being for the promotion of
Speaker 1: the common good were of such import that debate on
Speaker 1: how to reconcile the obligation and prohibition must be held publicly.
Speaker 1: The National Commission recommended that research entailing this level of
Speaker 1: risk could only be approved as an quote exception to
Speaker 1: the general rules end quote. In other words, when quote
Speaker 1: the outlome prohibition of such research on grounds of risk
Speaker 1: might have consequences which themselves appear unethical end and could
Speaker 1: only go forward after one and IRB determines that for
Speaker 1: urgent or unique reasons the research should be permitted, and
Speaker 1: two the research is reviewed and approved at the national
Speaker 1: level to determine that it does not violate the principles
Speaker 1: of respect for persons, beneficence and justice, with opportunity for
Speaker 1: public comment. Additionally, appropriate parental permission and meaningful child assent
Speaker 1: would be required. Now Commission recommended that this national level
Speaker 1: review include judgment by the Secretary of the responsible Agency,
Speaker 1: and that approved research should be delayed pending congressional notification
Speaker 1: and a reasonable opportunity for Congress to take action regarding
Speaker 1: the proposed research. As enacted, the regulations provide that research
Speaker 1: may be approved if one and IRB determines that the
Speaker 1: research quote presents a reasonable opportunity to further the understanding,
Speaker 1: prevention or alleviation of a serious problem affecting the health
Speaker 1: or welfare of children end quote, but is not approvable
Speaker 1: under sections four zero four to Fords zero six and two.
Speaker 1: Upon convening a panel of experts and soliciting public comment,
Speaker 1: the Secretary of HHS determines that one the quote research
Speaker 1: presents a reasonable opportunity to further the understanding, prevention or
Speaker 1: alleviation of a serious problem affecting the health or welfare
Speaker 1: of children end quote. Two quote the research will be
Speaker 1: conducted in accordance with sound ethical principles end quote, and
Speaker 1: three Adequate provision is made for permission of parents and
Speaker 1: guardians in meaningful assent or affirmative agreement of children. This
Speaker 1: structure creates three independent bodies that must review or approve
Speaker 1: any protocol submitted for assessment under section four zero seven,
Speaker 1: one the LOCALRB, two the National Panel of Experts, and
Speaker 1: three the Secretary of HHS. As evidenced by the language
Speaker 1: of section four zero seven, HHS and FDA, in its regulations,
Speaker 1: modified the National Commission's recommendation. The provision adopted by HHS
Speaker 1: and FDA does not provide for notification of Congress and
Speaker 1: sufficient delay for Congress to intervene. The reasons for this
Speaker 1: omission are unclear. In addition, the regulations depart from the
Speaker 1: National Commission's recommendations by providing for an ad hoc panel
Speaker 1: of experts to conduct the National level review rather than
Speaker 1: a standing quote national Ethical Advisory body end quote. Unlike
Speaker 1: the standing committee, a system that HHS expected to prove
Speaker 1: quote cumbersome, inflexible, and unadaptable to the variety of different
Speaker 1: research problems likely to be encountered within the scope of
Speaker 1: the department's activities end quote. The agency hoped that an
Speaker 1: ad hoc structure would provide the flexibility necessary to to
Speaker 1: convene sufficiently expert individuals in a range of scientific specialties,
Speaker 1: ethics concentrations, legal fields, and other relevant disciplines for a
Speaker 1: given protocol. Similarly, regulations adopting National level Review, rather than
Speaker 1: enumerting the principles in the National Commission's recommendation Respect for Persons,
Speaker 1: beneficence and Justice, simply require that research be conducted in
Speaker 1: accordance with sound ethical principles. Although the provision permits necessary
Speaker 1: flexibility for review of research required by extraordinary circumstances, many
Speaker 1: expert panels have reported great uncertainty in determining whether a
Speaker 1: protocol was consistent with sound ethical principles, especially in the
Speaker 1: context of extraordinary circumstances that would justify approval. National level
Speaker 1: review case study driveax smallpox vaccine protocol. In two thousand
Speaker 1: and two, an independent panel reviewed a protocol to test
Speaker 1: smallpox vaccine in forty children two to five years of age.
