United States federal regulations for pediatric research with no prospect of direct benefit restrict institutional review board (IRB) approval to procedures presenting: 1) no more than "minimal risk" (§ 45CFR46.404); or 2) no more than a "minor increase over minimal risk" if the research is commensurate with the subjects' previous or expected experiences and intended to gain vitally important information about the child's disorder or condition (§ 45CFR46.406) (DHHS 2001). During the 25 years (...) since their adoption, these regulations have helped IRBs balance subject protections with the pursuit of scientific knowledge to advance children's welfare. At the same time, inconsistency in IRB application of these regulations to pediatric protocols has been widespread, in part because of the ambiguity of the regulatory language. During the past decade, three federally-charged committees have addressed these ambiguities: 1) the National Human Research Protections Advisory Committee (NHRPAC) (Washington, DC), 2) the Institute of Medicine (IOM) Committee on the Ethical Conduct of Clinical Research Involving Children (Washington, DC); and 3) the United States Department of Health and Human Services Secretary's Advisory Committee for Human Research Protections (SACHRP) (Washington, DC). The committees have reached similar conclusions on interpretation of language within regulations § § 45CFR46.404 and 406; these conclusions are remarkably consistent with recent international recommendations and those of the original National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) report from which current regulations are based. Drawing on the committees' public reports, this article identifies the ethical issues posed by ambiguities in regulatory language, summarizes the committees' deliberations, and calls for a national consensus on recommended criteria. (shrink)

This article reviews four areas of pediatric research in which we have identified questionable levels of allowable risk, exceeding those foreseen by the Commission. They are the following: the categorization of increasingly risky interventions as minimal risk in a variety of protocols; the increasing number of applications for federal panel review of research not otherwise approvable because of higher projected risk levels; research on asymptomatic at risk children; and the inclusion of (...) children and adolescents in placebo-controlled trials for participants of all ages without performing subgroup analysis. While embracing the imperative to include children in research is an encouraging step towards providing the pediatric population with effective medical care and finally eradicating the therapeutic orphan, we must ensure that this research does not become overly permissive. (shrink)

Volume 20, Issue 4, May 2020, Page 8-10.

Federal regulations require that the level of risk posed by pediatric research be classified as “minimal,” “greater than minimal,” or “a minor increase over minimal.” Interpretation of the meaning of the levels has produced a significant literature exploring the ethical basis for making these determinations. This article examines the ethical basis of a variety of approaches proposed in the literature for classifying pediatric research risk. These approaches strive to take into account (...) how society decides which risks are routinely accepted for children outside of research. It is concluded that ways of classifying risk should compare research risks to normal risks for children without special disability and take into account the concerns of the research subject’s community. (shrink)

Volume 20, Issue 4, May 2020, Page 106-108.

One of the central problems concerning research with children is the delineation of appropriate levels of risk exposure. In the U.S. Code of Federal Regulations, the "minimal risk" concept serves as an anchoring measure for allowable risk. While the regulations sought to promote a balance between scientific advances and the protection of children's vulnerable status, ambiguities in the language of the regulations and the regulatory definition of "minimal risk" have given rise to a (...) great deal of confusion. Research ethics boards and the medical community espouse a multitude of varying opinions regarding the interpretation and application of the federal regulations with more recent research demonstrating an apparent increase in risk without corresponding benefit in pediatric research. Informed by ethical theory, law, and science, this project analyzes the apparent increase in allowable risk, calls for a reassessment of the concept of "minimal risk," and recommends modifications to the federal regulations. (shrink)

In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled in (...) a given study (the subjective interpretation). The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. (shrink)

: In Grimes v. Kennedy Krieger Institute (KKI), the Maryland Court of Appeals, while noting that U.S. federal regulations include risk standards for pediatric research, endorses its own risk standards. The Grimes case has implications for the debate over whether the minimal risk standard should be interpreted based on the risks in the daily lives of most children (the objective interpretation) or the risks in the daily lives of the children who will be enrolled (...) in a given study (the subjective interpretation). The court's use of the objective interpretation to block studies like the KKI study protects individual children who are worse off than the average child. Unfortunately, this approach also may block research intended to improve the lives of these same individuals. A similar dilemma arises in the context of multinational research, suggesting that a "modified objective standard," proposed to address this dilemma in the multinational setting, may offer a framework for addressing the dilemma in the context of pediatric research as well. (shrink)

