Steven Labkoff - Academia.edu (original) (raw)
Papers by Steven Labkoff
Blood, Nov 5, 2021
Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages o... more Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages of Wearing and Folding Clothes Student NW AF QP Deskripsi Deskripsi Deskripsi Initial Condition Achievements Initial Condition Achievements Initial Condition Achievements
Blood, Nov 5, 2020
Direct-to-Patient (DTP) Multiple Myeloma (MM) research studies have been launched recently, inclu... more Direct-to-Patient (DTP) Multiple Myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595) and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a set of myeloma-specific liquid biopsy approaches were developed. First, a hybrid selection panel was developed that detects somatic variants present in a patient's circulating-free DNA (cfDNA) in 70 commonly altered MM and Clonal Hematopoiesis of Indeterminate Potential (CHIP) genes. For this MM 70-Gene cfDNA Assay, samples are received as blood in a StreckTM tube designed for stabilization of cfDNA and DNA is extracted from buffy coat using magnetic bead-based chemistry. Deep coverage sequencing (80,000x depth) is performed and duplex BAM files generated with UMI alignment and error correction allowing for sensitive detection of clinically relevant variants. Technical validation data on healthy donor cfDNA mixes was generated using samples with a range of cfDNA inputs. This data determined that the assay is capable of achieving >90% sensitivity for detecting somatic events present at 1% variant allele frequency with a specificity of <0.2 false positives per megabase. Using a clinical cohort, we observed a strong correlation between Bone Marrow Aspirate (BMA) and cfDNA samples with the vast majority of variants previously detected in BMA also identified via the MM-70 Gene panel analysis. Interestingly, we also saw evidence of additional somatic variants identified in cfDNA previously undetected in BMA analysis. Because one the aims of this effort is to return results to treating physicians, a clinical-grade (CLIA) pipeline was established. For that CLIA pipeline, the variants reported are a subset of all the events detected by the MM 70-Gene Assay. The events detected in the assay are reviewed by experienced molecular pathologists at the Dana Farber Cancer Institute (DFCI) who have developed a customized reporting process. These reports utilize an internally-developed knowledgebase of variant/gene annotations that leverages the DFCI expertise in hematologic malignancies and myeloma specifically. The reports are then provided back through providers to the patient via the CureCloud system for their use in clinical care and trial identification. In order to complement the MM-70 Gene panel with copy number and translocation information, we have been exploring Circulating Multiple Myeloma Cells (CMMCs). Our current approach involves automated capture of CMMCs using ferrofluids coated with MM-selective and discriminating antibodies to immunomagnetically enrich circulating plasma cells. The highly enriched CMMCs fractions generated in such a fashion are then submitted for molecular characterization. At the submission date of this abstract, 163 patients have been fully enrolled into CureCloud from which results will be presented. In summary, we have developed a robust and very sensitive clinical-grade next-gen liquid biopsy sequencing platform allowing for minimally invasive monitoring of MM disease genomics that can be used to complement other more classical approaches and to help support our Direct-To-Patient Initiatives. Especially in this post-COVID19 era, such liquid biopsy-based approaches that avoid clinic visits for the patients and can be performed through at-home mobile phlebotomy are emerging as important new options. Kim: LabCorp: Consultancy; Quanterix, Inc: Consultancy; PapGene, Inc: Consultancy. Ghobrial:AbbVie: Consultancy; GNS Healthcare: Consultancy; GlaxoSmithKline: Consultancy; Genentech: Consultancy; Noxxon Pharma: Consultancy; Novartis: Consultancy; Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Cellectar: Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.
Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, inclu... more Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595), and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a myeloma-specific hybrid selection panel was developed that captures 70 commonly altered genes. The assay detects somatic point mutations and indels present in a patient’s circulating-free DNA (cfDNA). For this MM 70-Gene cfDNA Assay, samples are received as blood in a Streck’s tube and DNA is extracted from buffy coat using magnetic bead-based chemistry. Coverage sequencing (80,000x depth) is performed and duplex BAM files are generated with UMI alignment and de-duplication. As will be presented, MM blood specimens present a unique challenge as circulating MM cells are often present at significant levels in the buffy coat blood fraction used as the source of normal genomic DNA. The performance of the 70-Gene cfDNA Assay was thoroughly validated in order to establish the sensitivity, specificity, and reproducibility of the technical approach. First, the reference genomic DNA from unrelated healthy individuals was sequenced in replicate at deep coverage. Next, two cohorts were used, one from Dana-Farber and one from the MMRF CureCloud pilot. For both cohorts, tumor DNA samples from bone marrow aspirates (BMAs) with matched normal DNA from blood were sequenced on an orthogonal platform and compared to results from the MM 70-Gene Assay on cfDNA extracted from the same individuals. The yield of extracted cfDNA ranged from 6 ng to 80 ng, and about two third of cases yielded enough material to attempt sequencing, with failures coming mostly from individuals in remission. As will be presented, there was a very strong correlation between BMA and cfDNA and additional events could actually be detected in the blood that were not seen in the BMAs. Because this MM 70-Gene cfDNA Assay may potentially be used by treating physicians for management of care, a clinical-grade (CLIA) pipeline was established. For that CLIA pipeline, the variants reported are a subset of all the events detected by the MM 70-Gene Assay. The events detected in the assay are reviewed by a Genomic Tumor Board within the appropriate subset of territory predefined for reporting. The territory limitations are defined by the Genomic Tumor Board knowledgebase of actionable genomic territory available. In summary, we have developed a robust and very sensitive clinical-grade next-gen liquid biopsy sequencing platform allowing for less invasive monitoring of MM disease genomics that can be used to complement other more classical approaches and to help support direct-to-patient Initiatives. Citation Format: Mark W. Bustoros, Carrie Cibulskis, Teni Dowdell, Svetlana Gavrilov, Cody Boehner, Jennifer Yesil, Steven E. Labkoff, Shaadi Mehr, Jihye Park, Romanos Sklavenitis Pistofidis, Salomon Manier, Annette S. Kim, Keith L. Ligon, Niall Lennon, Viktor Adalsteinsson, Jane Wilkinson, Irene M. Ghobrial, Daniel Auclair. A novel clinical-grade liquid biopsy platform for multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A38.
Blood, Nov 5, 2020
: Title: Architecture of sample preparation and data governance of Immuno-genomic data collected ... more : Title: Architecture of sample preparation and data governance of Immuno-genomic data collected from bone marrow and peripheral blood samples obtained from multiple myeloma patients In multiple myeloma (MM), the interactions between malignant plasma cells and the bone marrow microenvironment is crucial to fully understand tumor development, disease progression, and response to therapy. The core challenge in understanding those interactions has been the establishment of a standard process and a standard model for handling the data quality workflow and the underlying data models. Here we present the Platform (Figure 1), an integrated data flow architecture designed to create data inventory and process tracking protocols for multi-dimensional and multi-technology immune data files. This system has been designed to inventory and track peripheral blood and bone marrow samples from multiple myeloma subjects submitted for immune analysis under the MMRF Immune Atlas initiative (figure 2), and the processing and storage of Single Cell RNA-seq (scRNA-seq) and Mass Cytometry time-of-flight (CyTOF) data files derived from these immune analyses. While these methods have been previously applied on both tumor and immune populations in MM [2,3], this level of multi-institutional and multi-technology is unique. The Cloud Immune-Precision platform contains standardized protocols and bioinformatics workflows for the identification and categorization of immune cell populations and functional states based upon scRNA-seq gene signatures (ref: Bioinformatics manuscript in submission) and CyTOF protein signatures. Upon further expansion, it will contain high dimensional scRNAseq and CyTOF immune data from both bone marrow and peripheral blood samples from myeloma patients enrolled in the Multiple Myeloma Research Foundation (MMRF) CoMMpass study (NCT01454297) [1] (Figure 3). The architecture covers the automation of data governance protocols, data transformation and ETL model developments that will create an immune proteomic and profiling database and its integration into clinical and genomics databases: e.g. the MMRF CoMMpass clinical trial. This large-scale data integration will establish a cutting-edge Immune-Precision central platform supporting large scale, immune-focused advanced analytics in multiple myeloma patients. This platform will allow researchers to interrogate the relationships between immune transcriptomic and proteomic signatures and tumor genomic features, and their impact on clinical outcomes, to aid in the optimization of therapy and therapeutic sequencing. Furthermore, this platform also promotes the potential to (further) elucidate the mechanisms-of-action of approved and experimental myeloma therapies, drive biomarker discovery, and identify new targets for drug discovery. Figure 1: Cloud Immune-Precision Platform (Integrated data flow architecture designed to create data inventory and process tracking protocols for multi-dimensional and multi-technology immune data files) Figure 2: Sample tracking process architecture Figure 3: Data file creation and repository process tracking References: 1- Settino, Marzia et al. "MMRF-CoMMpass Data Integration and Analysis for Identifying Prognostic Markers." Computational Science - ICCS 2020: 20th International Conference, Amsterdam, The Netherlands, June 3-5, 2020, Proceedings, Part III vol. 12139 564-571. 22 May. 2020, doi:10.1007/978-3-030-50420-5_42 2- Ledergor, Guy et al. "Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma." Nature medicine vol. 24,12 (2018): 1867-1876. doi:10.1038/s41591-018-0269-2 3- Hansmann, Leo et al. "Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma." Cancer immunology research vol. 3,6 (2015): 650-60. doi:10.1158/2326-6066.CIR-14-0236-T Figure 1 Disclosures Bhasin: Canomiiks Inc: Current equity holder in private company, Other: Co-Founder. Dhodapkar:Amgen: Membership on an entity's Board of Directors or advisory committees, Other; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other; Janssen: Membership on an entity's Board of Directors or advisory committees, Other; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other; Kite: Membership on an entity's Board of Directors or advisory committees, Other.
