Search

A leading concern about single IRB (sIRB) review for multisite studies, as is now required by federal policies, is whether and how sIRBs consider local context in their review. While several types of local context considerations have been proposed, there is no shared agreement among those charged with the ethics oversight of human subjects research as to the goals and content of local context review, nor the types of research studies for which sIRB review might be inappropriate. Through a scoping review of published scholarship, public comments, and federal guidance documents, we identified five assumed goals for local context review: protecting the rights and welfare of local participants; ensuring compliance with applicable laws and policies; assessing feasibility; promoting the quality of research; and promoting procedural justice. While a variety of content was proposed to be relevant, it was largely grouped into four domains: population/participant-level characteristics; investigator and research team characteristics; institution-level characteristics; and state and local laws. Proposed characteristics for exclusion from sIRB requirements reflected both protection- and efficiency-based concerns. These findings can inform ongoing efforts to assess the implications of policies mandating sIRB review, and when exceptions to those policies might be appropriate., (© 2024 by The Hastings Center. All rights reserved.)

In an effort to minimize protocol noncompliance in neurological research studies that can potentially compromise patient safety, delay completion of the study, and result in premature termination and added costs, we determined the effect of investigator trainings and site initiation visits (SIVs) on the occurrence of noncompliance events. Results of protocol audits conducted at the National Institute of Neurological Disorders and Stroke from 2003 to 2019 on 97 research protocols were retrospectively analyzed. Based on the depth of auditing and provision of investigator research training, audit data were separated into four arms: 1) Early Period, 2003 to 2012; 2) Middle Period, 2013 to 2016; and Late Period, 2017 to 2019, further divided into 3) Late Period without SIVs; and 4) Late Period with SIVs. Events of noncompliance were classified by the type of protocol deviation, the category, and the cause. In total, 952 events occurred across 1080 participants. Protocols audited during the Middle Period, compared to the Early Period, showed a decrease in the percentage of protocols with at least 1 noncompliance event. Protocols with SIVs had a further decrease in major, minor, procedural, eligibility, and policy events. Additionally, protocols audited during the Early Period had on average 0.46 major deviations per participant, compared to 0.26 events in protocols audited during the Middle Period, and 0.08 events in protocols audited during the Late Period with SIVs. Protocol deviations and noncompliance events in neurological clinical trials can be reduced by targeted investigator trainings and SIVs. These measures have major impacts on the integrity, safety, and effectiveness of human subjects research in neurology., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

In 1966, Henry Beecher published his foundational paper "Ethics and Clinical Research," bringing to light unethical experiments that were routinely being conducted by leading universities and government agencies. A common theme was the lack of voluntary consent. Research regulations surrounding laboratory experiments flourished after his work. More than half a century later, we seek to follow in his footsteps and identify a new domain of risk to the public: certain types of field experiments. The nature of experimental research has changed greatly since the Belmont Report. Due in part to technological advances including social media, experimenters now target and affect whole societies, releasing interventions into a living public, often without sufficient review or controls. A large number of social science field experiments do not reflect compliance with current ethical and legal requirements that govern research with human participants. Real-world interventions are being conducted without consent or notice to the public they affect. Follow-ups and debriefing are routinely not being undertaken with the populations that experimenters injure. Importantly, even when ethical research guidelines are followed, researchers are following principles developed for experiments in controlled settings, with little assessment or protection for the wider societies within which individuals are embedded. We strive to improve the ethics of future work by advocating the creation of new norms, illustrating classes of field experiments where scholars do not appear to have recognized the ways such research circumvents ethical standards by putting people, including those outside the manipulated group, into harm's way., Competing Interests: The authors declare no competing interest.