While an accurate assessment of risk is always important, it is especially so in pediatric research. Recognizing the pivotal nature of the minimal-risk standard, we set out to determine under what circumstances pediatric magnetic resonance imaging research does or does not meet this standard. We found that while the physical and psychological risks that attend the MRI procedure do not exceed minimal risk, the sedation and contrast enhancement that are sometimes associated (...) with MRI research do, as both exceed the level of risk encountered by typical, healthy children in their everyday experiences. (shrink)

Net‐risk pediatric research encompasses interventions and studies that pose risks and do not offer a compensating potential for clinical benefit. These interventions and studies are central to efforts to improve pediatric clinical care. Yet critics argue that it is unethical to expose children to research risks for the benefit of unrelated others. While a number of ethical justifications have been proposed, none have received widespread acceptance. This leaves funders with uncertainty over whether they should support (...) and institutional review boards with uncertainty over whether they should approve net‐risk pediatric research. To try to answer these questions, this article describes a justification that I previously proposed and considers two objections to it. This analysis reveals that the opportunity to contribute to a valuable project can justify exposing children to risks even though some trials turn out to be valueless and others turn out to be harmful. It follows that, to protect pediatric participants, institutional review boards need to assess whether trials have the potential to collect socially valuable information and whether they are likely to enroll and retain a sufficient number of participants. (shrink)

We argue that the current ethical and regulatory framework for permissible risk levels in pediatric research can be helpfully understood in terms of children’s moral right to adequate protection from harm. Our analysis provides a rationale for what we propose as the highest level of permissible risk in pediatric research without the prospect of direct benefit: what we call “relatively minor” risk. We clarify the justification behind the usual standards of “minimal (...) class='Hi'>risk” and “a minor increase over minimal risk” and explain why it is permissible to impose any risks at all on child participants who do not stand to benefit directly from enrollment in research. Finally, we illuminate some aspects of the concept of “best interests.”. (shrink)

How should the definition of “minimal risk” in the federal research regulations be interpreted in regard to pregnant women and fetuses? Surprisingly, there has been little discussion of this question. There is, after all, a substantial amount of published work addressing the question of how “minimal risk” should be interpreted. Similarly, there is a large body of literature on the ethics of research involving pregnant women and fetuses, particularly maternal-fetal surgery. However, in neither of (...) these bodies of work can one find an analysis of minimal risk in regard to fetuses or pregnant women.The concept of minimal risk is defined in the regulations as follows:Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (shrink)

The concept of minimal risk plays a key role in federal regulations on the protection of human research subjects. Although there has been considerable discussion of the meaning of minimal risk, the question of how this concept should be interpreted in research involving pregnant women and fetuses has not been addressed. This essay reviews the literature on minimal risk and argues for an interpretation of that concept in the context of research (...) involving pregnant women and fetuses. (shrink)

Pediatric participation in non-therapeutic research that poses greater than minimal risk has been the subject of considerable thought-provoking debate in the research ethics literature. While the need for more pediatric research has been called morally imperative, and concerted efforts have been made to increase pediatric medical research, the importance of protecting children from undue research risks remains paramount.United States research regulations are derived largely from the deliberations and report of (...) the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The authors of this report specifically designated children as a vulnerable population and suggested additional protections, most of which became U.S. law. One of the more contested sets of regulations surrounds non-therapeutic research, e.g., research that does not offer the potential for direct benefit to participants. Federal regulations allow local Institutional Review Boards to approve non-therapeutic research posing a minor increase above minimal risk when it involves children who have the disease or medical condition that the research addresses. (shrink)

