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INTRODUCTION: Pharmacogenomics (PGx) investigates how genomes control enzyme expression. Developmental pharmacology (DP) describes the temporal sequence of enzymes impacting absorption, distribution, metabolism, and excretion (ADME) of food and drugs. AREAS COVERED: US and European Union (EU) legislation facilitate and/or enforce pediatric studies for all new drugs, called overall 'pediatric drug development' (PDD). DP and PDD look at patients' chronological age, but oscillate between legal and physiological meanings of the term 'child.' Children's bodies become mature with puberty. EXPERT OPINION: Decades after first DP observations in babies, PGx offers a better understanding of the variability of safety and efficacy of drugs, of the process of aging, and of shifting enzyme patterns across aging. We should rethink and revise outdated interpretations of ADME changes in minors. The Declaration of Helsinki forbids pointless studies that some pediatric researchers and regulatory agencies, more so the EMA than the FDA, demand pointless pediatric studies is regrettable. Medicine needs to differentiate between legal and physiological meanings of the term 'child' and should use objective measures of maturity.

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This article attempts to highlight the importance of including research sustainability as imperative when assessing human medical research in terms of ethical principles. Using a scoping review of recent literature, the complexity of research sustainability is highlighted with key themes and concepts surrounding this important topic being recognized and discussed. An overall paucity of guidance documents was identified and recommendations have been made to practically address this deficiency. An example of a research sustainability evaluation tool which is currently being piloted has been provided for possible adaptation and use by Ethics Committees and Institutional Review Boards to bolster the concept and inclusion of sustainability during the research approval process.

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This article examines the ethics of research design and the initiation of a study (e.g., recruitment of participants) involving refugee participants. We aim to equip investigators and members of IRBs with a set of ethical considerations and pragmatic recommendations to address challenges in refugee-focused research as it is developed and prepared for IRB review. We discuss challenges including how refugees are being defined and identified; their vulnerabilities before, during, and following resettlement that impacts their research participation; recruitment; consent practices including assent and unaccompanied minors; and conflicts of interest. Ethical guidance and regulatory oversight provided by international bodies, federal governments, and IRBs are important for enforcing the protection of participants. We describe the need for additional ethical guidance and awareness, if not special protections for refugee populations as guided by the National Institutes of Health (NIH) Guiding Principles for Ethical Research.

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We performed a qualitative review of 50 consent forms posted on Clinicaltrials.gov, examining the content of key information sections. We found that key information disclosures are typically focused on procedures, risks, potential benefits, and alternatives. Drawing upon reviews of the large literature examining the reasons people do or do not take part in research, we propose that these disclosures should be based more directly on what we know to be the real reasons why people choose to take part or refuse participation. We propose key information language for consideration by researchers and institutional review boards.

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It is a common practice in qualitative research to transcribe audio or video files from interviews or focus groups and then destroy the files at some future time, usually after validating the transcript or concluding the research. We argue that it is time to rethink this practice and that retention of original qualitative data-including audio and video recordings-should be the default stance in most cases.

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Indigenous nations and communities in the United States have rights as sovereign governments to exercise control and ownership over all data and information generated by or from the tribes, tribal members, or tribal resources. Indigenous nations exercise these rights through data ownership policies established in response to unethical research practices in research involving Indigenous communities. Most universities in the U.S. have "openness in research" policies to ensure academic freedom to publish freely, exercised by retaining university control of data. Here, we describe our study of cultural ecosystem services in the St. Louis River estuary region (Nagaajiwanaang in the language Ojibwemowin) in Duluth, Minnesota, and Superior, Wisconsin, U.S., an area that includes portions of the 1854 and 1842 Ceded Territories and reservation lands of a local band of Ojibwe (hereafter referred to as "the Band"). In this university-led, Band-supported study, both the university and the Band sought ownership of data collected based on their respective policies, resulting in a research delay of nearly a year. We found that open research policies that do not consider Indigenous sovereignty can hamper collaboration between university researchers and tribal nations, even when there is broad agreement on research goals and objectives. University open research policies that do not explicitly address Indigenous sovereignty fall short of the open research principles they intend to support and should be revised. Formal adoption of principles for ethical research with sovereign tribal governments by universities is needed to improve coordination and trust among university and tribal researchers and members.