Evaluating the quality and effectiveness of the institutional review boards (IRBs) responsible for overseeing research involving human participants is critically important but perpetually challenging. Seemingly common-sense measures, such as the number of proposals approved with and without major modifications and the number of unexpected adverse events occurring in approved protocols, can be misleading indicators of participant protection, and regulatory compliance may not correspond to achieving ethical goals. These measurement challenges make it difficult to assess the validity of concerns about different IRB models. A group of U.S. senators recently raised questions about the increasing use of for-profit IRBs to review research proposals (as opposed to boards typically housed at academic medical centers and health care institutions) and, more specifically, about the growing trend of private equity ownership and consolidation of for-profit IRBs. Although all IRBs face pressure to speed reviews and none are entirely free of conflicts of interest, the private equity model is particularly susceptible to approaches that could undercut the ethical mission of IRBs to protect and promote the rights and welfare of research participants. Ideally, the quality of board oversight could be measured directly, rather than relying on the heuristic of board type; this article describes several current efforts toward this goal. In the meantime, one improvement may be to pursue a new model of IRB oversight: independent nonprofit boards that stand apart from research institutions, take advantage of business approaches to research review, and minimize conflicts of interest.

Controlled human infection models (CHIMs) are useful for vaccine development. To improve on existing models, we developed a CHIM using a lyophilized preparation of Shigella sonnei strain 53G produced using current good manufacturing practice (cGMP). Healthy adults were enrolled in an open-label dose-ranging study. Following administration of a dose of rehydrated S. sonnei strain 53G, subjects were monitored for development of disease. The first cohort received 500 CFU of 53G, and dosing of subsequent cohorts was based on results from the previous cohort. Subjects were administered ciprofloxacin on day 5 and discharged home on day 8. Subjects returned as outpatients for clinical checks and sample collection. Attack rates increased as the dose of S. sonnei was increased. Among those receiving the highest dose (1,760 CFU), 70% developed moderate to severe diarrhea, 50% had dysentery, and 40% had fever. Antilipopolysaccharide responses were observed across all cohorts. An S. sonnei CHIM using a lyophilized lot of strain 53G was established. A dose in the range of 1,500 to 2,000 CFU of 53G was selected as the dose for future challenge studies using this product. This model will enable direct comparison of study results between institutions and ensure better consistency over time in the challenge inoculum. IMPORTANCE Controlled human infection models (CHIMs) are invaluable tools utilized to understand the human response to infection, potentially leading to protective immune mechanisms and allowing efficacy testing of enteric countermeasures, including vaccines, antibiotics, and other products. The development of an improved Shigella CHIM for both Shigella sonnei and Shigella flexneri is consistent with international efforts, supported by international donors and the World Health Organization, focused on standardizing Shigella CHIMs and using them to accelerate Shigella vaccine development. The use of lyophilized Shigella challenge strains rather than plate-grown inoculum preparations is considered an important step forward in the standardization process. Furthermore, the results of studies such as this justify the development of lyophilized preparations for additional epidemiologically important S. flexneri serotypes, including S. flexneri 3a and S. flexneri 6.

Clinical research remains at the forefront of academic practice and evidence-based medicine. Unfortunately, history has shown that human subjects are vulnerable to experimentation without regard for their own dignity and informed decision-making. Subsequently, it is vital for research institutes to uphold safeguards and ethical conscientiousness toward human subjects. The establishment of federal regulations and the development of institutional review boards have set guidance on these processes. On January 21, 2019, final revisions to the Federal Policy for the Protection of Human Subjects (the "Common Rule") went into effect. The purpose of this article is to review changes to the Common Rule and discuss their impact on plastic surgery research.

