Single Institutional Review Board Research Articles

Linking genetic counseling communication skills to patient outcomes and experiences using a community-engagement and provider-engagement approach: research protocol for the GC-PRO mixed methods sequential explanatory study

IntroductionIn over 50 years since the genetic counseling (GC) profession began, a systematic study of GC communication skills and patient-reported outcomes in actual sessions across multiple clinical specialties has never...

Rapid Review of Therapy Protocols for Public Health Emergencies.

How research during a public health emergency is conducted is recognized as essential to the public health response to that emergency. Such research needs to undergo substantive and meaningful ethical review in a timely manner. Rapid ethical review may be accomplished through a number of mechanisms, including use of local rapid-response institutional review boards (IRBs). We describe use of such a model in the setting of the 2014 Ebola virus disease epidemic and the Rapid-Response IRB's subsequent transition to a multisite single IRB model during the current Covid-19 pandemic. The rapid-response review model is characterized by a small IRB with extensive use of alternate members with specific expertise and by close collaboration with the investigator in an iterative process.

IRB challenges in multisite studies: A case report and commentary from the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA)

A shift from single to multi-site health studies enabled a range of research benefits including faster recruitment of larger and more diverse samples; increased statistical power, greater rigour, generalisability, and external reliability; and increased likelihood of impacting policy and clinical practice. However, ethical review of multi-site studies by Institutional Review Boards (IRBs) raises specific challenges compared with single site studies, with requirements to apply to multiple local IRBs increasing the burden on research, possibly endangering the integrity of the research process or inhibiting development of multi-site studies. The option of a single centralised IRB may offer a clearer, more consistent and efficient review process. This study presents a case report and commentary from 15 years engaging with IRBs in multiple sites in Ireland by the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA). It examines the ethics review process for IDS-TILDA through its first four waves. While the majority of 48 IRBs granted ethical approval within 13 weeks, six IRBs took 21–47 weeks to approve, leading to delays in data collection of up to 11 months. Despite additional review time, no changes were required to the study protocol. Therefore, a critical impact of the process was the delay in starting data collection within a small number of organisations, and reduced involvement in the study for one organisation. The ethical review process with multiple IRBs increased the degree of complexity of the process, with added bureaucracy and far greater communication required across 48 IRBs, substantially adding to the resource commitment for the review process. The relatively quick approval from the majority of IRBs was partially a result of the longitudinal study building relationships with organisations throughout multiple waves. That other health studies may not accrue this benefit supports calls for a single IRB system for multi-site health studies.

Institutional Review Boards' Assessment of Local Context: A Mixed Methods Study.

The nature of the review of local context by institutional review boards (IRBs) is vague. Requirements for single IRB review of multicenter trials create a need to better understand interpretation and implementation of local-context review and how to best implement such reviews centrally. We sought a pragmatic understanding of IRB local-context review by exploring stakeholders' attitudes and perceptions. Semistructured interviews with 26 IRB members and staff members, institutional officials, and investigators were integrated with 80 surveys of similar stakeholders and analyzed with qualitative theme-based text analysis and descriptive statistical analysis. Stakeholders described what they considered to be local context, the value of local-context review, and key processes used to implement review of local context in general and for emergency research conducted with an exception from informed consent. Concerns and potential advantages of centralized review of local context were expressed. Variability in perspectives suggests that local-context review is not a discrete process, which presents opportunities for defining pathways for single IRB review.

Correlation of a Shape Factor and Degree of Saturation of Sickle Cell Red Blood Cells to Vaso-Occulsive Episodes in Sickle Cell Disease

