Human Research Protections Research Articles

Development proposals of Human Research Protection Program.

China's ethics committees alone are unable to meet the growing need for human participant protection. Several scandals in recent years indicate weaknesses in the protection of human participants in China. The aim of the study is to summarize the status and problems of human research protection program in China and to explore its establishment proposals at national and hospital levels. To conduct literature retrieval, Chinese National Knowledge Infrastructure, Chinese Biomedical Document Database, and English databases Web of Science and PubMed were searched; laws, guidelines, and regulations were also searched on web by Google and Chinese search engine Baidu. No data were collected from human participants, and ethical review was not required. There are problems for China's Human Research Protection Program, such as weak relevant legal systems, insufficient administrative supervision, and incompetent ethics committee capacities. To fully protect human participants, China should promote the development of Human Research Protection Program, which can formulate ethics-related laws, improve regulations for the protection of the safety and rights of human participants, strengthen supervision, and enforce compensation for human participants. Owing to the frequency with which human participants are recruited in hospitals in China, hospitals can utilize existing ethics committees and establish data and safety monitoring committees, quality control, fund and contract management, and conflict of interest management offices. As a growing program, it remains necessary to learn from the experience of developed countries with high ethics standards and reformulate them to fit China's conditions to explore potential future development. The program will also be an experience for other developing countries. Human Research Protection Program can strengthen communication and coordination among various hospital departments to effectively protect the rights and welfare of human participants.

Development and External Validation of a Clinical Decision Support Tool for Managing Children with Minor Head Trauma and Intracranial Injuries

Background: There are no validated tools guiding the appropriate level-of-care for children with minor head trauma (MHT) and radiographic intracranial injuries. We developed and externally validated a clinical decision support tool for risk-stratifying these patients. Methods: The derivation cohort included children enrolled in the PECARN head injury study from 2004-2006. The validation group consisted of a separate cohort of children with MHT treated at six centers from 2006-2019. Children < 18 years were included if they presented within 24 hours of injury, had a Glasgow Coma Scales (GCS) score of 13-15, and had intracranial injury on neuroimaging. A risk model was developed using recursive partitioning to predict serious neurological events, defined as neurosurgical intervention, intubation longer than 24 hours due to head injury, or death from head injury. Risk thresholds were determined for clinical decision-making. This model was compared to a logistic regression model previously developed using the PECARN cohort. Findings: Based on 839 patients meeting inclusion criteria in the PECARN cohort, the tree-based model included seven predictors, with midline shift, depressed skull fracture, epidural hematoma, and GCS score being the most influential. Three risk thresholds were evaluated to classify patients as ‘low’ risk. In the validation cohort consisting of 1,630 patients, the most conservative cutoff (i.e. any predictor present) identified 119/119 children with serious neurological events (sensitivity 100%; 95% CI 96·9-100), but had the lowest specificity (26.3%; 95% CI 24·1-28·6). All three thresholds had negative predictive values above 99% and collectively outperformed the logistic regression model. Using these thresholds, a clinical decision support tool was created that identified 75% of the population as ‘low’ or ‘very low’ risk. Interpretation: We developed and validated a clinical decision support tool that accurately risk-stratifies children with MHT and radiographic intracranial injuries. This tool can potentially improve patient safety and reduce resource use. Funding : Thrasher Research Fund and the Agency for Healthcare Research and Quality. Funding Statement: This study was funded by grants from the Agency for Healthcare Research and Quality (1F32HS027075-01A1) and the Thrasher Research Fund (#15024). Declaration of Interests: MAO reports grant funding from Merck, Sanofi Pasteur, and Pfizer, and consulting fees from Pfizer. EJ reports medical expert testimony and patent holdings (US Patent 9993631). DDL has received research funds and/or research equipment for unrelated projects from Medtronic, Inc., Karl Storz, Inc., and Microbot Medical, Inc, and has received philanthropic equipment contributions for humanitarian relief work from Karl Storz, Inc. and Aesculap, Inc. No other authors disclose any competing interests. Ethics Approval Statement: All data analyzed were from the deidentified, public-use dataset, and consequently the Washington University in St. Louis Human Research Protection Office deemed the analysis not subject to institutional review board (IRB) oversight.