Applied Clinical Informatics, Apr 1, 2017
The rise in the use of electronic health records (EHRs) and associated resources over the last de... more The rise in the use of electronic health records (EHRs) and associated resources over the last decade is leading to the end of the paper medical record and all the risks associated with the use of a paper chart. However, there has not been a concomitant creation of a systematic oversight body that is specifically charged with ensuring the public's safety through the use of EHR knowledge resource tools or EHRs themselves. We recommend the formation a Health Information Technology Safety Center. Such a center could collect error reports, review EHRs and the knowledge resources incorporated within them, and investigate particularly challenging EHR-related safety issues at participating health care delivery organizations. Safety issues could be identified, corrected, and the solutions widely disseminated.
Journal of the American Medical Informatics Association, Sep 1, 2008
The Pfizer Healthcare Informatics team conducted a series of guided interviews with 35 Pfizer sen... more The Pfizer Healthcare Informatics team conducted a series of guided interviews with 35 Pfizer senior leaders to elicit their understanding, desires, and expectations of how Electronic Health Records (EHR) might be used in the pharmaceutical industry today and/or in the future. The interviews yielded fourteen use case categories comprising 42 specific use cases. The highest priority use cases were "Drug Safety & Surveillance," "Clinical Trial Recruitment," and "Support Regulatory Approval." Fifteen EHR companies were surveyed to assess their functionality against the specified use cases. Self-reported responses from the EHR companies were highest for "Virtual Phase IV Trials" and "Document Management for Clinical Trials." This research identifies preliminary opportunities for EHR products to provide aggregate, blinded data to address the interests of the pharmaceutical industry. However, further collaboration between the stakeholders will be necessary to ensure the full realization of the opportunities for data re-use.
Journal of Biomedical Informatics, Apr 1, 2007
It is widely agreed that major improvements in the safety, quality, and efficiency of health care... more It is widely agreed that major improvements in the safety, quality, and efficiency of health care in the US require a National Health Information Infrastructure. To accomplish this, efforts are now underway in many communities to build local or regional health information infrastructures (HIIs) that provide secure, ubiquitous access to complete health care information. To facilitate the assessment and monitoring of the progress of operational HIIs toward completion, we propose a framework of four key measures of requirements that must be ultimately be met: (1) completeness of information, (2) degree of usage, (3) types of usage, and (4) financial sustainability. To evaluate the framework, it was used by the authors to qualitatively assess HII projects in cooperation with four leading communities, resulting in ratings of 78% for Bellingham, WA, 63% for Indianapolis, IN, 60% for South Bend, IN, and 74% for Spokane, WA. Qualitative assessment of community HII systems may be helpful in monitoring progress, comparing projects, and understanding the remaining tasks needed for completion. Additional testing and refinement of the proposed framework is needed to further understand and improve HII progress measurement capabilities.
Conference of American Medical Informatics Association, 1996
... Copyright notice. Health Care Enterprise Integration Tools Using a WWW Platform: Application ... more ... Copyright notice. Health Care Enterprise Integration Tools Using a WWW Platform: Application in an Infectious Disease Service. Steven E. Labkoff, Johanna P. Daily, Tom Karson, Jonathan Schaffer, Luke Sato, Greg McHolm, Jihad Obeid, Patrick Shareck, and Robert A. Greenes ...
