This document describes the principles, organization, and operation of a DNA bank established by the Department of Veterans Affairs Cooperative Studies Program. The DNA bank was created to facilitate genetic research using DNA samples collected from participants in clinical trials and studies. Key aspects discussed include obtaining informed consent from participants, ensuring privacy and confidentiality, resolving issues around ownership and future use of genetic material, and providing an infrastructure to support linking genetic and clinical data. The DNA bank is intended to be a shared resource that can support future genetic research across multiple clinical studies in different disease areas over time.
Capstone thesis submitted for undergraduate studies on the utility of genomic surveying tools in improving sudden cardiac arrest risk stratification and prediction of sudden cardiac death.
Computational challenges in precision medicine and genomicsGary Bader
Genomics is mapping complex data about human biology and promises major medical advances. In particular, genomics is enabling precision medicine, the use of a patient's genome and physiological state to improve therapeutic efficacy and outcome. However, routine use of genomics data in medical research is in its infancy, due mainly to the challenges of working with "Big data". These data are so complex and large that typical researchers are not able to cope with them. Collectively, these data require an understanding of many aspects of experimental biology and medicine to correctly process and interpret. Data size is also an issue, as individual researchers may need to handle tens of terabytes (genomes from a few hundred patients), which is challenging to download and store on typical workstations. To effectively support precision medicine, scientists from a wide range of disciplines, including computer science, must develop algorithms to improve precision medicine (e.g. diagnostics and prognostics), genome interpretation, raw data processing and secure high performance computing.
Crowdsourcing applied to knowledge management in translational research: the ...SC CTSI at USC and CHLA
Date: November 8th, 2018
Speaker: Andrew Su, PhD, Professor, Department of Integrative, Structural and Computational Biology, The Scripps Research Institute
Overview: Crowdsourcing involves the engagement of large communities of individuals to collaboratively accomplish tasks at massive scale. These tasks could be online or offline, paid or for free. But how can crowdsourcing science help your research? This webinar will describe two crowdsourcing projects for translational research, both of which aim to better organize biomedical information so that it can be more easily accessed, integrated, and queried:
First, the goal of the Gene Wiki project is to create a community-maintained knowledge base of all relationships between biological entities, including genes, diseases, drugs, pathways, and variants. This project draws on the collective efforts of informatics researchers from a wide range of disciplines, including bioinformatics, cheminformatics, and medical informatics.
Second, the Mark2Cure project partners with the citizen scientist community to extract structured content from biomedical abstracts with an emphasis on rare disease. Although citizen scientists do not have any specialized expertise, after receiving proper training, Mark2Cure has shown that in aggregate they perform bio-curation at an accuracy comparable to professional scientists.
Capstone thesis submitted for undergraduate studies on the utility of genomic surveying tools in improving sudden cardiac arrest risk stratification and prediction of sudden cardiac death.
Computational challenges in precision medicine and genomicsGary Bader
Genomics is mapping complex data about human biology and promises major medical advances. In particular, genomics is enabling precision medicine, the use of a patient's genome and physiological state to improve therapeutic efficacy and outcome. However, routine use of genomics data in medical research is in its infancy, due mainly to the challenges of working with "Big data". These data are so complex and large that typical researchers are not able to cope with them. Collectively, these data require an understanding of many aspects of experimental biology and medicine to correctly process and interpret. Data size is also an issue, as individual researchers may need to handle tens of terabytes (genomes from a few hundred patients), which is challenging to download and store on typical workstations. To effectively support precision medicine, scientists from a wide range of disciplines, including computer science, must develop algorithms to improve precision medicine (e.g. diagnostics and prognostics), genome interpretation, raw data processing and secure high performance computing.
Crowdsourcing applied to knowledge management in translational research: the ...SC CTSI at USC and CHLA
Date: November 8th, 2018
Speaker: Andrew Su, PhD, Professor, Department of Integrative, Structural and Computational Biology, The Scripps Research Institute
Overview: Crowdsourcing involves the engagement of large communities of individuals to collaboratively accomplish tasks at massive scale. These tasks could be online or offline, paid or for free. But how can crowdsourcing science help your research? This webinar will describe two crowdsourcing projects for translational research, both of which aim to better organize biomedical information so that it can be more easily accessed, integrated, and queried:
First, the goal of the Gene Wiki project is to create a community-maintained knowledge base of all relationships between biological entities, including genes, diseases, drugs, pathways, and variants. This project draws on the collective efforts of informatics researchers from a wide range of disciplines, including bioinformatics, cheminformatics, and medical informatics.
Second, the Mark2Cure project partners with the citizen scientist community to extract structured content from biomedical abstracts with an emphasis on rare disease. Although citizen scientists do not have any specialized expertise, after receiving proper training, Mark2Cure has shown that in aggregate they perform bio-curation at an accuracy comparable to professional scientists.
Tools and Technology for Advancing Rare Disease Research and Drug DevelopmentCovance
This white paper discusses virtual mapping of natural histories, the application of predictive modeling to better understand comorbidities and disease progressions as well as linkage to longitudinal real-world data sets. The goal is to improve diagnosis of patients, improve the design and conducting of trials, and enable development of more treatment options for people living with rare diseases.
