Journal of Personalized Medicine

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19 pages, 720 KiB

Open AccessArticle

An Idealized Clinicogenomic Registry to Engage Underrepresented Populations Using Innovative Technology

by Patrick Silva, Deborah Vollmer Dahlke, Matthew Lee Smith, Wendy Charles, Jorge Gomez, Marcia G. Ory and Kenneth S. Ramos

J. Pers. Med. 2022, 12(5), 713; https://doi.org/10.3390/jpm12050713 - 29 Apr 2022

Cited by 12 | Viewed by 3892

Abstract

Current best practices in tumor registries provide a glimpse into a limited time frame over the natural history of disease, usually a narrow window around diagnosis and biopsy. This creates challenges meeting public health and healthcare reimbursement policies that increasingly require robust documentation [...] Read more.

Current best practices in tumor registries provide a glimpse into a limited time frame over the natural history of disease, usually a narrow window around diagnosis and biopsy. This creates challenges meeting public health and healthcare reimbursement policies that increasingly require robust documentation of long-term clinical trajectories, quality of life, and health economics outcomes. These challenges are amplified for underrepresented minority (URM) and other disadvantaged populations, who tend to view the institution of clinical research with skepticism. Participation gaps leave such populations underrepresented in clinical research and, importantly, in policy decisions about treatment choices and reimbursement, thus further augmenting health, social, and economic disparities. Cloud computing, mobile computing, digital ledgers, tokenization, and artificial intelligence technologies are powerful tools that promise to enhance longitudinal patient engagement across the natural history of disease. These tools also promise to enhance engagement by giving participants agency over their data and addressing a major impediment to research participation. This will only occur if these tools are available for use with all patients. Distributed ledger technologies (specifically blockchain) converge these tools and offer a significant element of trust that can be used to engage URM populations more substantively in clinical research. This is a crucial step toward linking composite cohorts for training and optimization of the artificial intelligence tools for enhancing public health in the future. The parameters of an idealized clinical genomic registry are presented. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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14 pages, 1499 KiB

Open AccessEditor’s ChoiceArticle

Real-World Impact of a Pharmacogenomics-Enriched Comprehensive Medication Management Program

by Joseph P. Jarvis, Arul Prakasam Peter, Murray Keogh, Vince Baldasare, Gina M. Beanland, Zachary T. Wilkerson, Steven Kradel and Jeffrey A. Shaman

J. Pers. Med. 2022, 12(3), 421; https://doi.org/10.3390/jpm12030421 - 8 Mar 2022

Cited by 27 | Viewed by 14849

Abstract

The availability of clinical decision support systems (CDSS) and other methods for personalizing medicine now allows evaluation of their real-world impact on healthcare delivery. For example, addressing issues associated with polypharmacy in older patients using pharmacogenomics (PGx) and comprehensive medication management (CMM) is [...] Read more.

The availability of clinical decision support systems (CDSS) and other methods for personalizing medicine now allows evaluation of their real-world impact on healthcare delivery. For example, addressing issues associated with polypharmacy in older patients using pharmacogenomics (PGx) and comprehensive medication management (CMM) is thought to hold great promise for meaningful improvements across the goals of the Quadruple Aim. However, few studies testing these tools at scale, using relevant system-wide metrics, and under real-world conditions, have been published to date. Here, we document a reduction of ~$7000 per patient in direct medical charges (a total of $37 million over 5288 enrollees compared to 22,357 non-enrolled) in Medicare Advantage patients (≥65 years) receiving benefits through a state retirement system over the first 32 months of a voluntary PGx-enriched CMM program. We also observe a positive shift in healthcare resource utilization (HRU) away from acute care services and toward more sustainable and cost-effective primary care options. Together with improvements in medication risk assessment, patient/provider communication via pharmacist-mediated medication action plans (MAP), and the sustained positive trends in HRU, we suggest these results validate the use of a CDSS to unify PGx and CMM to optimize care for this and similar patient populations. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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11 pages, 1136 KiB

