Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-8 (of 8 Records) |
Query Trace: Goddard KA[original query] |
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Leveraging biospecimen resources for discovery or validation of markers for early cancer detection.
Schully SD , Carrick DM , Mechanic LE , Srivastava S , Anderson GL , Baron JA , Berg CD , Cullen J , Diamandis EP , Doria-Rose VP , Goddard KA , Hankinson SE , Kushi LH , Larson EB , McShane LM , Schilsky RL , Shak S , Skates SJ , Urban N , Kramer BS , Khoury MJ , Ransohoff DF . J Natl Cancer Inst 2015 107 (4) Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts. |
Evidence synthesis and guideline development in genomic medicine: current status and future prospects.
Schully SD , Lam TK , Dotson WD , Chang CQ , Aronson N , Birkeland ML , Brewster SJ , Boccia S , Buchanan AH , Calonge N , Calzone K , Djulbegovic B , Goddard KA , Klein RD , Klein TE , Lau J , Long R , Lyman GH , Morgan RL , Palmer CG , Relling MV , Rubinstein WS , Swen JJ , Terry SF , Williams MS , Khoury MJ . Genet Med 2014 17 (1) 63-7 PURPOSE: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field. METHODS: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust." RESULTS: The participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence. CONCLUSION: Ongoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine. |
Comparative effectiveness research in cancer genomics and precision medicine: current landscape and future prospects.
Simonds NI , Khoury MJ , Schully SD , Armstrong K , Cohn WF , Fenstermacher DA , Ginsburg GS , Goddard KA , Knaus WA , Lyman GH , Ramsey SD , Xu J , Freedman AN . J Natl Cancer Inst 2013 105 (13) 929-36 A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting the uptake of these tools into clinical practice. Comparative effectiveness research (CER) is intended to generate evidence on the "real-world" effectiveness compared with existing standards of care so informed decisions can be made to improve health care. Capitalizing on funding opportunities from the American Recovery and Reinvestment Act of 2009, the National Cancer Institute funded seven research teams to conduct CER in genomic and precision medicine and sponsored a workshop on CER on May 30, 2012, in Bethesda, Maryland. This report highlights research findings from those research teams, challenges to conducting CER, the barriers to implementation in clinical practice, and research priorities and opportunities in CER in genomic and precision medicine. Workshop participants strongly emphasized the need for conducting CER for promising molecularly targeted therapies, developing and supporting an integrated clinical network for open-access resources, supporting bioinformatics and computer science research, providing training and education programs in CER, and conducting research in economic and decision modeling. |
Transforming epidemiology for 21st century medicine and public health.
Khoury MJ , Lam TK , Ioannidis JP , Hartge P , Spitz MR , Buring JE , Chanock SJ , Croyle R , Goddard KA , Ginsburg GS , Herceg Z , Hiatt RA , Hoover RN , Hunter DJ , Kramer BS , Lauer MS , Meyerhardt JA , Olopade OI , Palmer JR , Sellers TA , Seminara D , Ransohoff DF , Rebbeck TR , Tourassi G , Zauber AG , Winn DM , Schully SD . Cancer Epidemiol Biomarkers Prev 2013 22 (4) 508-16 In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving towards more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating "big data" science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits. |
Stakeholder assessment of the evidence for cancer genomic tests: insights from three case studies.
Deverka PA , Schully SD , Ishibe N , Carlson JJ , Freedman A , Goddard KA , Khoury MJ , Ramsey SD . Genet Med 2012 14 (7) 656-62 PURPOSE: Insufficient evidence on the net benefits and harms of genomic tests in real-world settings is a translational barrier for genomic medicine. Understanding stakeholders' assessment of the current evidence base for clinical practice and coverage decisions should be a critical step in influencing research, policy, and practice. METHODS: Twenty-two stakeholders participated in a workshop exploring the evidence of genomic tests for clinical and coverage decision making. Stakeholders completed a survey prior to and during the meeting. They also discussed if they would recommend for or against current clinical use of each test. RESULTS: At baseline, the level of confidence in the clinical validity and clinical utility of each test varied, although the group expressed greater confidence for epidermal growth factor receptor mutation and Lynch syndrome testing than for Oncotype DX. Following the discussion, survey results reflected even less confidence for Oncotype DX, intermediate levels of confidence for [corrected] epidermal growth factor receptor mutation testing and stable levels of confidence [corrected] for Lynch syndrome testing. The majority of stakeholders would consider clinical use for all three tests, but under the conditions of additional research or a shared clinical decision-making approach. CONCLUSION: Stakeholder engagement in unbiased settings is necessary to understand various perspectives about evidentiary thresholds in genomic medicine. Participants recommended the use of various methods for evidence generation and synthesis. |
Building the evidence base for decision making in cancer genomic medicine using comparative effectiveness research.
