WEBVTT

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<v Speaker 1>Section two of Safeguarding Children Pediatric Medical Countermeasure Research by

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<v Speaker 1>Presidential Commission for the Study of Bioethical Issues. This LIVERVOK

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<v Speaker 1>recording is in the public domain. Recording by Patrick mccaffee,

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<v Speaker 1>Merritt Island. Chapter one introduction. Our sense of justice, beneficence

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<v Speaker 1>and respect for human dignity calls upon the country to

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<v Speaker 1>do what it reasonably can to safeguard all children in

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<v Speaker 1>the event of a public health emergency. This protection includes,

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<v Speaker 1>for example, providing medicine, vaccines, and other interventions as needed.

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<v Speaker 1>Our same sense of justice, beneficence, and respect for human

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<v Speaker 1>dignity calls on us to safeguard individual children who participate

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<v Speaker 1>in scientifically and ethically sound clinical research to develop these interventions,

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<v Speaker 1>and to protect individual children from participating in research that

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<v Speaker 1>could impose undue risks on them. In other words, as

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<v Speaker 1>a country, we have both a fundamental duty to protect

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<v Speaker 1>individual children from undue risk during research and an obligation

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<v Speaker 1>to protect all children during an emergency to the extent

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<v Speaker 1>ethically and practically possible by being prepared both with the

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<v Speaker 1>fruits of scientifically and ethically sound research and with a

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<v Speaker 1>fulsome national readiness to respond. In January twenty twelve, the

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<v Speaker 1>Secretary of Health and Human Services HHS asked the Presidential

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<v Speaker 1>Commission for the Study of Bioethical Issues, the Bioethics Commission,

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<v Speaker 1>to advise the U S Government in its mission to

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<v Speaker 1>be fully prepared to mitigate the impact of biol terrorism

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<v Speaker 1>attacks on ethical considerations in evaluating and conducting pediatric medical

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<v Speaker 1>countermeasure MCM research. Pediatric MCM research involves testing interventions with

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<v Speaker 1>children that will be used in response to an attack,

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<v Speaker 1>either before it occurs in other words, pre event research,

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<v Speaker 1>or testing such interventions following an attack in other words,

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<v Speaker 1>post event research. Pre and post event pediatric MCM research

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<v Speaker 1>pose risks to the individual children enrolled in research, who,

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<v Speaker 1>in many cases do not stand to benefit directly from

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<v Speaker 1>the research. The tension between the need to conduct pediatric

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<v Speaker 1>MCM research to protect children in the event of a

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<v Speaker 1>future attack and the risks of this research to individual

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<v Speaker 1>children who do not stand to directly benefit from it

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<v Speaker 1>creates the central ethical challenge of pediatric MCM research. As

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<v Speaker 1>noted in the Belmont Report, the ethical dilemma facing the

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<v Speaker 1>Bioethics Commission derives in part from the principle of beneficence,

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<v Speaker 1>which quote requires that we protect against risk of harm

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<v Speaker 1>to subjects, and also that we be concerned about the

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<v Speaker 1>loss of the substantial benefits that might be gained from

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<v Speaker 1>research end The Bioethics Commission addresses this tension in this report.

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<v Speaker 1>A major bioterrorism attack could require deployment of pediatric MCMs

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<v Speaker 1>to safeguard children. In the event of a bioterrorism attack,

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<v Speaker 1>m cms should be ready and available for pediatric use

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<v Speaker 1>under current federal plans. In the event of an emergency,

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<v Speaker 1>children would be provided with at least some MCMs that

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<v Speaker 1>have been approved for adults, even though many of these

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<v Speaker 1>treatments have not been tested with children. Extrapolating from data

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<v Speaker 1>in adult populations may be insufficient to determine safety and

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<v Speaker 1>proper doses of MCMs for children. Pediatric research might therefore

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<v Speaker 1>be necessary to determine the safest doses and formulations of