Evaluation of comorbid autoimmune diseases among patients and family members enrolled in the Alopecia
Areata Registry, Biobank & Clinical Trials Network.
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Death prompts a review of gene therapy vectorLindsay Meyer
Case study and analysis of Targeted Genetics' adeno-associated virus, tgAAC94. Includes overview of clinical trial design, FDA action, NIH investigation, and outcomes surrounding the death of a patient enrolled in the investigational trial.
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
Lecture Objectives:
1) To use examples from my research to define and introduce the ideals of precision medicine and digital health. 2) To introduce how large scale population-wide analysis of data can be used to facilitate these two ideals. 3) To introduce how freely available open data can be used to facilitate these two ideals. 4) To show how mobile technology can be used to facilitate these two ideals.
Fluoroquinolone resistant rectal colonization predicts risk of infectious com...TC İÜ İTF Üroloji AD
Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy. Evidence based on journal club by Samed Verep
Ethical, legal, social, and policy issues in the use of genomic technology by...Ilya Klabukov
"Ethical, legal, social, and policy issues in the use of genomic technology by the U.S. Military"
Maxwell J. Mehlman and Tracy Yeheng Li
Advances in genomic science are attracting the interest of the U.S. military for their potential to improve medical care for members of the military and to aid in military recruitment, training, specialization, and mission accomplishment. While researchers have explored the ethical, legal, and social issues raised by the use of genomic science in a wide variety of contexts, there has been virtually no examination of these issues in connection with the use of genomics by the military. This article identifies potential uses of genomic science by the military, proposes an applicable ethical and legal framework, and applies the framework to provide ethical and legal guidance for military decision-makers.
Tools and Technology for Advancing Rare Disease Research and Drug DevelopmentCovance
This white paper discusses virtual mapping of natural histories, the application of predictive modeling to better understand comorbidities and disease progressions as well as linkage to longitudinal real-world data sets. The goal is to improve diagnosis of patients, improve the design and conducting of trials, and enable development of more treatment options for people living with rare diseases.
Evaluation of comorbid autoimmune diseases among patients and family members enrolled in the Alopecia
Areata Registry, Biobank & Clinical Trials Network.
Statin therapy associated with improved thrombus resolution in patients with ...TÀI LIỆU NGÀNH MAY
Để xem full tài liệu Xin vui long liên hệ page để được hỗ trợ
: https://www.facebook.com/thuvienluanvan01
HOẶC
https://www.facebook.com/garmentspace/
https://www.facebook.com/thuvienluanvan01
https://www.facebook.com/thuvienluanvan01
tai lieu tong hop, thu vien luan van, luan van tong hop, do an chuyen nganh
Death prompts a review of gene therapy vectorLindsay Meyer
Case study and analysis of Targeted Genetics' adeno-associated virus, tgAAC94. Includes overview of clinical trial design, FDA action, NIH investigation, and outcomes surrounding the death of a patient enrolled in the investigational trial.
From Bits to Bedside: Translating Big Data into Precision Medicine and Digita...Dexter Hadley
Lecture Objectives:
1) To use examples from my research to define and introduce the ideals of precision medicine and digital health. 2) To introduce how large scale population-wide analysis of data can be used to facilitate these two ideals. 3) To introduce how freely available open data can be used to facilitate these two ideals. 4) To show how mobile technology can be used to facilitate these two ideals.
Fluoroquinolone resistant rectal colonization predicts risk of infectious com...TC İÜ İTF Üroloji AD
Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy. Evidence based on journal club by Samed Verep
Ethical, legal, social, and policy issues in the use of genomic technology by...Ilya Klabukov
"Ethical, legal, social, and policy issues in the use of genomic technology by the U.S. Military"
Maxwell J. Mehlman and Tracy Yeheng Li
Advances in genomic science are attracting the interest of the U.S. military for their potential to improve medical care for members of the military and to aid in military recruitment, training, specialization, and mission accomplishment. While researchers have explored the ethical, legal, and social issues raised by the use of genomic science in a wide variety of contexts, there has been virtually no examination of these issues in connection with the use of genomics by the military. This article identifies potential uses of genomic science by the military, proposes an applicable ethical and legal framework, and applies the framework to provide ethical and legal guidance for military decision-makers.
Easy automation choices for landscape businessesDavid Marciniak
Running a landscape business can be a huge challenge. The right tools can make that a lot easier, and I've found some technology tools that are low cost and REALLY useful.
This year's 3rd Annual TCGC: The Clinical Genome Conference, held June 10-12, 2014 in San Francisco, is a three-day event that weaves together the science of sequencing and the business of implementing genomics in the clinic. It uniquely illustrates the mutual influence of those areas and the need to therefore consider the needs, challenges and opportunities of both - from next-generation sequencing and variant interpretation to insurance reimbursement and electronic health records - throughout the entire research process.Learn more at http://www.clinicalgenomeconference.com
TCGC The Clinical Genome Conference 2015Nicole Proulx
Bio-IT World and Cambridge Healthtech Institute are again proud to host the Fourth Annual TCGC: The Clinical Genome Conference, inviting stakeholders impacting clinical genomics to share new findings and solutions for advancing the applications of clinical genome medicine.
