Implementing the Single Institutional Review Board Model: Lessons from the Undiagnosed Diseases Network.
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ABSTRACT:
SUBMITTER: Splinter K
PROVIDER: S-EPMC5759723 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Implementing the Single Institutional Review Board Model: Lessons from the Undiagnosed Diseases Network.
Splinter Kimberly K Hull Sara Chandros SC Holm Ingrid A IA McDonough Tara L TL Wise Anastasia L AL Ramoni Rachel B RB
Clinical and translational science 20171023 1
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Project description:One of the most significant changes to the Common Rule is the requirement that institutions use a single Institutional Review Board (IRB) for cooperative research in the United States, unless more than one IRB is required by state, local, or tribal law, or a signatory federal agency decides an exception is warranted. We surveyed Human Research Protection Program (HRPP) officials at the top U.S. research institutions to understand their knowledge and opinion of the mandate, what steps their institutions are taking, and difficulties their institutions are facing. One-hundred seven institutions (56.9%) responded to the survey. While support for the single-IRB mandate was positive overall, most respondents acknowledged that their institution is likely to face some difficulties complying with it. Regulatory agencies can help institutions to comply with the mandate by providing guidance concerning such issues as exceptions to the mandate, local context review, oversight, and implementation of reliance agreements, and development of policies, procedures, and best practices.
| S-EPMC6336442 | biostudies-literature
Project description:BackgroundResources within the Undiagnosed Diseases Network (UDN), such as genome sequencing (GS) and model organisms aid in diagnosis and identification of new disease genes, but are currently difficult to access by clinical providers. While these resources do contribute to diagnoses in many cases, they are not always necessary to reach diagnostic resolution. The UDN experience has been that participants can also receive diagnoses through the thoughtful and customized application of approaches and resources that are readily available in clinical settings.MethodsThe UDN Genetic Counseling and Testing Working Group collected case vignettes that illustrated how clinically available methods resulted in diagnoses. The case vignettes were classified into three themes; phenotypic considerations, selection of genetic testing, and evaluating exome/GS variants and data.ResultsWe present 12 participants that illustrate how clinical practices such as phenotype-driven genomic investigations, consideration of variable expressivity, selecting the relevant tissue of interest for testing, utilizing updated testing platforms, and recognition of alternate transcript nomenclature resulted in diagnoses.ConclusionThese examples demonstrate that when a diagnosis is elusive, an iterative patient-specific approach utilizing assessment options available to clinical providers may solve a portion of cases. However, this does require increased provider time commitment, a particular challenge in the current practice of genomics.
| S-EPMC7549585 | biostudies-literature
Project description:Background/aimsTimely review of research protocols by institutional review boards leads to more rapid initiation of clinical trials, which is critical to expeditious translation from bench to bedside. This observational study examined the impact of a single institutional review board on time and efforts required to initiate clinical trials by the National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network.MethodsCollection of data from the same six main clinical sites for three current clinical trials and two past clinical trials, including time from institutional review board submission to approval, pages submitted, consent form length, number of required attachments, other regulatory requirements, order of review at central or local sites, and language in documents at individual participating sites. Results from two past clinical trials were also included.ResultsWhile time required for actual institutional review board submission's review and initial approval was reduced with use of a single institutional review board for multicenter trials (from a mean of 66.7-24.0 days), total time was increased (to a mean of 111.2 or 123.3 days). In addition to single institutional review board approval, all institutions required local approval of some components (commonly consent language and use of local language), which varied considerably. The single institutional review board relied on local institutions for adding or removing personnel, conflict of interest review, and auditing of activities.ConclusionA single institutional review board reduced time for initial review and approval of protocols and informed consents, although time for the entire process was increased, as individual institutions retained oversight of components of required regulatory review. In order to best achieve the National Institute of Health's goals for improved efficiency in initiation and conduct of multisite clinical research, greater coordination with local institutional review boards is key to streamlining and accelerating initiation of multisite clinical research.
| S-EPMC6384136 | biostudies-literature
Project description:Rare genetic disorders, when considered together, are relatively common. Despite advancements in genetics and genomics technologies as well as increased understanding of genomic function and dysfunction, many genetic diseases continue to be difficult to diagnose. The goal of this Review is to increase the familiarity of genetic testing strategies for non-genetics providers. As genetic testing is increasingly used in primary care, many subspecialty clinics, and various inpatient settings, it is important that non-genetics providers have a fundamental understanding of the strengths and weaknesses of various genetic testing strategies as well as develop an ability to interpret genetic testing results. We provide background on commonly used genetic testing approaches, give examples of phenotypes in which the various genetic testing approaches are used, describe types of genetic and genomic variations, cover challenges in variant identification, provide examples in which next-generation sequencing (NGS) failed to uncover the variant responsible for a disease, and discuss opportunities for continued improvement in the application of NGS clinically. As genetic testing becomes increasingly a part of all areas of medicine, familiarity with genetic testing approaches and result interpretation is vital to decrease the burden of undiagnosed disease.
