Open AccessConcept Paper
Precision Health Economics and Outcomes Research to Support Precision Medicine: Big Data Meets Patient Heterogeneity on the Road to Value
J. Pers. Med. 2016, 6(4), 20; doi:10.3390/jpm6040020 -
Abstract
The “big data” era represents an exciting opportunity to utilize powerful new sources of information to reduce clinical and health economic uncertainty on an individual patient level. In turn, health economic outcomes research (HEOR) practices will need to evolve to accommodate individual patient–level
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The “big data” era represents an exciting opportunity to utilize powerful new sources of information to reduce clinical and health economic uncertainty on an individual patient level. In turn, health economic outcomes research (HEOR) practices will need to evolve to accommodate individual patient–level HEOR analyses. We propose the concept of “precision HEOR”, which utilizes a combination of costs and outcomes derived from big data to inform healthcare decision-making that is tailored to highly specific patient clusters or individuals. To explore this concept, we discuss the current and future roles of HEOR in health sector decision-making, big data and predictive analytics, and several key HEOR contexts in which big data and predictive analytics might transform traditional HEOR into precision HEOR. The guidance document addresses issues related to the transition from traditional to precision HEOR practices, the evaluation of patient similarity analysis and its appropriateness for precision HEOR analysis, and future challenges to precision HEOR adoption. Precision HEOR should make precision medicine more realizable by aiding and adapting healthcare resource allocation. The combined hopes for precision medicine and precision HEOR are that individual patients receive the best possible medical care while overall healthcare costs remain manageable or become more cost-efficient. Full article
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Open AccessArticle
IDICAP: A Novel Tool for Integrating Drug Intervention Based on Cancer Panel
J. Pers. Med. 2016, 6(4), 19; doi:10.3390/jpm6040019 -
Abstract
Cancer is a heterogeneous disease afflicting millions of people of all ages and their families worldwide. Tremendous resources have been and continue to be devoted to the development of cancer treatments that target the unique mutation profiles of patients, namely targeted cancer therapy.
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Cancer is a heterogeneous disease afflicting millions of people of all ages and their families worldwide. Tremendous resources have been and continue to be devoted to the development of cancer treatments that target the unique mutation profiles of patients, namely targeted cancer therapy. However, the sheer volume of drugs coupled with cancer heterogeneity becomes a challenge for physicians to prescribe effective therapies targeting patients’ unique genetic mutations. Developing a web service that allows clinicians as well as patients to identify effective drug therapies, both approved and experimental, would be helpful for both parties. We have developed an innovative web service, IDICAP, which stands for Integrated Drug Intervention for CAncer Panel. It uses genes that have been linked to a cancer type to search for drug and clinical trial information from ClinicalTrials.gov and DrugBank. IDICAP selects and integrates information pertaining to clinical trials, disease conditions, drugs under trial, locations of trials, drugs that are known to target the queried gene, and any known single nucleotide polymorphism (SNP) effects. We tested IDICAP by gene panels that contribute to breast cancer, ovarian cancer, and cancer in general. Clinical trials and drugs listed by our tool showed improved precision compared to the results from ClinicalTrials.gov and Drug Gene Interaction Database (DGIdb). Furthermore, IDICAP provides patients and doctors with a list of clinical facilities in their proximity, a characteristic that lends credence to the Precision Medicine Initiative launched by the White House in the United States in 2015. Full article
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Open AccessEditorial
Implementing Personalized Medicine in the Academic Health Center
J. Pers. Med. 2016, 6(3), 18; doi:10.3390/jpm6030018 -
Abstract Recently we at Partners Health Care had a series of articles in the Journal of Personalized Medicine describing how we are going about implementing Personalized Medicine in an academic health care system [1–10].[...] Full article
Open AccessArticle
Implementation of Electronic Consent at a Biobank: An Opportunity for Precision Medicine Research
J. Pers. Med. 2016, 6(2), 17; doi:10.3390/jpm6020017 -
Abstract
The purpose of this study is to characterize the potential benefits and challenges of electronic informed consent (eIC) as a strategy for rapidly expanding the reach of large biobanks while reducing costs and potentially enhancing participant engagement. The Partners HealthCare Biobank (Partners Biobank)