Background: Assistive technologies have become more important owing to the aging population, especially when they foster healthy behaviors. Because of their natural interface, virtual agents are promising assistants for people in need of support. To engage people during an interaction with these technologies, such assistants need to match the users´ needs and preferences, especially with regard to social outcomes., Objective: Prior research has already determined the importance of an agent's appearance in a human-agent interaction. As seniors can particularly benefit from the use of virtual agents to maintain their autonomy, it is important to investigate their special needs. However, there are almost no studies focusing on age-related differences with regard to appearance effects., Methods: A 2×4 between-subjects design was used to investigate the age-related differences of appearance effects in a human-agent interaction. In this study, 46 seniors and 84 students interacted in a health scenario with a virtual agent, whose appearance varied (cartoon-stylized humanoid agent, cartoon-stylized machine-like agent, more realistic humanoid agent, and nonembodied agent [voice only]). After the interaction, participants reported on the evaluation of the agent, usage intention, perceived presence of the agent, bonding toward the agent, and overall evaluation of the interaction., Results: The findings suggested that seniors evaluated the agent more positively (liked the agent more and evaluated it as more realistic, attractive, and sociable) and showed more bonding toward the agent regardless of the appearance than did students. In addition, interaction effects were found. Seniors reported the highest usage intention for the cartoon-stylized humanoid agent, whereas students reported the lowest usage intention for this agent. The same pattern was found for participant bonding with the agent. Seniors showed more bonding when interacting with the cartoon-stylized humanoid agent or voice only agent, whereas students showed the least bonding when interacting with the cartoon-stylized humanoid agent., Conclusions: In health-related interactions, target group-related differences exist with regard to a virtual assistant's appearance. When elderly individuals are the target group, a humanoid virtual assistant might trigger specific social responses and be evaluated more positively at least in short-term interactions., (©Carolin Straßmann, Nicole C Krämer, Hendrik Buschmeier, Stefan Kopp. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.04.2020.)

The pinnacle of success achieved by the medical science and the benefits accrued to the patients have become possible through the medical research where human participants in the research are exposed to hazards inherent to the experiments. To protect the human subjects and to maintain high ethical standards, the World Medical Association has adopted "The Declaration of Helsinki" in 1964. After two years of consultation with the experts throughout the world, the seventh revision of the Declaration was adopted on 19th October 2013 in Brazil. The aim of this article is to review the seventh revision of the Declaration of Helsinki in relation to medical research involving human subjects and highlight the amendments made in the latest revision which are relevant to clinical research in human subjects. The latest revision has made four substantial changes on the existing Declaration, whch include dealing with the compensation of the trial-related injuries, approval of use of placebos in the clinical trials, protection of vulnerable groups and the post-trial provisions. The implications of these amendments in the clinical research are highlighted. Keywords: Consent; Declaration of Helsinki; ethics; experimental medicine; research; seventh revision.

The Belmont Report attested to the cardinal importance of informed consent for ethical research on human subjects. Important challenges to securing informed consent have emerged since its publication more than 40 years ago. Among some of the most significant of these challenges are those that highlight social psychological factors that have the potential to impair the appreciation of relevant information disclosed in the informed consent process. Responding to these challenges requires us to think harder about the content of the principle of informed consent and the demands that it imposes on investigators. This article focuses on two challenges in particular, that presented by the so-called therapeutic misconception, and that presented by the psychological bias of unrealistic optimism. After outlining an account of the principle of informed consent as it applies to the research context, the article briefly reviews the empirical literature on the therapeutic misconception and the bias of unrealistic optimism. It then relates these phenomena to the principle of informed consent, paying special attention to the ethical demands they impose on investigators. The article concludes by considering how recent trends to integrate research and clinical care affect the main points it has advanced.

Whether there is an upper limit of net risk that volunteers can consent to in research, and what that limit happens to be, has been the subject of persistent controversy in research ethics. This article defends the concept of an upper limit of risk in research against recent critics and supports the most promising approach for identifying this limit, that of finding comparator activities that are generally accepted in society and pose high levels of risk. However, high-risk activities that have been proposed as relevant comparators involve more certain benefits and confer considerable social esteem to those who take on the risks. This suggests that developing a robust approach to identifying social value, whether by developing a procedural safeguard or a systematic framework, could more effectively identify research with sufficient social value to justify high net risk. Additionally, the social status of research participants should be elevated to be more on par with others who laudably take on high risk for the benefit of others. By attending to the benefits necessary for the justification of high-risk research, the level of allowable risk will no longer be so controversial.

