Federalwide Assurance Research Articles

Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial

IntroductionPreterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week...

HIDDEN BARRIERS TO ENGAGING HOME- AND COMMUNITY-BASED SERVICES IN DEMENTIA CARE RESEARCH

Abstract The high prevalence of dementia in the United States has resulted in a reliance on home-and community-based services (HCBS) to assist in the provision of care for community-dwelling persons living with dementia. Partnering with HCBS organizations, like Adult Day Services (ADS), is beneficial to disseminating evidence-based dementia care interventions as it is an existing service that can be leveraged to foster relationships between research staff and clients. While benefits exist, challenges in identifying community-partner organization, ethical approval, and community-partner staffing can be unintended barriers. Using the ADS Plus Program as a case-study, this presentation will detail hidden barriers in engaging HCBS partnerships into dementia care research. Specifically, we will discuss barriers to 1) developing relationships to implement a multi-site national-trial, 2) high touch points necessary to engage sites from underrepresented populations, 3) institutional review board requirements (e.g. CiTi training, Federal Wide Assurance Forms), and 4) staff readiness to participate in research. We also offer recommendations based on lessons learned from the ADS Plus Program to enhance the pipeline from engagement with HCBS to participate in research to implementing an evidence-based interventions. Lessons learned from the ADS Plus Program demonstrates that changes are needed to improve the efficiency of the pipeline from community-based participation into dementia care research and implementation of evidence-based interventions.

Analgesic Effect of Addition of Pectointercostal Block to Serratus Anterior Plane Block in Breast Surgeries: A Randomized, Controlled Trial

BACKGROUND: Ultrasound-guided serratus anterior plane block (SAPB) is an efficient perioperative analgesic modality for breast surgeries. SAPB does not block the anterior cutaneous branches of the intercostal nerves; thus, it does not provide adequate analgesia for the parasternal region and the medial side of the breast. A new parasternal block, the pectointercostal fascial plane block (PIFB) has been developed to overcome this issue. OBJECTIVES: The study aimed to evaluate the perioperative analgesic effect of using PIFB in addition to SAPB. The primary outcome was to evaluate the postoperative pain score. The secondary outcomes were to assess perioperative opioid requirements, hemodynamic stability, and the satisfaction of the patient and surgeon. STUDY DESIGN: The current study was a prospective, double-blinded, randomized controlled study. The current study was registered at the Pan-African Clinical Trials Registry (PACTR202001789968542) and was designed after obtaining ethical institutional approval (Institutional Review Board No 00012098, Federalwide Assurance No 00018699). SETTING: The study involved 60 women between 21 and 69 years old with breast cancer who were scheduled for modified radical mastectomy or conservative breast surgeries in a university hospital. METHODS: After verbal and informed written consent, the patients were allocated to Group 1, which received SAPB, and Group 2, which received SAPB with PIFB. We assessed the Visual Analog Scale (VAS), perioperative opioid requirements, intraoperative hemodynamic stability, rescue analgesia, and complications. Patient and surgeon satisfaction were surveyed using a questionnaire where one is very dissatisfied and 5 is very satisfied. RESULTS: Intraoperative mean arterial blood pressure (MABP) and heart rate were significantly lower in Group 2 (SAPB+PIFB). The number of patients who needed intraoperative fentanyl was also significantly lower in Group 2 (SAPB+PIFB) (P value = 0.010). Postoperative VAS showed no significant difference in both groups. The number of patients who needed postoperative rescue morphine, time for the first rescue analgesia, first morphine dose (mg), and total opioid consumption were also comparable for both groups. Patient satisfaction and surgeon satisfaction were comparable for both groups (P values = 1.000 and 0.496, respectively). LIMITATIONS: VAS was not recorded during movements and no follow-up was done to detect the potential effect on chronic postmastectomy pain. Moreover, after reviewing the literature, there was no efficient data about adding PIFB with different regional blocks for breast surgery. CONCLUSIONS: The number of patients who needed intraoperative fentanyl, as well as the MABP and heart rate were significantly lower in Group 2 (SAPB+PIFB). Postoperative vital signs, VAS, postoperative analgesic requirements, and opioid consumption were comparable for both groups. Patient satisfaction was comparable for both groups, while surgeon satisfaction was higher in Group 2 (SAPB+PIFB) but statistically not significant. KEY WORDS: Pectointercostal, fascial plane block, serratus anterior plane block, breast surgery, regional analgesia for mastectomy

Institutional Review Boards and post-approval monitoring (PAM) of human research: content analysis of select university (academic health center) web pages across the USA

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

Measuring adherence, acceptability and likability of an artificial-intelligence-based, gamified phone application to improve the quality of dietary choices of adolescents in Ghana and Vietnam: Protocol of a randomized controlled pilot test.

