Individual Institutional Review Board Research Articles

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.

Personalising Outcomes after Child Cardiac Arrest (POCCA): design and recruitment challenges of a multicentre, observational study

IntroductionBlood and imaging biomarkers show promise in prognosticating outcomes after paediatric cardiac arrest in pilot studies. We describe the methods and early recruitment challenges and solutions for an ongoing multicentre...

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF).

Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P=.01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P=.005). SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Using big data analytics to improve HIV medical care utilisation in South Carolina: A study protocol

Introduction Linkage and retention in HIV medical care remains problematic in the USA. Extensive health utilisation data collection through electronic health records (EHR) and claims data represent new opportunities for...

Immune Tolerance Induction for FIX Inhibitors Using Combined B and T Cell Immune Modulation Therapy in Severe Hemophilia B

IntroductionDevelopment of an inhibitor to Factor IX is a potentially life-threatening complication that occurs in 2-4% of severe hemophilia B patients. Attempt to eradicate these neutralizing alloantibodies with immune tolerance induction (ITI) regimens using prolonged repeated exposure to FIX fails to induce tolerance in ~70% of cases, and is limited by severe complications including FIX hypersensitivity and nephrotic syndrome. Cases of FIX ITI with immunosuppressive drugs have been reported infrequently. In light of increased understanding of the role of active T lymphocyte regulation of clotting factor-directed B lymphocyte-mediated humoral immunity, an approach combining immune modulating agents and frequent FIX infusions was reported by Beutel, et al (Haemostaseologie, 2009; 2014). We report a multi-institutional retrospective experience with combination immune modulation therapy (CIT), including B cell suppression with anti-CD20 monoclonal antibody Rituximab and T cell modulation using mycophenylate mofetil (MMF) with FIX ITI in 11 males with severe congenital hemophilia B.MethodsThe originally published regimen of Beutel, et al involves a 50 day course including FIX 100 IU/kg twice daily, rituximab 375 mg/m2 x 4 doses, mycophenolate (MMF) 300 mg/m2/dose daily, dexamethasone 6 mg/m2/dose pulses and IVIG 1 g/kg x 6 doses. Following individual Institutional Review Board approval, data on 11 patients was contributed by the INPH investigators and via outreach internationally and collected retrospectively using a uniform data collection form. Cases were included in the CIT series if the combination of FIX, rituximab and MMF was used. Approaches varied in the concomitant use of IVIG and pulse corticosteroids (dexamethasone or prednisone).ResultsCIT was the first immune tolerance therapy for 9/11 patients. Patients were 14-222 months of age at time of CIT, with a median time from inhibitor diagnosis to CIT 20 (range 0-207) months. Median historical peak inhibitor titer prior to initiation of CIT was 3.2 (range 1-42) BU/ml. Inhibitor titers at the initiation of CIT ranged from undetectable to 7 BU/ml. Eighty-onepercent of patients had a history of FIX hypersensitivity reaction. Prior to initiation of therapy, 27% of the patients underwent FIX desensitization during the initial course.The patients received FIX BID (9/11 patients) or QD (2/11 patients), 4 doses of rituximab 375 mg/m2, MMF for a minimum of 49 days (varying duration from 49-1247 days). IVIG was infused in 10/11 patients, with most receiving 3-7 doses during each course of CIT. 6/11 patients received between 2-10 courses of pulse corticosteroids during a CIT course.Each course of CIT achieved disappearance of the titer of FIX inhibitor at a median time of 1 month (range 1-41 months) Hypersensitivity reactions did not limit the courses of CIT, but did recur with inhibitor recurrence in 1 patient. Recurrence occurred in 6/11 patients at a median time of 11 months from time of CIT, in some cases soon after documented B cell recovery with a median inhibitor titer of 1.8 (range 0.7-7) BU/ml. In cases of recurrence, a negative inhibitor titer was achieved again in 1 patient by increasing FIX dose and in 4 patients who received additional courses of CIT. Repeat recurrence was seen in these patients following repeat CIT, although at low titer with a median of 1 BU/ml (range 1-4), allowing ongoing management with FIX in 3 of the 4. Overall, patients have had a median follow-up of 61 months following CIT, 9/11 patients are currently managed with factor IX for prophylaxis and bleeding, while 2/11 use bypassing agents.The most common complication was hospitalization for central venous catheter-related bacterial infection that occurred from < 1 to > 12 months after the use of rituximab in 3/11 patients. Nephrotic syndrome occurred in 3/11 patients. In each case, nephrotic syndrome responded to corticosteroids or re-initiation of CIT and FIX could be resumed.ConclusionsFIX ITI with CIT targeting both B and T cells in hemophilia B is an effective means of achieving a negative inhibitor titer with tolerable safety in this series, allowing return to use of FIX for hemostasis and prophylaxis in most patients. Although recurrence is common and longer follow up is needed, when compared to the experience with using FIX alone, outcomes appear to be improved using CIT with FIX ITI as an initial approach. DisclosuresAbajas:Bayer: Honoraria; CSL Limited: Honoraria. Allen:Shire: Employment, Equity Ownership. Oldenburg:Pfizer: Honoraria, Research Funding; Biogen: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Grifols: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Shire: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Swedish Orphan Biovitrum: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding.