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Autism research frequently seeks to evaluate interventions or inform their development. Unfortunately, researchers often assume that autism intervention should reduce autistic traits, effectively setting as a goal of treatment that autistic people attempt to "pass" as nonautistic. A growing body of evidence highlights serious potential harms from passing demands. We discuss why it is important for institutional review boards (IRBs) to scrutinize autism research for clinical passing demands, and we document the existence of such demands in outcome measures commonly employed in autism research. We propose an ethical framework for IRBs and others to make use of in evaluating the ethical appropriateness of particular treatment goals in autism intervention or intervention-adjacent research, emphasizing that treatment goals should be in pursuit of a beneficial nonpassing purpose and be the least burdensome means of accomplishing such a purpose. We also highlight potential promising practices for IRBs, investigators, and other stakeholders seeking to address these issues in autism research.

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BACKGROUND: When reviewing a protocol, research ethics committees (RECs, equivalent to institutional review boards - IRBs) have the responsibility to consider whether the proposed research is justified. If research is not justified, it can waste participants' time, researchers' time and resources. As RECs are not constituted to cover all areas of scientific or academic expertise, it can be difficult for RECs to decide whether research is scientifically or methodologically justified especially in the absence of authoritative (often in the form of systematic) reviews. Where such reviews are absent, some have argued that RECs should insist on a new review of existing evidence as a condition of the REC favourable opinion. However, as RECs review a wide range of research, such requests must be proportionate to the type, and extent, of proposed projects. Risk is one factor that may influence the extent of evidence need for a REC to determine that the new project is justified, but not the only factor. The aim of the work described here was to determine whether REC members and researchers specifically link risk to the type of research methodology, and if so, whether this link could be used to help guide the need for systematic, or other, types of reviews. METHOD: We conducted a cross-sectional study, gathering data between November 2020 and January 2021, to examine whether proposed research methodologies impact how RECs perceive risk to participants. We presented 31 research methodologies to REC members and researchers in the form of an international survey. RESULTS: We collected 283 responses that included both qualitative and quantitative data as to how research methodology impacts perceptions of risk to participants. We used the data to conclude that RECs did see a link between risk and type of research. We therefore constructed a hierarchy of risk with Phase 1 and 2 clinical trials, and clinical psychology/psychiatry intervention studies, at the top (i.e. viewed as most risky). CONCLUSIONS: We discuss whether this hierarchy is useful for guiding RECs as to the level of scientific justification that they should seek when reviewing proposed research protocols, and present a one-page guidance sheet to help RECs during their reviews.

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BACKGROUND: Institutional Review Boards (IRBs) play a vital role in safeguarding the rights and interests of both research participants and researchers. However, China initiated the establishment of its own IRB system relatively late in comparison to international standards. Despite commendable progress, there is a pressing need to strengthen the organizational capacity building of Chinese IRBs. Hence, this study aims to analyze the key factors driving the enhancement of organizational capacity within these committees. METHOD: The cross-sectional survey for this research was conducted from July 2020 to January 2022. Following the statistical grouping based on the "2020 China Health Statistical Yearbook", a systematic investigation of IRBs in various provinces of China was carried out. In-depth interviews and questionnaire surveys were conducted with the chairpersons and administrative executives (or secretaries) of highly cooperative IRBs. Subsequently, data were collected from 107 IRBs. Qualitative Comparative Analysis (QCA) was employed as the method to analyze the factors influencing the organizational capacity of medical ethics committees and explore the diverse combinations of these factors. RESULTS: Through a singular necessary condition analysis, the variable "protection of rights and interests" emerges as a critical factor contributing to the robust construction of Institutional Review Boards Institutional Review Boards (IRBs). Conversely, the variables of "lack of member ability, absence of review process, and deficiency in the supervision mechanism" collectively constitute a sufficient condition leading to weaker IRB construction. The state analysis uncovers three interpretation modes: member ability-oriented (M1), system process-oriented mode (M2), and resource system-oriented mode (M3). CONCLUSIONS: The results of this study are effectively explicable using the "Triangular Force" model proposed for the hypothesis of IRBs' organizational capacity, which provides a solid foundation for the development of organizational capabilities in IRBs. To enhance the organizational capacity of IRBs in China, it is imperative to elevate the competence of committee members and strengthen team development. This can be achieved by establishing a comprehensive regulatory framework and refining procedural protocols. Moreover, clarifying the organizational structure and optimizing resource allocation are essential steps in bolstering the overall organizational capabilities of these committees.