Blood, Nov 5, 2020
Introduction Clinical decision support (CDS) technology has the potential to improve health outco... more Introduction Clinical decision support (CDS) technology has the potential to improve health outcomes by offering physicians an informational resource to support review and application of best pratices.1 The Multiple Myeloma Research Foundation (MMRF) and Intermountain Healthcare (IMH) conducted a study to assess the suitability of a single health system's data for a myeloma-specific CDS tool that visualizes treatment pathways, and to assess the effort needed to support a CDS program.2 This research is part of a longer-term effort to explore how CDS technology can help: - increase awareness of and apply treatment guidelines by visualizing pathways for specific MM patient cohorts - improve understanding of treatment variation within health systems - improve outcomes research by showing relationships between treatments and outcomes Methods IA12 data from the CoMMpass study3 was used to create a CDS tool prototype. These data were aggregated into state and transition maps to identify nodes and pathways with corresponding outcomes, including response, progression-free survival (PFS), and overall survival (OS). Intervening patient states were displayed using Sankey diagrams [Fig. 1]. We also tested if EMR data from a community health system (i.e., IMH) could support such visualization. The team designed a study protocol and obtained IRB approval. Inclusion criteria included patients with active MM between January 2016-June 2018; adult aged 18 years to 89 years at diagnosis of active or smoldering MM. An IMH-specific data dictionary was assessed for variable importance, quantity, and ease of acquisition. [Table 1]. IMH then manually abstracted prioritized structured (eg: labs) and non-structured (eg: notes) data for use in the tool. Results Ninety-six of an initial 146 patients meeting eligibility criteria had sufficient data usable for the study, reflecting 44 unique drug combinations across 9 lines of therapy. The tool was able to associate and visualize all patients and their clinical states and transitions to their outcomes. Clinical data was typically complete (99% of the time), including key clinician-derived data, such as ECOG scores (78%) and treatment response (99%). 569 person-hours were required to conduct the abstraction activity on 96 cases, averaging 5.9 hours/patient Discussion The IMH portion of the study supports the hypothesis that a community health system can provide sufficient high-quality information to power a CDS tool with priority features. Only 65% (96/146) of the initial study group had usable data because some patients had received partial care outside of the IMH integrated delivery network (IDN) leaving associated data inaccessible. Initial biostatistical analysis suggests that roughly 750-1000 complete patient records would be required for statistically significant outcomes research with granularly stratified cohorts. The MMRF is currently recruiting 5-7 additional large IDNs to obtain the patients to power more generalizable functionality. References 1 McKie PM, Kor DJ, Cook DA, Kessler ME, Carter RE, Wilson PM, et al. Computerized advisory decision support for cardiovascular diseases in primary care: a cluster randomized trial. Am J Med [Internet]. 2019 Dec 18 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/j.amjmed.2019.10.039 2 Garcelon N, Burgun A, Salomon R, Neuraz A. Electronic health records for the diagnosis of rare diseases. Kidney Int [Internet]. 2020 Jan 14 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/ j.kint.2019.11.037 3 Christofferson A, Nasser S, Aldrich J, Penaherrera D, Legendre C, Benard B, et al. Integrative analysis of the genomic landscape underlying multiple myeloma at diagnosis: an Mmrf Commpass analysis. Blood. 2017 Dec 7; 130 (Supplement 1): 326. Disclosures No relevant conflicts of interest to declare.
Proceedings / the ... Annual Symposium on Computer Application [sic] in Medical Care. Symposium on Computer Applications in Medical Care, 1995
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF... more Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (884K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Blood, Nov 5, 2021
Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages o... more Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages of Wearing and Folding Clothes Student NW AF QP Deskripsi Deskripsi Deskripsi Initial Condition Achievements Initial Condition Achievements Initial Condition Achievements
Clinical Cancer Research, 2020
Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, inclu... more Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595), and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a myeloma-specific hybrid selection panel was developed that captures 70 commonly altered genes. The assay detects somatic point mutations and indels present in a patient’s circulating-free DNA (cfDNA). For this MM 70-Gene cfDNA Assay, samples are received as blood in a Streck’s tube and DNA is extracted from buffy coat using magnetic bead-based chemistry. Coverage sequencing (80,000x depth) is performed and duplex BAM files are generated with UMI alignment and de-duplication. As will be pr...
Applied Clinical Informatics, 2017
SummaryThe rise in the use of electronic health records (EHRs) and associated resources over the ... more SummaryThe rise in the use of electronic health records (EHRs) and associated resources over the last decade is leading to the end of the paper medical record and all the risks associated with the use of a paper chart. However, there has not been a concomitant creation of a systematic oversight body that is specifically charged with ensuring the public’s safety through the use of EHR knowledge resource tools or EHRs themselves. We recommend the formation a Health Information Technology Safety Center. Such a center could collect error reports, review EHRs and the knowledge resources incorporated within them, and investigate particularly challenging EHR-related safety issues at participating health care delivery organizations. Safety issues could be identified, corrected, and the solutions widely disseminated. Citation: Labkoff SE, Sittig DF. Who watches the watchers: working towards safety for EHR knowledge resources. Appl Clin Inform 2017; 8: 680–685 https://doi.org/10.4338/ACI-2017...