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The purpose of this study is to characterize the potential benefits and challenges of electronic informed consent (eIC) as a strategy for rapidly expanding the reach of large biobanks while reducing costs and potentially enhancing participant engagement. The Partners HealthCare Biobank (Partners Biobank) implemented eIC tools and processes to complement traditional recruitment strategies in June 2014. Since then, the Partners Biobank has rigorously collected and tracked a variety of metrics relating to this novel recruitment method. From June 2014 through January 2016, the Partners Biobank sent email invitations to 184,387 patients at Massachusetts General Hospital and Brigham and Women’s Hospital. During the same time period, 7078 patients provided their consent via eIC. The rate of consent of emailed patients was 3.5%, and the rate of consent of patients who log into the eIC website at Partners Biobank was 30%. Banking of biospecimens linked to electronic health records has become a critical element of genomic research and a foundation for the NIH’s Precision Medicine Initiative (PMI). eIC is a feasible and potentially game-changing strategy for these large research studies that depend on patient recruitment. Full article
Open AccessArticle
Personalized Medicine in the U.S. and Germany: Awareness, Acceptance, Use and Preconditions for the Wide Implementation into the Medical Standard
J. Pers. Med. 2016, 6(2), 15; doi:10.3390/jpm6020015 -
Abstract
The aim of our research was to collect comprehensive data about the public and physician awareness, acceptance and use of Personalized Medicine (PM), as well as their opinions on PM reimbursement and genetic privacy protection in the U.S. and Germany. In order to
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The aim of our research was to collect comprehensive data about the public and physician awareness, acceptance and use of Personalized Medicine (PM), as well as their opinions on PM reimbursement and genetic privacy protection in the U.S. and Germany. In order to give a better overview, we compared our survey results with the results from other studies and discussed Personalized Medicine preconditions for its wide implementation into the medical standard. For the data collection, using the same methodology, we performed several surveys in Pennsylvania (U.S.) and Bavaria (Germany). Physicians were contacted via letter, while public representatives in person. Survey results, analyzed by means of descriptive and non-parametric statistic methods, have shown that awareness, acceptance, use and opinions on PM aspects in Pennsylvania and Bavaria were not significantly different. In both states there were strong concerns about genetic privacy protection and no support of one genetic database. The costs for Personalized Medicine were expected to be covered by health insurances and governmental funds. Summarizing, we came to the conclusion that for PM wide implementation there will be need to adjust the healthcare reimbursement system, as well as adopt new laws which protect against genetic misuse and simultaneously enable voluntary data provision. Full article
Open AccessArticle
Barriers and Facilitators to Adoption of Genomic Services for Colorectal Care within the Veterans Health Administration
J. Pers. Med. 2016, 6(2), 16; doi:10.3390/jpm6020016 -
Abstract
We examined facilitators and barriers to adoption of genomic services for colorectal care, one of the first genomic medicine applications, within the Veterans Health Administration to shed light on areas for practice change. We conducted semi-structured interviews with 58 clinicians to understand use
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We examined facilitators and barriers to adoption of genomic services for colorectal care, one of the first genomic medicine applications, within the Veterans Health Administration to shed light on areas for practice change. We conducted semi-structured interviews with 58 clinicians to understand use of the following genomic services for colorectal care: family health history documentation, molecular and genetic testing, and genetic counseling. Data collection and analysis were informed by two conceptual frameworks, the Greenhalgh Diffusion of Innovation and Andersen Behavioral Model, to allow for concurrent examination of both access and innovation factors. Specialists were more likely than primary care clinicians to obtain family history to investigate hereditary colorectal cancer (CRC), but with limited detail; clinicians suggested templates to facilitate retrieval and documentation of family history according to guidelines. Clinicians identified advantage of molecular tumor analysis prior to genetic testing, but tumor testing was infrequently used due to perceived low disease burden. Support from genetic counselors was regarded as facilitative for considering hereditary basis of CRC diagnosis, but there was variability in awareness of and access to this expertise. Our data suggest the need for tools and policies to establish and disseminate well-defined processes for accessing services and adhering to guidelines. Full article
Open AccessFeature PaperReview
Personal Genome Sequencing in Ostensibly Healthy Individuals and the PeopleSeq Consortium
J. Pers. Med. 2016, 6(2), 14; doi:10.3390/jpm6020014 -
Abstract
Thousands of ostensibly healthy individuals have had their exome or genome sequenced, but a much smaller number of these individuals have received any personal genomic results from that sequencing. We term those projects in which ostensibly healthy participants can receive sequencing-derived genetic findings