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In February 2023, the U.S. Government Accountability Office (GAO) released another report acknowledging that we still lack meaningful, validated, widely-accepted measures for evaluating institutional review board (IRB) quality and effectiveness. This challenge is well known to the Consortium to Advance Effective Research Ethics Oversight (www.AEREO.org), a collaborative group of human research protection (HRP) professionals, researchers, and research ethicists founded in 2018 to do precisely what GAO recommends: examine approaches for measuring IRB effectiveness in protecting human subjects, and implement the approaches as appropriate. Two underlying tenets have been central to AEREO's as approach to thinking about IRB quality and effectiveness: (1) IRBs exist to protect participants and thus the participant perspective should be central to all IRBs do; and (2) because IRBs are tasked with applying subjective ethical and regulatory standards about which people may disagree, their approach and decisions should at least meet the basic standard of reasonableness in terms of accounting for relevant perspectives, considering key factors, and providing defensible justifications. Critical to each of these tenets, IRBs should include diverse perspectives in their deliberations, find ways to meaningfully engage with relevant communities about their views regarding ethical research and appropriate participant protections, and be accountable to the public.

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Although racial and ethnic categories are social constructs without inherent biologic or genetic meaning, race and ethnicity impact health outcomes through racism. The use of racial categories in biomedical research often misattributes the cause of health inequities to genetic and inherent biological differences rather than to racism. Improving research practices around race and ethnicity is an urgent priority and requires education as well as structural change. We describe an evidence-based intervention for an institutional review board (IRB). Our IRB now requires all biomedical study protocols to define racial and ethnic classifications they plan to use, to state whether they are describing or explaining differences between groups, and to provide justification for any use of racial or ethnic group variables as covariates. This antiracist IRB intervention is an example of how research institutions can help ensure the scientific validity of studies and avoid the unscientific reification of race and ethnicity as inherently biological or genetic concepts.

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From 2018 to 2020, U.S. federal mandates began requiring the use of a single institutional review board (sIRB) of record for federally funded, multisite studies. With an interest in the efficiency of site activation, we compared the frequency with which local review and approval and three different reliance options (ways to establish a reliance agreement between the sIRB and the relying institution) were used during this period in a multisite, non-federally funded study (ClinicalTrials.gov identifier: NCT03928548). Using general linear models, we analyzed the relationships between local reliance or approval and sIRB of record approval times and (a) the regulatory option selected and (b) relying-site and process characteristics. Eighty-five sites received sIRB approval through 72 submissions (40% using local review, 46% using the SMART IRB agreement, 10% using an IRB authorization agreement, and 4% using a letter of support). Median time to establish a local reliance or study approval and sIRB approval were longest for sites using a SMART IRB agreement. Study-site region and the time of submission were significantly associated with local reliance or approval time, which averaged 129 and 107 days faster for Midwestern (p = 0.03) or Western (p = 0.02) sites, respectively, and 70 days slower for Northeastern sites (p = 0.42) compared with sites in the South, and 91 days slower when regulatory communication was initiated during or after February 2019 compared with before (p = 0.02). Similar relationships between sIRB approval time and region and time frame were observed; in addition, approval time was 103 days slower for sites affiliated with a research 1 (R1) university versus not (p = 0.02). Region of the country, time frame, and R1 university affiliation were associated with variations in study-site activation in a non-federally funded, multisite study.