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<v Speaker 1>MCMs for children pre event. MCM research presents challenges that

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<v Speaker 1>are distinct from other types of research, as it involves

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<v Speaker 1>research on a hypothetical condition with an undefined and perhaps

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<v Speaker 1>unknowable likelihood of occurring, and while the knowledge gained could

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<v Speaker 1>be profoundly useful, we may never have and hope never

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<v Speaker 1>to have occasion to use it. The ramifications of these

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<v Speaker 1>characteristics are discussed in greater detail below. Post event research

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<v Speaker 1>poses its own challenges because this research generally will be

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<v Speaker 1>conducted in very stressful circumstances. In post event MCM research,

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<v Speaker 1>the experimental intervention will often be provided in concert with

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<v Speaker 1>additional tested treatments that could confound data collected regarding the MCM. Moreover,

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<v Speaker 1>the stressful circumstances in which post event research likely will

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<v Speaker 1>be conducted might make safeguards such as obtaining adequate, informed

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<v Speaker 1>parental permission and meaningful child assent particularly difficult. In this report,

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<v Speaker 1>the Bioethics Commission also addresses research conducted when the threat

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<v Speaker 1>of an attack is imminent, because, as discussed in greater

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<v Speaker 1>detail below, in these cases, the ethical and practical concerns

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<v Speaker 1>track those of a post event study, even if technically

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<v Speaker 1>conducted pre event pediatric research itself presents particular ethical complications.

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<v Speaker 1>Competent adults can generally consent to accept risks for the

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<v Speaker 1>benefit of others during research through the informed consent process.

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<v Speaker 1>Agreeing to place oneself at risk for the good of

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<v Speaker 1>others is often viewed as admirable, generous, and honorable. Children,

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<v Speaker 1>on the other hand, are ethically and legally incompetent to

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<v Speaker 1>consent on their own behalf, and therefore cannot agree to

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<v Speaker 1>assume research risks for the benefit of others. A child's

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<v Speaker 1>reduced autonomy and increased vulnerability, along with the inability to

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<v Speaker 1>provide informed consent, necessitates additional protections during research. These protections

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<v Speaker 1>include limits on the level and types of research risks

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<v Speaker 1>a child can be asked to assume, and generally require

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<v Speaker 1>some prospect of direct benefit to the participant if research

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<v Speaker 1>risks exceed the minimal ones that a healthy child living

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<v Speaker 1>in a safe environment routinely encounters in daily life or

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<v Speaker 1>during a routine medical examination. The Bioethics Commission's ethical analysis

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<v Speaker 1>lies at the intersection of the unique characteristics of MCM

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<v Speaker 1>research and pediatric research. In its nineteen seventy seven report

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<v Speaker 1>Research Involving Children, the National Commission for the Protection of

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<v Speaker 1>Human Subjects of Biomedical and Behavioral Research, the National Commission

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<v Speaker 1>presently described this type of challenge. The ethical principles at

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<v Speaker 1>stake are the moral obligation to protect the community and

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<v Speaker 1>the moral prohibition against using unconsenting persons at considerable risk

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<v Speaker 1>to their well being for the promotion of the common

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<v Speaker 1>good end. Although the National Commission did not address pediatric

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<v Speaker 1>MCM research specifically, the principles it articulated respect for persons,

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<v Speaker 1>beneficence and its corollary non maleficence and justice offer a

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<v Speaker 1>way to frame the complexities of MCM research involving children.