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Thousands of ostensibly healthy individuals have had their exome or genome sequenced, but a much smaller number of these individuals have received any personal genomic results from that sequencing. We term those projects in which ostensibly healthy participants can receive sequencing-derived genetic findings and may also have access to their genomic data as participatory predispositional personal genome sequencing (PPGS). Here we are focused on genome sequencing applied in a pre-symptomatic context and so define PPGS to exclude diagnostic genome sequencing intended to identify the molecular cause of suspected or diagnosed genetic disease. In this report we describe the design of completed and underway PPGS projects, briefly summarize the results reported to date and introduce the PeopleSeq Consortium, a newly formed collaboration of PPGS projects designed to collect much-needed longitudinal outcome data. Full article
Open AccessArticle
Bioinformatics Workflow for Clinical Whole Genome Sequencing at Partners HealthCare Personalized Medicine
J. Pers. Med. 2016, 6(1), 12; doi:10.3390/jpm6010012 -
Abstract
Effective implementation of precision medicine will be enhanced by a thorough understanding of each patient’s genetic composition to better treat his or her presenting symptoms or mitigate the onset of disease. This ideally includes the sequence information of a complete genome for each
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Effective implementation of precision medicine will be enhanced by a thorough understanding of each patient’s genetic composition to better treat his or her presenting symptoms or mitigate the onset of disease. This ideally includes the sequence information of a complete genome for each individual. At Partners HealthCare Personalized Medicine, we have developed a clinical process for whole genome sequencing (WGS) with application in both healthy individuals and those with disease. In this manuscript, we will describe our bioinformatics strategy to efficiently process and deliver genomic data to geneticists for clinical interpretation. We describe the handling of data from FASTQ to the final variant list for clinical review for the final report. We will also discuss our methodology for validating this workflow and the cost implications of running WGS. Full article
Open AccessArticle
Infrastructure for Personalized Medicine at Partners HealthCare
J. Pers. Med. 2016, 6(1), 13; doi:10.3390/jpm6010013 -
Abstract
Partners HealthCare Personalized Medicine (PPM) is a center within the Partners HealthCare system (founded by Massachusetts General Hospital and Brigham and Women’s Hospital) whose mission is to utilize genetics and genomics to improve the care of patients in a cost effective manner. PPM
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Partners HealthCare Personalized Medicine (PPM) is a center within the Partners HealthCare system (founded by Massachusetts General Hospital and Brigham and Women’s Hospital) whose mission is to utilize genetics and genomics to improve the care of patients in a cost effective manner. PPM consists of five interconnected components: (1) Laboratory for Molecular Medicine (LMM), a CLIA laboratory performing genetic testing for patients world-wide; (2) Translational Genomics Core (TGC), a core laboratory providing genomic platforms for Partners investigators; (3) Partners Biobank, a biobank of samples (DNA, plasma and serum) for 50,000 Consented Partners patients; (4) Biobank Portal, an IT infrastructure and viewer to bring together genotypes, samples, phenotypes (validated diagnoses, radiology, and clinical chemistry) from the electronic medical record to Partners investigators. These components are united by (5) a common IT system that brings researchers, clinicians, and patients together for optimal research and patient care. Full article
Open AccessArticle
The Biobank Portal for Partners Personalized Medicine: A Query Tool for Working with Consented Biobank Samples, Genotypes, and Phenotypes Using i2b2
J. Pers. Med. 2016, 6(1), 11; doi:10.3390/jpm6010011 -
Abstract
We have designed a Biobank Portal that lets researchers request Biobank samples and genotypic data, query associated electronic health records, and design and download datasets containing de-identified attributes about consented Biobank subjects. This do-it-yourself functionality puts a wide variety and volume of data
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We have designed a Biobank Portal that lets researchers request Biobank samples and genotypic data, query associated electronic health records, and design and download datasets containing de-identified attributes about consented Biobank subjects. This do-it-yourself functionality puts a wide variety and volume of data at the fingertips of investigators, allowing them to create custom datasets for their clinical and genomic research from complex phenotypic data and quickly obtain corresponding samples and genomic data. The Biobank Portal is built upon the i2b2 infrastructure [1] and uses an open-source web client that is available to faculty members and other investigators behind an institutional firewall. Built-in privacy measures [2] ensure that the data in the Portal are utilized only according to the processes to which the patients have given consent. Full article
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Open AccessArticle
The Translational Genomics Core at Partners Personalized Medicine: Facilitating the Transition of Research towards Personalized Medicine
J. Pers. Med. 2016, 6(1), 10; doi:10.3390/jpm6010010 -
Abstract