OBJECTIVE: To apply component analysis, a structured approach to the ethical analysis of risks and potential benefits in research, to published emergency research using a waiver of/exception from informed consent. The hypothesis was that component analysis could be used with a high degree of interrater reliability, and that the vast majority of emergency research would comply with a minimal-risk threshold. METHODS: A Medline search and manual search were done to identify studies using a waiver of/exception (...) from informed consent published between July 1996 and December 2000. A review panel of physicians and bioethicists independently classified nontherapeutic procedures in each study as minimal risk, probably minimal risk, or probably more than minimal risk. RESULTS: Seventy studies using a waiver of/exception from informed consent were identified. A majority of reviewers classified nontherapeutic procedures in 62 studies (88.6%) as minimal risk. Reviewers classified nontherapeutic procedures in six studies (8.6%) as minimal risk or probably minimal risk. In two studies (2.9%), nontherapeutic procedures were classified as probably more than minimal risk. The intraclass correlation coefficient was 0.89 (95% CI = 0.85 to 0.93), indicating very high interrater reliability. CONCLUSIONS: Component analysis can be used with high reliability to review emergency research and may improve the consistency of institutional review board review of emergency research. The vast majority of published emergency research performed using a waiver of/exception from consent complies with a properly-applied minimal-risk threshold. A minimal-risk threshold for nontherapeutic procedures protects subjects better than current U.S. regulations while permitting important emergency research to continue. (shrink)

Classifying research proposals by risk of harm is fundamental to the approval process and the most pivotal risk category in most regulations is that of “minimal risk.” If studies have no more than a minimal risk, for example, a nearly worldwide consensus exists that review boards may sometimes: (1) expedite review, (2) waive or modify some or all elements of informed consent, or (3) enroll vulnerable subjects including healthy children, incapacitated persons and prisoners (...) even if studies do not hold out direct benefits to them. The moral and social purposes behind this threshold are discussed along with relevant views from the National Commission, NBAC, NHRPAC, Grimes v. Kennedy Krieger Institute, The Nuremberg Code, and The WMA's Declaration of Helsinki. Representative policies from Australia, Canada, South Africa, the U.S., and CIOMS are reviewed revealing different understandings of this sorting threshold. Six of nine frequently cited interpretations of “minimal risk” are untenable. The “absolute” interpretation of the “routine examination” standard is defended as best. (shrink)

One of the fundamental ethical concerns about biomedical research is that it frequently exposes participants to risks for the benefit of others. To protect participants’ rights and interests in this context, research regulations and guidelines set out a mix of substantive and procedural requirements for research involving humans. Risk thresholds play an important role in formulating both types of requirements. First, risk thresholds serve to set upper risk limits in certain types of research. (...) Second, risk thresholds serve to demarcate risk categories that streamline risk-adapted systems of ethical oversight. But although risk thresholds play such an important role in research governance, there is a need both to better define the existing risk thresholds and to delineate new thresholds in order to develop more risk-adapted systems of research oversight. The present paper examines the existing minimal risk threshold and the surrounding debates with the goal of deriving a systematic approach to setting thresholds of research risk. (shrink)

Volume 20, Issue 4, May 2020, Page 102-103.

Non-beneficial paediatric research is vital to improving paediatric healthcare. Nevertheless, it is also ethically controversial. By definition, subjects of such studies are unable to give consent and they are exposed to risks only for the benefit of others, without obtaining any clinical benefits which could compensate those risks. This raises ethical concern that children participating in non-beneficial research are treated instrumentally; that they are reduced to mere instruments for the benefit of science and society. But this would make (...) the research incompatible with the widely endorsed principle of the primacy of the human subject, which stipulates that the interests of the participating individual should prevail over the interests of science and society. This paper deals with this conflict. It analyses solutions to this problem developed in the literature, and shows that they are unsuccessful. Finally, it offers a new idea of how to reconcile the conduct of non-beneficial paediatric research with the PP. The paper argues for a new formula of the PP, and shows that it implies a specific non-comparative definition of the minimal risk threshold. (shrink)