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<v Speaker 1>An additional principle implicit in the National Commission's work, democratic deliberation,

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<v Speaker 1>further informs this analysis. For this report, the Bioethics Commission

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<v Speaker 1>examined these existing, well established ethical principles that guide pediatric

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<v Speaker 1>research to enumerate considerations for the ethical conduct of pre

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<v Speaker 1>event and post event MCM studies with children. The Bioethics

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<v Speaker 1>Commission first considered pre event studies those posing minimal risk

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<v Speaker 1>in other words, no greater risk than that faced by

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<v Speaker 1>a healthy child in daily life or at a routine

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<v Speaker 1>medical examination, as well as those posing greater than minimal

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<v Speaker 1>risk while offering no direct prospect of benefit to the

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<v Speaker 1>individual child participants, but that are important to the potential

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<v Speaker 1>future benefit of many or all children. The Bioethics Commission

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<v Speaker 1>then considered post event studies those posing minimal risk as

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<v Speaker 1>well as those posing some additional risk but also offering

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<v Speaker 1>the prospect of direct benefit to the individual children who participate,

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<v Speaker 1>or offering the prospect of generalizable knowledge about the participant's

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<v Speaker 1>condition both pre and post event. MCM research studies with

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<v Speaker 1>children are ethically challenging for each of these categories, and

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<v Speaker 1>consistent with its charge, the Bioethics Commission also existed the

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<v Speaker 1>specific ethical issues raised in the context of proposed research

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<v Speaker 1>on anthrax vaccine absorbed AVA with children anthrax vaccine absorbed.

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<v Speaker 1>The complexities of pediatric MCM research were highlighted by government

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<v Speaker 1>actions surrounding AVA, a particular MCM for anthrax. In early

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<v Speaker 1>twenty eleven, the US government conducted an exercise called dark

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<v Speaker 1>Zephyr to test local, state, and federal government responses to

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<v Speaker 1>a large scale anthrax release in a major metropolitan area.

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<v Speaker 1>Dark Zephyr revealed that about seven point six million individuals

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<v Speaker 1>would be exposed to anthrax during such an event, including

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<v Speaker 1>as many as one point seven million children, all of

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<v Speaker 1>whom would require treatment. Although the government had plans in

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<v Speaker 1>place to treat adults, officials involved in the exercise quickly

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<v Speaker 1>realized that there was no evidence supporting a clear course

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<v Speaker 1>of action for the treatment of children. The planned response

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<v Speaker 1>during the exercise involved administering AVA for post exposure prophylaxis

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<v Speaker 1>to both adults and children in combination with antibiotics. The

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<v Speaker 1>US Food and Drug Administration FDA has approved AVA for

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<v Speaker 1>use by adults before an anthrax exposure, but has not

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<v Speaker 1>approved AVA for post exposure prophylaxis by adults or for

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<v Speaker 1>any use by children, and there are no data on

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<v Speaker 1>the use of AVA by children. While antibiotics help prevent

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<v Speaker 1>or treat immediate infection with anthrax and are the only

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<v Speaker 1>current approved post exposure treatment for children, they cannot provide

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<v Speaker 1>the long term protection that vaccination confers against the persistence

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<v Speaker 1>of dormant spores. Long term use of antibiotics is also

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<v Speaker 1>associated with side effects, including gastrointestinal discomfort, which can result

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<v Speaker 1>in intolerance and poor adherents. In addition, evidence from animal

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<v Speaker 1>models suggests that even the initial response to combined antibiotic

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<v Speaker 1>and vaccine treatment is superior to antibiotics alone. In the

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<v Speaker 1>absence of data on the use of AVA by children

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<v Speaker 1>and the corresponding lack of FDA approval for its post

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<v Speaker 1>exposure use in pediatric populations, current HHS plans based on

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<v Speaker 1>recommendations by the Advisory Committee on Immunization Practices ACIP include

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<v Speaker 1>making available a three dose course of AVA in combination

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<v Speaker 1>with antibiotics to children who have been exposed to anthrax,

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<v Speaker 1>and conducting post event observational research with a subgroup of

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<v Speaker 1>those children who received it to better understand the effects

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<v Speaker 1>of AVA. Research protections would be in place for all

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<v Speaker 1>children receiving AVA, whether as treatment or as part of