The Translational Genomics Core (TGC) at Partners Personalized Medicine (PPM) serves as a fee-for-service core laboratory for Partners Healthcare researchers, providing access to technology platforms and analysis pipelines for genomic, transcriptomic, and epigenomic research projects. The interaction of the TGC with various components
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The Translational Genomics Core (TGC) at Partners Personalized Medicine (PPM) serves as a fee-for-service core laboratory for Partners Healthcare researchers, providing access to technology platforms and analysis pipelines for genomic, transcriptomic, and epigenomic research projects. The interaction of the TGC with various components of PPM provides it with a unique infrastructure that allows for greater IT and bioinformatics opportunities, such as sample tracking and data analysis. The following article describes some of the unique opportunities available to an academic research core operating within PPM, such the ability to develop analysis pipelines with a dedicated bioinformatics team and maintain a flexible Laboratory Information Management System (LIMS) with the support of an internal IT team, as well as the operational challenges encountered to respond to emerging technologies, diverse investigator needs, and high staff turnover. In addition, the implementation and operational role of the TGC in the Partners Biobank genotyping project of over 25,000 samples is presented as an example of core activities working with other components of PPM. Full article
Open AccessArticle
Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia
J. Pers. Med. 2016, 6(1), 9; doi:10.3390/jpm6010009 -
Abstract
This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A
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This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p ≤ 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p ≤ 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype. Full article
Open AccessCommunication
The Changing Landscape of Molecular Diagnostic Testing: Implications for Academic Medical Centers
J. Pers. Med. 2016, 6(1), 8; doi:10.3390/jpm6010008 -
Abstract
Over the last decade, the field of molecular diagnostics has undergone tremendous transformation, catalyzed by the clinical implementation of next generation sequencing (NGS). As technical capabilities are enhanced and current limitations are addressed, NGS is increasingly capable of detecting most variant types and
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Over the last decade, the field of molecular diagnostics has undergone tremendous transformation, catalyzed by the clinical implementation of next generation sequencing (NGS). As technical capabilities are enhanced and current limitations are addressed, NGS is increasingly capable of detecting most variant types and will therefore continue to consolidate and simplify diagnostic testing. It is likely that genome sequencing will eventually serve as a universal first line test for disorders with a suspected genetic origin. Academic Medical Centers (AMCs), which have been at the forefront of this paradigm shift are now presented with challenges to keep up with increasing technical, bioinformatic and interpretive complexity of NGS-based tests in a highly competitive market. Additional complexity may arise from altered regulatory oversight, also triggered by the unprecedented scope of NGS-based testing, which requires new approaches. However, these challenges are balanced by unique opportunities, particularly at the interface between clinical and research operations, where AMCs can capitalize on access to cutting edge research environments and establish collaborations to facilitate rapid diagnostic innovation. This article reviews present and future challenges and opportunities for AMC associated molecular diagnostic laboratories from the perspective of the Partners HealthCare Laboratory for Molecular Medicine (LMM). Full article
Open AccessEditorial
Acknowledgement to Reviewers of Journal of Personalized Medicine in 2015
J. Pers. Med. 2016, 6(1), 7; doi:10.3390/jpm6010007 -
Abstract The editors of Journal of Personalized Medicine would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article
Open AccessTechnical Note
The Information Technology Infrastructure for the Translational Genomics Core and the Partners Biobank at Partners Personalized Medicine
J. Pers. Med. 2016, 6(1), 6; doi:10.3390/jpm6010006 -
Abstract
The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT) infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent
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The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT) infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent to the time that genomic data is distributed for research, and enables the management of complex genetic data. Here, we describe the functional components of the research IT infrastructure at Partners Personalized Medicine and how they integrate with existing clinical and research systems, review some of the ways in which this IT infrastructure maintains data integrity and security, and discuss some of the challenges inherent to building and maintaining such infrastructure. Full article
Open AccessArticle
Information Technology Support for Clinical Genetic Testing within an Academic Medical Center
J. Pers. Med. 2016, 6(1), 4; doi:10.3390/jpm6010004 -
Abstract