The word genome can refer specifically to the DNA in the nucleus of a cell, but it can also refer to the genome of organelles
that contain their own DNA. Additionally, the genome can include
non-chromosomal genetic elements - viruses, plasmids and transposons. When the genome of a sexually reproducing organism is
said to be sequenced, it is typically understood that one haploid set
of autosomes and one of each type of sex chromosome has been sequenced, which together describe the genomes of both sexes. The
term “genomic sequence” can include a mosaic of data collected
from the chromosomes of different individuals, so this sequence is
representative of the genetic material of a given species. The study
of the general properties of the genome, their evolution and the
connection with the phenotype is called genomics, and thus differs
from genetics, which in principle studies the properties of a single
gene or group of genes.
MseqDR consortium: a grass-roots effort to establish a global resource aimed ...Human Variome Project
The success of whole exome sequencing (WES) for highly heterogeneous disorders, such as mitochondrial disease, is limited by substantial technical and bioinformatics challenges to correctly identify and prioritize the extensive number of sequence variants present in each patient. The likelihood of success can be greatly improved if a large cohort of patient data is assembled in which sequence variants can be systematically analysed, annotated, and interpreted relative to known phenotype. This effort has engaged and united more than 100 international mitochondrial clinicians, researchers, and bioinformaticians in the Mitochondrial Disease Sequence Data Resource (MSeqDR) consortium that formed in June 2012 to identify and prioritize the specific WES data analysis needs of the global mitochondrial disease community. Through regular web-based meetings, we have familiarized ourselves with existing strengths and gaps facing integration of MSeqDR with public resources, as well as the major practical, technical, and ethical challenges that must be overcome to create a sustainable data resource. We have now moved forward toward our common goal by establishing a central data resource (http://mseqdr.org/) that has both public access and secure web-based features that allow the coherent compilation, organization, annotation, and analysis of WES and mtDNA genome data sets generated in both clinical- and research-based settings of suspected mitochondrial disease patients. The most important aims of the MSeqDR consortium are summarized in the MSeqDR portal within the Consortium overview sections. Consortium participants are organized in 3 working groups that include (1) Technology and Bioinformatics; (2) Phenotyping, databasing, IRB concerns and access; and (3) Mitochondrial DNA specific concerns. The online MSeqDR resource is organized into discrete sections to facilitate data deposition and common reannotation, data visualization, data set mining, and access management. With the support of the United Mitochondrial Disease Foundation (UMDF) and the NINDS/NICHD U54 supported North American Mitochondrial Disease Consortium (NAMDC), the MSeqDR prototype has been built. Current major components include common data upload and reannotation using a novel HBCR based annotation tool that has also been made publicly available through the website, MSeqDR GBrowse that allows ready visualization of all public and MSeqDR specific data including labspecific aggregate data visualization tracks, MSeqDR-LSDB instance of nearly 1250 mitochondrial disease and mitochodnrial localized genes that is based on the Locus Specific Database model, exome data set mining in individuals or families using the GEM.app tool, and Account & Access Management. Within MSeqDR GBrowse it is now possible to explore data derived from MitoMap, HmtDB, ClinVar, UCSC-NumtS, ENCODE, 1000 genomes, and many other resources that bioinformaticians recruited to the project are organizing.
Use of Genetic Databases to Advance Diagnostic Test DevelopmentEMMAIntl
In December 2018, the U.S. Food and Drug Administration formally recognized a public database that contains information about genes, genetic variants, and their relationship to disease. This blog discusses the motivation for creating such public databases and the implications for developers of genetic tests...
Modern Genomics in conjunction with Patients IP on the value chainJohn Peter Mary Wubbe
Perhaps it is now time to move past the classical dichotomy of privacy or data utility and to seize the possibilities of emerging health technologies, processes, and projects. Far from being harmful, Patient-controlled health records in collaboration with emerging technologies that work within a defined, over sighted and legislated regulatory framework will facilitate innumerable benefits.
There are a number of forthcoming statistical solutions that would permit assembly of data sets at a patient level with limited risk to privacy and also delineate the cumbersome contentions of data ownership and access
Annals of behavioral medicine volume 49 issue 1 supplement april 2015Monique Tsang, BS, CNA
The current study investigated whether a single presentation on sleep hygiene could result in improvement in reported sleep quality and quantity for undergraduate students newly entering university.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
3. 224 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
Progress in clinical genomics in the next decade is likely to come from resolution of the com-
plex organizational, social, political, and ethical issues that arise when linking clinical and DNA
information to create a resource for future scientific use (a “DNA bank”). Stored DNA without
linked information about diagnosis, treatment, and follow-up is much less valuable, while a clini-
cal dataset without stored genetic material is incomplete. Yet concerns about subjects’ rights
(both as individuals and as groups), privacy, ownership of genetic material, and the stability of ar-
rangements made to resolve these concerns require attention in the development of plans to store
DNA [6,9,10]. In this paper we describe one approach to the solution of these problems that was
adopted by one clinical trials group, the Department of Veterans Affairs (VA) Cooperative Stud-
ies Program (CSP). Our decisions were determined in part by the special research context of our
group. However, we hope this approach may be useful to others confronting similar problems.