Ethical standards for medical research in the Israeli military - review of the changes in the last decade.

BackgroundThe Israel Defense Forces Medical Corps (IDF MC) institutional review board (IRB) is one of approximately 50 IRBs active in Israel. In addition to routine IRB considerations it must also address in its deliberations specific safeguards in place in the IDF to protect research volunteers in the military environment. In this report, we present the characteristics of the IDF IRB, including the unique circumstances that led to a 2008 change in the pre-IRB advisory and preparatory process (APP). We also present quantitative data on the IRB’s throughput and outcomes, in order to provide a benchmark for other IRBs.MethodsWe reviewed all relevant IDF regulations, both historical and current, pertaining to the structure, activity and oversight of the IRB and of medical research conducted in the IDF. Additionally, we analyzed the ethical review process for all research proposals submitted to the IDF APP between January 1, 2013 and December 31, 2015.ResultsIn 2008 the IDF implemented several major changes which have had a substantial impact on the ethical regulation of military medical research. The period following these changes has seen a rise in the number of research proposals submitted to the IDF IRB annually. During the years 2013–2015, 377 research proposals entered the APP, of which 329 were deemed appropriate for IRB deliberation. Eight study protocols were granted waivers, 19 were rejected, and the remaining 302 were authorized. Overall, 345 of the 377 research proposals submitted (92 %) were ultimately cleared for execution; 310 of 329 proposals (94 %) deliberated by the IRB were authorized. The IRB required protocol revisions for 47 % of the research proposals, one-third of which were revisions directly associated with military-specific ethical precautions.ConclusionsGuided by the principles of protecting personal autonomy in the complex military setting, the IDF has implemented several unique measures aimed at maintaining the highest ethical standards in medical research. By sharing research approval process data similar to those presented here, medical institutions can help build and support a peer-based benchmarking process through which individual IRBs can appraise their own processes and approval rates.

MP81-16 PERIOPERATIVE AND EARLY ONCOLOGICAL OUTCOMES FOLLOWING ROBOT ASSISTED RETROPERITONEAL LYMPH NODE DISSECTION FOR TESTICULAR CANCER: A MULTI-INSTITUTIONAL STUDY

