Many participants are motivated to enroll in clinical trials both for the prospect of individual benefit and for altruistic reasons. When a clinical trial is stopped early, it may significantly alter the participant trial experience and impact the likelihood that the trial will contribute to generalizable knowledge. Despite the frequency with which trials are stopped early, occurring in ten to thirty percent of trials, participants are rarely informed of this possibility during the informed consent process. Therefore, they are not given the opportunity to take this into consideration in their decision-making process. To redress this, we advance a framework for disclosing the possibility of early trial termination to prospective participants, arguing that disclosure is justified because it supports participant decision-making and promotes transparency and trust in the research enterprise.

Recruitment is often the most time-consuming and expensive step of clinical trials. As such, it is the most common stage for AI implementation, due to its power to hasten timelines, reduce costs and workloads, and potentially increase the representativeness of study cohorts. Yet, formal regulatory guidance on the use and ethics of AI specifically for clinical trial recruitment is limited, and best practices have yet to be defined. Here, we discuss the use of AI in the trial recruitment process across five domains, synthesize the ethical elements that apply to AI recruitment, and advance a framework of considerations and recommendations across use cases and ethical elements. The ethical elements, tensions, and recommendations discussed here will help inform the practices of and oversight by investigators, commercial recruitment entities, contract research organizations, sponsors, regulators, and IRBs as they develop, test, use, and evaluate AI models for clinical trial recruitment.

e24186 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxane chemotherapy and includes both sensory neuropathy and neuropathic pain. The longitudinal course of these symptoms among patients without neuropathy at treatment initiation is not well characterized. Describing symptom trajectories during taxane therapy may inform monitoring and prevention strategies. Methods: PACT, a multinational coordinated study, pooled data from three parallel randomized trials in patients with early-stage breast cancer receiving taxane chemotherapy. Participants screened negative for neuropathy at baseline using PRO-CTCAE items. Trials compared acupuncture with an active relaxation–nature-video control. Sensory neuropathy was assessed using the EORTC CIPN-20 sensory subscale (0–100), and neuropathic pain using a 0–10 worst pain Likert scale at baseline, week 12 (primary timepoint), and week 24 (follow-up). Longitudinal mixed-effects models estimated symptom trajectories, adjusting for site, chemotherapy schedule, and number of neurotoxic agents. Pairwise time comparisons use model-adjusted estimates with Tukey–Kramer adjustment. Given no treatment differences, values are presented as averages across arms. Results: Among 127 evaluable participants, model-adjusted mean CIPN-20 sensory scores increased 7.7 points (95% adj CI: 4.8 to 10.6, adj p<0.0001) from baseline to week 12 and remained stable at 24 weeks. Worst neuropathic pain increased 0.64 points (95% adj CI: 0.18–1.09; adj p=0.004) at 12 weeks with no further significant change at 24 weeks. Median worst pain scores remained 0 at all timepoints, while sensory scores rose from 0 at baseline to 3.7 at week 12. (Table 1) Conclusions: Sensory neuropathy and worst pain scores increased during taxane chemotherapy. Sensory changes were clinically significant, while changes in pain were subclinical and the majority of patients remained free of pain at all time points. These findings highlight the heterogeneous manifestation of CIPN during standard chemotherapy in an integrative medicine primary CIPN prevention trial and underscore the importance of carefully assessing both sensory and pain-related outcomes in prevention strategies. Clinical trial information: NCT05528263, ChiCTR2200066714, KCT0008470 . Model-adjusted symptom trajectories. Mean Change (95% adj CI; adj p-value) Outcome Baseline Week 12 Week 24 Week 12 - Baseline Week 24 – Week 12 Week 24 - Baseline CIPN-20 sensory(0–100) 0.6 8.3 8.5 7.7 (4.8 to 10.6; <0.0001) 0.2 (-2.8 to 3.1; 0.99) 7.8 (4.7 to 10.9; <0.0001) Worst neuropathic pain(0–10) 0.33 0.97 1.19 0.64 (0.18 to 1.09; 0.004) 0.22 (-0.16 to 0.60; 0.35) 0.86 (0.35 to 1.36; 0.0003) Predicted means and pairwise changes averaged across arms; CI and p-values adjusted for multiple comparisons (Tukey–Kramer).