Open AccessArticle

Education and Training of Non-Genetics Providers on the Return of Genome Sequencing Results in a NICU Setting

by Kelly M. East, Meagan E. Cochran, Whitley V. Kelley, Veronica Greve, Candice R. Finnila, Tanner Coleman, Mikayla Jennings, Latonya Alexander, Elizabeth J. Rahn, Maria I. Danila, Greg Barsh, Bruce Korf and Greg Cooper

J. Pers. Med. 2022, 12(3), 405; https://doi.org/10.3390/jpm12030405 - 5 Mar 2022

Cited by 20 | Viewed by 2536

Abstract

To meet current and expected future demand for genome sequencing in the neonatal intensive care unit (NICU), adjustments to traditional service delivery models are necessary. Effective programs for the training of non-genetics providers (NGPs) may address the known barriers to providing genetic services [...] Read more.

To meet current and expected future demand for genome sequencing in the neonatal intensive care unit (NICU), adjustments to traditional service delivery models are necessary. Effective programs for the training of non-genetics providers (NGPs) may address the known barriers to providing genetic services including limited genetics knowledge and lack of confidence. The SouthSeq project aims to use genome sequencing to make genomic diagnoses in the neonatal period and evaluate a scalable approach to delivering genome sequencing results to populations with limited access to genetics professionals. Thirty-three SouthSeq NGPs participated in a live, interactive training intervention and completed surveys before and after participation. Here, we describe the protocol for the provider training intervention utilized in the SouthSeq study and the associated impact on NGP knowledge and confidence in reviewing, interpreting, and using genome sequencing results. Participation in the live training intervention led to an increased level of confidence in critical skills needed for real-world implementation of genome sequencing. Providers reported a significant increase in confidence level in their ability to review, understand, and use genome sequencing result reports to guide patient care. Reported barriers to implementation of genome sequencing in a NICU setting included test cost, lack of insurance coverage, and turn around time. As implementation of genome sequencing in this setting progresses, effective education of NGPs is critical to provide access to high-quality and timely genomic medicine care. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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11 pages, 1652 KiB

Open AccessCommunication

Clin.iobio: A Collaborative Diagnostic Workflow to Enable Team-Based Precision Genomics

by Alistair Ward, Matt Velinder, Tonya Di Sera, Aditya Ekawade, Sabrina Malone Jenkins, Barry Moore, Rong Mao, Pinar Bayrak-Toydemir and Gabor Marth

J. Pers. Med. 2022, 12(1), 73; https://doi.org/10.3390/jpm12010073 - 8 Jan 2022

Cited by 1 | Viewed by 3825

Abstract

The primary goal of precision genomics is the identification of causative genetic variants in targeted or whole-genome sequencing data. The ultimate clinical hope is that these findings lead to an efficacious change in treatment for the patient. In current clinical practice, these findings [...] Read more.

The primary goal of precision genomics is the identification of causative genetic variants in targeted or whole-genome sequencing data. The ultimate clinical hope is that these findings lead to an efficacious change in treatment for the patient. In current clinical practice, these findings are typically returned by expert analysts as static, text-based reports. Ideally, these reports summarize the quality of the data obtained, integrate known gene–phenotype associations, follow allele segregation and affected status within the sequenced samples, and weigh computational evidence of pathogenicity. These findings are used to prioritize the variant(s) most likely to cause the given patient’s phenotypes. In most diagnostic settings, a team of experts contribute to these reports, including bioinformaticians, clinicians, and genetic counselors, among others. However, these experts often do not have the necessary tools to review genomic findings, test genetic hypotheses, or query specific gene and variant information. Additionally, team members often rely on different tools and methods based on their given expertise, resulting in further difficulties in communicating and discussing genomic findings. Here, we present clin.iobio—a web-based solution to collaborative genomic analysis that enables diagnostic team members to focus on their area of expertise within the diagnostic process, while allowing them to easily review and contribute to all steps of the diagnostic process. Clin.iobio integrates tools from the popular iobio genomic visualization suite into a comprehensive diagnostic workflow, encompassing (1) genomic data quality review, (2) dynamic phenotype-driven gene prioritization, (3) variant prioritization using a comprehensive set of knowledge bases and annotations, (4) and an exportable findings summary. In conclusion, clin.iobio is a comprehensive solution to team-based precision genomics, the findings of which stand to inform genomic considerations in clinical practice. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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13 pages, 542 KiB