An approach towards individualized lower rate settings for pacemakers.

Author(s): Infeld, Margaret; Avram, Robert; Wahlberg, Kramer; Silverman, Daniel N; Habel, Nicole; Lustgarten, Daniel L; Pletcher, Mark J; Olgin, Jeffrey E; Marcus, Gregory M; Meyer, Markus

Reducing the Single IRB Burden: Streamlining Electronic IRB Systems

Electronic institutional review board systems (eIRBs) have become an integral component in ensuring compliance with Human Research Protection Program (HRPP) and IRB requirements. Despite this, few of these systems are configured to administer the single IRB (sIRB) process mandated by the National Institutes of Health (NIH) for multisite research. We interviewed 103 sIRB administrators, chairs, members, and staff members about their experiences with sIRB multisite research review. We observed three main obstacles to adapting existing eIRB systems to accommodate the sIRB process: (1) Existing systems are not designed for sIRBs and are not configured to administer sIRB responsibilities, (2) they are not interoperable, and (3) resources to improve existing systems are lacking. Our findings suggest that IRBs that act as an sIRB will need major changes to their electronic systems in order to accommodate sIRB processes. These difficulties threaten both the ability of IRBs to focus on ethical rather than bureaucratic problems and the efficiency of multisite trials.

Assessing the Quality and Performance of Institutional Review Boards: Levels of Initial Reviews.

How well institutional review boards (IRBs) follow Common Rule criteria for levels of initial protocol review has not been systematically evaluated. We compared levels of review as determined using the Office for Human Research Protections (OHRP) human subject regulations decision charts of 313 protocols that had been approved by IRBs. There was a 97.8% agreement between 140 protocols that were reviewed by full board and the levels of review according to OHRP criteria. Likewise, there was a 93.8% agreement between 113 protocols that were reviewed using an expedited review procedure and OHRP criteria. However, there was only 75% agreement for exempt protocols. Specifically, 10 (16.7%) of the 60 exempt protocols were found to require IRB review, that is, six protocols requiring expedited review and four protocols requiring full board review. Conducting non-exempt research without prior IRB approval constitutes serious noncompliance. Our data suggest that exempt protocols need more scrutiny.

Evaluating the Quality of Research Ethics Review and Oversight: A Systematic Analysis of Quality Assessment Instruments

Background Research ethics review committees (RERCs) and Human Research Protection Programs (HRPPs) are responsible for protecting the rights and welfare of research participants while avoiding unnecessary inhibition of valuable research. Evaluating RERC/HRPP quality is vital to determining whether they are achieving these goals effectively and efficiently, as well as what adjustments might be necessary. Various tools, standards, and accreditation mechanisms have been developed in the United States and internationally to measure and promote RERC/HRPP quality. Methods We systematically reviewed 10 quality assessment instruments, examining their overall approaches, factors considered relevant to quality, how they compare to each other, and what they leave out. For each tool, we counted the number of times each of 34 topics (divided into structure, process, and outcome categories) was mentioned. We generated lists of which topics are most and least mentioned for each tool, which are most prevalent across tools, and which are left unmentioned. We also conducted content analysis for the 10 most common topics. Results We found wide variability between instruments, common emphasis on process and structure with little attention to participant outcomes, and failure to identify clear priorities for assessment. The most frequently mentioned topics are Review Type, IRB Member Expertise, Training and Educational Resources, Protocol Maintenance, Record Keeping, and Mission, Approach, and Culture. Participant Outcomes is unmentioned in 8 tools; the remaining 2 tools include assessments based on adverse events, failures of informed consent, and consideration of participant experiences. Conclusions Our analysis confirms that RERC/HRPP quality assessment instruments largely rely on surrogate measures of participant protection. To prioritize between these measures and preserve limited resources for evaluating the most important criteria, we recommend that instruments focus on elements relevant to participant outcomes, robust board deliberation, and procedures most likely to address participant risks. Validation of these approaches remains an essential next step.