The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) was formed over 20 years ago with a goal of harmonizing research regulations among the European Union, United States, and Japan. Harmonization was intended to speed approval of pharmaceuticals, avoid unnecessary repetition of studies, and ensure protection of research participants. This paper examines United States, European Union, and ICH pediatric research regulations in five domains: parental permission, assent/dissent, payment, risk/benefit (...) and inclusion of disabled children/wards of state. The purpose is to examine similarities and differences among the regulations to help investigators, policy makers and the public to understand what each regulatory framework can learn from the others. Additionally, the paper suggests philosophical differences in how these entities view pediatric research which may serve as barriers to harmonization in the future. (shrink)

This paper examines the culture, the dynamics and the financial underpinnings that determine how medical research is being conducted on children in the United States. Children have increasingly become the subject of experiments that offer them no potential direct benefit but expose them to risks of harm and pain. A wide range of such experiments will be examined, including a lethal heartburn drug test, the experimental insertion of a pacemaker, an invasive insulin infusion experiment, and a fenfluramine "violence prediction" (...) experiment. Emphasis, however, is given to psychoactive drug tests because of the inherent ethical and diagnostic problems involved in the absence of any objective, verifiable diagnostic tool. Effort is made to provide readers comprehensive reference sources to evidence-based reports about the serious risks these drugs pose for adults and children so that the reader may judge whether the benefits (if any) outweigh the risks for children. The first ethical issue raised by these experiments is: did the severity of illness in these children justify their exposure to short and long-term risks? The ethics of the experiments will be evaluated by referring to existing codes of medical research ethics-the Nuremberg Code, the Declaration of Helsinki, and the federal Code of Regulations. The thirteen cases presented will demonstrate that children are being used in ever more speculative experiments, often in the absence of a therapeutic intent, but a significant chance for causing harm and / or discomfort. Some of the experiments were designed to explore the mechanisms of pathology and pharmacological interventions, or the response of neurological brain receptors to chemical provocation ("challenge"). Others were designed to test the safety or efficacy of new drugs, even to test these drugs on healthy children who were hypothesized to be "at risk." Children and adolescents have been subjected to "forced dose titration" experiments that induced a spectrum of severe adverse effects, including insomnia, extreme restlessness, agitation, (akathisia) and self-injurious behavior. FDA reports show that suicide is a significant issue in psychotropic drug trials-in pediatric trials the problem is even greater. The paper aims to demonstrate how the enactment of the Better Pharmaceuticals for Children Act (incorporated into the Food and Drug Administration Modernization Act, FDAMA), set in motion a radical shift in public policy by providing huge financial incentives to pharmaceutical companies to test new or patented drugs in children. Federal policy shifted from one aimed at protecting children by setting limits on permissible research risks, to a policy aimed at broadening the inclusion of children as test subjects. It will be shown how the FDA and the Department of Health and Human Services lifted regulatory restrictions to permit research involving greater than minimal risk to be conducted on healthy children, claiming that all children are potentially "at risk" of a future condition. Children were in this way deprived of regulatory protections. An argument will be made that the approval of nontherapeutic, harmful experiments-such as exposure of toddlers to lead poison-under the current gate keeping system raises serious doubts about the sustainability of institutional review boards (IRBs) as protectors of human research subjects. Children, who are precluded from exercising the adult human's right to informed consent, are being exploited as commodities for commercial ends. It is the position of the author that nothing less than the enactment of a federal law mandating a radical overhaul of the current research review system, with independent checks and balances, will provide children the legal protections they need. Ten specific recommendations are offered to protect children from harmful experiments. (shrink)

To protect children in research, procedures that are not administered in the medical interests of a child must be restricted. The risk threshold for these procedures is generally measured according to the concept of minimal risk. Minimal risk is often defined according to the risks of “daily life.” But it is not clear whose daily life should serve as the baseline; that is, it is not clear to whom minimal risk should refer. (...) Commentators in research ethics often argue that “minimal risk” should refer to healthy children or the subjects of the research. I argue that neither of these interpretations is successful. I propose a new interpretation in which minimal risk refers to children who are not unduly burdened by their daily lives. I argue that children are not unduly burdened when they fare well, and I defend a substantive goods account of children’s welfare. (shrink)

To what risks may children participating in research be subjected? Institutional review boards can stand surrogate for parents by filtering out studies whose risk is unacceptably high.