Open AccessArticle

Feasibility of a Traceback Approach for Using Pathology Specimens to Facilitate Genetic Testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) Study Protocol

by Tia L. Kauffman, Yolanda K. Prado, Ana A. Reyes, Jamilyn M. Zepp, Jennifer Sawyer, Larissa Lee White, Jessica Martucci, Suzanne Bianca Salas, Sarah Vertrees, Alan F. Rope, Sheila Weinmann, Nora B. Henrikson, Sandra Soo-Jin Lee, Heather Spencer Feigelson and Jessica Ezzell Hunter

J. Pers. Med. 2021, 11(11), 1194; https://doi.org/10.3390/jpm11111194 - 13 Nov 2021

Cited by 4 | Viewed by 2854

Abstract

Guidelines currently state that genetic testing is clinically indicated for all individuals diagnosed with ovarian cancer. Individuals with a prior diagnosis of ovarian cancer who have not received genetic testing represent missed opportunities to identify individuals with inherited high-risk cancer variants. For deceased [...] Read more.

Guidelines currently state that genetic testing is clinically indicated for all individuals diagnosed with ovarian cancer. Individuals with a prior diagnosis of ovarian cancer who have not received genetic testing represent missed opportunities to identify individuals with inherited high-risk cancer variants. For deceased individuals, post-mortem genetic testing of pathology specimens allows surviving family members to receive important genetic risk information. The Genetic Risk Assessment in Ovarian Cancer (GRACE) study aims to address this significant healthcare gap using a “traceback testing” approach to identify individuals with a prior diagnosis of ovarian cancer and offer genetic risk information to them and their family members. This study will assess the potential ethical and privacy concerns related to an ovarian cancer traceback testing approach in the context of patients who are deceased, followed by implementation and evaluation of the feasibility of an ovarian cancer traceback testing approach using tumor registries and archived pathology tissue. Descriptive and statistical analyses will assess health system and patient characteristics associated with the availability of pathology tissue and compare the ability to contact and uptake of genetic testing between patients who are living and deceased. The results of this study will inform the implementation of future traceback programs. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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12 pages, 446 KiB

Open AccessArticle

Population Genomic Screening for Genetic Etiologies of Neurodevelopmental/Psychiatric Disorders Demonstrates Personal Utility and Positive Participant Responses

by Karen E. Wain, Kasia Tolwinski, Emily Palen, Alexis R. Heidlebaugh, Karahlyn Holdren, Lauren Kasparson Walsh, Matthew T. Oetjens, David H. Ledbetter and Christa Lese Martin

J. Pers. Med. 2021, 11(5), 365; https://doi.org/10.3390/jpm11050365 - 1 May 2021

Cited by 6 | Viewed by 2742

Abstract

Genomic variants that cause neurodevelopmental/psychiatric disorders (NPD) are relatively prevalent and highly penetrant. This study aimed to understand adults’ immediate responses to receiving NPD-related results to inform inclusion in population-based genomic screening programs. Nine recurrent, pathogenic copy number variants (CNVs) were identified from [...] Read more.

Genomic variants that cause neurodevelopmental/psychiatric disorders (NPD) are relatively prevalent and highly penetrant. This study aimed to understand adults’ immediate responses to receiving NPD-related results to inform inclusion in population-based genomic screening programs. Nine recurrent, pathogenic copy number variants (CNVs) were identified from research exome data, clinically confirmed, and disclosed to adult participants of the Geisinger MyCode Community Health Initiative DiscovEHR cohort by experienced genetic counselors. A subset of in-person genetic counseling sessions (n = 27) were audio-recorded, transcribed, and coded using a grounded theory approach. Participant reactions were overwhelmingly positive and indicated that an NPD genetic etiology was highly valuable and personally useful. Participants frequently reported learning disabilities or other NPD that were not documented in their electronic health records and noted difficulties obtaining support for NPD needs. Most intended to share their genetic result with family members and health care providers and were interested in how their result could improve their healthcare. This study indicates that results from population-based NPD genomic screening can provide personal value for adults with NPD, were viewed positively by participants, and could improve clinical outcomes by informing symptom monitoring for NPD and co-morbidities, promoting improved health behaviors, and enhancing psychotherapeutic approaches. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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Review