Blood, Nov 5, 2021
Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages o... more Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages of Wearing and Folding Clothes Student NW AF QP Deskripsi Deskripsi Deskripsi Initial Condition Achievements Initial Condition Achievements Initial Condition Achievements
Blood, Nov 5, 2020
Direct-to-Patient (DTP) Multiple Myeloma (MM) research studies have been launched recently, inclu... more Direct-to-Patient (DTP) Multiple Myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595) and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a set of myeloma-specific liquid biopsy approaches were developed. First, a hybrid selection panel was developed that detects somatic variants present in a patient's circulating-free DNA (cfDNA) in 70 commonly altered MM and Clonal Hematopoiesis of Indeterminate Potential (CHIP) genes. For this MM 70-Gene cfDNA Assay, samples are received as blood in a StreckTM tube designed for stabilization of cfDNA and DNA is extracted from buffy coat using magnetic bead-based chemistry. Deep coverage sequencing (80,000x depth) is performed and duplex BAM files generated with UMI alignment and error correction allowing for sensitive detection of clinically relevant variants. Technical validation data on healthy donor cfDNA mixes was generated using samples with a range of cfDNA inputs. This data determined that the assay is capable of achieving >90% sensitivity for detecting somatic events present at 1% variant allele frequency with a specificity of <0.2 false positives per megabase. Using a clinical cohort, we observed a strong correlation between Bone Marrow Aspirate (BMA) and cfDNA samples with the vast majority of variants previously detected in BMA also identified via the MM-70 Gene panel analysis. Interestingly, we also saw evidence of additional somatic variants identified in cfDNA previously undetected in BMA analysis. Because one the aims of this effort is to return results to treating physicians, a clinical-grade (CLIA) pipeline was established. For that CLIA pipeline, the variants reported are a subset of all the events detected by the MM 70-Gene Assay. The events detected in the assay are reviewed by experienced molecular pathologists at the Dana Farber Cancer Institute (DFCI) who have developed a customized reporting process. These reports utilize an internally-developed knowledgebase of variant/gene annotations that leverages the DFCI expertise in hematologic malignancies and myeloma specifically. The reports are then provided back through providers to the patient via the CureCloud system for their use in clinical care and trial identification. In order to complement the MM-70 Gene panel with copy number and translocation information, we have been exploring Circulating Multiple Myeloma Cells (CMMCs). Our current approach involves automated capture of CMMCs using ferrofluids coated with MM-selective and discriminating antibodies to immunomagnetically enrich circulating plasma cells. The highly enriched CMMCs fractions generated in such a fashion are then submitted for molecular characterization. At the submission date of this abstract, 163 patients have been fully enrolled into CureCloud from which results will be presented. In summary, we have developed a robust and very sensitive clinical-grade next-gen liquid biopsy sequencing platform allowing for minimally invasive monitoring of MM disease genomics that can be used to complement other more classical approaches and to help support our Direct-To-Patient Initiatives. Especially in this post-COVID19 era, such liquid biopsy-based approaches that avoid clinic visits for the patients and can be performed through at-home mobile phlebotomy are emerging as important new options. Kim: LabCorp: Consultancy; Quanterix, Inc: Consultancy; PapGene, Inc: Consultancy. Ghobrial:AbbVie: Consultancy; GNS Healthcare: Consultancy; GlaxoSmithKline: Consultancy; Genentech: Consultancy; Noxxon Pharma: Consultancy; Novartis: Consultancy; Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Cellectar: Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.
Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, inclu... more Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595), and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a myeloma-specific hybrid selection panel was developed that captures 70 commonly altered genes. The assay detects somatic point mutations and indels present in a patient’s circulating-free DNA (cfDNA). For this MM 70-Gene cfDNA Assay, samples are received as blood in a Streck’s tube and DNA is extracted from buffy coat using magnetic bead-based chemistry. Coverage sequencing (80,000x depth) is performed and duplex BAM files are generated with UMI alignment and de-duplication. As will be presented, MM blood specimens present a unique challenge as circulating MM cells are often present at significant levels in the buffy coat blood fraction used as the source of normal genomic DNA. The performance of the 70-Gene cfDNA Assay was thoroughly validated in order to establish the sensitivity, specificity, and reproducibility of the technical approach. First, the reference genomic DNA from unrelated healthy individuals was sequenced in replicate at deep coverage. Next, two cohorts were used, one from Dana-Farber and one from the MMRF CureCloud pilot. For both cohorts, tumor DNA samples from bone marrow aspirates (BMAs) with matched normal DNA from blood were sequenced on an orthogonal platform and compared to results from the MM 70-Gene Assay on cfDNA extracted from the same individuals. The yield of extracted cfDNA ranged from 6 ng to 80 ng, and about two third of cases yielded enough material to attempt sequencing, with failures coming mostly from individuals in remission. As will be presented, there was a very strong correlation between BMA and cfDNA and additional events could actually be detected in the blood that were not seen in the BMAs. Because this MM 70-Gene cfDNA Assay may potentially be used by treating physicians for management of care, a clinical-grade (CLIA) pipeline was established. For that CLIA pipeline, the variants reported are a subset of all the events detected by the MM 70-Gene Assay. The events detected in the assay are reviewed by a Genomic Tumor Board within the appropriate subset of territory predefined for reporting. The territory limitations are defined by the Genomic Tumor Board knowledgebase of actionable genomic territory available. In summary, we have developed a robust and very sensitive clinical-grade next-gen liquid biopsy sequencing platform allowing for less invasive monitoring of MM disease genomics that can be used to complement other more classical approaches and to help support direct-to-patient Initiatives. Citation Format: Mark W. Bustoros, Carrie Cibulskis, Teni Dowdell, Svetlana Gavrilov, Cody Boehner, Jennifer Yesil, Steven E. Labkoff, Shaadi Mehr, Jihye Park, Romanos Sklavenitis Pistofidis, Salomon Manier, Annette S. Kim, Keith L. Ligon, Niall Lennon, Viktor Adalsteinsson, Jane Wilkinson, Irene M. Ghobrial, Daniel Auclair. A novel clinical-grade liquid biopsy platform for multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A38.