Unhealthy diets are a critical global concern while dietary measure methods are time consuming and expensive. There is limited evidence that phone-based interventions can improve nutrition data collection and dietary quality, especially for adolescents in developing countries. We developed an artificial-intelligence-based phone application called Food Recognition Assistance and Nudging Insights (FRANI) to address these problems. FRANI can recognize foods in images, track food consumption, display statistics and use gamified nudges to give positive feedback on healthy food choice. This study protocol describes the design of new pilot studies aimed at measuring the feasibility (acceptability, adherence, and usability) of FRANI and its effects on the quality of food choice of adolescents in Ghana and Vietnam. In each country, 36 adolescents (12-18 years) will be randomly allocated into two groups: The intervention group with the full version of FRANI and the control group with the functionality limited to image recognition and dietary assessment. Participants in both groups will have their food choices tracked for four weeks. The control groups will then switch to the full version of FRANI and both groups will be tracked for a further 2 weeks to assess acceptability, adherence, and usability. Analysis of outcomes will be by intent to treat and differences in outcomes between intervention and control group will use Poisson and odds ratio regression models, accounting for repeated measures at individual levels. If deemed feasible, acceptable and usable, FRANI will address gaps in the literature and advance the nutrition field by potentially improving the quality of food choices of adolescent girls in developing countries. This pilot study will also provide insights on the design of a large randomized controlled trial. The functioning and dissemination of FRANI can be an important step towards highly scalable nutrition data collection and healthier food choices for a population at risk of malnutrition. The study protocol and the methods and materials were approved by the Institutional Review Board (IRB) of the IFPRI on April 29th, 2020 (registration number #00007490), the Thai Nguyen National Hospital on April 14th, 2020 (protocol code 274/ĐĐĐ-BVTWTN) and the University of Ghana on August 10th, 2020 (Federalwide Assurance FWA 00001824; NMIMR-IRB CPN 078-19/20). The study protocol was registered in the International Standard Randomized Controlled Trial Number (ISRCTN 10681553; https://doi.org/10.1186/ISRCTN10681553) on November 12, 2021.

Retention of knowledge and clinical competence among Ugandan mid-level health providers 1\xa0year after intensive clinical mentorship in TB and HIV management

IntroductionClinical mentorship is effective in improving knowledge and competence of health providers and may be a useful task sharing approach for improving antiretroviral therapy. However, the endurance of the effect of clinical mentorship is uncertain.MethodsThe midlevel health providers who participated in a cluster-randomized trial of one-on-one, on-site, clinical mentorship in tuberculosis and HIV for 8 h a week, every 6 weeks over 9 months were followed to determine if the gains in knowledge and competence that occurred after the intervention were sustained 6- and 12-months post-intervention. In December 2014 and June 2015, their knowledge and clinical competence were respectively assessed using vignettes and a clinical observation tool of patient care. Multilevel mixed effects regression analysis was used to compare the differences in mean scores for knowledge and clinical competence between times 0, 1, 2, and 3 by arm.ResultsAt the end of the intervention phase of the trial, the mean gain in knowledge scores and clinical competence scores in the intervention arm was 13.4% (95% confidence interval ([CI]: 7.2, 19.6), and 27.8% (95% CI: 21.1, 34.5) respectively, with no changes seen in the control arm. Following the end of the intervention; knowledge mean scores in the intervention arm did not significantly decrease at 6 months (0.6% [95% CI − 1.4, 2.6]) or 12 months (− 2.8% [95% CI: − 5.9, 0.3]) while scores in the control arm significantly increased at 6 months (6.6% [95% CI: 4.4, 8.9]) and 12 months (7.9% [95% CI: 5.4, 10.5]). Also, no significant decrease in clinical competence mean scores for intervention arm was seen at 6 month (2.8% [95% CI: − 1.8, 7.5] and 12 months (3.7% [95% CI: − 2.4, 9.8]) while in the control arm, a significant increase was seen at 6 months (5.8% [95% CI: 1.2, 10.3] and 12 months (11.5% [95% CI: 7.6, 15.5]).ConclusionsMentees sustained the competence and knowledge gained after the intervention for a period of one year. Although, there was an increase in knowledge in the control group over the follow-up period, MLP in the intervention arm experienced earlier and sustained gains. One-on-one clinical mentorship should be scaled-up as a task-sharing approach to improve clinical care.Trial Registration The study received ethics approvals from 3 institutions—the US Centers for Disease Control and Prevention Institutional Review Board (USA), the Institutional Review Board “JCRC’s HIV/AIDS Research Committee” IRB#1-IRB00001515 with Federal Wide Assurance number (FWA00009772) based in Kampala and the Uganda National Council of Science and Technology (Uganda) which approves all scientific protocols to be implemented in Uganda.