Buddy Care, a Peer-to-Peer Intervention: A Pilot Quality Improvement Project to Decrease Occupational Stress Among an Overseas Military Population.

Occupational stress can have a direct influence on worker safety and health. Navy medical professionals are known to neglect self-care, putting them at risk for deteriorations in psychological health that can lead to adverse patient outcomes. To support medical professionals, a peer-to-peer intervention called Buddy Care, embedded in Navy Medicine's Caregiver Occupational Stress Control (CgOSC) program, was evaluated. Strategies to prevent and better manage occupational stress are vital to improve the health care providers' abilities to cope with day-to-day stressors, which is crucial to maintaining mission readiness. The overarching aim of this quality improvement pilot project was to implement and evaluate Buddy Care and to provide context as an evidenced-based peer intervention and leadership tool at a military hospital in Guam. This project is the first to implement and evaluate Buddy Care intervention for an active duty U.S. Navy population stationed overseas. A convenience sample of 40 Navy active duty assigned to three inpatient units were offered Buddy Care intervention, which was introduced by conducting a Unit Assessment. A pre-test and 3- and 6-month post-test intervention design used a self-administered, 79-item CgOSC Staff Wellness Questionnaire which included five validated measures to assess the independent variable: (1) Response to Stressful Experience Scale, (2) Perception of Safety, (3) Horizontal Cohesion, (4) Perceived Stress Scale, and (5) Burnout Measure, short version. This project was determined as exempt by the Department of Navy Human Research Protection Program and did not require further review by the Institutional Review Board. Of the 40 questionnaires collected, 39 were partially completed. Paired sample t-tests were conducted between designated time-points to maximize the sample size and retain the repeated measures nature of the outcome variables. The small sample size allowed for statistical comparisons; however no statistically significant differences were found across the time-points. There was a large effect size for Perceptions of Safety and a medium effect size for Burnout Measure from baseline to 3 months, with both lowered at the 6 months. Although the sample size was too small to achieve statistical significance, the effect size analysis suggested that significance might be obtained with a larger sample. The small number of participants and missing data significantly limited the ability to identify reliable changes across time-points. Despite the lack of statistically significant findings, there was an unintended positive result. The Unit Assessment piqued the interest of other departments, and during the project period, 11 departments requested a Unit Assessment. Although there were no requests for Buddy Care intervention from the targeted sample, it was occurring an average of 40 times per month throughout the command. Replication of this project in a similar setting is encouraged so that Buddy Care can be further evaluated. Understanding the effectiveness of well-mental health programs that promote early intervention and prevention efforts may contribute to a psychologically tougher medically ready force. Shortly after project completion, a CgOSC Instruction was approved by the Navy Surgeon General, highlighting the importance of CgOSC and Buddy Care on the operational readiness of Navy Medicine.

Human Subject Research Protection Ethics in the Research and Development (R&D) of Non-lethal Weapons

ABSTRACT Non-lethal weapons (NLW) have become an increasingly important class of weapons. Creating these armaments requires examination of ethical issues in their research and development processes. Chief among these ethical concerns is the need for research, testing, and evaluation of these weapons against their intended targets: people. Research and development of NLW can be compromised by the avoidance of human target experimentation. At the root of this avoidance is a lack of knowledge of the ethical and regulatory guidelines that govern human subject research within the NLW community. As with all research, NLW research activities must comply with regulations that rest on the ethical concepts of Beneficence, Justice, and Respect for Persons. However, moderate modification must be made in the typical framework surrounding ethical oversight of NLW experimentation. The process discussed entails a sequence of questions “Is the activity research?”, “Is the risk worth the benefit?”, “How is the potential subject informed of the risks of participating?” and “How are the risks of harm to the subject mitigated throughout the experiment?” The ethical conduct of NLW research is vital to protecting the rights of subjects and increasing the pace of developments of NLW armaments.