We focus here on high-risk pediatric research with the prospect of direct benefit and point out some aspects that have raised significant debate. In particular, we call attention to disagreements related to two essential aspects of this type of research: (i) determining what constitutes a “prospect of direct benefit” in phase I trials that involve gene transfer technologies and (ii) assessing when in these trials the risk is justified by the anticipated benefit to the participant (...) children. Although much of our discussion is applicable to other types of high-risk pediatric trials, as an example of the dilemma this type of research poses we use pediatric trials that involve gene transfer technologies. We focus on clinical trials for late infantile neuronal ceroid lipofuscinosis (LINCL). Exploring the ethical implications of some of these disagreements might identify resources for determining how best to deal with the ethical concerns at stake in high-risk pediatric research. We thus offer some recommendations for responding to these concerns. (shrink)

Surveys and routine clinical procedures applied in research protocols are typically considered only minimally risky to participants. The apparent benign nature of "minimal risk" tasks increases the chance that investigators and Institutional Review Boards (IRBs) will overlook the probability that clinical tools will identify signs, symptoms, or definitive test results that are clinically-relevant to subjects' welfare. "Minimal risk" procedures may also pose a particular hazard to participants in clinical research by increasing the therapeutic misconception (...) because the tasks mimic clinical care and are often conducted in clinical settings. Investigators should anticipate which measures could yield clinically-important findings and should describe explicit plans for data monitoring, disclosure, and follow-up. Protocols that include reliable and valid clinical measures should prompt a more detailed risk assessment by the IRB, even when the tasks meet the regulatory criteria for minimal physical, psychological, or emotional risk. (shrink)

In a recent commentary, Kim and colleagues argued that minimal-risk research should be deregulated so that such studies do not require review by an institutional review board. They claim that regulation of minimal-risk studies provides no adequate counterbalancing good and instead leads to a costly human subjects oversight system. We argue that the counterbalancing good of regulating minimal-risk studies is that oversight exists to ensure that respect for persons and justice requirements are satisfied (...) when they otherwise might not be. (shrink)

Since children are considered incapable ofgiving informed consent to participate inresearch, regulations require that bothparental permission and the assent of thepotential child subject be obtained. Assent andpermission are uniquely bound together, eachserving a different purpose. Parentalpermission protects the child from assumingunreasonable risks. Assent demonstrates respectfor the child and his developing autonomy. Inorder to give meaningful assent, the child mustunderstand that procedures will be performed,voluntarily choose to undergo the procedures,and communicate this choice. Understanding theelements of informed consent has been theparadigm for (...) assessing capacity to give assent.This method leaves the youngest, leastcognitively mature children vulnerable towaiver of assent and forced researchparticipation. Voluntariness can also becompromised by the influence of authorityfigures who can exert undue influence andcoerce children to participate in research. This paper discusses factors that may influencethe decision to give assent/permission,potential parent-child conflict in theassent/permission process and how it isresolved, and potential parental undueinfluence on research participation. Theseissues are illustrated with quotations drawnfrom a larger qualitative study of parentalpermission and child assent (data notpresented). We suggest a developmentalapproach, viewing assent as a continuum rangingfrom mere affirmation in the youngest childrento the equivalent of the informed consentprocess in the mature adolescent. (shrink)

The American Journal of Bioethics, Volume 12, Issue 1, Page 35-36, January 2012.

This essay reflects on arguments by Paul Ramsey, in The Patient as Person: Explorations in Medical Ethics (1970) and elsewhere, that continue to challenge policy‐makers and those doing clinical and translational research involving children. Ramsey argued that parents cannot morally authorize their child's participation in research unless the research is designed to benefit the child. He acknowledged that abiding by this position could have adverse impacts on improving child health, and he concluded, in a 1976 Hastings Center (...) Report piece, that researchers must “sin bravely.” Many philosophers and theologians, including Richard McCormick, have argued against Ramsey. The Ramsey‐McCormick debate played out in the bioethics literature and, by invitation, at the deliberations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which was tasked with developing an ethics framework and policies for human subjects protections. Although in its final recommendations, the commission sided with McCormick, the strict limitations on risks and harms to which a child can be exposed were clearly influenced by Ramsey. (shrink)