Plurihormonal pituitary macroadenoma:\xa0 a case report

BackgroundPlurihormonal pituitary adenomas are a unique type of pituitary adenomas that secrete two or more pituitary hormones normally associated with separate cell types that have different immunocytochemical and ultrastructural features. Although they represent 10–15% of all pituitary tumors, only a small fraction of plurihormonal pituitary adenomas clinically secrete multiple hormones. The most common hormone combinations secreted by plurihormonal pituitary adenomas are growth hormone, prolactin, and one or more glycoprotein hormones. The most common hormonal symptom is acromegaly (50%). The aim of this case report is to bring awareness about this rare type of pituitary adenomas and to describe the unique presentation of our patient, even though plurihormonal pituitary adenomas are known mostly as a clinically silent tumors.Case presentationHerein, we describe an unusual case of plurihormonal pituitary adenoma with triple-positive staining for adrenocorticotropic hormone, growth hormone, and prolactin. The patient is a 65-year-old Egyptian woman who presented with mass effect symptoms of the pituitary tumor, which primarily manifested as severe headache and visual field defects. She also presented with some cushingoid features, and further analysis confirmed Cushing’s disease; slightly high prolactin and normal growth hormone levels were observed. She underwent transsphenoidal surgery and has been in remission thus far. Only a few cases have been reported in the literature, but none has exhibited silent acromegaly or mass effect symptoms as the initial presentation.ConclusionThis case highlights an unusual plurihormonal pituitary adenoma case with a rare combination of secreted hormones; mass effect symptoms were dominant, as were uncommon visual field defects. Our case further proves that immunohistochemical analyses of all pituitary hormones are needed to ensure correct diagnosis and to alert clinicians to the need for more rigorous follow-up due to the higher morbidity of these patients. Our case report approval number Federal Wide Assurance NIH, USA is FWA00018774 IRB registration number with OHRP/NIH is IRB00010471.

Evaluation of Feasibility and User Acceptance of Lateral-Flow Self Testing for Viral Illness in a Correctional Center Rehabilitation Facility

Background: The role of rapid testing has proven vital in reducing infection incidence in communities through swift identification and isolation of infected individuals. The COVID-19 pandemic has been particularly catastrophic for residential carceral and rehabilitation facilities that are high-risk settings for transmission of contagious diseases. Centralized provider-based viral testing employing conventional diagnostic techniques is labor-intensive and time consuming. There is a marked unmet need for quick, inexpensive, and simple viral testing strategies. We hypothesized that rehabilitation residents could successfully test themselves employing inexpensive, disposable, antigen-based lateral-flow tests and would be willing to self-isolate and self-report to health authorities if positive.Methods: We evaluated self-testing among 50 rehabilitation residents ages 18 and older in Pomona, California, where participants self-administered an influenza lateral-flow diagnostic test (without specimen collection) with the goal of appropriately observing a control line and completed two brief written surveys, one before self-administering the lateral-flow test and one after, to determine the overall feasibility of viral self-testing and to characterize attitudes comparing self-testing and provider-based testing.Findings: A total of 50 rehabilitation residents were enrolled in this study and all 50 conducted a lateral-flow test and answered the provided surveys. Among the participants, 96% (48 of 50) achieved a positive-control line from their lateral-flow test. Most participants, 83% (34 of 41) indicated that they would prefer to perform their own rapid test instead of having a health care provider administer the test. Notably, 98% (49 of 50) indicated that they would self-isolate if the lateral-flow test returned a positive indicator suggesting the presence of a viral infection and 96% (48 of 50) would report positive results to their corresponding public health department.Interpretation: Residents in a residential rehabilitation center were widely able to successfully self-administer standard lateral-flow antigen-based rapid diagnostic kits. Self-testing was strongly preferred over tests administered by a healthcare provider. Reassuringly, almost every resident indicated that they would report any positive test result to the health department and self-isolate accordingly. Self-testing offers a promising adjunct to centralized testing, potentially better enabling swift and effective management of life-threatening infectious outbreaks among those living in high-risk congregate living settings.Funding: This study was funded by a grant awarded to Benjamin Sievers from the Pitzer College Racial Justice Initiative.Declaration of Interest: None to declare. Ethical Approval: This study was approved by both the Institutional Review Board at Pitzer College and HealthRIGHT 360’s IRB committee, project number: 2020-32R1. Pitzer College’s institutional review board’s review was carried out in accordance with the requirements of Part 46, “Protection of Human Subjects” of Title 45 of the Code of Federal Regulations and the “US Department of Health and Human Services (DHHS) Federal-Wide Assurance (FWA) for the Protection of Human Subjects for Domestic (US) Institutions,” Pitzer College Assurance #FWA00001138.

Brain Structural Associations with Depression in a Large Early Adolescent Sample (The ABCD Cohort)

Background: Depression is the leading cause of disability worldwide with >50% of cases emerging before the age of 25yrs. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain unknown. This has important implications for understanding aetiology and informing timings of potential intervention. Methods: Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample of early adolescents from the Adolescent Brain and Cognitive Development (ABCD) Study (N=9981, 9-11-year olds). Findings: We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen’s d = -0.018 to -0.041, β = -0.019 to -0.057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β=0.048 to 0.169). Interpretation: Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology. Funding: The study is funded by Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z) and MRC Mental Health Data Pathfinder Award (Reference MC_PC_17209). HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. AMM receives the Wellcome Trust Strategic Award (Reference 104036/Z/14/Z). Declaration of Interests: AMM has received research funding from The Sackler Trust, Eli Lilly and Janssen. No other conflicts of interest declared by other authors. Ethics Approval Statement: The study was approved by the National Institute of Mental Health Data Archive, United States (NIMH). Data was accessed through the NDA data base (http://nda.nih.gov/abcd, Federal-Wide Assurance: FWA00018101).

Food and Drug Administration and Institutional Review Board Approval of a Novel Prehospital Informed Consent Process for Emergency Research

Research on the management of acute pain in the prehospital setting is fraught with challenges. The prehospital setting is complex due to constrained time, resources, and training. Research activities must not interfere with the underlying clinical priorities of immediate patient stabilization and rapid transport to an appropriate hospital. The patient’s pain, fear, and anxiety immediately after a traumatic event may interfere with undertaking an adequate informed consent process. Pain management trials do not satisfy the criteria for application of the U.S. Food and Drug Administration (FDA) 21 CFR 50.24 exception from informed consent. While nonstandard informed consent processes exist, waiver or alteration of informed consent may be limited if Institutional Review Boards or the FDA consider these studies to involve more than minimal risk related to the setting of the study, even if the interventions themselves might involve no more than minimal risk in other settings. In addition, any study requiring an Investigational New Drug application requires fully documented standard informed consent. Emergency Medical Services agencies and fire departments become research institutions, and paramedics become study staff, but both the institutions and the staff often lack experience conducting human subjects research and are rarely formally affiliated with the academic institution overseeing the research. As such, additional administrative burdens must be overcome in interventional prehospital studies, including additional training in the study protocol, research operations, and human subjects protections. Institutions conducting federally funded studies commit to regulations covering human subjects protections in the form of a Federalwide Assurance (FWA); prehospital organizations participating in research must either obtain an FWA or have coverage extended to them from an academic partner. We describe how these challenges were addressed during Institutional Review Board review and approval of an FDA-regulated randomized placebo-controlled trial of intranasal ketamine (vs. placebo) in acutely injured patients receiving standard of care fentanyl for prehospital pain management (NCT02866071). To our knowledge, this trial is the first instance in the United States of paramedics screening, consenting, enrolling, and administering study medications to patients without direct, real-time support from a dedicated clinical research team.