Blood, Nov 5, 2020
: Title: Architecture of sample preparation and data governance of Immuno-genomic data collected ... more : Title: Architecture of sample preparation and data governance of Immuno-genomic data collected from bone marrow and peripheral blood samples obtained from multiple myeloma patients In multiple myeloma (MM), the interactions between malignant plasma cells and the bone marrow microenvironment is crucial to fully understand tumor development, disease progression, and response to therapy. The core challenge in understanding those interactions has been the establishment of a standard process and a standard model for handling the data quality workflow and the underlying data models. Here we present the Platform (Figure 1), an integrated data flow architecture designed to create data inventory and process tracking protocols for multi-dimensional and multi-technology immune data files. This system has been designed to inventory and track peripheral blood and bone marrow samples from multiple myeloma subjects submitted for immune analysis under the MMRF Immune Atlas initiative (figure 2), and the processing and storage of Single Cell RNA-seq (scRNA-seq) and Mass Cytometry time-of-flight (CyTOF) data files derived from these immune analyses. While these methods have been previously applied on both tumor and immune populations in MM [2,3], this level of multi-institutional and multi-technology is unique. The Cloud Immune-Precision platform contains standardized protocols and bioinformatics workflows for the identification and categorization of immune cell populations and functional states based upon scRNA-seq gene signatures (ref: Bioinformatics manuscript in submission) and CyTOF protein signatures. Upon further expansion, it will contain high dimensional scRNAseq and CyTOF immune data from both bone marrow and peripheral blood samples from myeloma patients enrolled in the Multiple Myeloma Research Foundation (MMRF) CoMMpass study (NCT01454297) [1] (Figure 3). The architecture covers the automation of data governance protocols, data transformation and ETL model developments that will create an immune proteomic and profiling database and its integration into clinical and genomics databases: e.g. the MMRF CoMMpass clinical trial. This large-scale data integration will establish a cutting-edge Immune-Precision central platform supporting large scale, immune-focused advanced analytics in multiple myeloma patients. This platform will allow researchers to interrogate the relationships between immune transcriptomic and proteomic signatures and tumor genomic features, and their impact on clinical outcomes, to aid in the optimization of therapy and therapeutic sequencing. Furthermore, this platform also promotes the potential to (further) elucidate the mechanisms-of-action of approved and experimental myeloma therapies, drive biomarker discovery, and identify new targets for drug discovery. Figure 1: Cloud Immune-Precision Platform (Integrated data flow architecture designed to create data inventory and process tracking protocols for multi-dimensional and multi-technology immune data files) Figure 2: Sample tracking process architecture Figure 3: Data file creation and repository process tracking References: 1- Settino, Marzia et al. "MMRF-CoMMpass Data Integration and Analysis for Identifying Prognostic Markers." Computational Science - ICCS 2020: 20th International Conference, Amsterdam, The Netherlands, June 3-5, 2020, Proceedings, Part III vol. 12139 564-571. 22 May. 2020, doi:10.1007/978-3-030-50420-5_42 2- Ledergor, Guy et al. "Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma." Nature medicine vol. 24,12 (2018): 1867-1876. doi:10.1038/s41591-018-0269-2 3- Hansmann, Leo et al. "Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma." Cancer immunology research vol. 3,6 (2015): 650-60. doi:10.1158/2326-6066.CIR-14-0236-T Figure 1 Disclosures Bhasin: Canomiiks Inc: Current equity holder in private company, Other: Co-Founder. Dhodapkar:Amgen: Membership on an entity's Board of Directors or advisory committees, Other; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other; Janssen: Membership on an entity's Board of Directors or advisory committees, Other; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other; Kite: Membership on an entity's Board of Directors or advisory committees, Other.