Data-sharing among genomic researchers is promoted for its potential to accelerate our understanding of the molecular basis of cancer. However, with genomic data sharing the risks of re-identifying study participants, revealing personal genomic information and data misuse might increase. This study aims at exploring perceptions of patients and physicians in Oncology regarding their assessment of the informational risks resulting from participating in whole genomic research studies in order to improve the informed consent process. For this purpose, we conducted a (...) qualitative focus group study at the National Center for Tumor Diseases. Patients and oncologists assessed the informational risks either as minimal or as greater than minimal, depending on the context factors of occupational status, age, and patients’ prognosis. Interestingly, even patients who assumed a greater risk did not refrain from participating in genomic research, provided that certain informational and institutional safeguards are implemented. Moreover, they expected comprehensive disclosure of the risks resulting from genomic data sharing. These results suggest comprehensive disclosure of the risks of genomic research to potential study participants in genomic research to facilitate risk assessment and sound decision making, establishing independent governance entities in order to minimize the informational risks of genomic research, and implementing data sharing policies which offer guidance for physicians and researchers involved in genomic research. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences (...) of parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

Data-sharing among genomic researchers is promoted for its potential to accelerate our understanding of the molecular basis of cancer. However, with genomic data sharing the risks of re-identifying study participants, revealing personal genomic information and data misuse might increase. This study aims at exploring perceptions of patients and physicians in Oncology regarding their assessment of the informational risks resulting from participating in whole genomic research studies in order to improve the informed consent process. For this purpose, we conducted a (...) qualitative focus group study at the National Center for Tumor Diseases (NCT). Patients and oncologists assessed the informational risks either as minimal or as greater than minimal, depending on the context factors of occupational status, age, and patients’ prognosis. Interestingly, even patients who assumed a greater risk did not refrain from participating in genomic research, provided that certain informational and institutional safeguards are implemented. Moreover, they expected comprehensive disclosure of the risks resulting from genomic data sharing. These results suggest (1) comprehensive disclosure of the risks of genomic research to potential study participants in genomic research to facilitate risk assessment and sound decision making, (2) establishing independent governance entities in order to minimize the informational risks of genomic research, and (3) implementing data sharing policies which offer guidance for physicians and researchers involved in genomic research. (shrink)

Pediatric research without the potential for clinical benefit is vital to improving pediatric medical care. This research also raises ethical concern and is regarded by courts and commentators as unethical. While at least 10 justifications have been proposed in response, all have fundamental limitations. This article describes and defends a new justification based on the fact that enrollment in clinical research offers children the opportunity to contribute to a valuable project. Contributing as children to valuable (...) projects can benefit individuals in two ways. First, individuals may come to ?embrace? the contributions they made as children. Second, contributing to valuable projects can lead to a better overall life. Because these potential benefits can outweigh small research risks, they provide a justification for pediatric research without the potential for clinical benefit, when it poses low risks and has the potential to benefit others in important ways. (shrink)

ABSTRACT Despite Institutional Review Board concerns about psychological harm arising from research participation, evidence from trauma-questionnaire research suggests that participation is typically well-tolerated by participants. Yet, it is unclear how participant experiences of in-lab trauma simulations align with IRB ethical guidelines. Thus, we compared reactions to a trauma film paradigm with reactions to a positive film task or cognitive tasks. Overall, relative to other conditions, the trauma film was well-tolerated by participants: they generally reported low-to-moderate negative emotions, moderate (...) benefits, and that participation was not worse than everyday stressors. Our results have implications for the research community in designing trauma-based research. (shrink)

Hastings Center Report, Volume 52, Issue 3, Page 18-29, May–June 2022.

In this case, the investigator should be allowed to enroll incompetent adults into this study, with certain safeguards. If an incompetent adult has an agent or a legally authorized representative (...