The Cooperative Studies Program
The VA CSP is one of the oldest clinical trials organizations in the world. At any time,
over 30 clinical trials and observational studies are ongoing in diseases that affect veterans.
Many CSP studies enroll over 1000 patients, and follow-up may extend for several years, as-
sessing outcomes such as mortality, major morbidity, and utilization of health resources. The
multicenter clinical trials and prospective cohort studies in the CSP provide an opportunity
for collecting and storing DNA for research into specific diseases.
To respond to this opportunity, the CSP initiated study #478 “Genetic Tissue Banking in
VA Clinical Research” aimed at providing a format for human subjects protection and a sci-
entific, technical, and statistical infrastructure to support DNA banking in its studies. This ini-
tiative aims to develop standard tools and protections that can be offered to investigators who
want to integrate genetic information into CSP studies.
The DNA Bank grew out of the CSP’s experience jointly managing a DNA bank with the
National Heart, Lung, and Blood Institute. The joint DNA bank was part of the Beta-Blocker
Evaluation of Survival Trial (BEST), a heart failure clinical trial, which collected over 1000
DNA specimens from BEST patients. The CSP DNA Bank was approved as a demonstration
project in May 1999 and was approved as a regular part of CSP in May 2001. Currently two
studies are collecting samples, and the Bank has provided planning support for another.
Conceptual foundations for the CSP DNA Bank
DNA bank versus genetics substudy
Even in an individual clinical trial (single- or multisite), a DNA bank differs importantly
from a genetics substudy. A substudy focuses on specific genetic hypotheses, which in turn
define the extent of genotyping as well as the plans for analyses relating the genotypes to the
clinical phenotypes and outcome of disease. In contrast, a DNA bank is oriented toward fu-
ture hypotheses that may not be framed at the outset. It must justify itself on the basis of the
latent scientific value of the clinical data in the context of substantial current ignorance about
what will emerge from the genotyping. Thus, a DNA bank is not limited a priori to specific
loci or genotyping techniques. Rather, the entire genome is in play.
4. P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239 225
DNA banking for a program of studies
The CSP DNA Bank serves several different “parent” clinical studies, in different disease
areas, over a longer period of time than would a DNA bank for a single study. Thus, the
Bank must be able to call on a broad variety of expertise for planning and monitoring its ac-
tivities. The scientific and ethical context of DNA banking is likely to evolve at a rapid pace.
To respond, a bank must follow a dynamic and adaptive operational plan, rather than adher-
ing to the fixed assumptions, methods, and design of a typical single scientific project. Scien-
tific and ethics oversight committees play a central operating role in a multistudy bank and
are the main routes for uptake of the changing rules and practices in the world outside the
bank. In a bank serving a single study, these oversight functions might be served by some
combination of existing committees (such as the study steering committee and the data and
safety monitoring board) or even by the principal investigator in a single-site study.
Guiding principles
The CSP DNA Bank operations are guided by six key principles:
Respect for autonomy
The Bank requires a genetic tissue banking consent process that is separate from that of the
clinical study through which the subject is recruited (the “parent study”). This gives the prospec-
tive subject the opportunity to refuse to participate in the Bank while still taking part in the parent
study. A separate process also provides an opportunity for complete disclosure of the scope of the
linked clinical and genetic information. The Bank asks for consent to genetic tissue analysis by all
present and future methods, including individual gene typing as well as genomewide scans. In
contrast to the open-ended scope of genotyping, the Bank calls for limiting the clinical data to that
collected in the parent study protocol. That is, without obtaining new informed consent the Bank
would not collect or link additional phenotypic data on the subject beyond the parent study data-
base. This limitation would also require new consent for post-parent-study follow-up and search
of VA or other databases. Explicitly limiting the information base for future studies helps to en-
sure that the participant’s specimen will not be used in research against his or her wishes.
The decision to limit clinical data may reduce the value of the linked data; however, we
are persuaded to do so by three arguments. First, the CSP trial datasets are particularly rich,
since they are designed to support the needs of an intensive clinical investigation. Second,
while the genetic analysis technology is still in flux, the clinical hypotheses are relatively familiar
and likely to be well covered by the typical follow-up period in a CSP trial (often 3 or more
years for each subject). Therefore, little is lost by requiring a unique and separate informed
consent process in order to go beyond the originally contemplated data collection. Finally, asking
permission to use the subject’s specimen for completely unspecified future study would appear
to conflict with the need to provide truly informed consent and with the responsibility of in-
stitutional review boards (IRBs) to weigh risks and benefits, since the possible risks associ-
ated with such future research cannot be known at the time of consent or review (see page
65, National Bioethics Advisory Committee report Research Involving Human Biological
Materials: Ethical Issues and Policy Guidance, August 1999).