Applied Clinical Informatics, Apr 1, 2017
The rise in the use of electronic health records (EHRs) and associated resources over the last de... more The rise in the use of electronic health records (EHRs) and associated resources over the last decade is leading to the end of the paper medical record and all the risks associated with the use of a paper chart. However, there has not been a concomitant creation of a systematic oversight body that is specifically charged with ensuring the public's safety through the use of EHR knowledge resource tools or EHRs themselves. We recommend the formation a Health Information Technology Safety Center. Such a center could collect error reports, review EHRs and the knowledge resources incorporated within them, and investigate particularly challenging EHR-related safety issues at participating health care delivery organizations. Safety issues could be identified, corrected, and the solutions widely disseminated.
Journal of the American Medical Informatics Association, Sep 1, 2008
The Pfizer Healthcare Informatics team conducted a series of guided interviews with 35 Pfizer sen... more The Pfizer Healthcare Informatics team conducted a series of guided interviews with 35 Pfizer senior leaders to elicit their understanding, desires, and expectations of how Electronic Health Records (EHR) might be used in the pharmaceutical industry today and/or in the future. The interviews yielded fourteen use case categories comprising 42 specific use cases. The highest priority use cases were "Drug Safety & Surveillance," "Clinical Trial Recruitment," and "Support Regulatory Approval." Fifteen EHR companies were surveyed to assess their functionality against the specified use cases. Self-reported responses from the EHR companies were highest for "Virtual Phase IV Trials" and "Document Management for Clinical Trials." This research identifies preliminary opportunities for EHR products to provide aggregate, blinded data to address the interests of the pharmaceutical industry. However, further collaboration between the stakeholders will be necessary to ensure the full realization of the opportunities for data re-use.
Journal of Biomedical Informatics, Apr 1, 2007
It is widely agreed that major improvements in the safety, quality, and efficiency of health care... more It is widely agreed that major improvements in the safety, quality, and efficiency of health care in the US require a National Health Information Infrastructure. To accomplish this, efforts are now underway in many communities to build local or regional health information infrastructures (HIIs) that provide secure, ubiquitous access to complete health care information. To facilitate the assessment and monitoring of the progress of operational HIIs toward completion, we propose a framework of four key measures of requirements that must be ultimately be met: (1) completeness of information, (2) degree of usage, (3) types of usage, and (4) financial sustainability. To evaluate the framework, it was used by the authors to qualitatively assess HII projects in cooperation with four leading communities, resulting in ratings of 78% for Bellingham, WA, 63% for Indianapolis, IN, 60% for South Bend, IN, and 74% for Spokane, WA. Qualitative assessment of community HII systems may be helpful in monitoring progress, comparing projects, and understanding the remaining tasks needed for completion. Additional testing and refinement of the proposed framework is needed to further understand and improve HII progress measurement capabilities.
Conference of American Medical Informatics Association, 1996
... Copyright notice. Health Care Enterprise Integration Tools Using a WWW Platform: Application ... more ... Copyright notice. Health Care Enterprise Integration Tools Using a WWW Platform: Application in an Infectious Disease Service. Steven E. Labkoff, Johanna P. Daily, Tom Karson, Jonathan Schaffer, Luke Sato, Greg McHolm, Jihad Obeid, Patrick Shareck, and Robert A. Greenes ...