Forty years ago, the Belmont Report counseled that a "systematic, nonarbitrary analysis of risks and benefits" is vital to ensuring the ethical appropriateness of research with human subjects. Since then, research ethics has devoted considerable attention to the first half of this advice, emphasizing the ethical importance of assessing and minimizing the risks of research with human subjects. Significantly less attention has been devoted to a systematic assessment of the potential benefits of research participation. To the extent that benefits for individual participants are considered at all, commentators tend to focus on their potential to undermine the goal of minimizing risks. A chance for clinical benefit may obscure the fact that research poses risks not present in clinical care, while an offer of financial compensation or ancillary care may induce individuals to accept risks that conflict with their long-term interests. This article argues that, while undoubtedly important, minimizing risks fails to offer sufficient protection for research participants, especially those who cannot consent, because it neither ensures that the risks of research are justified nor protects participants from exploitation. Belmont's advice to develop systematic and nonarbitrary ways to ensure that research participants receive appropriate benefits needs to be heeded as well.

The Belmont Report was written by a US Commission charged by the US Congress to advise on research supported by the US government. Its focus was understandably domestic. In the 40 years since its publication, clinical research has become increasingly international. Many clinical trials have sites in multiple countries, and many of the host countries are relatively impoverished. Such research raises some distinctive ethical issues. This paper outlines some of the key ethical challenges that have been raised by clinical research conducted in low- and middle-income countries (LMICs) and sponsored by high-income country (HIC) institutions. It then considers whether the Belmont Report has the resources to address these problems and argues that it does not. The article closes by noting some parallels between this international research and domestic US research, which suggest that the US might benefit from the discussions abroad.

In 2007, Taylor proposed to move beyond compliance to develop measures for assessing the ethical quality of institutional review board (IRB) reviews. To date, no such tool has been developed. In 2018, Lynch et al. proposed to move beyond quality to advance effective research ethics oversight. Instead of providing a set of measures, they proposed to define and specify ways to measure the effectiveness of IRBs in protecting human subjects. They further claimed that any attempts to measure the quality and performance of IRBs without using such measures, to be developed by them in the unforeseeable future, were not helpful. The realities are that nearly 50 years after its establishment, there has been no systematic assessment of the quality and performance of IRBs, and that nearly two decades after the deaths of Jesse Gelsinger and Ellen Roche and the implementation of reform processes to improve our system of protecting human subjects, there is still plenty of room for improvement. The challenges today are for Taylor to come up with a tool to measure the ethical quality of IRB reviews, for Lynch et al. to develop measures for assessing the effectiveness of IRBs in protecting human subjects, and for the IRB community to decide whether to continue to wait for Taylor and Lynch et al. to develop their promised tools or to start taking advantage of performance measurements to improve the quality and performance of IRBs by using existing IRB performance metrics or to improve those existing performance metrics.

The institutional review board (IRB) is a group federally mandated to review and monitor research involving humans to ensure protection of their rights and welfare as research participants. Clinicians engaged in research require IRB approval for all research involving human participants, whether living individuals, data, or specimens. The process for obtaining IRB approval may seem like a daunting task. However, it is critical for clinical researchers to conduct research in a manner that protects human participants, and it is the mission of the IRB to help researchers accomplish this task. The purpose of this article is to review the role and purpose of the IRB, highlight federal and regulatory standards in human research participants protection, and help clinical researchers have a broader understanding of IRB functions that will help them conduct high-quality research with human participants., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Perinatal clinical research to improve the quality of care and outcomes for newborn infants relies on transparency, trust, and respect for the autonomy and well-being of study participants and their families., Methods: Here we consider the underpinning principles of ethical research with a focus on perinatal clinical research in the acute care or emergency setting where particular challenges to parental engagement and informed consent exist., Results: Several approaches to improving the validity of the consent process for perinatal research have been proposed and evaluated. These include consent waiver, antenatal consent, deferred consent preceded by verbal assent, and continuous consent. These have strengths and weaknesses and uncertainty remains about their validity and acceptability in certain research contexts. Prior exploration with parents and parent-advocacy groups of approaches to engagement and consent, and independent evaluation and ongoing monitoring of research studies, can enhance adherence to the ethical principles of justice and autonomy, and ensure that benefits to participants and their families exceed harm., Conclusions: High-quality research and ethics are interdependent. Only research that meets ethical standards can be regarded as valid and applicable, and only research designs that are methodologically rigorous and appropriate can be regarded as ethical., (© 2019 S. Karger AG, Basel.)