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<v Speaker 1>a research study. See Authorizing Distribution of NA approved Drugs

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<v Speaker 1>in an emergency Chapter three scientific recommendation by the National

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<v Speaker 1>Biodefense Science Board in response to the findings of dark Zephyr,

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<v Speaker 1>in particular the nation's lack of preparedness to treat children

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<v Speaker 1>in the event of an anthrax attack, Doctor Nicole Lurie,

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<v Speaker 1>HHS Assistant Secretary for Preparedness and Response, asked the National

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<v Speaker 1>Biodefense Science Board NBSB to recommend the best course of

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<v Speaker 1>action to prepare for a potential use of AVA vaccine

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<v Speaker 1>in a pediatric population end quote. In addition, doctor Lewie

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<v Speaker 1>requested that NBSB consider the risk involved in conducting a

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<v Speaker 1>study of AVA with children before or after an attack,

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<v Speaker 1>and the logistical challenges of administering AVA to children during

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<v Speaker 1>an attack. The National Biodefense Science Board. The Pandemic and

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<v Speaker 1>All Hazards Preparedness Act established NBSB in two thousand and six.

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<v Speaker 1>The thirteen member board advises the Secretary of HHS on quote, scientific, technical,

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<v Speaker 1>and other matters of special interest to HHS regarding activities

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<v Speaker 1>to prevent, prepare for, and respond to adverse health effects

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<v Speaker 1>of public health emergencies resulting from quote, chemical, biological, nuclear,

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<v Speaker 1>and radiological events, whether naturally occurring, accidental, or deliberate. NBSB

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<v Speaker 1>members come from diverse backgrounds and a range of experience

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<v Speaker 1>in both medicine and public health. The members are required

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<v Speaker 1>to meet at least twice a year in a public forum.

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<v Speaker 1>NBSB has advised the Secretary on many issues, including H

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<v Speaker 1>one one, immunization, home stockpiling of MCMs, mental health issues

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<v Speaker 1>during a disaster, and prioritization in MCM development. In its

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<v Speaker 1>October twenty eleven report, NBSB considered whether to conduct pre

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<v Speaker 1>event research to gather safety and immunogenicity degree of immune

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<v Speaker 1>response data about AVA with children, or whether instead to

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<v Speaker 1>gather such data post event. In conducting its analysis, NBSB

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<v Speaker 1>accepted quote the US government's threat analysis and recognized that

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<v Speaker 1>the dissemination of basilis and thrasis spores is a threat

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<v Speaker 1>to the US population, including its large proportion of children

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<v Speaker 1>end quote. NBSB also explicitly stated that quote administering AVA

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<v Speaker 1>to children would present more than a minor increase over

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<v Speaker 1>minimal risk end quote, due specifically to the lack of

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<v Speaker 1>data about AVA with children. NBSB ultimately recommended that the

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<v Speaker 1>US government conduct a pre event study to test the

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<v Speaker 1>safety and immunogenicity of AVA with children before an anthrax

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<v Speaker 1>attack occurs, but noted that any pre event AVA study

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<v Speaker 1>should proceed only following a thorough review of the ethical

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<v Speaker 1>considerations involved. This ethical review became part of the Bioethics

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<v Speaker 1>Commission's task outlined here, and nbsb's scientific and technical assessment

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<v Speaker 1>informed this ethical review. The Bioethics Commission's charge catalyzed by

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<v Speaker 1>nbsb's recommendation, HHS Secretary Kathleen Sabelius asked the Bioethics Commission

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<v Speaker 1>in January twenty twelve to quote conduct a thorough review

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<v Speaker 1>of the ethical considerations of conducting clinical trials of medical

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<v Speaker 1>countermeasures in children, and to include the ethical considerations in

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<v Speaker 1>conducting a pre and post event study of AVA post

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<v Speaker 1>exposure prophylaxis in children as part of its review end

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<v Speaker 1>Because of the sensitivity of the involvement of children in research,

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<v Speaker 1>nbsb's recommendation voiced its desire to have other focused experts,

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<v Speaker 1>like the Presidential Commission for the Study of Bioethical Issues

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<v Speaker 1>formerly review and address these issues from an ethical perspective.