Speaker 1: Because smallpox was eradicated in nineteen seventy nine, no manufacturer
Speaker 1: still produced the vaccine, and only a limited supply of
Speaker 1: stockpiled vaccine doses remained. Motivated by concerns about a possible
Speaker 1: bioterrorism attack using smallpox virus, the study was intended to
Speaker 1: demonstrate the safety of diluted vaccine and its immune response,
Speaker 1: a allowing emergency responders to stretch the existing supply. Reviewers
Speaker 1: agreed that the existing evidence about adverse reactions and secondary
Speaker 1: infections in adults suggested that the vaccine trial would pose
Speaker 1: more than minimal risk to children. The experts struggled, however,
Speaker 1: with putting these risks in context because they could not
Speaker 1: foresee the likelihood of a bietarism attack. Many found it
Speaker 1: difficult to quantify the possibility of future benefit to children
Speaker 1: as a class. Further complicating the reviewer's considerations was news
Speaker 1: of a potentially safer next generation vaccine in development, which
Speaker 1: might be available by the time a smallpox attack occurred.
Speaker 1: Reviewers also us debated subject selection problems that might result
Speaker 1: if only parents particularly concerned about bioterrorism attacks permitted their
Speaker 1: children to participate. Ultimately, HHS did not approve the protocol
Speaker 1: because biopreparedness plans changed, meaning that drive acts would not
Speaker 1: be used for children in an emergency. In practice, and
Speaker 1: as permitted by regulation, National level review is used primarily
Speaker 1: for research that could not otherwise be approved under another
Speaker 1: section in Subpart D sections four zero four to four
Speaker 1: zero six, but most of the research to date that
Speaker 1: has been considered under section four zero seven has not
Speaker 1: risen to the level of extraordinary circumstances. This practice is
Speaker 1: intension with both the tenor of the National Commission's discussion
Speaker 1: and the language of its recommendation. However, the ethical difficulties
Speaker 1: inherent in enrolling healthy children as experimental controls create persistent
Speaker 1: challenges difficult to resolve in a way that would permit
Speaker 1: approval under sections four zero four through four zero six.
Speaker 1: Healthy controls are scientifically essential to ensure high quality scientific results.
Speaker 1: Such broad application of the national level review process might
Speaker 1: result from inadequate specification of the term serious or from
Speaker 1: the codification of Section four zero seven as a catch
Speaker 1: all provision. Nevertheless, while national review has been used more
Speaker 1: frequently in recent years, it remains rare. From nineteen ninety
Speaker 1: one to twenty twelve, this level of review has been
Speaker 1: used in only fourteen cases, ten of which were approved. Conclusion,
Speaker 1: the ethical foundations for research with children are rooted in
Speaker 1: long and widely held principles respect for persons, beneficence and
Speaker 1: non maleficence, justice, and democratic deliberation, articulated and embodied by
Speaker 1: the National Commission's recommendations in nineteen seventy seven and later
Speaker 1: codified in federal regulations. In general, the current ethical and
Speaker 1: regulatory framework functions well, fostering research and advancing medical progress
Speaker 1: for children while adequately protecting them. Although there are historical
Speaker 1: examples of unethical research with children, most of these pre
Speaker 1: date the current regulations. The Belmont principles, in conjunction with
Speaker 1: the principle of democratic deliberation, continue to guide contemporary pediatric
Speaker 1: research and set the backdrop for the Bioethics Commission's deliberations
Speaker 1: on the ethics of MCM research with children. In the
Speaker 1: next chapter, the Bioethics Commission examines how the characteristics of
Speaker 1: MCM research and these ethical principles interact to present unique
Speaker 1: circumstances to consider when deciding whether to proceed with pediatric
Speaker 1: MCM research in general and with specifica protocols. End of
Speaker 1: Section four. Recording by Patrick mccafey, Merritt, Island,