IntroductionAccess to cross-border clinical trials may represent the sole therapeutic option for children living with rare diseases for which no approved medicines exist. Many children are excluded from participation in trials due to language restrictions. There are insufficient comprehensive analyses of the experiences and preferences of parents across Europe concerning participation and exclusion of their child in international clinical trials, particularly regarding language support during enrollment in cross-border clinical research studies.MethodsAn anonymous online survey was designed and translated into 22 official European languages to collect data from parents of children living with a disease across Europe. The survey included five sections: (1) sociodemographic information; (2) experience participating in a clinical trial; (3) experience in cases where the patient was unable to take part in a study abroad; (4) experience participating in a clinical trial abroad; and (5) preferences regarding decentralized trial options.Results1,436 responses were analyzed from parents across 34 European countries. Key findings: 55.7% of the parents reported being able to communicate in English. 10.7% had prior clinical trial experience, of whom 30.1% traveled abroad to enable their child to participate. Among those reporting being excluded from cross-border trials, 34.7% cited language barriers or country of residence as the reason. Most families expressed a strong willingness to accept decentralized trial options, regardless of where the study may be conducted.ConclusionsAccommodating language translation to permit participation in a clinical trial abroad is feasible. While a significant percentage of caregivers of pediatric patients in Europe could communicate in English, approximately one-third of those excluded from clinical trials cited language barriers or country of residence as the reason. When translation was required, the most commonly offered solution was the use of professional interpreters, an accommodation that could enable broader patient participation in essential research.

AbstractInterventional clinical research often involves risks to participants of reproductive potential, requiring pregnancy testing, contraception, and reporting of incidental pregnancies. Since the Dobbs v. Jackson Women's Health Organization (2022) decision that eliminated the constitutional right to abortion, these routine research practices present new risks to participants, clinicians, and investigators. This review examines the emerging reproductive privacy concerns in clinical research post-Dobbs and provides practical considerations for investigators and institutional review boards navigating this evolving legal environment.

Clinical trials drive therapeutic innovation but often underrepresent populations most affected by the disease. Despite efforts to include women, minorities, and children, participation still lags behind intent. Ensuring equitable representation is essential to maximize the impact of new therapies. This perspective offers actionable insights from a diverse panel—including patients, clinicians, researchers, and advocates—shared during the 2025 American Society for Clinical Pharmacology and Therapeutics Patient Forum.

One of the challenges in accessing cross-border clinical trials involving international participants in Europe is language diversity, with 32 official languages in the European continent. Some patients have reported being excluded from trials owing to their native language, and in certain studies, language has been used as an eligibility criterion for participation. Considering that pediatric studies in Europe are not conducted in all countries, cross-border access to clinical trials may represent the only therapeutic opportunity for children living with rare diseases for which no approved treatment exists. This study aimed to assess the use of language as an eligibility criterion in pediatric clinical trial protocols conducted in Europe (2007–2024) and published in the Clinicaltrials.gov database. It evaluated the frequency and context of language requirements and whether these were scientifically justified. The overall objective was to identify potential sources of language-based discrimination that may prevent cross-border access to pediatric clinical trials. The 32 official languages of the European continent were used as keywords to search the eligibility criteria of 1,754 pediatric clinical trial protocols for studies conducted in Europe between 2007 and 2024 and registered in the largest clinical trial registry, ClinicalTrials.gov, via an Application Programming Interface. Acceptable scientific justifications to use language as an eligibility criterion were defined as being (1) related to specific therapeutic areas that required language or cognitive assessments in communication with the health professionals, who do not speak the patient’s language or (2) related to the use of patient- or caregiver-reported outcome measures that had only been validated in specific languages. The majority of the study protocols (95.2

Federal disability anti-discrimination laws expect clinical trials to render study processes and sites accessible to potential participants, including through the provision of reasonable accommodations. Nonetheless, people with disabilities, and particularly people with mental illness, are often excluded from clinical trials. Supported decision-making, a strategy that allows people to select trusted others to help them understand and communicate decisions, is an important accommodation to further inclusion. However, because mental illness can be dynamic and vary widely in nature (e.g., diagnosis, symptom severity, functional impairment) and duration (e.g., short-term, intermittent, progressive, permanent), supported decision-making is neither a one-size-fits-all strategy nor one that can serve as a reasonable accommodation in every situation. While prior work on supported decision-making has focused predominantly on adults with intellectual and developmental disabilities or dementias, people with mental illness may also benefit from supported decision-making, although the variability in decision-making capacity in mental illness presents nuanced challenges. Here, we explore supported decision-making in the case of people with intermittent or episodic mental illness that may impact decision-making capacity to varying degrees at different times.