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II1 Apr 2016MP81-16 PERIOPERATIVE AND EARLY ONCOLOGICAL OUTCOMES FOLLOWING ROBOT ASSISTED RETROPERITONEAL LYMPH NODE DISSECTION FOR TESTICULAR CANCER: A MULTI-INSTITUTIONAL STUDY Haidar Abdul-Muhsin, Michael Marshall, Sean Stroup, James L'esperance, Michael Woods, James Porter, and Erik Castle Haidar Abdul-MuhsinHaidar Abdul-Muhsin More articles by this author , Michael MarshallMichael Marshall More articles by this author , Sean StroupSean Stroup More articles by this author , James L'esperanceJames L'esperance More articles by this author , Michael WoodsMichael Woods More articles by this author , James PorterJames Porter More articles by this author , and Erik CastleErik Castle More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2069AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate the perioperative outcomes and postoperative complication rates for robot assisted retroperitoneal lymph node dissection (RA-RPLND) in a large multi-Institutional cohort. METHODS After individual institutional review board approval in four participating institutions, the data of all testicular cancer patients treated with RA-RPLND at these tertiary institutions were collected and retrospectively analyzed. The procedures were performed by a single robotic surgeon at each participating institution. All demographic, Intraoperative variables, post-operative pathological outcomes and complications were reported. Additionally, Recurrence rates were reported at then end of follow up. RESULTS There were 103 patients who underwent RA-RPLND. The mean patients age was 29.6 years (SD 9.7), mean BMI was 26.4 Kg/m2 (SD 5.1). Bilateral Full template dissection was performed in 65 (63.1%) patients compared to 36 patients (35%) who had modified templates of dissection. Nerve sparing was attempted in 68 (66%) patients. There were 70 (68%) patients who underwent primary RA-RPLND compared to 33 (32%) patients who received previous chemotherapy. Mean operative time was 339 min (SD 108). Estimated blood loss was 244.1 ml (SD 486). Length of postoperative hospital stay was 2.1 days (SD 1.5). There were six conversions (5.8%) to open RPLND. Postoperatively, there were 28 total complications (Grade I=22, II=5, IIIB=1). From oncological point of view, mean lymph node (LN) yield was 24.1 LNs (SD 10.8) with positive LN identified in 35 patients (33.9%). Among the primary RARPLND, adjuvant chemotherapy was given to 21.4% (3/14) of pIIA, 50% (3/6) of pIIB and 50% of pIIC patients. There were five lung recurrences (4.8%) identified at a mean follow up of 26.9 months (SD 22.4). No in field recurrences were identified CONCLUSIONS To our knowledge this study represents the largest study of RA-RPLND outcomes in testicular cancer patients. It demonstrates that this procedure is safe and reproducible. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1059 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Haidar Abdul-Muhsin More articles by this author Michael Marshall More articles by this author Sean Stroup More articles by this author James L'esperance More articles by this author Michael Woods More articles by this author James Porter More articles by this author Erik Castle More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Review of multicenter studies by multiple institutional review boards: characteristics and outcomes for perinatal studies implemented by a multicenter network

The objective of the study was to describe characteristics and outcomes of a review of multisite perinatal studies by individual institutional review boards (IRBs) and identify barriers and opportunities for streamlined IRB review. We compared the review of 5 collaborative protocols by individual IRBs at National Perinatal Research Consortium centers from 2007 through 2012. Three randomized trials, 1 observational study, and 1 follow-up study of a trial were selected. IRB logs and communications were reviewed and abstracted by trained team members. Seven or 8 IRBs reviewed each protocol. Monthly IRB meeting frequency varied from 1 to 6. Full board review was required by all IRBs for the primary trials but not by all for the observational protocols. The overall duration from submission to approval (P = .024) and number of stipulations (P = .007) differed across protocols but not across IRBs. However, times from submission-to-IRB review (P = .011) and IRB review-to-initial letter (P < .007) differed across sites. Both overall submission-to-approval and initial review-to-approval times increased with the increasing number of IRB review stipulations (both values P < .001). Significant delays (>60 days) were few and not consistent across IRBs or protocols. Most stipulations were stylistic or editorial modifications rather than regulatory requests. All protocols were approved without changes, and no more than 1 IRB meeting was needed at each site. Findings confirm unnecessary duplication and variability and some similarities in IRB review processes and outcomes for multisite perinatal studies. This may help guide initiatives to streamline IRB review and reduce research delays and burdens.

The relationship between TSH and systemic inflammation in extremely preterm newborns.