5. 226 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
If a subject at any time chooses to withdraw consent, the Bank will destroy the subject’s
specimen and delete linking information from its databases. The ability to guarantee that the
subject’s wishes have been honored in this respect depends on the close control of linked
data (see below).
Protection of privacy
In the terminology of the National Bioethics Advisory Committee (NBAC) report, the
Bank is a repository of identified specimens, since it would be possible to identify the subject
from whom the specimen was obtained. Genotyping will be performed by investigators who
are provided coded samples by the Bank. The resulting genotypes are linked to the clinical
data by the DNA Bank. Tissue samples or genotype data that are merged with clinical data
may not properly be termed unlinked if a subject’s identity could be ascertained. These
linked datasets are the source of the threat to privacy, and many of the Bank’s procedures are
devoted to minimizing the risk of inappropriate disclosure of private information.
It is important not to overstate the ability of the Bank to guarantee the research subject’s
privacy [8,11]. But the investigator must be able to assure that the risks of inappropriate dis-
closure are small. By controlling the availability of linked datasets, the Bank limits access to
sources of information that might potentially be used to identify the individual subjects asso-
ciated with the genetic tissue analysis. Taking steps to “de-identify” datasets before export-
ing them to scientists outside the Bank may not be sufficient protection. The potential for
“re-identifying” such data exists, by using unique combinations of clinical and demographic
data to point to specific individuals.
To avoid the risk of reidentification, the CSP DNA Bank proposes, as far as possible, to
provide the service of genetic and clinical data analysis, in collaboration with scientists (“cli-
ents”) who propose to access the specimens stored in the Bank. Such a service is a natural
extension of the role of the CSP coordinating center in the conduct of its studies. It is possi-
ble that some clients might make a strong case for obtaining and analyzing their own copies
of a coded dataset, containing both clinical and genetic information. The Bank’s oversight
committees will evaluate the rationale for such departures from normal operations and will
verify that the released data do not pose a risk of breaching any subject’s privacy. If the ratio-
nale is compelling, the Bank will release the information necessary to perform the analyses
specified in the use proposal. The client must agree to maintain control over the dataset and
limit use of the dataset to the stated purposes.
This restricted access is one of the “working assumptions” that will need to be reevaluated
over time, to test whether or not scientific productivity is compromised. At the outset we seek
to minimize the number of people and institutions that the research subject is asked to trust
with his or her genetic and clinical data. One cost of our position is that a sophisticated client
would have to go through the steps of convincing the oversight committees that direct access
to data is warranted. Another cost is that the CSP DNA Bank must maintain the necessary
expertise to make the service available. We recognize that our decision is based in part on the
special circumstance that the CSP coordinating centers are already charged with statistical
and data management responsibilities for CSP studies. Other groups might believe that the
reidentification possibility is sufficiently remote as to be an ignorable threat to privacy. The
CSP DNA Bank oversight committees may come to this conclusion in the future, as well.
6. P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239 227
Appropriate disclosure
The consent process and supporting documents must specify what will be done with po-
tentially important emergent information about individual subjects [12–14]. There are three
options: (1) never report information to anyone about an individual subject’s results, (2) of-
fer the subject choices for each foreseeable contingency and let the subject decide, and (3) as
a matter of policy, do not report back, but if unusual circumstances arise refer the specific in-
dividual matter to the Bank oversight committees for a detailed plan.
The CSP DNA Bank has rejected the rigid “no disclosure” option (1), even though it is a
way to deal with a difficult problem. If something in the genetic profile of an individual dis-
closes a substantial risk that could be averted by an intervention and the Bank has the ability
to identify that person (through the patient’s enrollment site), it is obliged to act. Further-
more, the richness of a clinical trials dataset makes it nearly impossible to truly anonymize
linked data at the coordinating center. Even a randomly reordered data set (“scrambled iden-
tifiers”) is relatively easy to decode. Therefore, although it is possible to guarantee that one
will not seek to identify a patient, it is not possible to guarantee that one is unable to do so.
Because the CSP is part of a nationwide medical care system and not a freestanding research
enterprise, it has responsibilities that derive from its intramural role. Other groups might
come to a different conclusion given different responsibilities and capabilities.
Option (2) calls for the subject to determine the detailed rules for disclosure of test information
during the consent process. Determining whether such a policy makes sense involves several con-
siderations. First, the probability of discovering clinically relevant and reliable information in a
particular individual is small given the present state of knowledge. The fact that an individual has
a predisposing genetic profile may not be relevant if there is nothing that can be done about it. A
genetic finding whose significance is speculative or purely statistical may not be helpful and may,
in fact, be harmful in the sense that persons may have great difficulty interpreting the results [15].
If the information has been revealed by an experimental test, it would need to be repeated with
standard procedures in a certified clinical laboratory. These options multiply confusingly, and
each has a low probability of occurring. Similar (and more complex) issues arise if we consider
disclosure of information that may be important to the relatives of a subject.
This reasoning led the Bank to option (3), as described in the model informed consent
document (see appendix). Since there is a very small chance of uncovering individual infor-
mation that would be important for the subject to know, the subject should not expect to
learn the results of his or her own genetic analyses. However, in the unlikely event that facts
of individual import should arise, the model informed consent document states that the Bank
will bring that case to the scientific and ethics oversight committees for their help in prepar-
ing an individualized plan to use that information appropriately. A specific option to fore-
close that possibility entirely will be made available to the subject.