Conducting pediatric clinical trials across borders in Europe presents unique challenges, especially when studies target rare conditions, require specialized expertise at participating sites, and demand active family involvement in the research process. Including international patients in clinical trials is essential for both scientific development and equity in healthcare, but it requires adapting study protocols, informed consent processes, and patient-reported outcome measures (PROMs) to ensure trial feasibility in diverse linguistic and cultural contexts. The current regulatory and legislative frameworks offer limited solutions to address the language barriers and logistical complexities that still limit cross-border access to clinical trials. The aim of this study was to investigate the experience, expertise, and practices of managing international participants in the pediatric clinical trials conducted by clinical trial units (CTUs) in 17 European countries. To assess experiences with cross-border pediatric clinical trials for rare diseases across multiple domains, three online surveys were developed and disseminated to Clinical Trial Units (CTUs) within healthcare organizations across Europe. The first survey captured information on general expertise, the second focused on reported good practices in trials involving international patients, and the third aimed to identify documented cases of discrimination, particularly those related to native language requirements. All surveys were reviewed by an expert advisory board and distributed through multiple European research networks and other channels. Data were analyzed using descriptive statistics and thematic analysis. A total of 43 CTUs from 17 European countries participated in this study, representing a mix of children’s hospitals, general hospitals, and university hospitals. International patients who travelled to the 43 CTUs to participate in clinical trials came from 81 different European and non-European countries, mostly from Morocco, Ukraine, Ecuador, and Venezuela. Among the reported good practices supporting cross-border access (N = 113), the most common involved providing written and verbal translations of informed consent documents, patient-reported outcome measures (PROMs), and quality of life (QoL) scales when these were not available in patients’ native languages. Twenty cases of discrimination were reported, primarily due to language requirements included in eligibility criteria, which negatively affected trial access for non-native speakers. Most of these cases occurred in industry-sponsored trials for rare diseases (65

Dozens of gene therapies (GTs) have received regulatory approval, and hundreds more are in various research phases. To characterize the ethical, legal, and social implications (ELSI) associated with the clinical development of this relatively new therapeutic class, we conducted a scoping review of the literature. Articles were eligible if they were written in English and discussed ELSI in the context of human somatic GT clinical research. 273 articles published from 2013 to 2024 met the eligibility criteria. To characterize and synthesize the ELSI associated with human somatic GT clinical research, thematic analysis was performed on extracted ELSI-relevant text from 179 articles published between 2019 and early 2024, including reviews, empirical research articles, opinions/commentaries, reports, news articles, and blog posts. Twenty-four themes were identified, leading to the generation of five high-level themes: (1) assessment of the risks and benefits of GTs is scientifically and ethically challenging, (2) communication and engagement with the patient community is crucial, (3) access and justice issues are heightened, (4) ethical GT trial design requires thoughtful consideration, and (5) strategic decision-making about GT research has ethical implications and is impacted by financial considerations and the regulatory context. Potential approaches to the identified ELSI are explored and discussed.

Abstract Clinical trial design for classical hematologic diseases is difficult because samples sizes are often small and not representative of the disease population. The American Society of Hematology initiated a roadmap project to identify barriers and make progress to integrate diversity, equity, and inclusion into trial design and conduct. Focus groups of international experts from across the clinical trial ecosystem were conducted. Eight issues identified include (1) harmonization of demographic terminology; (2) engagement of lived experience experts across the entire study timeline; (3) awareness of how implicit biases impede patient enrollment; (4) the need for institutional review boards to uphold the justice principle of clinical trial enrollment; (5) broadening of eligibility criteria; (6) decentralized trial design; (7) improving access to clinical trial information; and (8) increased community physician involvement. By addressing these issues, the hematology community can promote accessible and inclusive trials that will further inform research, clinical decision-making, and care for patients.

Multi-institutional scientific research projects are increasingly common. Nevertheless, regulations and guidelines do not yet adequately address which entity should assume responsibility for research misconduct proceedings in multi-institutional research. This article explores the challenges of determining jurisdictional roles in research misconduct matters in collaborative science and proposes the application of a "jurisdictional interests test" as a framework for determining jurisdiction in multi-institutional research misconduct proceedings.

Researchers, academic institutions, and journals have an ethical obligation to correct the research record expeditiously and publicly to maintain the integrity of science.

Control group selection in clinical trials is challenging, especially in acupuncture studies. A PubMed literature review of control groups in breast cancer acupuncture studies was performed and identified 67 studies for analysis. Although the types of acupuncture controls varied, sham acupuncture was the most common type of control. The rationale and specification of the sham procedures, however, were incomplete and not standardized, despite the availability of guidelines. This may impact the interpretation and replicability of the study findings. A standardized and complete description and rationale for all acupuncture controls are necessary.