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<v Speaker 1>The NBSB is confident that the Bioethics Commission will help

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<v Speaker 1>us and our nation deliberate this very complex issue ensuring

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<v Speaker 1>safe medical countermeasures for our children. Although the Bioethics Commission's

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<v Speaker 1>charge stemmed from nbsb's recommendation, the charge was significantly broader

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<v Speaker 1>than a review of the ethical considerations associated with a

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<v Speaker 1>pre event pediatric study of AVA. As stated in Secretary

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<v Speaker 1>Sabilius's request, the Bioethics Commission was charged with considering the

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<v Speaker 1>ethical issues associated with pediatric research for all MCMs, that is,

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<v Speaker 1>drugs and vaccines intended to treat or prevent physical harm

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<v Speaker 1>or to diagnose a condition resulting from a bioterrorism attack.

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<v Speaker 1>The Bioethics Commission considered the terms to encompass all FDA

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<v Speaker 1>regulated products and intervisions used in response to chemical, biological, radiological,

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<v Speaker 1>and nuclear attacks. Ethical and regulatory framework for pediatric research.

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<v Speaker 1>Pediatric research is critical for identifying safe and effective ways

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<v Speaker 1>to diagnose, prevent, and treat disease and injury in children.

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<v Speaker 1>Ethical pediatric research should minimize risks and, when possible, provide

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<v Speaker 1>a reasonable prospect of direct benefit to individual participants. Unlike

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<v Speaker 1>research with freely consenting adults, in which greater levels of

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<v Speaker 1>risk might be permissible even without the prospect of direct benefit,

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<v Speaker 1>children who participate in research are afforded special protections due

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<v Speaker 1>to their vulvulnerability and inability to legally consent to participate.

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<v Speaker 1>Any research conducted with children must therefore respect children's well

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<v Speaker 1>being and dignity as persons, as well as their current

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<v Speaker 1>and future capacities for self determination, and must protect children

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<v Speaker 1>from exploitation. These ethical imperatives are dictated by the foundational

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<v Speaker 1>principles of respect for persons, beneficence and its corollary non maleficence, justice,

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<v Speaker 1>and democratic deliberation. The current regulatory framework adopts an approach

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<v Speaker 1>recommended by the National Commission that is categorizing pediatric research

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<v Speaker 1>based on both the level of research risk and the

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<v Speaker 1>prospect of direct benefit. To participants, research that proposes only

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<v Speaker 1>minimal risk to participants, research that offers the prospect of

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<v Speaker 1>direct benefit to participants, or research that provides the opportunity

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<v Speaker 1>to gain generalizable knowledge about the participant's condition. Each fits

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<v Speaker 1>neatly into one of the regulatory categories of research approvable

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<v Speaker 1>at the local level, which are intended to govern the

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<v Speaker 1>majority of pediatric research. Some proposed MCM research, however, might

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<v Speaker 1>involve exposing healthy children to greater than minimal risk while

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<v Speaker 1>offering no prospect of direct benefit, and therefore does not

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<v Speaker 1>fit into one of these categories. In its report Research

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<v Speaker 1>Involving Children, the National Commission recognized the ethical challenge inherent

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<v Speaker 1>in considering whether research that poses more than minimal risk

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<v Speaker 1>and offers no prospect of direct benefit to participants nevertheless

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<v Speaker 1>might be justified by the quote promise of substantial long

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<v Speaker 1>term benefit to children in general end quote. The National

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<v Speaker 1>Commission did not reach a conclusion about the permissibility of

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<v Speaker 1>any such research with healthy children, instead recommending that decisions

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<v Speaker 1>taking into account quote sound ethical principles end quote, along

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<v Speaker 1>with other important considerations, be made at the national level

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<v Speaker 1>on a case by case basis. It intended this type

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<v Speaker 1>of review only for rare and exceptional cases about this report.