Vitamin B12 and Risk of Diabetes: New Insight from Cross-Sectional and Longitudinal Analyses of the China Stroke Primary Prevention Trial (CSPPT)

Background: Previous studies in mostly Western populations, have yielded conflicting findings on the association of vitamin B12 with diabetes risk, in part, due to differences in study design and population characteristics. This study sought to examine the vitamin B12 – diabetes association in Chinese hypertensive adults by both cross-sectional and longitudinal analyses. Methods: This report included a total of 16699 participants from the China Stroke Primary Prevention Trial (CSPPT), with pertinent baseline and follow-up data. Diabetes mellitus (DM) was defined as either physician-diagnosed diabetes, the use of glucose-lowering drugs, or fasting blood glucose (FBG) ≥7·0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or fasting blood glucose (FBG) ≥7·0 mmol/L at the exit visit. Findings: At baseline, there were 1872 (11 ·2%) diabetic patients; less than 1·5% had clinical B12 deficiency (<148·0 pmol/L). Over a median follow-up period of 4·5 years, there were 1589 (10·7%) cases of new-onset diabetes. Cross-sectional analyses showed a positive association between baseline vitamin B12 levels and FBG levels (β=0·18, 95%CI [0·15, 0·21], p <0·001) and diabetes (OR=1·42, 95%CI [1·33, 1·51], p <0·001). However, longitudinal analyses showed no association between baseline vitamin B12 and new-onset diabetes (OR=1·01, 95%CI [0·94, 1·09] , p = 0·734) or changes in FBG levels (β= -0·02, 95%CI [-0·05, 0·01], p =0·154). Among a subset of the sample (N=4366) with both baseline and exit B12 measurements, we analyzed the relationship between the change in B12 levels and the change in FBG levels from the baseline to the exit visit, and found a positive association between an increase in B12 and an increase in FBG. Interpretation: In this large Chinese hypertensive population mostly sufficient with vitamin B12, parallel cross-sectional and longitudinal analyses provided new insight into the conflicting findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B12 and its longitudinal trajectory in order to better elucidate the role of vitamin B12 in the development of diabetes. Such findings, if further confirmed, would have important clinical and public health implications. Funding Statement: The China Stroke Primary Prevention Trial (CSPPT) was jointly supported by Shenzhen AUSA Pharmed (Shenzhen, China) and national, provincial and private funding, including from the Major State Basic Research Development Program of China (973 program; grant no. 2102 CB517703); the National Science and Technology Major Projects Specialized for “Innovation and Development of Major New Drugs” during the 12th Five-year Plan Period: the China Stroke Primary Prevention Trial (grant no. zx09101105), a Clinical Center grant (no. zx09401013); the Projects of the National Natural Science Foundation of China (grant no. 81473052, 81441091, and 81402735); the National Clinical Research Center for Kidney Disease, Nanfang Hospital, Nanfang Medical University, Guangzhou, China; the State Key Laboratory for Organ Failure Research, Nanfang Hospital; and research grants from the Department of Development and Reform, Shenzhen Municipal Government (grant no. SFG 20201744). Declaration of Interests: Dr. Xiping Xu reports grants from the National Key Research and Development Program [2016YFE0205400, 2018ZX09739010, 2018ZX09301034003], the Science and Technology Planning Project of Guangzhou, China [201707020010], the Science, Technology and Innovation Committee of Shenzhen [JSGG20170412155639040, GJHS20170314114526143, JSGG20180703155802047], the Economic, Trade and Information Commission of Shenzhen Municipality [20170505161556110, 20170505160926390]. Dr. Youbao Li reports grants from the President Foundation of Nanfang Hospital, Southern Medical University [2017C007, 2018Z009]. Dr. Xianhui Qin reports grants from the National Natural Science Foundation of China [81730019, 81973133], Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University [2017J009]. Dr. Huiyuan Guo reports grants from the 111 project from the Education Ministry of China [No. B18053]. Dr. Xiao Huang reports grants from the National Natural Science Foundation of China [81960074, 81500233], Jiangxi Outstanding Person Foundation [20192BCBL23024], Major projects of the Science and Technology Department, Jiangxi [20171BAB205008] No other disclosures were reported. Ethics Approval Statement: The parent study (the CSPPT) was approved by the Ethics Committee of the Institute of Biomedicine, Anhui Medical University, Hefei, China (Federal-wide Assurance Number: FW1263). All participants provided written, informed consent.