This article analyzes how a formal text (the Ethics Review Form) available at National Health Service Research Ethics Committees (NHSRECs) in the United Kingdom was used in meetings. Derived from the work of Dorothy Smith on incorporating texts into institutional ethnography (IE), it proposes the concept of "text work" as a way into understanding more about decision-making in ethics review and describes the extent to which this formal text shaped and influenced review work. The research study used observations of committee meetings, field-notes and interviews to produce an ethnographic mapping of Research Ethics Committees' (RECs) work. This article draws on one aspect of the research which was the process of isolating a particular, ubiquitous text and analyzing how it worked and was worked on in the meetings. The analysis contributes to contemporary discussion offering an alternative to ongoing debates about idealized ways of conducting ethics review. Finally, some tentative suggestions are made about improving training, based on and starting from the work which reviewers undertake.

OMICs subsume different physiological layers including the genome, transcriptome, proteome and metabolome. Recent advances in analytical techniques allow for the exhaustive determination of biomolecules in all OMICs levels from less invasive human specimens such as blood and urine. Investigating OMICs in deeply characterized population-based or experimental studies has led to seminal improvement of our understanding of genetic determinants of thyroid function, identified putative thyroid hormone target genes and thyroid hormone-induced shifts in the plasma protein and metabolite content. Consequently, plasma biomolecules have been suggested as surrogates of tissue-specific action of thyroid hormones. This review provides a brief introduction to OMICs in thyroid research with a particular focus on metabolomics studies in humans elucidating the important role of thyroid hormones for whole body metabolism in adults., (© 2018 Society for Endocrinology.)

Research in critical care patients is an ethical obligation. The ethical conflicts of intensive care research arise from patient vulnerability, since during ICU admission these individuals sometimes lose all or part of their decision making capacity and autonomy. We therefore must dedicate effort to ensure that neither treatment (sedation or mechanical ventilation) nor the disease itself can affect the right to individual freedom of the participants in research, improving the conditions under which informed consent must be obtained. Fragility, understood as a decrease in the capacity to tolerate adverse effects derived from research must be taken into account in selecting the participants. Research should be relevant, not possible to carry out in non-critical patients, and a priori should offer potential benefits that outweigh the risks that must be known and assumable, based on principles of responsibility., (Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

The history of health research, and concerns about the protection of human participants, dates back as far as the 1800s. The regulation, legislation and ethics-review requirements regarding the protection of the human research participants cause lively debates among researchers and scientists. The objective of this article is to share the findings of a structured review that was aimed at investigating the impact of and challenges with regard to the legislation, governance and research regulations aimed at protecting human research participants. The thematic analysis of the findings revealed dissatisfaction with diverse operational practices; different legislation and regulation practices; and institutional governance. Simplified and universally agreed-upon regulations and operational practices are needed, as is a common understanding of all concepts relating to ethical research conduct.