Elevated thyrotropin (TSH) levels in critically ill extremely premature infants have been attributed to transient hypothyroidism of prematurity or non-thyroidal illness syndrome. We evaluated the hypothesis that relatively high TSH levels in the first 2 postnatal weeks follow recovery from systemic inflammation, similar to non-thyroidal illness syndrome. The study was conducted in 14 Neonatal Intensive Care Units and approved by each individual Institutional Review Board. We measured the concentrations of TSH and 25 inflammation-related proteins in blood spots obtained on postnatal days 1, 7, and 14. We then evaluated the temporal relationships between hyperthyrotropinemia (HTT), defined as a TSH concentration in the highest quartile for gestational age and postnatal day, and elevated levels of inflammation-related proteins. 880 newborns less than 28 weeks of gestation were included. Elevated concentrations of inflammation-related proteins during the first or second week did not precede day-14 HTT. Systemic inflammation on day 7 was associated with day-14 HTT only if inflammation persisted through the end of the 2 week period. HTT frequently accompanied elevated concentrations of inflammation-related proteins on the same day. The hypothesis that HTT follows recovery from severe illness, defined as preceding systemic inflammation, is weakly supported by our study. Our findings more prominently support the hypothesis that TSH conveys information about concomitant inflammation in the extremely premature newborn.

Recommendations for Implementation of Community Consultation and Public Disclosure Under the Food and Drug Administration’s “Exception From Informed Consent Requirements for Emergency Research”

In addition to the usual requirement of appropriate study design and institutional review board (IRB) approval, research studies performed under the Food and Drug Administration (FDA) and Department of Health and Human Services regulations regarding “Informed Consent and Waiver of Informed Consent Requirements in Certain Emergency Research” (21 CFR §50.24)1 require community consultation and public disclosure. This special report discusses the general issues related to consent in emergency circumstances and provides a template to help IRBs implement community consultation and public disclosure appropriately. A portion of the material in this special report was presented as testimony by Dr Halperin on October 11, 2006, at the FDA’s public hearing on “Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception From Informed Consent Requirements for Emergency Research.” More than 300 000 Americans die each year due to catastrophic medical and surgical emergencies.2,3 New interventions based on sound research could save lives. These research studies must be done within an ethical framework that traditionally includes obtaining prospective informed consent from the research subject. The ethical framework for the conduct of human research began with the development of the Nuremberg Code4,5 in 1949. This code states that (1) informed consent of volunteers must be obtained without coercion of any form, (2) human experiments should be based on prior animal experiments, (3) the anticipated scientific results should justify the experiment, (4) only qualified scientists should conduct medical research, (5) physical and mental suffering should be avoided, and (6) no expectation of death or disabling injury should be expected from the research study. The Declaration of Helsinki6 was issued in 1964 and defines rules for clinical research. It repeats the ethical concerns stated in the Nuremberg Code but also gives a provision for enrolling certain patients in clinical research without …

Computer-aided Detection of Colorectal Polyps: Can It Improve Sensitivity of Less-Experienced Readers? Preliminary Findings

To determine whether computer-aided detection (CAD) applied to computed tomographic (CT) colonography can help improve sensitivity of polyp detection by less-experienced radiologist readers, with colonoscopy or consensus used as the reference standard. The release of the CT colonographic studies was approved by the individual institutional review boards of each institution. Institutions from the United States were HIPAA compliant. Written informed consent was waived at all institutions. The CT colonographic studies in 30 patients from six institutions were collected; 24 images depicted at least one confirmed polyp 6 mm or larger (39 total polyps) and six depicted no polyps. By using an investigational software package, seven less-experienced readers from two institutions evaluated the CT colonographic images and marked or scored polyps by using a five-point scale before and after CAD. The time needed to interpret the CT colonographic findings without CAD and then to re-evaluate them with CAD was recorded. For each reader, the McNemar test, adjusted for clustered data, was used to compare sensitivities for readers without and with CAD; a Wilcoxon signed-rank test was used to analyze the number of false-positive results per patient. The average sensitivity of the seven readers for polyp detection was significantly improved with CAD-from 0.810 to 0.908 (P=.0152). The number of false-positive results per patient without and with CAD increased from 0.70 to 0.96 (95% confidence interval for the increase: -0.39, 0.91). The mean total time for the readings was 17 minutes 54 seconds; for interpretation of CT colonographic findings alone, the mean time was 14 minutes 16 seconds; and for review of CAD findings, the mean time was 3 minutes 38 seconds. Results of this feasibility study suggest that CAD for CT colonography significantly improves per-polyp detection for less-experienced readers.