Introduction: Patients with sickle cell disease (SCD) can experience intermittent episodes of vaso-occlusive episodes (VOE) leading to acute pain. Additionally, patients can experience changes in pain over their lifetime such that they can have nociceptive, neuropathic, and opiate induced hyperalgesia, all contributing to the development of chronic pain. Developing a test that can delineate VOE from steady state and also differentiate it from chronic pain continues to pose an elusive problem in SCD. It not only impacts endpoints in clinical studies, it can pose a significant challenge for the patient in terms of timely clinical diagnosis and treatment of pain. Cell Tracking Velocimetry, (CTV), tracks cells on a single cell basis in a very high magnetic energy gradient. This instrument allows us to use the cell's magnetic, v x, and settling velocities, v y, to be transformed into estimates of the oxygen saturation and deformity of the red blood cells, (RBCs). Based on statistical correlations of these measurements to patient status, VOE can be independently identified. Results: Patients were consented in a single center Institutional Review Board, (IRB) approved study. Clinical data including genotype of the patients were collected in 5 clinical states, including healthy donors (0). Steady State no chronic pain ≤ 3 crisis/year (1), Steady state with chronic pain 3 ≤ crisis/year (2), Steady state with no chronic pain > 3 crisis/year (3), Steady state with chronic pain > 3 crisis/year (4), and during acute pain crisis (5). Steady state was defined as no VOC requiring health care intervention for > 4 weeks and no VOE crisis on day of clinic. The patients' samples (n=49; distributed between each state) and clinical state was deidentified for initial laboratory evaluation. The CTV instruments returns two types of data: magnetic velocity and settling velocity. It was demonstrated that the range of the magnetic velocity of the top and bottom 1 percent of the measured velocities (i.e the fastest and slowest moving RBCs) correlates to a patient in VOE, when compared to normal, healthy RBCs and SCD patients in steady state (p > 0.0168). Further, the ratio of the magnetic to settling velocity of the top and bottom 1 percent of these ratios correlates to a patient in VOE, when compared to normal RBCs and SCD patients in steady state (p > 0.0003). These correlations are significant for both RBCs under deoxygenated and ambient air conditions. Discussion: We suggest that these correlations have physical significance since further mathematical modeling of these experimental velocities can be reduced to two factors: a shape factor, fe-x/fe-y, (velocities are proportional to the effective diameter of the cells) and the oxygen-hemoglobin saturation of the RBCs. This ratio of this shape factor can be considered as a measure of how “deformed” the RBC is, while the degree of oxygen-hemoglobin saturation is consistent with the traditional oxygen saturation measurement. Conclusion: While further studies on a larger patient population are warranted, these data suggests that the CTV instrument could potentially provide a biological point of care test to help diagnose VOE. Furthermore, this seems to delineate chronic pain and steady state from acute VOE. A longitudinal study in a consistent patient population would help further delineate and refine this for the specific patient but may offer significant insight over time to correlate the clinical phenotype with a laboratory correlation.

Stratification of risk for emergent intracranial abnormalities in children with headaches: a Pediatric Emergency Care Applied Research Network (PECARN) study protocol

IntroductionHeadache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%–1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than...

Achieving diagnostic excellence through prevention and teamwork (ADEPT)study protocol: A multicenter, prospective quality and safety program to improve diagnostic processes in medical inpatients.

Few hospitals have built surveillance for diagnostic errors into usual care or used comparative quantitative and qualitative data to understand their diagnostic processes and implement interventions designed to reduce these errors. To build surveillance for diagnostic errors into usual care, benchmark diagnostic performance across sites, pilot test interventions, and evaluate the program's impact on diagnostic error rates. Achieving diagnostic excellence through prevention and teamwork (ADEPT)is a multicenter, real-world quality and safety program utilizing interrupted time-series techniques to evaluate outcomes. Study subjects will be a randomly sampled population of medical patients hospitalized at 16 US hospitals who died, were transferred to intensive care, or had a rapid response during the hospitalization. Surveillance for diagnostic errors will occur on 10 events per month per site using a previously established two-person adjudication process. Concurrent reviews of patients who had a qualifying event in the previous week will allow for surveys of clinicians to better understand contributors to diagnostic error, or conversely, examples of diagnostic excellence, whichcannot be gleaned from medical record review alone. With guidance from national experts in quality and safety, sites will report and benchmark diagnostic error rates, share lessons regarding underlying causes, and design, implement, and pilot test interventions using both Safety I and Safety II approaches aimed at patients, providers, and health systems. Safety II approaches will focus on cases where diagnostic error did not occur, applying theories of how people and systems are able to succeed under varying conditions. The primary outcome will be the number of diagnostic errors per patient, using segmented multivariable regression to evaluate change in y-intercept and change in slope after initiation of the program. The study has been approved by the University of California, San Francisco Institutional Review Board (IRB), which is serving as the single IRB. Intervention toolkits and study findings will be disseminated through partners including Vizient, The Joint Commission, and Press-Ganey, and through national meetings, scientific journals, and publications aimed at the general public.

Stakeholder Reflections on Implementing the National Institutes of Health's Policy on Single Institutional Review Boards.

The National Institutes of Health (NIH) requires use of a single institutional review board (sIRB) for multisite, nonexempt, NIH-funded research with human participants. The Clinical Trials Transformation Initiative (CTTI) conducted in-depth interviews with 34 stakeholders at two universities and in research administration leadership positions at multiple institutions about their experiences implementing the sIRB model, focusing on the NIH policy's goals soon after the policy was enacted. While some stakeholders suggested that using an sIRB has streamlined and reduced inefficiencies associated with the local IRB model, more stakeholders indicated that the sIRB model has not simplified the ethics review process and instead created new inefficiencies due to unclear roles and responsibilities for staff and institutions; a lack of systems and processes for implementing the sIRB model, including communication systems; and increased workloads. CTTI used these findings to propose a new framework for evaluating the NIH sIRB policy.