As the ability to use genetic information for the benefit of individual patients increases, the
list of genotypes that might be disclosed will grow. The experiences of the oversight committees
in this DNA Bank may contribute to ongoing consensus about proper actions in this area. At
present, there are no foreseeable clinical benefits that can be promised to subjects who participate
in DNA banking. However, as specific concerns regarding whether disclosure is appropriate
arise, the potential for specific benefit will also increase, calling for continued assessment of ap-
propriate disclosures in light of evolving knowledge.
7. 228 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
Protection from harm to individuals
The risks to subjects from genetic research and genetic test results have been widely dis-
cussed. The risks of discrimination in insurance and employment have been particularly
stressed [8,14,16–19]. Also important are other possible harms that disclosure of information
about their genomes might cause research subjects, such as familial discord or personal psy-
chological problems [15,20]. The privacy protections outlined above should prevent un-
planned or inadvertent disclosure. When, in exceptional circumstances, the information must
be made available for medical reasons, the process would be planned specifically to avoid or
minimize these kinds of harms.
Avoiding harm to groups
Of primary concern here are perceptions about the possible harm to racial or ethnic groups
that might follow even scientifically well-grounded and well-intentioned proposals. Individ-
ual members of those groups might not be willing to see their tissue used in studies contain-
ing ethnic identifiers [14,21–23]. The Bank will seek out the views of individuals from po-
tentially affected groups and include them in the review and oversight process. The oversight
committees (see “Organization and operations”) will review all proposals for use with these
sensitivities in mind and will consider whether additional consent requirements are appropri-
ate for genetic analyses that focus on topics of particular sensitivity, such as genetic links to
addictive behaviors. The Veterans Advisory Group (see “Organization and operations”) will
be asked to advise the Bank on matters of policy and organization.
Dealing fairly with commercial interests
The DNA specimens and clinical information in the Bank could lead to the development
of medically important and financially lucrative products. Whether any such value can or
will follow from the Bank is highly uncertain; that uncertainty itself contributes to the con-
cerns of some patients and others about possible exploitation [14,21,23,24]. Fairness to the
research subjects may, in some cases, require that when tissues and information from an
identifiable group (such as veterans) contribute to a commercially valuable product, some
share of the value should be used to benefit the group. This principle suggests that if the
Bank is able to recapture some of that value, the proceeds should be used for the direct bene-
fit of VA patients. VA research and development staff may negotiate licensing agreements or
other contracts to accomplish this goal. Other groups, such as a consortium of universities or
managed care organizations, might see these opportunities in a different way.
Organization and operations
In this section, we describe the organization of the Bank and step through the standard op-
erating procedures, beginning with informed consent and proceeding through handling, ship-
ping, and storage of specimens, linking of clinical and genetic data, and review of proposals
for use. The Bank has five components, providing it with adequate resources to store DNA,
to conduct analyses that relate the genetic and clinical information, to manage and maximize
the scientific use of the Bank, and to address the ethical, legal, and social implications of this
8. P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239 229
sensitive material. These components are the Genetic Tissue Core Laboratory, the DNA Co-
ordinating Center, the Scientific Advisory Committee, the Ethics Oversight Committee, and
the Veterans Advisory Group. Members of oversight committees are appointed by the VA
Research and Development Office and serve overlapping terms.
The Genetic Tissue Core Laboratory (GTCL), housed at the Massachusetts VA Epidemi-
ology Research and Information Center (MAVERIC) in Boston, serves as a central reposi-
tory for specimens. The GTCL trains and equips study personnel for the collection of genetic
tissue, extracts and stores DNA, and performs some genotyping. The GTCL ships DNA
specimens to investigators with approved requests for use of the DNA Bank. Such technical
support for collection, storage, shipping, and processing of material is designed to minimize
the extra burden on study personnel and to ensure that genetic material is handled and stored
in a manner that preserves its value.
The DNA Coordinating Center (DNACC), a subunit of the Palo Alto CSP Coordinating
Center, administers the Bank and makes its resources available to CSP investigators who
plan to collect DNA specimens. The director of the Palo Alto CSPCC is the administrative
head of the DNA Bank. The DNACC is responsible for maintaining the protection of human
subjects as standards evolve and for obtaining administrative assurances of confidentiality. It
is responsible for updating regulatory documents and consent forms and handling IRB que-
ries related to collection of DNA specimens. DNACC staff coordinate the committees that
deal with the ethical, legal, and social implications of banking and using genetic tissue.
Protecting the confidentiality of genetic information is a central responsibility of the
DNACC, which maintains appropriate linkages to clinical datasets and controls all access to
genetic information. The DNACC takes overall responsibility for assuring that the genetic tissue
and clinical data repositories have physical, legal, and administrative security. The DNACC pro-
vides statistical and data management support to investigators planning a DNA bank and to cli-
ents who wish to access specimens and conduct analyses.
