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- All Subjects: IRB
- All Subjects: Genetic disorders in children
- Creators: Craig, David W.
- Creators: Lindor, Keith
Description
This paper will chronicle my personal experience in trying to design and initiate a retrospective patient data study to determine the prevalence of Primary Sclerosing Cholangitis (“PSC”) in certain races/ethnic groups in Arizona. This experience will also be the basis for my proposed roadmap for a more successful future study.
My nearly 10 month thesis project of trying to complete a study yielded considerable ‘learning opportunities’ in large part due to my inexperience. I made numerous errors in sequencing tasks, grossly under-scoping elapsed time and hours for other tasks, completely overlooking other critical tasks, and being insensitive to how irrelevant I and my project were to the many professionals whose help I needed to complete the study. Based upon the knowledge I gained through this process, I will describe the design of a future study of retrospective patient data that will assess whether PSC patients in Phoenix, Arizona follow racial/ethnic trends. I chose Phoenix as an ideal location to perform this proposed study because of the diverse racial/ethnic population in the greater Phoenix area. The goal will be to obtain and review 20 years of retrospective patient data from three large hospital groups in Phoenix, identify the races/ethnicities of PSC patients, and quantify the prevalence and incidence of PSC in such races/ethnicities. The lack of IRB uniformity among the subject hospitals/clinics will pose a challenge, but a detailed outline of how to approach the IRB approval process and obtain PSC patient data from each institution is provided.
My nearly 10 month thesis project of trying to complete a study yielded considerable ‘learning opportunities’ in large part due to my inexperience. I made numerous errors in sequencing tasks, grossly under-scoping elapsed time and hours for other tasks, completely overlooking other critical tasks, and being insensitive to how irrelevant I and my project were to the many professionals whose help I needed to complete the study. Based upon the knowledge I gained through this process, I will describe the design of a future study of retrospective patient data that will assess whether PSC patients in Phoenix, Arizona follow racial/ethnic trends. I chose Phoenix as an ideal location to perform this proposed study because of the diverse racial/ethnic population in the greater Phoenix area. The goal will be to obtain and review 20 years of retrospective patient data from three large hospital groups in Phoenix, identify the races/ethnicities of PSC patients, and quantify the prevalence and incidence of PSC in such races/ethnicities. The lack of IRB uniformity among the subject hospitals/clinics will pose a challenge, but a detailed outline of how to approach the IRB approval process and obtain PSC patient data from each institution is provided.
ContributorsBuness, James Gage (Author) / Lindor, Keith (Thesis director) / Ali, Ahmad (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Rapid advancements in genomic technologies have increased our understanding of rare human disease. Generation of multiple types of biological data including genetic variation from genome or exome, expression from transcriptome, methylation patterns from epigenome, protein complexity from proteome and metabolite information from metabolome is feasible. "Omics" tools provide comprehensive view into biological mechanisms that impact disease trait and risk. In spite of available data types and ability to collect them simultaneously from patients, researchers still rely on their independent analysis. Combining information from multiple biological data can reduce missing information, increase confidence in single data findings, and provide a more complete view of genotype-phenotype correlations. Although rare disease genetics has been greatly improved by exome sequencing, a substantial portion of clinical patients remain undiagnosed. Multiple frameworks for integrative analysis of genomic and transcriptomic data are presented with focus on identifying functional genetic variations in patients with undiagnosed, rare childhood conditions. Direct quantitation of X inactivation ratio was developed from genomic and transcriptomic data using allele specific expression and segregation analysis to determine magnitude and inheritance mode of X inactivation. This approach was applied in two families revealing non-random X inactivation in female patients. Expression based analysis of X inactivation showed high correlation with standard clinical assay. These findings improved understanding of molecular mechanisms underlying X-linked disorders. In addition multivariate outlier analysis of gene and exon level data from RNA-seq using Mahalanobis distance, and its integration of distance scores with genomic data found genotype-phenotype correlations in variant prioritization process in 25 families. Mahalanobis distance scores revealed variants with large transcriptional impact in patients. In this dataset, frameshift variants were more likely result in outlier expression signatures than other types of functional variants. Integration of outlier estimates with genetic variants corroborated previously identified, presumed causal variants and highlighted new candidate in previously un-diagnosed case. Integrative genomic approaches in easily attainable tissue will facilitate the search for biomarkers that impact disease trait, uncover pharmacogenomics targets, provide novel insight into molecular underpinnings of un-characterized conditions, and help improve analytical approaches that use large datasets.
ContributorsSzelinger, Szabolcs (Author) / Craig, David W. (Thesis advisor) / Kusumi, Kenro (Thesis advisor) / Narayan, Vinodh (Committee member) / Rosenberg, Michael S. (Committee member) / Huentelman, Matthew J (Committee member) / Arizona State University (Publisher)
Created2015
Description
In 2014, the Centers for Medicare and Medicaid Services (CMS), which oversees the federal Clinical Laboratories Improvement Amendments (CLIA) program, issued guidance that the CLIA requirements apply when researchers seek to return individual-level research findings to study participants or their physician (Centers for Medicare & Medicaid Services, 2014). The present study explores the stance of U.S. Institutional Review Boards (IRBs) toward the applicability of and compliance with the CLIA regulations when studies plan to return individual research results (RIRR). I performed a document content analysis of 73 IRB policies and supporting documents from 30 United States (U.S.) institutions funded for biomedical research by the National Institutes of Health in 2017. Documents analyzed included policies, procedures, guidance, protocol and consent templates, and miscellaneous documents (such as IRB presentations) found to address the RIRR to study participants. I used qualitative content and document analysis to identify themes across institutions related to the CLIA regulations and the RIRR. Basic descriptive statistics were used to represent the data quantitatively. The study found that 96.67% (n=29) of institutions had documents that addressed the RIRR to participants. The majority of the institutions had at least one document that referenced the CLIA regulations when discussing the practice of disclosing participant-specific results [76.67% (n=23)]. The majority of institutions [56.67% (n=17)] indicated that they require compliance with the CLIA regulations for returning individual study findings to participants, while 13.33% (n=4) recommended compliance. The intent of two (6.67%) institutions was vague or unclear, while seven (26.67%) institutions were silent on the topic altogether. Of the 23 institutions that referenced “CLIA” in their documents, 52.17% only mentioned CLIA in a one or two-sentence blurb, providing very little guidance to investigators. The study results provide evidence that the majority of U.S. biomedical institutions require or recommend compliance with CLIA stipulations when investigators intend to return individual research results to study participants. However, the data indicates there is heterogeneity and variation in the quality of the guidance provided.
ContributorsBuchholtz, Stephanie (Author) / Robert, Jason S. (Thesis advisor) / Ellison, Karin D. (Committee member) / Carpten, John D. (Committee member) / Craig, David W. (Committee member) / Marchant, Gary E. (Committee member) / Arizona State University (Publisher)
Created2021