Jana Shirey-Rice

Secondary use of clinical data

The last decade has seen an exponential growth in the quantity of clinical data collected nationwide, triggering an increase in opportunities to reuse the data for biomedical research. The Vanderbilt research data warehouse framework consists of identified and de-identified clinical data repositories, fee-for-service custom services, and tools built atop the data layer to assist researchers across the enterprise. Providing resources dedicated to research initiatives benefits not only the research community, but also clinicians, patients and institutional leadership. This work provides a summary of our approach in the secondary use of clinical data for research domain, including a description of key components and a list of lessons learned, designed to assist others assembling similar services and infrastructure.

Motivation for Launching a Cancer Metastasis Inhibition (CMI) Program

Metastatic cancers impose significant burdens on patients, affecting quality of life, morbidity, and mortality. Even during remission, microscopic metastases can lurk, but few therapies directly target tumor cell metastasis. Agents that interfere with this process would represent a new paradigm in cancer management, changing the ‘waiting game’ into a time of active prevention. These therapies could take multiple forms based on the pathways involved in the metastatic process. For example, a phenome-wide association study showed that a single nucleotide polymorphism in the gene TBXA2R is associated with increased metastasis in multiple primary cancers (P = 0.003), suggesting clinical applicability of TBXA2R antagonists. Emerging data related to the role of platelets in metastasis are concordant with our sense that these pathways present significant opportunities for therapeutic development. However, before real progress can be made toward clinical targeting of the metastatic process, foundational work is needed to define informative measures of critical elements such as circulating tumor cells and tumor DNA, and circulatory vs. lymphatic spread. These challenges require an expansion of team science and composition to obtain competitive funding. At our academic medical center, we have implemented a Cancer Metastasis Inhibition (CMI) program investigating this approach across multiple cancers.

Reply to Ward and Colleagues’ Comment on “Using Human Experiments of Nature to Predict Drug Safety Issues: An Example with PCSK9 Inhibitors”

We appreciate Ward and colleagues’ interest in our work [1] and the opportunity to respond. We confirm that the spina bifida cases we reviewed are carriers of the R46L variant minor allele. As acknowledged in our paper, both the size of our observed spectrum of p values and the limited spectrum of PCSK9 variants in our existing genotyping platform suggest our data may be underpowered for fully understanding the connections identified. We note that the most conservative Bonferroni correction for multiplicity in this dataset would be approximately 6 × 10−6, and the authors are correct that our association with neural tube defects is below this threshold. The association with a diagnosis of hypercholesterolemia, a known association with the R46L variant, is also below the threshold. However, the existence of animal and human data suggestive of a potential link between PCSK9 and spina bifida, in concordance with the association we observed, suggests prudence in safety signal reporting is warranted. As described in our paper, decreased PCSK9 was found in both a rat fetal model of neural tube defects and women carrying a fetus affected by a neural tube defect, with PCSK9 level additionally noted to be a potentially useful biomarker in humans, with sensitivity of 57% and specificity of 98% [2]. Furthermore, the UK Biobank is an epidemiologic cohort of middle-aged subjects and thus may underrepresent phenotypes such as spina bifida seen primarily in younger patients.

Abstract 222: PathLink: Leveraging clinical informatics to empower translational pathology by connecting biospecimens to outcomes

Biorepositories are valuable resources to the cancer research community and arguably invaluable if they include detailed longitudinal health information such as personal risk factors, disease progression, and treatment outcomes. However, manual review of patient records is comparatively inefficient (expensive, time-intensive, and less reliable) than data extraction from the electronic health record (EHR). Using Research Data Network funds granted from the Patient Centered Outcomes Research Institute (PCORI), PathLink is being developed as an institution-wide biorepository linked to Vanderbilt9s EHR data warehouses, the Synthetic and Research Derivatives, and utilizing pathological specimens that exist or would otherwise be discarded, without duplicating existing biorepositories and other core resources. We are cataloging samples from clinical and research collections and creating a sustainable and prospective link to structured health information. PathLink will de-identify samples on-demand, permitting translational investigators real-time sample access while also preserving tissue for future clinical assays. The EHR derivatives already include fundamental review features and standardized data extraction mechanisms that can be easily leveraged for tissue-based research projects. Projects proposing a de-identified research approach can also be crosslinked to our germline genetic biobank of >200,000 subjects and will have lower barriers to access through a streamlined regulatory mechanism. Proof-of-concept studies underway include the banking of tissues with molecular genetic pathology testing (n = 3642), a large subset already annotated with SNaPshot tumor mutation profiling. Macrodissected tumor cells were collected from cases accessioned from 2010 to 2013 and stored as a tumor lysate reserve (B-tubes) pending successful completion of clinical assays. After extraction and quality testing of genomic material, PathLink was seeded with the transfer of these remnant samples to the biorepository. Pilot studies suggest that more than 75% of B-tubes will contain sufficient genomic material of high quality for targeted gene sequencing (>250ng, n = 120). We will digitally scan corresponding tissue sections and create tissue microarrays from cases with adequate tissue. In conclusion, PathLink is a new concept in biobanking, minimizing time and cost, and enabling more efficient translation of tissue-based discoveries from bench to clinical care and back again. A unique feature is that much of the collection is a virtual catalog of partner biorepositories, and most of the sample processing is executed by existing core facilities, minimizing overhead while also increasing interdepartmental collaboration. By July 2015, we expect to have catalogued at least 300,000 pathological specimens and have 3,000 tumor DNA samples ready for distribution to approved translational projects. Citation Format: Jennifer M. Giltnane, Jana Shirey-Rice, Jodell Linder, Erica Bowton, James Cowan, Xiaoming Wang, Jon Scherdin, Melissa Basford, Kimberly Dahlman, Joseph Roland, Kerry Wiles, Cynthia Vnencak-Jones, Kay Washington, Jill Pulley. PathLink: Leveraging clinical informatics to empower translational pathology by connecting biospecimens to outcomes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 222. doi:10.1158/1538-7445.AM2015-222

The CTSA Consortium's Catalog of Assets for Translational and Clinical Health Research (CATCHR).

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortiums effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open‐access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web‐based tool. Additional easy‐to‐use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources.

The CTSA Consortium's Catalog of Assets for Translational and Clinical Health Research (CATCHR): The Ctsa Consortium's Catchr

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortiums effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open‐access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web‐based tool. Additional easy‐to‐use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources.

The CTSA Consortium’s CATCHR (Catalog of Assets for Translational and Clinical Health Research)

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortiums effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open‐access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web‐based tool. Additional easy‐to‐use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources.