Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007) / Chapter Skim
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10 Sample and Data Collection and Analysis
10 Sample and Data Collection and Analysis
Pages 152-171
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From page 152... ...
LEVERAGING SAMPLES AND INFORMATION IN POPULATION BASED STUDIES AND CLINICAL TRIALS FOR TOXICOGENOMIC STUDIES Because the potential of toxicogenomic studies is to improve human risk assessment, it is imperative that susceptible human populations be studied with toxicogenomics. Given the hundreds of millions of dollars already spent on clinical trials, environmental cohort studies, and measurements of human exposures to environmental chemicals, it is imperative that toxicogenomic studies make the best possible use of the human population and clinical resources already in hand.
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From page 153... ...
What are the limitations of using existing cohorts for toxicogenomic studies? Given the limitations of existing cohorts with respect to the informed consent, sample collection, and data formats, how should future population-based studies be designed?
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From page 154... ...
The clinical trials were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements as well as ovarian hormone therapies. The observational study had several goals, including estimating the extent to which known risk factors predict heart disease, cancers, and fractures; identifying risk factors for these and other diseases; and creating a future resource to identify biologic indicators of disease, especially substances found in blood and urine.
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From page 155... ...
Sample/data repositories are also being assembled in the private sector, where pharmaceutical companies are increasingly eager to form cooperative groups or collaborations with academia and health care providers that provide access to patient cohorts for clinical trials and other population-based studies. In some cases, companies have assembled their own cohorts with samples purchased directly from medical providers.
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From page 156... ...
However, for a wide variety of reasons, ranging from the types of samples collected to issues of informed consent, this is rarely possible given the structure of existing cohorts. Structure of Cohorts Given the cost and logistics of assembling, obtaining consent, and following large cohorts, many studies are designed to address only a few specific questions.
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From page 157... ...
Sample Collection A major impediment to the use of existing cohorts is that many studies have not collected appropriate types of specimens, or the available specimens are in a format that is not amenable to toxicogenomic studies. For example, the NCI funded the Cancer Genetic Network to identify and collect data on families at elevated risk for different forms of cancer.
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From page 158... ...
There are both a need and an opportunity to standardize methodologies in ongoing studies and to design future studies to accommodate the requirements of new toxicogenomic platforms. Data Uniformity Another impediment to using existing cohorts for toxicogenomic applications is the lack of uniformity in data collection standards among populationbased studies.
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From page 159... ...
Because it may be possible to combine limited access data with other publicly available data to identify particular study participants, those who want to obtain these datasets must agree in advance to adhere to established datadistribution agreements through the Institute, with the understanding that violation of the agreement may lead to legal action by study participants, their families, or the U.S. government.
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From page 160... ...
Despite the significant barriers imposed by patient confidentiality and issues of informed consent, mechanisms exist for assembling large cohorts and collecting samples that can be used for multiple studies and applications to benefit public health. For example, the NHANES program under the aegis of the CDC collects blood samples for measurement of chemicals, nutritional biomarkers, and genotypes from large numbers of individuals using a consent mechanism that expressly authorizes multiple uses of biologic samples.
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From page 161... ...
The remaining needs that must be met to move forward are described in the Conclusions section of this chapter. Standards for Toxicogenomic Data Although each individual study conducted using toxicogenomic approaches may provide insight into particular responses produced by compounds, the real value of the data goes beyond the individual assays.
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From page 162... ...
However, these are essentially passive databases that apply standards to data structure but provide little or no curation for data quality, quality assurance, or annotation. Other small-scale, publicly available tools and resources that have been developed for sharing, storing, and mining toxicogenomic data include db Zach
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From page 163... ...
The pharmaceutical industry, for example, has generated very large compendia of toxicogenomic data on both proprietary and public compounds. These data are high quality but in general are not accessible to the public.
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From page 164... ...
PharmGKB encourages submission of primary data from any study on how genes and genetic variation affect drug responses and disease phenotypes. The NIEHS Toxicogenomics Research Consortium As a complement to its ongoing participation with the International Life Sciences Institute's Health and Environmental Sciences Institute (ILSI-HESI)
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From page 165... ...
. In addition to helping develop data standards, the consortium was also the first large-scale experimental program to offer practical insights into genomic data exchange issues.
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From page 166... ...
CONCLUSIONS Leveraging Existing Studies Given the potential of toxicogenomic studies to improve human risk assessment, it is imperative to conduct toxicogenomic studies of human populations. Academic institutions, government agencies, health care providers, and the private sector have already invested tremendous effort and resources into accruing cohorts for population-based studies to predict responses to drug therapy, to improve disease classification, to find genetic markers of disease susceptibility, to understand gene-environment interactions, and to assess effects of human exposures to environmental chemicals.
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From page 167... ...
Although there will always be a need to collect data specific to a particular study or application, much can be done to standardize collection of samples and of demographic, dietary, occupational, and lifestyle data common to all studies. Databases and Building a Toxicogenomic Database Toxicogenomic technologies generate enormous amounts of data -- on a scale even larger than sequencing efforts like the Human Genome Project.
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From page 168... ...
However, developing such a database is important enough that it needs to be actively pursued and not delayed for an extensive time. One potential source of toxicogenomic data is repositories maintained by companies, both commercial toxicogenomic database companies and drug or chemical companies that have developed their own datasets.
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From page 169... ...
, and work with the relevant organizations to gain access to samples and data and address ethical and legal issues.1 3. Develop standard operating procedures and formats for collecting samples and epidemiologic data that will be used for toxicogenomic studies.
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From page 170... ...
Intermediate 4. Develop approaches to populate a database with high-quality toxicogenomic data.
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From page 171... ...
Long Term 7. Work with public and private agencies to develop large, well-designed epidemiologic toxicogenomic studies of potentially informative populations -- studies that include collecting samples over time and carefully assessing environmental exposures.
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