A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol

IntroductionPre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far more fetal losses. There is no definitive treatment other than delivery. A...

Allergen-specific immunotherapy modulates the balance of circulating Tfh and Tfr cells

Abstract Follicular helper T cells (Tfh cells) are a CD4 T cell subset essential for germinal center formation and B cell responses, although their role in allergy and allergen-specific immunotherapy (AIT) is unclear. Here, we show that AIT-treated patients have a higher ratio of regulatory Tfh cells (Tfr) to follicular T cells (Tfh) and hypothesize an IL-2 dependent mechanism.

Research Ethics Board of Health: a seven year review of the only ethics review board in Bhutan

Introduction: Research Ethics Board of Health (REBH), established in 2009, is the only ethics review board in Bhutan. The REBH was certified by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER), Forum for Ethical Review Committees in the Asian and Western Pacific Regions (FERCAP) in 2010 and recertified in 2013, and it received the Federal Wide Assurance (FWA) from the Office for Human Research Protections (OHRP), USA, in 2010 and in 2013. All researchers conducting health related research in Bhutan have to seek prior ethical clearance from REBH under the requirements of the National Health Policy 2011. Objective: The article aims to describe the performance of REBH, its standard and review procedure.&#x0D; Methods: A descriptive study of records and database of REBH from 2009 to 2015.&#x0D; Results: As of December 2015, the REBH has received 227 protocols with an average of 32 protocols per year. The median number of days for the initial review was 21 days (Min 0 days; Max 85 days). The median duration for approval of protocols from the date of receiving the application was 48 days. The average number of times the protocols were reviewed before issuing the approval letter was 2.&#x0D; Conclusions: There has been a progressive increase in the number of protocols submitted to REBH. This indicated an increasing research culture in Bhutan. It takes about one and half months to get an approval from REBH; therefore, researchers have to consider the time required for ethical clearance process while planning research projects.

Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol

IntroductionPre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than...

To Check, or Not to Check?

The box, that is. We are referring to the box next to the questions on the Federalwide Assurance (FWA)[1][1] form that asks if the organization providing (and the individual signing) the form agrees to apply the assurance to all human research, regardless of funding source. (There are actually two

Central institutional review board review for an academic trial network.

Translating discoveries into therapeutics is often delayed by lengthy start-up periods for multicenter clinical trials. One cause of delay can be multiple institutional review board (IRB) reviews of the same protocol. When developing the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT; hereafter, NN), the National Institute of Neurological Disorders and Stroke (NINDS) established a central IRB (CIRB) based at Massachusetts General Hospital, the academic medical center that received the NN clinical coordinating center grant. The 25 NN sites, located at U.S. academic institutions, agreed to required CIRB use for NN trials. To delineate roles and establish legal relationships between the NN sites and the CIRB, the CIRB executed reliance agreements with the sites and their affiliates that hold federalwide assurance for the protection of human subjects (FWA); this took, on average, 84 days. The first NN protocol reviewed by the CIRB achieved full approval to allow participant enrollment within 56 days and went from grant award to the first patient visit in less than four months. The authors describe anticipated challenges related to institutional oversight responsibilities versus regulatory CIRB review as well as unanticipated challenges related to working with complex organizations that include multiple FWA-holding affiliates. The authors anticipate that CIRB use will decrease NN trial start-up time and thus promote efficient trial implementation. They plan to collect data on timelines and costs associated with CIRB use. The NINDS plans to promote CIRB use in future initiatives.

Creating an infrastructure for comparative effectiveness research in emergency medical services.