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Revisions to the Common Rule and NIH policy require the use of a single Institutional Review Board (sIRB) for the review of most federally funded, multisite research, with the intent of streamlining the review process. However, since initial implementation in 2018, many IRBs and institutions continue to struggle with the logistics of implementing this requirement. In this paper, we report the findings of a workshop held in 2022 to examine why sIRB review remains problematic and propose possible solutions. Workshop participants identified several issues as major barriers, including new responsibilities for study teams, persistent duplicative review processes, the lack of harmonization of policies and practices across institutions, the absence of additional guidance from federal agencies, and the need for greater flexibility in policy requirements. Addressing these problems will require providing additional resources and training to research teams, the commitment of institutional leaders to harmonize practice, and policymakers to critically evaluate the requirement and provide flexibility in applicability.

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OBJECTIVE: To conduct a content analysis of IRB webpages of select universities (academic health centers) in the USA that describe post IRB- approval monitoring activities. METHOD: This was a qualitative study. Thematic analysis was the method to review the webpage content of selected academic health centers (AHC) within the USA. RESULTS: Some US academic health "centers" IRB administrative or research compliance offices conduct post- approval monitoring (PAM) of human subjects' research including clinical trials. The goals of this PAM programmes are to (a) ensure compliance to approved protocols, (b) preserve research integrity, (c) manage institutional risks, d) provide advisory/educational support to researchers, (e) recommend corrective actions for identified issues, and most importantly, (f) to protect the safety, rights, and well-being of research participants. Although not a requirement by law, the PAM program has legislative support in the US Code of Federal Regulations as part of the US Office for Human Research Protection's (OHRP) Federal Wide Assurance (FWA). This is especially for institutions that conduct studies funded by the Federal government. PAM on-site checks reveal various incidents of protocol deviations and violations. This includes issues with recruitment processes, informed consent discrepancies, and incidents of non-compliance. When a study protocol is identified as non-compliant, the principal investigator works with the PAM monitor to develop a corrective action plan that would allow the study to become compliant and avoid sanctions from the IRB or the regulatory authority. CONCLUSIONS: REC/IRB post-approval monitoring of clinical trials is a valuable mechanism of protection for research participants while giving educational and quality assurance support to researchers. The program enables early detection and resolution of non-compliance to approved protocols. The impact of the program in the USA requires further exploration.

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BACKGROUND: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. OBJECTIVE: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. STUDY DESIGN: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. RESULTS: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. CONCLUSION: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.

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Few studies in sub-Saharan Africa evaluate Institutional Review Boards (IRBs) capacity. The study aims to explore the composition of IRBs, training, and challenges experienced in the ethics review processes by members of research institutions and universities in Addis Ababa, Ethiopia. Our findings indicate that most IRBs members were trained on research ethics and good clinical practice. However, majority perceived the trainings as basic. IRB members faced several challenges including: investigators wanting rapid review; time pressure; investigators not following checklists; limited expertise in reviewing clinical trials, studies on genetics, and traditional medicine; lack of IRB offices for administrative work; competing tasks; limited staffing and the lack of a standardized review system. There is need for advanced training on research ethics to meet the evolving research needs. In addition, investments in IRBs are needed in terms of funding, and physical and human resources in Addis Ababa and Ethiopia in general.

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Natural history studies of pediatric rare neurometabolic diseases are important to understand disease pathophysiology and to inform clinical trial outcome measures. Some data collections require sedation given participants' age and neurocognitive impairment. To evaluate the safety of sedation for research procedures, we reviewed medical records between April 2017 and October 2019 from a natural history study for CLN3 (NCT03307304) and one for GM1 gangliosidosis (NCT00029965). Twenty-two CLN3 individuals underwent 28 anesthetic events (age median 11.0, IQR 8.4-15.3 years). Fifteen GM1 individuals had 19 anesthetic events (9.8, 7.1-14.7). All participants had the American Society of Anesthesiology classification of II (8/47) or III (39/47). Mean sedation durations were 186 (SD = 54; CLN3) and 291 (SD = 33; GM1) min. Individuals with GM1 (6/19, 31%) were more frequently prospectively intubated for sedation (CLN3 3/28, 11%). Minor adverse events associated with sedation occurred in 8/28 (28%, CLN3) and 6/19 (32%, GM1) individuals, frequencies within previously reported ranges. No major adverse clinical outcomes occurred in 47 anesthetic events in pediatric participants with either CLN3 or GM1 gangliosidosis undergoing research procedures. Sedation of pediatric individuals with rare neurometabolic diseases for research procedures is safe and allows for the collection of data integral to furthering their understanding and treatment.