Quality and ethics need to be embedded into all areas of research with human participants. Good Clinical Practice (GCP) guidelines are international ethical and scientific quality standards for designing, conducting, recording and reporting trials involving human participants. Compliance with GCP is expected to provide public assurance that the rights, safety and wellbeing of participants are protected and that the clinical research data are credible. However, whilst GCP guidelines, particularly their principles, are recommended across all research types, it is difficult for non-clinical trial research to fit in with the exacting requirements of GCP. There is therefore a need for guidance that allows health researchers to adhere to the principles of GCP, which will improve the quality and ethical conduct of all research involving human participants. These concerns have led to the development of the Good Health Research Practice (GHRP) course. Its goal is to ensure that research is conducted to the highest possible standards, similar to the conduct of trials to GCP. The GHRP course provides training and guidance to ensure quality and ethical conduct across all health-related research. The GHRP course has been run so far on eight occasions. Feedback from delegates has been overwhelmingly positive, with most delegates stating that the course was useful in developing their research protocols and documents. Whilst most training in research starts with a guideline, GHRP has started with a course and the experience gained over running the courses will be used to write a standardised guideline for the conduct of health-related research outside the realm of clinical trials, so that researchers, funders and ethics committees do not try to fit non-trials into clinical trials standards.

In the spring of 2015, 11 years after a mentally ill young man named Dan Markingson stabbed himself to death in an industry-sponsored drug study, officials at the University of Minnesota suspended recruitment of subjects into drug trials in its Department of Psychiatry. University officials agreed to act only after a scathing investigation by Minnesota Office of the Legislative Auditor found damning evidence of coerced recruitment, inadequate clinical care, superficial research oversight, a web of serious, disturbing conflicts of interest, and a pattern of misleading public statements by university officials aimed at deflecting scrutiny. In this article, I examine the larger institutional factors leading up to Markingson's suicide and prevented corrective action for so long.

Objective To reflect on the problems faced by researchers from different areas, especially of Humanities and Social Sciences, when submitting research projects for evaluation by the research ethics committees in Brazil. Method A theoretical and reflective study based on international literature and the critical analysis of the authors. Results Although Resolution 466/2012, which addresses human research, contains some innovations, issues related to the research participants remain obscure and the project evaluation process is time-consuming. Conclusion The difficulties faced by researchers, especially in the fields of Humanities and Social Sciences, must be transposed to ensure that the ethical guidelines are applicable, in terms of principles and procedures, to the different research traditions. Appropriate human research standards must be managed by a system with a satisfactory operational capacity, according to the specificities of the different areas of knowledge.

In recent years, the development of research and the increased awareness of our moral duties beyond the human species have pushed the scientific community to revise widely-accepted ontological reductionist views that regard non-human animals as mere things. The new horizons offered by the development of advanced research methods therefore require an on-going commitment to new perspectives able to find the right balance between the need for scientific knowledge on one hand and the respect for animal life on the other. This is in line with increasing attention to animal welfare and expansion of the "3Rs model": replacement, reduction, refinement.With the view of promoting the adoption of alternative methods, human body donation for research can contribute not only to the acquisition of important information for human health and for doctors' training, but also can reduce significantly the number of animals sacrificed.By investigating the scientific and ethical reasons that may encourage cadaver donation, the authors aim to promote the adoption of the practice in Italy following other European experiences.

Barriers to informed consent are ubiquitous in the conduct of emergency care research across a wide range of conditions and clinical contexts. They are largely unavoidable; can be related to time constraints, physical symptoms, emotional stress, and cognitive impairment; and affect patients and surrogates. US regulations permit an exception from informed consent for certain clinical trials in emergency settings, but these regulations have generally been used to facilitate trials in which patients are unconscious and no surrogate is available. Most emergency care research, however, involves conscious patients, and surrogates are often available. Unfortunately, there is neither clear regulatory guidance nor established ethical standards in regard to consent in these settings. In this report-the result of a workshop convened by the National Institutes of Health Office of Emergency Care Research and Department of Bioethics to address ethical challenges in emergency care research-we clarify potential gaps in ethical understanding and federal regulations about research in emergency care in which limited involvement of patients or surrogates in enrollment decisions is possible. We propose a spectrum of approaches directed toward realistic ethical goals and a research and policy agenda for addressing these issues to facilitate clinical research necessary to improve emergency care., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

The purpose of consent is to let a person waive her rights of control over some aspects of her life. But becoming part of a research study does not always seriously undermine one's control.