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<v Speaker 1>This report by the Bioethics Commission enumerates the ethical conceit

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<v Speaker 1>iterations associated with conducting pre and post event MCM research

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<v Speaker 1>with children. The Bioethics Commission examined the current ethical and

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<v Speaker 1>regulatory framework to assess the types of ethically permissible pre

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<v Speaker 1>and post event research. It built on the work of

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<v Speaker 1>the National Commission to provide decision makers with necessary ethical

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<v Speaker 1>tools to assess whether research posing greater than minimal risk

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<v Speaker 1>with no prospect of direct benefit to healthy child participants,

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<v Speaker 1>the most ethically complex pre event pediatric MCM research can

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<v Speaker 1>proceed fulfilling its charge. The Bioethics Commission applied its analysis

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<v Speaker 1>to the particular case of AVA as well. Due to

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<v Speaker 1>the unique characteristics of pre event MCM research in US,

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<v Speaker 1>including uncertainty that the research results will ever be used

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<v Speaker 1>and the fact that children are not legally or ethically

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<v Speaker 1>competent to consent to participate in research. The Bioethics Commission

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<v Speaker 1>concluded that greater than minimal risk pre event research is

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<v Speaker 1>ethically unacceptable if valuable information about an MCM could be

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<v Speaker 1>obtained using a study designed involving only minimal risk. If

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<v Speaker 1>pre event pediatric MCM research cannot be designed as minimal risk,

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<v Speaker 1>the proposed research should pose no more than a minor

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<v Speaker 1>increase over minimal risk and proceed to national level review.

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<v Speaker 1>Although the regulations might allow pediatric research that poses greater

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<v Speaker 1>than a minor increase over minimal risks to be approved

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<v Speaker 1>if it also meets ethical standards, the Bioethics Commission concluded

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<v Speaker 1>that higher risk is unacceptable in the context of pre

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<v Speaker 1>event MCM research. Such research does not directly benefit the

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<v Speaker 1>child participants, and the likelihood that the results of such

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<v Speaker 1>research would benefit other children is unknown or unknowable. In

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<v Speaker 1>accordance with its commitment to democratic deliberation and transparency, the

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<v Speaker 1>Bioethics Commission held four public meetings to address the Secretary's request.

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<v Speaker 1>Experts addressed a range of ethical, public health, scientific, medical, security,

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<v Speaker 1>and regulatory issues associated with this report, providing a wide

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<v Speaker 1>array of professional and institutional perspectives, including those from scientific

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<v Speaker 1>and medical communities, nonprofit organizations, and other individuals and groups.

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<v Speaker 1>The Bioethics Commission published a request for information in the

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<v Speaker 1>Federal Register and received almost one hundred written responses. In

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<v Speaker 1>the course of its work, the Bioethics Commission performed an

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<v Speaker 1>in depth review of relevant literature and in its deliberations,

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<v Speaker 1>took into account the relevant work of prior commissions, in

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<v Speaker 1>particular the National Commission's path breaking work in establishing pediatric

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<v Speaker 1>research protections. Based on the Bioethic Commission's detailed examination, Chapter

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<v Speaker 1>two of this report provides an overview of the ethical

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<v Speaker 1>foundations for pediatric research protections and the current regulatory structure

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<v Speaker 1>governingaf Patrick research. Chapter three sets forth and analyzes the

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<v Speaker 1>ethical issues associated with conducting pre event and post event

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<v Speaker 1>MCM research with children, and applies this ethical analysis to

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<v Speaker 1>the particular case of AVA. End of Chapter one. Introduction

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<v Speaker 1>recording by Patrick mccaffee, Merritt, Island,