The Scientific Advisory Committee (SAC), a group of individuals with expertise in genet-
ics, epidemiology, molecular biology, and specific disease areas, helps set policy for the use
of the Bank and provides technical and scientific advice to the DNACC. The SAC helps
identify new studies that should be considered for genetic tissue collection. It advises on is-
sues such as the type and quantity of specimens for banking, storage requirements, and addi-
tional clinical information that should be included in the parent-study data collection to en-
sure the utility of the DNA specimens for later analysis. The SAC meets periodically to
review and recommend approval of proposals for use of the Bank.
The Ethics Oversight Committee (EOC) is composed of experts in the legal and ethical
implications of genetics research with humans, as well as experts in the relevant scientific
disciplines. It meets regularly to review provisions for the protection of human research vol-
unteers and to provide a disinterested review of the activities of the Bank, including propos-
als for use of the stored tissue.
The Veterans Advisory Group (VAG) consists of a group of veterans who will be asked to
provide their perspectives on the ethical and social implications of DNA banking in veteran
subjects of CSP studies. The advice of this group will help shape future operations of the
Bank, which is designed to adapt to meet the changing social consensus on the use of such
material and information. Some examples of the initial agenda items for such a group include
9. 230 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
the “disclosure” provisions (whether, when, and how to inform subjects about genetic infor-
mation that may be important to them or their families), subgroup sensitivities to certain re-
search topics (for example, minority group differences in genetic vulnerabilities and the ge-
netics of stigmatized disorders), and commercial use of Bank information.
Interaction of the Bank with the parent clinical study
The involvement of the Bank begins during planning of a new clinical study to help to assess
the added costs, risks, and benefits of a gene banking component and advise on the need for any
special procedures or data collection in the parent study. The DNACC works with the parent-
study investigators to adapt the generic protocol and template consent forms for the DNA compo-
nent of the parent study. The parent-study investigators are responsible for framing any genetic
hypotheses that are known at present, so that the initial plans for genotyping can be reviewed. It
also identifies study-specific issues relating to disclosure, privacy, or other matters that might af-
fect the design of the study or the study informed consent procedures. The DNACC also helps the
local site investigators to obtain local approvals, lending its experience with such IRB reviews to
investigators who might not have participated in a DNA bank before.
Collection, handling, shipping, and storage of specimens
The GTCL works with the parent-study investigators to prepare materials and supplies
and handles the logistics of specimen preparation and shipping. The study subjects are re-
cruited to participate in the DNA component after giving informed consent to enroll in the
parent study. Only those who choose to participate and who provide a separate consent form are
enrolled in the Bank. The blood specimen for DNA analysis is collected and sent to the
GTCL using labels from the kit supplied to the site. No identifying information other than the
“specimen code number” is placed on the biological specimen sent to the GTCL (see Fig. 1).
A duplicate specimen code number is attached by the site to a data form that also has the “pa-
tient code number” (the identifier of clinical information collected in the parent study). These
data are sent to the DNACC. Once received at the GTCL the specimens are usually pro-
cessed and frozen prior to DNA extraction in order to allow for high-volume batch extraction
once all the specimens have been collected. The GTCL stores the specimen under a “bank
code number,” which it assigns. After sending the log that matches specimen and bank code
numbers to the DNACC, the GTCL destroys the log. Thus, the only links between the patient
identification number and the bank code number are kept at the DNACC.
Access agreement
An investigator (the “client”) making a proposal for access to the tissue specimens or to the
linked clinical and genetic database, first provides the Bank with a statement of research intent
(SORI), outlining the hypotheses, proposed genotyping, and statistical analyses. The DNACC
may provide statistical assistance to the client preparing the SORI. The SORI is reviewed by the
SAC, and if approved, the investigator submits a full research proposal to the SAC and EOC for
review. Bank staff work with the client to satisfy the requirements of the committees. Upon final
approval, the applicant institution enters into a materials transfer agreement, which summarizes
10. P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239 231
the terms and conditions of the agreement to access the Bank. This agreement spells out the re-
sponsibilities of all parties in connection with the receipt, handling, storage, and use of DNA
specimens and the protection of the privacy and confidentiality of patient data.
The GTCL sends samples to the analytic laboratory identified with the bank code number.
The analytic lab returns the results of the genetic analyses (indexed by the bank code num-
ber) in secure electronic form to the DNACC.
Management of information at the GTCL and DNACC
The coding data described above are used by the DNACC to construct a protected cross-
walk database that links clinical and DNA information. After the DNACC receives genotype
data from the analytic lab, it uses the key matching bank code number and the specimen code
number, together with the key matching the DNA specimen code number and the clinical
(parent) study identifier, to link the genotype data and the clinical data. The analyses speci-
fied in the research proposal are then carried out by the statisticians at the DNACC. If the
DNACC cannot perform the analyses, it may create coded datasets for export to certain cli-
ents. The results of all genetic assays become part of the DNA Bank and are available for use
by other researchers. The DNACC serves as the entry point for all interested parties and ac-
tively seeks out such collaborators to maximize the utility of the Bank.