FFQ comprising food items, intake frequency categories and portion sizes have been used in large-scale observational studies to assess long-term dietary exposure. Although gender is an important influence on food choice and portion size, gender differences are not often analysed during FFQ development. This study investigated whether gender differences were considered sufficiently when developing FFQ, which affects the results of validation studies. A PubMed search using combinations of 'FFQ', 'Food Frequency Questionnaire', 'Validation' and 'Validity' identified 246 validation studies available in English, published between January 1983 and May 2014, which included healthy male and female adults. The development process of the 196 FFQ used in the 246 validation studies was examined. Of these, twenty-one FFQ (10·7%) considered gender during item selection or portion size determination, and were therefore classified as gender specific (GS), but 175 (89·3%) did not consider gender, and were classified as 'not gender specific (NGS)'. When the ratios between intake levels obtained using the FFQ and a reference method for energy and seven nutrients were compared between the GS group and the NGS group, more significant differences were observed in women than in men (four v. one nutrient). Intake of three nutrients was significantly underestimated in both sexes in the GS group. In the NGS group, nutrient intakes were significantly overestimated more often in women than in men (four v. one). These results indicate that not considering gender in FFQ development causes greater inaccuracy in dietary intake assessment in women than in men. Results of nutritional epidemiological studies should be re-evaluated for their validity, especially if the studies used NGS-FFQ.

Performing well-designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, 4 organizations (the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; European Crohn's and Colitis Organization; the Canadian Children IBD Network; and the Global Pediatric IBD Network) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94 of 100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo; for example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an "add-on" to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. It has been, however, agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD regarding pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD.

Innovation is a crucial part of surgical history that has led to enhancements in the quality of surgical care. This comprises both changes which are incremental and those which are frankly disruptive in nature. There are situations where innovation is absolutely required in order to achieve quality improvement or process improvement. Alternatively, there are innovations that do not necessarily arise from some need, but simply are a new idea that might be better. All change must assure a significant commitment to patient safety and beneficence. Innovation would ideally enhance patient care quality and disease outcomes, as well stimulate and facilitate further innovation. The tensions between innovative advancement and patient safety, risk and reward, and demonstrated effectiveness versus speculative added value have created a contemporary "surgical conundrum" that must be resolved by a delicate balance assuring optimal patient/provider outcomes. This article will explore this delicate balance and the rules that govern it. Recommendations are made to facilitate surgical innovation through clinical research. In addition, we propose options that investigators and institutions may use to address competing priorities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients' rights and interests., (© The Author(s) 2015.)