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There is significant debate over whether phase 1 pediatric oncology trials are ethical and approvable. We thus surveyed IRB members to answer four questions. First, do IRB members think the potential medical benefits of average phase 1 pediatric oncology trials justify the risks? Second, do they think these trials are ethically appropriate? Third, do they think these trials are approvable? Fourth, how do the views of IRB members on the first two questions compare to the views of the US public? Of the 80 respondents who answered the test questions correctly, 18.8% stated that the potential medical benefits of average phase 1 pediatric oncology trials outweigh the risks, 32.5% stated that the potential medical benefits and risks are about equal, and 48.8% stated that the risks outweigh the potential medical benefits. Compared to the general public, IRB members were significantly more likely to think the risks outweigh the potential medical benefits (p = 0.01). Finally, 68.8% of IRB members indicated that average phase 1 pediatric oncology trials are approvable, and 56.3% indicated that these trials are appropriate in children. These findings suggest two-thirds of IRB members believe average phase 1 pediatric oncology trials are approvable. Yet, almost half regard the risks as outweighing the potential medical benefits and almost half think these trials are inappropriate. These findings raise important questions regarding why IRB members and the general public evaluate the same risk/benefit profile differently, and whether it is possible to reconcile the two perspectives.

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Objective:This study aims to critically assess the 2023 updates in the governance of Conflicts of Interests (COIs) as outlined in the Ethical Review Measures for Life Sciences and Medical Research Involving Human Beings. It seeks to delve into the ethical implications of these new mandates and offers concrete strategies for effectively integrating them into ethics review practices.Methods:We conducted a comparative analysis of the COIs-related provisions in the 2016 Ethical Review Measures for Biomedical Research Involving Humans, examining them alongside current trends and challenges in COIs governance and ethics review practices.Results:The study identified key challenges posed by COIs to medical research ethics and addresses three principal areas for normative application: the declaration process for conflicts of interest, enhancing the COIs management framework, and the critical review points for COIs by ethics committees.Conclusions:In light of the international consensus on COIs governance, we advocate for the advancement of conflict of interest management at the institutional level. This includes a focus on informed consent processes, the development of robust systems within medical institutions, and the facilitation of ethical corporate collaborations.

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Background and Objective: The number of new drug clinical trials in China is surging, and ethics review played an important part in clinical trials. However, there are certain problems of ethical review in China. This review aims to conduct a review to propose recommendations of an ethical review mode for multicenter clinical trials and ultimately contribute to improving the ethics review mechanism and the efficiency. Methods: A literature review, publication research and interpretation of the related governmental policies and requirements in China were conducted to collect available information for analysis of the current situation in terms of the various ethical review modes for multicenter clinical research. The literatures and information were searched and selected from national and international database and related governance website by following some inclusion and exclusion criteria. And a comparation with the relevant practical experience in the USA was conducted to support the proposing of recommendations to China by referring to some successful practice in the USA. Key Content and Findings: China has undergone several stages of development. The most traditional and least efficient model is institutional review boards (IRBs) review, which is most commonly used. After IRB review mode, other modes such as central IRB and single IRB review have emerged, which have improved the efficiency of ethical review. However, multiple challenges exist like, no clear definition of regulatory responsibilities and the consensus is not easy to be made due to the gap of interpretation and the unbalanced development on ethic review system from Chinese hospitals. Conclusions: The multicenter ethical review should adopt the conditional 'approval' mode of the leading site's ethical review decisions, gradually establish a single IRB review and select the best ethics committee. Regional ethics committees can gradually take responsibility for the primary review in the multicenter ethics review model and ultimately contribute to improving the mechanism and efficiency of the ethics review.