Factors Associated with IRB Review Time in a Non-Federally Funded Study Using an sIRB of Record.

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

Creation of a Single Institutional Review Board for Collaborative Research in Nephrology: The APOLLO Experience.

Moore, J. Brian1,*,a; Smith, S. Carrie2,3,*; Russell, Laurie P.4; Serdoz, Emily S.3; Dilts, Natalie A.3; Alexander, Amir A.4; Reboussin, David M.4; Bagwell, Benjamin M.5; Spainhour, Mitzie H.5; Reeves-Daniel, Amber M.5; Wesley-Farrington, Deborah J.1; Ma, Lijun5; Freedman, Barry I.5,a; for the APOLLO Consortium Author Information

Research and Innovation in Organ Donation: Recommendations From an International Consensus Forum.

We identified topics impacting donation research through consensus using nominal group technique. Members performed narrative reviews and synthesized current knowledge on each topic, which included academic articles, policy documents, and gray literature. Using the nominal group technique, committee members discussed significant findings, which provided evidence for our recommendations. The Forum's scientific committee then vetted recommendations. We developed 16 recommendations in 3 key areas to provide stakeholders guidance in developing a robust deceased donor research framework. These include PFD and public involvement in research; donor, surrogate, and recipient consent within a research ethics framework; and data management. We highlight the importance of PFD and public partner involvement in research, we define the minimum ethical requirements for the protection of donors and recipients of both target and nontarget organ recipients, and we recommend the creation of a centrally administered donor research oversight committee, a single specialist institutional review board, and a research oversight body to facilitate coordination and ethical oversight of organ donor intervention research. Our recommendations provide a roadmap for developing and implementing an ethical deceased donation research framework that continually builds public trust. Although these recommendations can be applied to jurisdictions developing or reforming their organ and tissue donation and transplantation system, stakeholders are encouraged to collaborate and respond to their specific jurisdictional needs related to organ and tissue shortages.

Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial

IntroductionMillions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient...

Effectiveness of a targeted brief intervention for recent suicide attempt survivors: a randomised controlled trial protocol

IntroductionEffective, brief, low-cost interventions for suicide attempt survivors are essential to saving lives and achieving the goals of the National Strategy for Suicide Prevention and Zero Suicide. This study aims...

Impact of testosterone use on the vaginal microbiota of transgender men, including susceptibility to bacterial vaginosis: study protocol for a prospective, observational study

IntroductionThe effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to...

Comparative effectiveness and complications of intravenous ceftriaxone compared with oral doxycycline in Lyme meningitis in children: a multicentre prospective cohort study

IntroductionLyme disease is the most common vectorborne disease in the Northern hemisphere with more than 400 000 new cases in the USA annually. Lyme meningitis is an uncommon but potentially...

Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial

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

DirEct versus VIdeo LaryngosCopE (DEVICE): protocol and statistical analysis plan for a randomised clinical trial in critically ill adults undergoing emergency tracheal intubation

IntroductionAmong critically ill patients undergoing orotracheal intubation in the emergency department (ED) or intensive care unit (ICU), failure to visualise the vocal cords and intubate the trachea on the first...

Implementation of single IRB review for multisite human subjects research: Persistent challenges and possible solutions.

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

COVID-19 Vaccination Outcomes in Children, Adolescents, and Young Adults with Acute Lymphoblastic Leukemia