Informatics and statistical analysis
The informatics system of the CSP DNA Bank is designed to protect the patient’s privacy
by securing the linked clinical and genetic databases against intrusion, unauthorized copying,
loss, and other threats. At the same time, it is useful for potential clients of the Bank to be
able to browse the protocol, forms, and procedure manuals of the parent studies to assess the
suitability of the Bank data for testing their hypotheses. The Bank also will provide conve-
nient access to aggregate summaries of the diagnoses, demographics, outcomes, and other
pertinent characteristics of the participants in the parent studies of the Bank.
The core of the Bank informatics system is a cluster of computers, a printer, backup de-
vices, and other hardware that is physically isolated from other networks and computers in
the coordinating center and located in a secured room. This private system hosts the linked
databases and the linking information. The public face of the Bank is a web server providing
access for the purposes described above. In addition to document browsing, the Bank will
provide a system that would allow limited exploration of the clinical datasets without allow-
ing access to potentially unique identifiers. Enabling a broad range of potential collaborators
to perform these analyses by employing a user-friendly web-based interface will allow greater
use of these datasets and foster increased collaboration among researchers.
As discussed above, the staff of the DNACC is prepared to collaborate with the client in-
vestigators to perform the analyses of linked genetic and clinical data. The clients would be
able to test their hypotheses and publish the results without the need for a transfer of sensi-
tive data outside the Bank. Each of the parent studies is coordinated by one of the statistical
or epidemiologic centers of the CSP. Therefore the staff of the DNACC has ready access to the
experience of the biostatistician coordinating the study. Familiarity with the clinical dataset can
11. 232 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
Fig. 1. VA cooperative study program DNA banking and data collection process.
12. P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239 233
be an advantage. However, exploration sometimes produces important results and increasing
the number of researchers with access to data may be a better way to explore a large and
well-constructed dataset. This trade-off is similar to the one that arises in the analysis of data
from trials: whether to plan and test prespecified hypotheses to preserve the unique confir-
matory strength of the data collected in a clinical trial or to explore and exploit serendipity.
Client investigators who do not wish to avail themselves of the statistical services of the
DNACC must provide a specific rationale for obtaining custom-coded datasets, and the pro-
posal must be approved by the SAC and EOC, as well as the VA’s Chief Research and De-
velopment Officer. The Bank takes the view that exported datasets are outside its control,
and therefore it cannot guarantee that they will not be disseminated beyond the client. Re-
moval of ostensible identifiers may not be proof against malicious attempts to link the data to
specific individuals. If the risk of loss of privacy is even slightly increased by propagating
copies of the linked data, the risk must be justified by specific scientific benefits.
These concerns motivate the Bank’s current restrictive policy on export of linked data, but these
decisions are not immutable. If the future of responsible, safe DNA banking leads to a more re-
laxed, permissive environment, then coding may be seen as a sufficient guarantee of protection. Or,
it may be possible to fashion a compromise, allowing limited direct access to parts of the database.
Discussion
The undeniable scientific potential of gene science is accompanied by persistent public
wariness about the ends and means of genetics research. For public trust to flourish, rules, in-
stitutions, and methods for the ethical and efficient conduct of genetics research must de-
velop alongside the technical advances in genotyping. The CSP confronted the issues raised
by DNA banking in clinical research as part of a more general VA research and development
review of the implications of gene science for VA research and clinical care. This review led
to a programwide planning effort resulting in the current CSP DNA Bank.
The most difficult issues in planning the CSP DNA Bank emerged from the ethical, social, and
legal implications of the design choices that at first appeared necessary to maximize the scientific
value of the Bank. It is useful to make such apparent conflicts explicit, so they can be addressed.
More importantly, public trust is best earned by openness about ends and means. The implications
will also evolve over the life of the Bank, as some public fears abate and others increase.
The Bank purposely avoids some of the more difficult issues by limiting its purview to new
studies. The Bank’s procedures do not deal with the use of specimens collected in previous stud-
ies, without informed consent for genetics research (the “legacy” problem) [13]. The prospective
stance of the Bank is intentional. The primary aim of pharmacogenetics is to tailor treatments to
genotype, making it desirable to study the interaction of genotype with current treatments. The
Bank’s procedures have not been extended to the collection of genotype and phenotype informa-
tion for family studies. All of the issues raised in the foregoing take on added complexity in the
context of recruitment of family members for DNA banking. The Bank addresses scientific ques-
tions best answered in specimens of patients with well-defined diseases treated in a controlled, ex-
perimental context. On the other hand, we see no barrier to extending the Bank’s procedures to
the collection and storage of data on the expression of genes in various tissues or to the study of
13. 234 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
the “proteomics” of disease (the expression of genes and translation into proteins). These will no
doubt take on great importance in the years ahead as costs come down and techniques evolve.
Acknowledgments
The opinions expressed herein are the opinions of the authors and do not represent official
position of the Department of Veterans Affairs. This work was funded by the Department of
Veterans Affairs Cooperative Studies Program as CSP#478.
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Appendix
Sample consent form
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15. 236 P.W. Lavori et al./Controlled Clinical Trials 23 (2002) 222–239
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