The lack of diversity in clinical studies has significant ethical and health consequences, limiting the development of effective treatments for diverse populations. Homogeneous participation in clinical studies contributes to health disparities, particularly among historically underrepresented groups in the United States (US). Racial, ethnic, and other minoritized populations have long been excluded from clinical research. In response, the US Congress mandated the National Institutes of Health to assess the impacts of insufficient diversity in clinical studies. Despite efforts by the government, non-profit organizations, and industry players to improve diversity in clinical studies, progress has been slow due to fragmented approaches. For instance, the new US administration (2025) has recently released executive orders which threaten to reverse the progress made in inclusive clinical research. The Stanford Think Tank on Diversity and Equity in Clinical Trials, held in September 2023, brought together key partners across multiple sectors and professions to discuss barriers and explore potential solutions to participation in clinical studies. In this commentary, we discuss the importance of collaborative, inclusive strategies in clinical study design to advance equitable health outcomes for all. Further, we discuss potential implications of the government’s dismissal of diversity, equity, and inclusion initiatives on diverse research participation.

Background: Unwarranted exclusion of people with uncertain or impaired decision-making capacity from participation in research violates principles of justice and fairness and adversely impacts the health and welfare of these populations. Methods: We conducted a cross-sectional study of institutional review board (IRB) policies for investigators and IRB members at 94 top-funded U.S. research institutions to better understand the guidance they provide to investigators who work with populations that have a wide range in decisional capacity. We collected data from publicly available websites and used deductive and inductive methods to develop our coding framework. Results: We found that 41.5% of institutions had policies that require exclusion of people with uncertain or impaired decision-making capacity unless inclusion is scientifically justified. Only 5.3% had policies that require inclusion of these populations unless exclusion is scientifically justified. Eligibility criteria depended upon the risks of research in 54.3% of policies. Guidance on obtaining consent or assent was provided in 77.7% of policies and 44.7% provided guidance on assessing decision-making capacity. 30.9% of policies required that the IRB include a member who is knowledgeable of the needs and concerns of people with uncertain or impaired decision-making capacity when it reviews research pertaining to that population. Conclusion: Some IRB policies at U.S. research institutions may be unfairly excluding people with uncertain or impaired decision-making from research participation. Institutions should review their IRB policies to ensure that these policies protect adults with uncertain or impaired decision-making capacity from harm but also do not exclude them from research unfairly.

OBJECTIVES:This scoping review aims to synthesize the literature on pediatric health technology assessments (HTAs) and map out the challenges of assessing new technologies for use in children, with a particular focus on pharmaceutical interventions. METHODS:Conducted in accordance with the Joanna Briggs Institute Methodology, this scoping review addressed HTAs in the pediatric domain through searches of PubMed, Embase, Web of Science Core Collection, and EconLit through 22 January 2024, as well as the gray literature. Sources were excluded if they (i) were a clinical trial investigating a specific technology or an HTA of that technology, (ii) did not address the challenges of HTAs, or (iii) had no relevance to pediatrics. Two authors performed screening and data extraction independently and in duplicate. RESULTS:One hundred and three reports were included. Of these, sixty were full journal articles, twenty-three were conference abstracts, and twenty were guidelines, reports, and other documents. Two important themes emerged from this work. The first was the unique position of children within society and the resulting difficulty of incorporating them within a population-wide HTA system. The second was the uncertainty that characterized pediatric HTAs due to data constraints and either a lack of guidance by HTA bodies or variations in guidance between bodies. CONCLUSIONS:Many factors inherent to children, including the heterogeneity of pediatric disease populations, long-term outcomes, and children's distinct social positions, render conducting pediatric HTAs challenging. Innovative approaches are required to address these challenges and respond to the needs of pediatric populations.

The acquisition and retention of primary research data is fundamental to the reliability of and public trust in biomedical research. However, researchers are often unaware of or confused by applicable data retention requirements, in part due to the divergent requirements set forth by federal agencies, grant programs, and research institutions, as well as other applicable requirements under law, contract, and policy. This article summarizes current U.S. data retention standards applicable to biomedical research, including how institutional research retention practices have sought to reflect these standards, and discusses the importance of data retention in the context of research professionalism, data sharing efforts, intellectual property issues, and research integrity challenges, which increasingly have been the subject of much public interest. In conclusion, this article provides suggestions for both institutions and applicable federal agencies to streamline and clarify data retention standards, with the goal of improving research data retention practices.