| S-EPMC8970663 | biostudies-literature
Project description:BackgroundInstitutional Review Boards (IRBs) have been criticized for inconsistency, delay, and bias, suggesting an opportunity for quality improvement. To aid such quality improvement, this study aimed at determining IRB members' and investigators' priorities regarding IRB review at 10 Veterans Affairs (VA) IRBs.Methods680 anonymous internet surveys were sent to 252 IRB members and staff, and 428 principal investigators and project coordinators at 9 VA Medical Centers and the VA Central IRB. Surveys included 27 statements adapted from Koocher and Kieth-Spiegel's IRB-RAT describing IRB activities or functions (e.g., "An IRB that is open to reversing its earlier decisions"). Respondents indicated how each statement described both their "ideal" and "actual" IRBs. The difference between the ratings of the actual and ideal IRBs was calculated for each item along with estimated 95% confidence intervals. Ratings outside those intervals indicated activities or functions with relatively good or poor performance compared to the ideal IRB.Results390 (57.4%) responses from 165 IRB members and staff (65.5%) and 225 investigators and project coordinators (52.6%) demonstrated that these IRBs were closest to the ideal when protecting human subjects, treating investigators with respect, and taking appropriate action for alleged scientific misconduct. The IRBs were furthest from the ideal regarding duplicative forms, timeliness of review, and provision of complete rationales for decisions. Although IRB members reported near-ideal willingness to reverse earlier decisions, investigators rated this capacity far from ideal. Investigators rated IRB members' knowledge about procedures and policy as nearly ideal, but IRB members themselves rated this aspect far from ideal. Noteworthy site-level differences in the ratings of IRB functions and activities were also identified.ConclusionsAlthough these VA IRBs perform well in some areas, these data support the need for ongoing quality improvement. The described method of administering and analyzing the IRB-RAT may help identify and monitor site- and activity- specific initiatives for quality improvement.
| S-EPMC7409436 | biostudies-literature
Project description:The aim of this study was to evaluate the process of accreditation resulting in improvement of the Institutional Review Board (IRB) functioning.Randomly selected projects from years 2007 (before accreditation), 2010 (after accreditation), and 2013 (after reaccreditation) were evaluated to assess parameters, namely, submission of good clinical practices (GCPs), completeness of IRB submission form, fulfillment of quorum, documentation of the declaration of conflict of interests, and submission of the status reports. Compliance to these parameters was compared over a period of 3 years.A total of seventy projects were evaluated retrospectively. Compliance of the principal investigators regarding submission of GCP certificates increased substantially from 5% to 53.1%. Completeness of IRB forms was 80% in 2007 while it became 100% in 2010 and continued even in 2013. Fulfillment of quorum increased significantly from 35% in 2007 to 100% in 2010 and 2013 after the accreditation procedures. Out of the selected twenty projects (2007), nonfinancial conflict of interest was not declared in all three applicable projects, while of 18 projects (2010), nonfinancial conflict of interest was declared in all three applicable cases. Of 32 projects (2013), nonfinancial conflict of interest was declared in seven out of eight applicable cases. Timely submission of status reports increased from 10% in 2007 to 38.9% in 2010 and 37.5% in 2013.Accreditation plays a vital role in the improvement of IRB. The policies and procedures formulated and implemented during the process of accreditation resulted in improvement of IRB performance. Continuing training of the IRB and researchers is required to maintain the accreditation.