Prospective Study Evaluating a Pain Assessment Tool in a Postoperative Environment: Protocol for Algorithm Testing and Enhancement.

BackgroundAssessment of pain is critical to its optimal treatment. There is a high demand for accurate objective pain assessment for effectively optimizing pain management interventions. However, pain is a multivalent, dynamic, and ambiguous phenomenon that is difficult to quantify, particularly when the patient’s ability to communicate is limited. The criterion standard of pain intensity assessment is self-reporting. However, this unidimensional model is disparaged for its oversimplification and limited applicability in several vulnerable patient populations. Researchers have attempted to develop objective pain assessment tools through analysis of physiological pain indicators, such as electrocardiography, electromyography, photoplethysmography, and electrodermal activity. However, pain assessment by using only these signals can be unreliable, as various other factors alter these vital signs and the adaptation of vital signs to pain stimulation varies from person to person. Objective pain assessment using behavioral signs such as facial expressions has recently gained attention.ObjectiveOur objective is to further the development and research of a pain assessment tool for use with patients who are likely experiencing mild to moderate pain. We will collect observational data through wearable technologies, measuring facial electromyography, electrocardiography, photoplethysmography, and electrodermal activity.MethodsThis protocol focuses on the second phase of a larger study of multimodal signal acquisition through facial muscle electrical activity, cardiac electrical activity, and electrodermal activity as indicators of pain and for building predictive models. We used state-of-the-art standard sensors to measure bioelectrical electromyographic signals and changes in heart rate, respiratory rate, and oxygen saturation. Based on the results, we further developed the pain assessment tool and reconstituted it with modern wearable sensors, devices, and algorithms. In this second phase, we will test the smart pain assessment tool in communicative patients after elective surgery in the recovery room.ResultsOur human research protections application for institutional review board review was approved for this part of the study. We expect to have the pain assessment tool developed and available for further research in early 2021. Preliminary results will be ready for publication during fall 2020.ConclusionsThis study will help to further the development of and research on an objective pain assessment tool for monitoring patients likely experiencing mild to moderate pain.International Registered Report Identifier (IRRID)DERR1-10.2196/17783

Wellness and resilience for college and beyond: protocol for a quasi-experimental pilot study investigating a dialectical behaviour therapy skill-infused college course

IntroductionCollege students’ mental health problems and suicidal behaviour are serious, persistent and prevalent public health issues. With the need for mental health support greatly exceeding the availability of on-campus treatment,...

4186 Single IRB and the CTSI: Liaison Model for the IRB Reliance Process

OBJECTIVES/GOALS: Navigating the NIH Single IRB Policy has been challenging for investigators, study teams, and Human Research Protection Programs (HRPP). In response, the Indiana Clinical and Translational Sciences Institute (CTSI) created an innovative Single IRB Project Manager role (sIRB PM), uniquely placed within the Indiana CTSI. METHODS/STUDY POPULATION: The Single IRB Project Manager role was created in 2018 by the Indiana CTSI in response to the NIH Single IRB Policy for Multi-Site Research. The role of the sIRB PM is to serve as a liaison between the Indiana University HRPP, lead site, coordinating center, and participating sites when Indiana University serves as the Single IRB. This model has proven useful to both the IRB and lead site, notably in the following ways: At study start-up, the sIRB PM can handle complicated communications among sites and the IRB at the same time the lead site is responsible for many other administrative tasks related to start-up. By absorbing the workload of IRB approval for multiple sites, the sIRB PM provides the lead site more capacity to handle other essential tasks.The sIRB PM translates new terminology and facilitates processes that are new for sites.RESULTS/ANTICIPATED RESULTS: Early assessment of this program is predominantly positive. The sIRB PM currently supports 24 external sites. In an NIA-funded 13 site study, all sites were added within 9 months of initial IRB approval of the protocol. This role fills a gap that benefits: IRB staff by allowing them to fulfill their duties of screening and review while leaving some of the reliance organization to the sIRBPM.Lead PI by allowing them to focus on conducting the research instead of the many administrative tasks required for single IRB review.Participating sites by having a liaison to enter their amendments and reportable events into an otherwise closed IRB software system.All parties by having the sIRB PM manage document organization, storage, and distribution study-wide.DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI sIRB PM role effectively shifts administrative work caused by the sIRB mandate by merging research coordinator experience with regulatory experience while building upon an existing strong relationship with the HRPP. Future focus is on process education, standardizing pricing structure, and ensuring sufficient budget support in grants.