In 2014, recognizing the need to have a single document to guide scientific decision making at the Academy of Nutrition and Dietetics (Academy), the Council on Research was charged with developing a scientific integrity policy for the organization. From the Council on Research, four members volunteered to lead this workgroup, which reviewed the literature and best practices for scientific integrity from well-respected organizations, including federal funders of research. It became clear that the scope of this document would be quite broad, given the many scientific activities the Academy is involved in, and that it would be unreasonable to set policy for each of these many situations. Therefore, the workgroup set about defining the scope of scientific activities to be covered and envisioned a set of guiding principles, to which policies from every organizational unit of the Academy could be compared to ensure they were in alignment. While many relevant policies exist already, such as the requirement of a signed conflict of interest disclosure for Food & Nutrition Conference & Expo speakers, the Evidence Analysis Library funding policy, and the Academy's sponsorship policy, the scientific integrity principals are unique in that they provide a unifying vision to which future policies can be compared and approved based on their alignment with the principles. The six principles outlined in this article were approved by the full Council on Research in January 2015 and approved by the Academy's Board of Directors in March 2015. This article covers the scope of the principles, presents the principles and existing related resources, and outlines next steps for the Academy to review and revise current policies and create new ones in alignment with these principles., (Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Since the 18th century a wealth of knowledge regarding infectious disease pathogenesis, prevention, and treatment has been accumulated from findings of infection challenges in human beings. Partly because of improvements to ethical and regulatory guidance, human challenge studies-involving the deliberate exposure of participants to infectious substances-have had a resurgence in popularity in the past few years, in particular for the assessment of vaccines. To provide an overview of the potential use of challenge models, we present historical reports and contemporary views from experts in this type of research. A range of challenge models and practical approaches to generate important data exist and are used to expedite vaccine and therapeutic development and to support public health modelling and interventions. Although human challenge studies provide a unique opportunity to address complex research questions, participant and investigator safety is paramount. To increase the collaborative effort and future success of this area of research, we recommend the development of consensus frameworks and sharing of best practices between investigators. Furthermore, standardisation of challenge procedures and regulatory guidance will help with the feasibility for using challenge models in clinical testing of new disease intervention strategies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Pre-recruitment is the practice of recruiting potential participants to a list of potential research volunteers in general rather than to a specific research project. This is a relatively common practice in commercial medical research as it reduces the time and hence costs of recruitment and makes it possible to be more efficient by recruiting participants who may be useful for a variety of different pieces of research. It focuses on present practices in the UK although the conclusions and suggestions should be read more widely than this, applying in any situation where pre-recruitment is used as a recruitment tool for clinical trials and beyond. Current pre-recruitment practices in the UK clash significantly with what are seen as best practices and ethical guidance with regard to recruiting participants to individual trials, and insofar as this undermines these practices should be reformed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Institutions conducting research involving human subjects establish human research protection programs to ensure the rights and welfare of research participants as well as to meet ethical and regulatory requirements. It is important to determine whether human research protection programs have achieved these objectives., Methods: The Department of Veterans Affairs has developed quality indicators and annually collected human research protection program quality indicator data from its 108 research facilities since 2010., Results: Analysis of Department of Veterans Affairs human research protection program quality indicator data revealed that facilities using affiliated university institutional review boards performed as well as those using their own Department of Veterans Affairs institutional review boards and that facilities with small research programs, that is, less than 50 human research protocols, performed at least as well as those with larger research programs. These quality indicator data also provided Department of Veterans Affairs facilities with valuable information for quality improvement. Many of these quality indicators have improved in subsequent years, and none has deteriorated. Lapse rates in institutional review board continuing reviews remained high and relatively constant at above 6.0% over a 4-year period from 2010 through 2013., Discussion: Future efforts should be directed at developing a set of human research protection program quality indicators truly reflecting the quality of human research protection programs that are applicable to both Department of Veterans Affairs and non-Department of Veterans Affairs institutions and determining whether high-quality human research protection programs as measured using these quality indicators translate into better human subject protections., (© The Author(s) 2015.)

Research outlets are increasingly adopting open data policies as a requisite for publication, including studies with human subjects data. We investigated whether open data policies influence participants' rate of consent by randomly assigning participants to view consent forms with and without discussion of open data policies. No participants declined to participate, regardless of condition, nor did rates of drop-out vs. completion vary between conditions. Furthermore, no significant change in potential consent rates was reported when participants were openly asked about the influence of open data policies on their likelihood of consent. However, follow-up analyses indicated possible poor attention to consent forms, consistent with previous research. Moreover, thematic analysis of participants' considerations of open data policy indicated multiple considerations such as concerns regarding confidentiality, anonymity, data security, and study sensitivity. The impact of open data policies on participation raises complex issues at the intersection of ethics and scientific innovation. We conclude by encouraging researchers to consider participants as stakeholders in open data policy and by providing recommendations for open data policies in human subjects research.