| S-EPMC5543766 | biostudies-other
Project description:ObjectiveWhen studying any specific rare disease, heterogeneity and scarcity of affected individuals has historically hindered investigators from discerning on what to focus to understand and diagnose a disease. New nongenomic methodologies must be developed that identify similarities in seemingly dissimilar conditions.Materials and methodsThis observational study analyzes 1042 patients from the Undiagnosed Diseases Network (2015-2019), a multicenter, nationwide research study using phenotypic data annotated by specialized staff using Human Phenotype Ontology terms. We used Louvain community detection to cluster patients linked by Jaccard pairwise similarity and 2 support vector classifier to assign new cases. We further validated the clusters' most representative comorbidities using a national claims database (67 million patients).ResultsPatients were divided into 2 groups: those with symptom onset before 18 years of age (n = 810) and at 18 years of age or older (n = 232) (average symptom onset age: 10 [interquartile range, 0-14] years). For 810 pediatric patients, we identified 4 statistically significant clusters. Two clusters were characterized by growth disorders, and developmental delay enriched for hypotonia presented a higher likelihood of diagnosis. Support vector classifier showed 0.89 balanced accuracy (0.83 for Human Phenotype Ontology terms only) on test data.DiscussionsTo set the framework for future discovery, we chose as our endpoint the successful grouping of patients by phenotypic similarity and provide a classification tool to assign new patients to those clusters.ConclusionThis study shows that despite the scarcity and heterogeneity of patients, we can still find commonalities that can potentially be harnessed to uncover new insights and targets for therapy.
| S-EPMC8324228 | biostudies-literature
Project description:ObjectivesTo review the referral and clinical characteristics of adult patients diagnosed with lysosomal storage diseases (LSD) through the Undiagnosed Diseases Network (UDN).MethodsRetrospective review of both application and evaluation records for adults admitted to the UDN with a final diagnosis of a lysosomal storage disease.ResultsTen patients were identified. Final diagnoses included late onset Tay Sachs, attenuated MPS I, MPS IIIA, MPS IIIB, and MPS IIIC. Most patients presented with neurocognitive changes. Prior to referral, all patients had been evaluated by neurology, four patients underwent phenotype specific panel testing that did not include the causative gene, and four patients had non-diagnostic clinical exome sequencing.ConclusionsLSDs figure highly in the differential diagnosis of neurometabolic disorders in pediatric onset progressive diseases. In adults, their subtle initial presentations overlap with symptoms of more common disorders and less practitioner awareness may lead to prolonged diagnostic challenges.
| S-EPMC9482386 | biostudies-literature
Project description:The global burden of undiagnosed diseases, particularly in adults, is rising due to their significant socioeconomic impact. To address this, we enrolled 232 adult probands with undiagnosed conditions, utilizing bioinformatics tools for genetic analysis. Alongside exome and genome sequencing, repeat-primed PCR and Cas9-mediated nanopore sequencing were applied to suspected short tandem repeat disorders. Probands were classified into probable genetic (n = 128) or uncertain (n = 104) origins. The study found genetic causes in 66 individuals (28.4%) and non-genetic causes in 12 (5.2%), with a longer diagnostic journey for those in the probable genetic group or with pediatric symptom onset, emphasizing the need for increased efforts in these populations. Genetic diagnoses facilitated effective surveillance, cascade screening, drug repurposing, and pregnancy planning. This study demonstrates that integrating sequencing technologies improves diagnostic accuracy, may shorten the time to diagnosis, and enhances personalized management for adults with undiagnosed diseases.
| S-EPMC11604660 | biostudies-literature
Project description:BackgroundInstitutional review board (IRB) expertise is necessarily limited by maintaining a manageable board size. IRBs are therefore permitted by regulation to rely on outside experts for review. However, little is known about whether, when, why, and how IRBs use outside experts.MethodsWe conducted a national survey of U.S. IRBs to characterize utilization of outside experts. Our study uses a descriptive, cross-sectional design to understand how IRBs engage with such experts and to identify areas where outside expertise is most frequently requested.ResultsThe survey response rate was 18.4%, with 55.4% of respondents reporting their institution's IRB uses outside experts. Nearly all respondents who reported using outside experts indicated they do so less than once a month, but occasionally each year (95%). The most common method of identifying an outside expert was securing a previously known subject matter expert (83.3%). Most frequently, respondents sought consultation for scientific expertise not held by current members (69.6%). Almost all respondents whose IRBs had used outside experts reported an overall positive impact on the IRB review process (91.5%).ConclusionsJust over half of the IRBs in our sample report use of outside experts; among them, outside experts were described as helpful, but their use was infrequent overall. Many IRBs report not relying on outside experts at all. This raises important questions about what type of engagement with outside experts should be viewed as optimal to promote the highest quality review. For example, few respondents sought assistance from a Community Advisory Board, which could address expertise gaps in community perspectives. Further exploration is needed to understand how to optimize IRB use of outside experts, including how to recognize when expertise is lacking, what barriers IRBs face in using outside experts, and perspectives on how outside expert review impacts IRB decision-making and review quality.
| S-EPMC10360021 | biostudies-literature