It's the Wild, Wild West: Lessons Learned From IRB Members' Risk Perceptions Toward Digital Research Data

Digital technology that is prevalent in people's everyday lives, including smart home devices, mobile apps and social media, increasingly lack regulations for how the user data can be collected, used or disseminated. The CSCW and the larger computing community continue to evaluate and understand the potential negative impacts of research involving digital technologies. As more research involves digital data, Institutional Review Boards (IRBs) take on the difficult task of evaluating and determining risks--likelihood of potential harms--from digital research. Learning more about IRBs' role in concretizing harm and its likelihood will help us critically examine the current approach to regulating digital research, and has implications for how researchers can reflect on their own data practices. We interviewed 22 U.S.-based IRB members and found that, for the interviewees, "being digital" added a risk. Being digital meant increasing possibilities of confidentiality breach, unintended collection of sensitive information, and unauthorized data reuse. Concurrently, interviewees found it difficult to pinpoint the direct harms that come out of those risks. The ambiguous, messy, and situated contexts of digital research data did not fit neatly into current human subjects research protection protocols. We discuss potential solutions for understanding risks and harms of digital technology and implications for the responsibilities of the CSCW and the larger computing community in conducting digital research.

Circular RNA TRAPPC6B Inhibits Intracellular Mycobacterial Growth While Inducing Autophagy in Macrophages by Targeting microRNA-874-3p

Background: Genetic and epigenetic mechanisms appear to regulate antimicrobial immunity against Mycobacterium tuberculosis (Mtb) infection. Methods: We assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms whereby circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages. Findings: While Mtb infection of monocytes/macrophages resulted in a significantly decreased circTRAPPC6B level, circTRAPPC6B inhibited intracellular Mtb growth in macrophages. Whereas, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. The circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in FISH analysis and confocal imaging. Mechanistically, circTRAPPC6B could target an inhibiting element miR-874-3p, as evidenced by bioinformatics, dual-luciferase reporter gene analysis, and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppression of autophagy protein ATG16L1 expression by binding to its 3’-UTRin Mtb-infected macrophages and thus promoted intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb-infected macrophage by blocking the ability of miR-874-3p to inhibit ATG16L1. Thus, circTRAPPC6B can antagonize the ability of miR-874-3p to suppress ATG16L1 expression, and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages. Interpretation: Our findings suggest that both circTRAPPC6B and miR-874 mechanisms can be explored as potential therapeutics against Mtb infection. Funding: This work was supported by the National Natural Science Foundation of China (881870016, 1570009 and 81273237), the Natural Science Foundation of Guangdong Province (2015A030313513 and 2020A1515010283), and the Science and Technology Innovation Fund of Guangdong Medical University (STIF201110, B2012078). Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: The protocol of using human blood samples in vitro was approved by the Institutional Review Boards for Human Donors’ Research and Institutional Biosafety Committees at Institut Pasteur of Shanghai, Guangdong Medical University, and Dongguan 6th Hospital (China). The protocols of using macaque spleen tissue samples and mycobacterium H37Rv strain were approved by the Institutional Review Boards for Biosafety Committee at the University of Illinois–Chicago College of Medicine (IL, USA). All studies complied with the guidelines of the Office for Human Research Protections. All patients and healthy controls provided written informed consent before initiation of study.