Emergency medical services (EMS) providers deliver the initial care for millions of people in the United States each year. The Institute of Medicine noted a deficit in research necessary to improve prehospital care, created by the existence of data silos, absence of long-term outcomes, and limited stakeholder engagement in research. This article describes a regional effort to create a high-performing infrastructure in southwestern Pennsylvania addressing these fundamental barriers. Regional EMS records from 33 agencies in January 2011 were linked to hospital-based electronic health records (EHRs) in a single nine-hospital system, with manual review of matches for accuracy. The use of community stakeholder engagement was included to guide scientific inquiry, as well as 2-year follow up for patient-centered outcomes. Local EMS medicine stakeholders emphasized the limits of single-agency EMS research and suggested that studies focus on improving cross-cutting, long-term outcomes. Guided by this input, more than 95% of EMS records (2,675 of 2,800) were linked to hospital-based EHRs. More than 80% of records were linked to 2-year mortality, with more deaths among EMS patients with prehospital hypotension (30.5%) or respiratory distress (19.5%) than chest pain (5.4%) or nonspecific complaints (9.4%). A prehospital comparative effectiveness research infrastructure composed of patient-level EMS data, EHRs at multiple hospitals, long-term outcomes, and community stakeholder perspectives is feasible and may be scalable to larger regions and networks. The lessons learned and barriers identified offer a roadmap to answering community and policy-relevant research questions in prehospital care.

Perceptions of Research Ethics Practices: IntegratedEthics™ Staff Survey Data from the VA Health Care System

Background: There are limited empirical data on factors that influence ethical practices in research settings. To broaden our understanding of ethical practices in research in the U.S. Department of Veterans Affairs (VA) and to understand researcher- and organizational-level factors associated with positive perceptions of practices, we assessed researchers’ perceptions of practices in research ethics. Methods: We analyzed data from 10,661 respondents to the 2010 IntegratedEthics™ Staff Survey (IESS) at VA who self-identified as research staff and who worked at facilities with Federalwide Assurance for the Protection of Human Subjects. We used descriptive statistics to evaluate these respondents’ perceptions of ethical practices in research and multivariate logistic regression analyses to evaluate associations between researcher- and organization-level characteristics and positive perceptions of ethical practices. Results: The results suggest that the majority of researcher respondents have positive perceptions of ethical practices in research at VA; for example, 85% almost never feel pressured to compromise ethical standards. Physicians and staff with managerial responsibilities tend to have more favorable impressions of ethical practices in research. The results also indicate areas for improvement. For example, 14–16% of respondents report that there are research staff members who regularly engage in behaviors that may inappropriately affect their research. Furthermore, results suggest that approximately 14% of VA research staff are not completely comfortable raising ethical concerns or reporting ethical violations related to research. Conclusions: Results from this study identify areas for quality improvement that can serve as a complement to the required education and training in research ethics, policy guidance, and rigorous institutional review board oversight and monitoring.

Inhibition of nuclear factor kappa B activation in early stage chronic lymphocytic leukemia by omega 3 fatty acids

Targeting the NFκB pathway has been proposed for therapy of various malignancies including chronic lymphocytic leukemia (CLL). Omega 3 (n‐3) fatty acids consumption reduced NFκB activation in animals. Our pilot study tested the hypothesis that consumption of an n‐3 supplement would suppress NFκB activation in lymphocytes of patients with early stage CLL. The Marshall University Institutional Review Board reviewed and approved the protocol for this study under a Federal Wide Assurance (FWA #00002704) with the Office of Human Research Protections. Following informed consent, participants consumed an n‐3 supplement initially containing 2.4 g n‐3/day gradually increasing to 7.2 g n‐3/day. Blood cell counts and assay for NFκB activation of lymphocytes were performed before n‐3 initiation and monthly afterwards. Lymphocytes from 5 healthy individuals established normal NFκB activation. After n‐3 consumption: (1) n‐3 was increased in both red and white blood cells of all participants; (2) NFκB activation was suppressed in lymphocytes of all patients following consumption of n‐3; (3) expression of 32 genes in lymphocytes was significantly decreased by n‐3 in patients with higher initial NFκB activation. There was no disease progression. Omega 3 consumption suppressed NFκB activation in patients’ lymphocytes and would be expected to slow progression of early stage CLL.Grant Funding Source : Institutional Funds