Academic medical centers require many interconnected systems to fully support genetic testing processes. We provide an overview of the end-to-end support that has been established surrounding a genetic testing laboratory within our environment, including both laboratory and clinician facing infrastructure. We explain key
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Academic medical centers require many interconnected systems to fully support genetic testing processes. We provide an overview of the end-to-end support that has been established surrounding a genetic testing laboratory within our environment, including both laboratory and clinician facing infrastructure. We explain key functions that we have found useful in the supporting systems. We also consider ways that this infrastructure could be enhanced to enable deeper assessment of genetic test results in both the laboratory and clinic. Full article
Open AccessFeature PaperArticle
An eMERGE Clinical Center at Partners Personalized Medicine
J. Pers. Med. 2016, 6(1), 5; doi:10.3390/jpm6010005 -
Abstract
The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and
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The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and implementation research by leveraging biorepositories linked to EMRs. In its most recent phase, eMERGE III, the network is focused on facilitating implementation of genomic medicine by detecting and disclosing rare pathogenic variants in clinically relevant genes. Partners Personalized Medicine (PPM) is a center dedicated to translating personalized medicine into clinical practice within Partners HealthCare. One component of the PPM is the Partners Healthcare Biobank, a biorepository comprising broadly consented DNA samples linked to the Partners longitudinal EMR. In 2015, PPM joined the eMERGE Phase III network. Here we describe the elements of the eMERGE clinical center at PPM, including plans for genomic discovery using EMR phenotypes, evaluation of rare variant penetrance and pleiotropy, and a novel randomized trial of the impact of returning genetic results to patients and clinicians. Full article
Open AccessFeature PaperReview
Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics—Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer
J. Pers. Med. 2016, 6(1), 3; doi:10.3390/jpm6010003 -
Abstract
Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing
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Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice. Full article
Open AccessFeature PaperArticle
Building the Partners HealthCare Biobank at Partners Personalized Medicine: Informed Consent, Return of Research Results, Recruitment Lessons and Operational Considerations
J. Pers. Med. 2016, 6(1), 2; doi:10.3390/jpm6010002 -
Abstract
The Partners HealthCare Biobank is a Partners HealthCare enterprise-wide initiative whose goal is to provide a foundation for the next generation of translational research studies of genotype, environment, gene-environment interaction, biomarker and family history associations with disease phenotypes. The Biobank has leveraged in-person
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The Partners HealthCare Biobank is a Partners HealthCare enterprise-wide initiative whose goal is to provide a foundation for the next generation of translational research studies of genotype, environment, gene-environment interaction, biomarker and family history associations with disease phenotypes. The Biobank has leveraged in-person and electronic recruitment methods to enroll >30,000 subjects as of October 2015 at two academic medical centers in Partners HealthCare since launching in 2010. Through a close collaboration with the Partners Human Research Committee, the Biobank has developed a comprehensive informed consent process that addresses key patient concerns, including privacy and the return of research results. Lessons learned include the need for careful consideration of ethical issues, attention to the educational content of electronic media, the importance of patient authentication in electronic informed consent, the need for highly secure IT infrastructure and management of communications and the importance of flexible recruitment modalities and processes dependent on the clinical setting for recruitment. Full article
Open AccessFeature PaperArticle
Training the Future Leaders in Personalized Medicine
J. Pers. Med. 2016, 6(1), 1; doi:10.3390/jpm6010001 -
Abstract
The era of personalized medicine has arrived, and with it a need for leaders in this discipline. This generation of trainees requires a cadre of new skill sets to lead the implementation of personalized medicine into mainstream healthcare. Traditional training programs no longer
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The era of personalized medicine has arrived, and with it a need for leaders in this discipline. This generation of trainees requires a cadre of new skill sets to lead the implementation of personalized medicine into mainstream healthcare. Traditional training programs no longer provide trainees with all the skills they will need to optimize implementation of this revolution now underway in medicine. Today’s trainees must manage clinical teams, act as clinical and molecular diagnostic consultants, train other healthcare professionals, teach future generations, and be knowledgeable about clinical trials to facilitate genomic-based therapies. To prepare trainees for the transition to junior faculty positions, contemporary genomic training programs must emphasize the development of these management, teaching, and clinical skills. Full article