Protocol for a randomised trial of an interprofessional team-delivered intervention to support surrogate decision-makers in ICUs

IntroductionAlthough shortcomings in clinician–family communication and decision making for incapacitated, critically ill patients are common, there are few rigorously tested interventions to improve outcomes. In this manuscript, we present our...

How Should Organizations Respond to Repeated Noncompliance by Prominent Researchers?

This article considers a case in which a prominent researcher repeatedly made protocol deviations year after year while the institutional review board and university leadership failed to adequately address his continuing noncompliance. This article argues that, in addition to reporting this researcher's pattern of noncompliance to the Office for Human Research Protections, as required by federal regulations, the university should implement a remedial action plan.

Maintenance motives for physical activity among older adults: a protocol for a systematic review and meta-analysis

IntroductionPhysical activity (PA) is an important aspect for health and well-being, yet many older adults do not maintain their PA long term. The identification of key factors that are associated...

Exempting low-risk health and medical research from ethics reviews: comparing Australia, the United Kingdom, the United States and the Netherlands

BackgroundDisproportionate regulation of health and medical research contributes to research waste. Better understanding of exemptions of research from ethics review in different jurisdictions may help to guide modification of review processes and reduce research waste. Our aim was to identify examples of low-risk human health and medical research exempt from ethics reviews in Australia, the United Kingdom, the United States and the Netherlands.MethodsWe examined documents providing national guidance on research ethics in each country, including those authored by the National Health and Medical Research Council (Australia), National Health Service (United Kingdom), the Office for Human Research Protections (United States) and the Central Committee on Research Involving Humans (the Netherlands). Examples and types of research projects exempt from ethics reviews were identified, and similar examples and types were grouped together.ResultsNine categories of research were exempt from ethics reviews across the four countries; these were existing data or specimen, questionnaire or survey, interview, post-marketing study, evaluation of public benefit or service programme, randomised controlled trials, research with staff in their professional role, audit and service evaluation, and other exemptions. Existing non-identifiable data and specimens were exempt in all countries. Four categories – evaluation of public benefit or service programme, randomised controlled trials, research with staff in their professional role, and audit and service evaluation – were exempted by one country each. The remaining categories were exempted by two or three countries.ConclusionsExamples and types of research exempt from research ethics reviews varied considerably. Given the considerable costs and burdens on researchers and ethics committees, it would be worthwhile to develop and provide clearer guidance on exemptions, illustrated with examples, with transparent underpinning rationales.

Evaluation of Impact of Surgical Robotic Technology on Quality of Total Mesorectal Excision for Rectal Cancer:Chinese Experience of R-TME &lt;i&gt;via&lt;/i&gt; Diverse Robotic Technology

Objective: The advantages and disadvantages of robotic technology compared with conventional surgery for low rectal cancer has been discussed extensively, but few studies of the impact on total mesorectal excision (TME) efficacy based on different robotic technologies have been reported. This study aims to evaluate the differences in TME quality between two different robot-assisted TME (R-TME) methods. Methods: Between January 2017 and May 2019, patients who suffered from rectal cancer (cT1-3NxM0) were prospectively registered. Patients independently chose to undergo da Vinci R-TME, MicroHand S R-TME, or laparoscopic TME (L-TME). The integrity of the TME sample served as the primary outcome. Secondary outcomes included the involvement of circumferential and distal resection margins (CRM and DRM), lymph node retrieval number, blood loss, operative time (OT), conversion rate, comprehensive complication index (CCI) scores, IPSS,IIEF and FSFI scores. Results: In total, 46 patients underwent laparoscopic TME, 45 patients underwent da Vinci R-TME and 43 patients underwent MicroHand S R-TME. TME quality improved in both two R-TME groups, which was reflected by a reduced DRM involvement rate, more retrieved lymph nodes, reduced blood loss, reduced incidence of severe complications, and earlier urogenital function recovery. However, the operative times for both R-TME methods were significantly longer than that of the L-TME approach. Conclusion: In this study, compared with laparoscopic surgery, Da Vinci or MicroHand R-TME exhibit similar superiority in oncologic resection quality, postoperative morbidity, and recovery of postoperative function. Trial Registration: This study was registered with Clinicaltrials.gov (ID: NCT02752698). Funding Statement: This study was supported by the National Natural Science Foundation of China (No: 51875580) and National Key Research and Development Plan Fund (Grant No: 2017YFC0110402). Declaration of Interests: All authors declare that there are no conflicts of interest. Ethics Approval Statement: Approved by the Association for the Accreditation of Human Research Protection Program (AAHRPP) (Project number: T16007).