Research in the intensive care unit (ICU) is commonly thought to pose 'serious risk' to study participants. This perception may be at the root of a variety of impediments to the conduct of clinical trials in the ICU setting. Component analysis offers a promising approach to the ethical analysis of ICU research. Because clinical trials commonly involve a mixture of study interventions, therapeutic and nontherapeutic procedures must be analyzed separately. Therapeutic procedures must meet the requirement of clinical (...) equipoise. Risks associated with nontherapeutic procedures must be minimized consistent with sound scientific design, and be deemed reasonable in relation to the knowledge to be gained. When research involves a vulnerable population, such as adults incapable of providing informed consent, nontherapeutic risks are limited to a minor increase over minimal risk. Understood in this way, the incremental risk posed by participation in ICU research may be minimal. This realization has important implications for review by institutional review boards of such research and for the informed consent process. (shrink)

Canada’s Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans mandates that all research involving human subjects be reviewed and approved by a research ethics board . We have little evidence on how researchers are dealing with this requirement in multisite studies, which involve more than one REB. We retrospectively examined 22 REB submissions for two minimal-risk, multisite studies in leading Canadian institutions. Most REBs granted expedited review to the studies, while one declared the application (...) to be exempt from review. Time between submission and approval ranged greatly, from four to 546 days. We received a total of 155 REB queries for changes and clarifications, most of which asked for further information, clarification, or additional documents. Less than a third of the REB queries were requests for specific changes, and a vast majority had a very limited impact on the research projects. Institutions also varied broadly in their description of what was required of local principal investigators. We conclude that the organizational and practical challenges these results imply could deter researchers from embarking on multisite research projects, and that recently proposed changes to the TCPS will not solve these problems. (shrink)

ABSTRACT Controlled human infection (CHI) models have been developed for numerous pathogens in order to better understand disease processes and accelerate drug and vaccine testing. In the past, some researchers conducted highly controversial CHIs with vulnerable populations, including children. Ethical frameworks for CHIs now recommend vulnerable populations be excluded because they cannot consent to high risk research. In this paper we argue that CHI studies span a wide spectrum of benefit and risk, and that some CHI studies (...) may involve minimal risk. The categorical exclusion of children from CHIs therefore departs from the standard approach to evaluating research risks, as international regulations and ethical guidance for pediatric research generally permit non‐beneficial research with low risks. The paradigm in research ethics has also shifted from focusing on protecting vulnerable participants to recognizing that inclusion can be important as a matter of justice, providing new reasons to question this default exclusion of children from CHIs. Recognizing that pediatric CHIs can raise complex ethical issues and are easy to sensationalize in ways that may threaten the public’s trust in research and sponsor institutions, we conclude by describing additional complexities that must be addressed before pediatric CHIs beyond licensed vaccine studies might be ethically acceptable. (shrink)

Federal efforts beginning in the 1990's have successfully increased pediatric research to improve medical care for all children. Since 1997, the FDA has requested 800 pediatric studies involving 45,000 children. Much of this research is "non-beneficial"; that is, it exposes pediatric subjects to risk even though these children will not benefit from participating in the research. Non-beneficial pediatric research (NBPR) seems, by definition, contrary to the best interests of pediatric subjects, (...) which is why one state supreme court has essentially prohibited it. It also appears that the only plausible rationale for this research is utilitarian, as it risks some children for the good of all. But that rationale is troubling. This Article answers two related questions: (1) What is the appropriate legal relationship between NBPR and the "best interests of the child" standard? (2) What is the ethical justification for this research? I argue that courts should hold that the "best interests" standard governs pediatric research. But, contrary to existing case law, courts must consider the benefits to each child, including pediatric subjects, from a policy that permits NBPR, and not simply consider that a non-beneficial protocol presents more risk than potential benefit to a child. Moreover, I argue that the justification for the practice need not be utilitarian. There is no need to appeal to the greater good to justify the research because each child has reason to endorse a policy permitting NBPR where there is a very low ceiling on acceptable risk, and each child has reason to participate in a practice from which she benefits. More controversially, I argue that each child, like other persons, has reason to help others when she can do so at little to no cost to herself. The Article then highlights practical implications of the offered justifications. (shrink)