Blood, Nov 5, 2020
Introduction Clinical decision support (CDS) technology has the potential to improve health outco... more Introduction Clinical decision support (CDS) technology has the potential to improve health outcomes by offering physicians an informational resource to support review and application of best pratices.1 The Multiple Myeloma Research Foundation (MMRF) and Intermountain Healthcare (IMH) conducted a study to assess the suitability of a single health system's data for a myeloma-specific CDS tool that visualizes treatment pathways, and to assess the effort needed to support a CDS program.2 This research is part of a longer-term effort to explore how CDS technology can help: - increase awareness of and apply treatment guidelines by visualizing pathways for specific MM patient cohorts - improve understanding of treatment variation within health systems - improve outcomes research by showing relationships between treatments and outcomes Methods IA12 data from the CoMMpass study3 was used to create a CDS tool prototype. These data were aggregated into state and transition maps to identify nodes and pathways with corresponding outcomes, including response, progression-free survival (PFS), and overall survival (OS). Intervening patient states were displayed using Sankey diagrams [Fig. 1]. We also tested if EMR data from a community health system (i.e., IMH) could support such visualization. The team designed a study protocol and obtained IRB approval. Inclusion criteria included patients with active MM between January 2016-June 2018; adult aged 18 years to 89 years at diagnosis of active or smoldering MM. An IMH-specific data dictionary was assessed for variable importance, quantity, and ease of acquisition. [Table 1]. IMH then manually abstracted prioritized structured (eg: labs) and non-structured (eg: notes) data for use in the tool. Results Ninety-six of an initial 146 patients meeting eligibility criteria had sufficient data usable for the study, reflecting 44 unique drug combinations across 9 lines of therapy. The tool was able to associate and visualize all patients and their clinical states and transitions to their outcomes. Clinical data was typically complete (99% of the time), including key clinician-derived data, such as ECOG scores (78%) and treatment response (99%). 569 person-hours were required to conduct the abstraction activity on 96 cases, averaging 5.9 hours/patient Discussion The IMH portion of the study supports the hypothesis that a community health system can provide sufficient high-quality information to power a CDS tool with priority features. Only 65% (96/146) of the initial study group had usable data because some patients had received partial care outside of the IMH integrated delivery network (IDN) leaving associated data inaccessible. Initial biostatistical analysis suggests that roughly 750-1000 complete patient records would be required for statistically significant outcomes research with granularly stratified cohorts. The MMRF is currently recruiting 5-7 additional large IDNs to obtain the patients to power more generalizable functionality. References 1 McKie PM, Kor DJ, Cook DA, Kessler ME, Carter RE, Wilson PM, et al. Computerized advisory decision support for cardiovascular diseases in primary care: a cluster randomized trial. Am J Med [Internet]. 2019 Dec 18 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/j.amjmed.2019.10.039 2 Garcelon N, Burgun A, Salomon R, Neuraz A. Electronic health records for the diagnosis of rare diseases. Kidney Int [Internet]. 2020 Jan 14 [cited 2020 Mar 5]. Available from: https://doi.org/10.1016/ j.kint.2019.11.037 3 Christofferson A, Nasser S, Aldrich J, Penaherrera D, Legendre C, Benard B, et al. Integrative analysis of the genomic landscape underlying multiple myeloma at diagnosis: an Mmrf Commpass analysis. Blood. 2017 Dec 7; 130 (Supplement 1): 326. Disclosures No relevant conflicts of interest to declare.
Proceedings / the ... Annual Symposium on Computer Application [sic] in Medical Care. Symposium on Computer Applications in Medical Care, 1995
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF... more Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (884K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Blood, Nov 5, 2021
Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages o... more Table 3. Improving learning outcomes from initial conditions to student achievements. No Stages of Wearing and Folding Clothes Student NW AF QP Deskripsi Deskripsi Deskripsi Initial Condition Achievements Initial Condition Achievements Initial Condition Achievements
Clinical Cancer Research, 2020
Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, inclu... more Direct-to-patient (DTP) multiple myeloma (MM) research studies have been launched recently, including PCROWD (NCT02269592), PROMISE (NCT03689595), and the MMRF CureCloud Research Initiative (NCT03657251), aimed at enrolling thousands of individuals from whom comprehensive molecular and immune analyses will be generated from blood specimens and the resulting data aggregated with the correlating clinical information. To support the molecular characterization of liquid biopsies for such DTP efforts, a myeloma-specific hybrid selection panel was developed that captures 70 commonly altered genes. The assay detects somatic point mutations and indels present in a patient’s circulating-free DNA (cfDNA). For this MM 70-Gene cfDNA Assay, samples are received as blood in a Streck’s tube and DNA is extracted from buffy coat using magnetic bead-based chemistry. Coverage sequencing (80,000x depth) is performed and duplex BAM files are generated with UMI alignment and de-duplication. As will be pr...
Applied Clinical Informatics, 2017
SummaryThe rise in the use of electronic health records (EHRs) and associated resources over the ... more SummaryThe rise in the use of electronic health records (EHRs) and associated resources over the last decade is leading to the end of the paper medical record and all the risks associated with the use of a paper chart. However, there has not been a concomitant creation of a systematic oversight body that is specifically charged with ensuring the public’s safety through the use of EHR knowledge resource tools or EHRs themselves. We recommend the formation a Health Information Technology Safety Center. Such a center could collect error reports, review EHRs and the knowledge resources incorporated within them, and investigate particularly challenging EHR-related safety issues at participating health care delivery organizations. Safety issues could be identified, corrected, and the solutions widely disseminated. Citation: Labkoff SE, Sittig DF. Who watches the watchers: working towards safety for EHR knowledge resources. Appl Clin Inform 2017; 8: 680–685 https://doi.org/10.4338/ACI-2017...