The Impact of a Community Based Rehabilitation Program in Afghanistan: A Longitudinal Analysis Using Propensity Score Matching and Difference in Difference Analysis

Background: The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) ratified in 2006 states that the achievement of equal rights, empowerment and social inclusion of people with disabilities requires comprehensive rehabilitation services involving educational, social, economic and medical interventions all dimensions of the World Health Organization Community based rehabilitation (CBR) matrix. CBR programs aim at achieving those goals. In the present study, we investigated whether a large scale CBR program implementing the WHO CBR matrix in the context of Afghanistan is having a positive impact on those dimensions. Methods: We enrolled in the study 1861 newly recruited CBR participants with disabilities from 169 villages between July 2012 and December 2013 and 1132 controls screened with disabilities randomly selected with a two-stage process within 6000 households from 100 villages in the same provinces as the CBR but outside its catchment area. Using propensity score matching and difference in difference analysis, we estimated the impact of the CBR on various outcomes of interest, namely mobility, activities of daily living, communication, participation in social and community life, emotional well-being. Findings: There were statistically significant differences between participants and controls on all outcomes between baseline and endline, with impact ranging from the highest impact on emotional well-being (1.02, 95%CI 0.04-2.00) and the lowest impact on activities of daily living (0.08, CI 0.03-0.13). Interpretation: Our study indicates that a CBR program may provide positive rehabilitation outcomes for persons with disabilities even in a conflict context such as Afghanistan. It contributes to address the longstanding question whether CBR can actually improve overall well-being of all participants with disabilities, whatever their impairment and individual characteristics and whatever the component of the CBR matrix considered. Funding Statement: The funding source had no role in the conception and the design of the study, the data collection process, the data analysis, in the writing of the manuscript or the decision to submit it for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Declaration of Interests: None. Ethical Approval Statement: The present study was approved by the Human Research Protection Office of Washington University in St Louis (IRB ID #:201206117) and by the Institutional Review Board of the Ministry of Public Health of Afghanistan. All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Exemptions and Limited Institutional Review Board Review: A Practical Look at the 2018 Common Rule Requirements for Exempt Research.

Background: The revised Common Rule sought to modernize an outdated regulatory framework, provide clarity to the research community about the application of regulations, and reduce regulatory burden. From the advance notice of proposed rulemaking in 2011 to the implementation of the Final Rule, a significant amount of commentary and opinion was generated about the rules that govern most federally funded human subjects research.Methods: This article provides insight into the changes to the regulatory framework for low-risk research, clarifies when exemptions can be applied, and explains the use of limited institutional review board (IRB) review.Results: In attempting to fulfill the objectives of reducing regulatory burden, freeing IRB administrative resources, and protecting human subjects, the new regulations acknowledge low-risk research and privacy concerns, as well as the increased use of biospecimens. In the Final Rule, the Office for Human Research Protections updated the definition of human subject and expanded the exemption framework. The definition of human subject in the Final Rule includes biospecimens, and the new exemption framework includes expanded definitions, modifications to existing exemption categories, the creation of new categories, and the creation of a new concept called limited IRB review. The expanded exemption framework was designed to help alleviate the regulatory burdens of low-risk research.Conclusion: Whether the revised regulations will meet the needs of the research community and human subject participants is unknown. While the revised Common Rule includes some welcome modifications and additions, the changes have also introduced new concepts that are not fully elucidated and have therefore introduced new ambiguities.