Background:While several studies have shown that less than half of adults on active therapy for chronic hematological malignancies develop an immune response to COVID-19 vaccination, little is known about the efficacy of COVID-19 vaccines in the midst of active therapy for acute lymphoblastic leukemia (ALL). Furthermore, COVID-19 vaccine outcomes in pediatric leukemia remain uncharacterized. Given the differences in the intensity of chemotherapy regimens between pediatric ALL and adult chronic hematological malignancies as well as age related immune differences, there is a need to specifically define vaccination outcomes in pediatric ALL. This study aims to define the safety and efficacy of COVID-19 vaccination in children and adolescents and young adults with ALL, the most common pediatric leukemia. Methods: We conducted a prospective single center Institutional Review Board approved study. Eligible patients were ages 5-25 years with a diagnosis of ALL or receiving ALL-like therapy who had received COVID-19 vaccination. Pediatric oncology patients at our center undergo universal surveillance for COVID-19 via nasopharyngeal PCR regardless of symptom status, prior to any sedation or hospitalization. Labs were drawn at 3,6-, and 12-months post-vaccination for anti-COVID-19 spike (S) and nucleocapsid (N) IgG ELISA and anti S neutralizing antibody assays, in vitro COVID-19 peptide stimulation T-cell response studies, and T-cell receptor (TCR) sequencing for COVID specific TCR. These tests were validated in healthy COVID-19 infection convalescent and healthy post-vaccination cohorts. Results: Between April 2021 and April 2022, the study enrolled 21 patients (median age 12.5 years). Diagnoses included high risk B-ALL (n=13), mixed-phenotype acute leukemia (MPAL) (n=2), and standard risk B-ALL (n=6). Three had relapsed ALL. All were in complete remission and receiving chemotherapy at the time of vaccination (17 receiving maintenance therapy and 4 in an intensive chemotherapy phase). Twenty received the BNT162b2 mRNA vaccine (10mcg dose n=11 and 30mcg dose, n=9); one received the Ad26.COV2.S vaccine. One patient received one dose (excluded from efficacy analysis), 17 received 2 doses, and 2 received three doses (i.e. a booster dose) of BNT162b2. Vaccinations were well tolerated with no patient experiencing anaphylaxis or an allergic reaction, including 10 patients with PEG-asparaginase allergy (BNT162b2 contains PEG). Three patients presented to the emergency department with fever; one of those was hospitalized for hypotension. Thirteen of 20 patients (65%) were positive for spike (S) anti-COVID-10 IgG following two doses of BNT162b2 (n=12) or one dose of Ad26.COV2.S (n=1). Eleven of these 13 were negative for N IgG, an antibody profile (S IgG+, N IgG-) consistent with an immune response to vaccination rather than a prior undiagnosed COVID-19 infection. All three patients with ≥ 6 months post-vaccination data continue to be positive for S IgG. Notably, 6 of 12 lymphopenic patients (absolute lymphocyte count <500 at the time of vaccination) and 3 of 4 patients in an intense phase of therapy during vaccination showed an immune response. Six of 8 patients with PEG-allergy had an immune response. All patients with positive S IgG showed presence of neutralizing anti-S antibodies. There was no difference in immune response based on vaccine dose. Five of 20 patients (3 of 13 patients who were S IgG+ following vaccination) developed COVID-19 infection following vaccination; one of these occurred after the third dose. Hospitalization was needed in one of five cases of COVID-19. All infections occurred during the omicron wave and included 3 sequencing confirmed omicron infections (variant testing not done for 2). Conclusions: In our study, two doses of COVID-19 vaccination induced a neutralizing antibody response in over half of the children and AYA actively receiving ALL chemotherapy including those who were receiving intensive chemotherapy or had PEG allergy. Adverse events were uncommon. Omicron infections occurred in our study, a finding consistent with the occurrence of breakthrough omicron variant infections in immunocompetent vaccinated individuals. T-cell response studies for our cohort are ongoing. Additional long-term follow-up and larger studies are needed to investigate durability of immune response and optimal vaccine frequency especially in the setting of omicron variants. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Economic analysis of a single institutional review board data exchange standard in multisite clinical studies

BackgroundSingle Institutional Review Boards (sIRB) are not achieving the benefits envisioned by the National Institutes of Health. The recently published Health Level Seven (HL7®) Fast Healthcare Interoperability Resources (FHIR®) data exchange standard seeks to improve sIRB operational efficiency. Methods and resultsWe conducted a study to determine whether the use of this standard would be economically attractive for sIRB workflows collectively and for Reviewing and Relying institutions. We examined four sIRB-associated workflows at a single institution: (1) Initial Study Protocol Application, (2) Site Addition for an Approved sIRB study, (3) Continuing Review, and (4) Medical and Non-Medical Event Reporting. Task-level information identified personnel roles and their associated hour requirements for completion. Tasks that would be eliminated by the data exchange standard were identified. Personnel costs were estimated using annual salaries by role. No tasks would be eliminated in the Initial Study Protocol Application or Medical and Non-Medical Event Reporting workflows through use of the proposed data exchange standard. Site Addition workflow hours would be reduced by 2.50 h per site (from 15.50 to 13.00 h) and Continuing Review hours would be reduced by 9.00 h per site per study year (from 36.50 to 27.50 h). Associated costs savings were $251 for the Site Addition workflow (from $1609 to $1358) and $1033 for the Continuing Review workflow (from $4110 to $3076). ConclusionUse of the proposed HL7 FHIR® data exchange standard would be economically attractive for sIRB workflows collectively and for each entity participating in the new workflows.