Jump to: Research

15 pages, 297 KiB

Open AccessReview

Polygenic Scores in the Direct-to-Consumer Setting: Challenges and Opportunities for a New Era in Consumer Genetic Testing

by Jin K. Park and Christine Y. Lu

J. Pers. Med. 2023, 13(4), 573; https://doi.org/10.3390/jpm13040573 - 23 Mar 2023

Cited by 7 | Viewed by 2435

Abstract

Direct-to-consumer (DTC) genetic tests have generated considerable scholarly attention and public intrigue. Although the current consumer genetic testing regime relies on the reporting of individual variants of interest to consumers, there has recently been interest in the possibility of integrating polygenic scores (PGS), [...] Read more.

Direct-to-consumer (DTC) genetic tests have generated considerable scholarly attention and public intrigue. Although the current consumer genetic testing regime relies on the reporting of individual variants of interest to consumers, there has recently been interest in the possibility of integrating polygenic scores (PGS), which aggregate genetic liability for disease across the entire genome. While PGS have thus far been extensively explored as clinical and public health tools, the use of PGS in consumer genetic testing has not yet received systematic attention, even though they are already in use for some consumer genetic tests. In this narrative review, we highlight the ethical, legal, and social implications of the use of PGS in DTC genetic tests and synthesize existing solutions to these concerns. We organize these concerns into three domains: (1) industry variation; (2) privacy and commercialization; and (3) patient safety and risk. While previously expressed concerns in these domains will remain relevant, the emergence of PGS-based DTC genetic tests raises challenges that will require novel approaches. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

18 pages, 2249 KiB

Open AccessReview

Patient-Reported Outcomes following Genetic Testing for Familial Hypercholesterolemia, Breast and Ovarian Cancer Syndrome, and Lynch Syndrome: A Systematic Review

by Rachele M. Hendricks-Sturrup, Lucson Joseph and Christine Y. Lu

J. Pers. Med. 2021, 11(9), 850; https://doi.org/10.3390/jpm11090850 - 27 Aug 2021

Cited by 2 | Viewed by 3743

Abstract

Background: Patient-reported outcomes (PROs) and PRO measures (PROMs) are real-world evidence that can help capture patient experiences and perspectives regarding a clinical intervention such as genetic testing. Objective: To identify and capture methods and qualitative PRO themes among studies reporting PROs following genetic [...] Read more.

Background: Patient-reported outcomes (PROs) and PRO measures (PROMs) are real-world evidence that can help capture patient experiences and perspectives regarding a clinical intervention such as genetic testing. Objective: To identify and capture methods and qualitative PRO themes among studies reporting PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Methods: A systematic review was conducted via PubMed/MEDLINE, EMBASE, and Yale University’s TRIP Medical Databases on articles published by April 2021. Results: We identified 24 studies published between 1996 and 2021 representing 4279 participants that reported PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Studies collected and reported PROs from validated PROM instruments (n = 12; 50%), validated surveys (n = 7; 26%), and interviews (n = 10; 42%). PRO themes ranged across all collection methods (e.g., psychological, knowledge, coping and satisfaction, concern about stigma/discrimination, etc.). Conclusions: Important gaps identified include (1) most studies (n = 18; 75%) reported PROs following genetic testing for breast and ovarian cancer, and (2) populations reporting PROs overall were largely of White/Caucasian/Northern European/Anglo-Saxon descent. We offer recommendations and describe real-world implications for the field moving forward. Full article

(This article belongs to the Special Issue Precision Medicine in Clinical Practice)

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