Goddard KA , Knaus WA , Whitlock E , Lyman GH , Feigelson HS , Schully SD , Ramsey S , Tunis S , Freedman AN , Khoury MJ , Veenstra DL . Genet Med 2012 14 (7) 633-42 The clinical utility is uncertain for many cancer genomic applications. Comparative effectiveness research (CER) can provide evidence to clarify this uncertainty. The aim of this study was to identify approaches to help stakeholders make evidence-based decisions and to describe potential challenges and opportunities in using CER to produce evidence-based guidance. We identified general CER approaches for genomic applications through literature review, the authors' experiences, and lessons learned from a recent, seven-site CER initiative in cancer genomic medicine. Case studies illustrate the use of CER approaches. Evidence generation and synthesis approaches used in CER include comparative observational and randomized trials, patient-reported outcomes, decision modeling, and economic analysis. Significant challenges to conducting CER in cancer genomics include the rapid pace of innovation, lack of regulation, and variable definitions and evidence thresholds for clinical and personal utility. Opportunities to capitalize on CER methods in cancer genomics include improvements in the conduct of evidence synthesis, stakeholder engagement, increasing the number of comparative studies, and developing approaches to inform clinical guidelines and research prioritization. CER offers a variety of methodological approaches that can address stakeholders' needs and help ensure an effective translation of genomic discoveries. |
Awareness and utilization of BRCA1/2 testing among U.S. primary care physicians.
Bellcross CA , Kolor K , Goddard KA , Coates RJ , Reyes M , Khoury MJ . Am J Prev Med 2011 40 (1) 61-6 BACKGROUND: Testing for mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 (BRCA) has been commercially available since 1996. PURPOSE: This study sought to determine, among U.S. primary care physicians, the level of awareness and utilization of BRCA testing and the 2005 U.S. Preventive Services Task Force (USPSTF) recommendations. METHODS: In 2009, data were analyzed on 1500 physician respondents to the 2007 DocStyles national survey (515 family practitioners, 485 internists, 250 pediatricians, and 250 obstetricians/gynecologists). RESULTS: Overall, 87% of physicians were aware of BRCA testing, and 25% reported having ordered testing for at least one patient in the past year. Ordering tests was most prevalent among obstetricians/gynecologists in practice for more than 10 years, with more affluent patients. Physicians were asked to select indications for BRCA testing from seven different clinical scenarios representing increased (4) or low-risk (3) situations consistent with the USPSTF guidelines. Among ordering physicians (pediatricians excluded), 45% chose at least one low-risk scenario as an indication for BRCA testing. Only 19% correctly selected all of the increased-risk and none of the low-risk scenarios. CONCLUSIONS: A substantial majority of primary care physicians are aware of BRCA testing and many report having ordered at least one test within the past year. A minority, however, appear to consistently recognize the family history patterns identified by the USPSTF as appropriate indications for BRCA evaluation. These results suggest the need to improve providers' knowledge about existing recommendations-particularly in this era of increased BRCA direct-to-consumer marketing. |
Adapting the logical basis of tests for Hardy-Weinberg Equilibrium to the real needs of association studies in human and medical genetics
Goddard KA , Ziegler A , Wellek S . Genet Epidemiol 2009 33 (7) 569-80 The standard procedure to assess genetic equilibrium is a chi(2) test of goodness-of-fit. As is the case with any statistical procedure of that type, the null hypothesis is that the distribution underlying the data is in agreement with the model. Thus, a significant result indicates incompatibility of the observed data with the model, which is clearly at variance with the aim in the majority of applications: to exclude the existence of gross violations of the equilibrium condition. In current practice, we try to avoid this basic logical difficulty by increasing the significance bound to the P-value (e.g. from 5 to 10%) and inferring compatibility of the data with Hardy Weinberg Equilibrium (HWE) from an insignificant result. Unfortunately, such direct inversion of a statistical testing procedure fails to produce a valid test of the hypothesis of interest, namely, that the data are in sufficiently good agreement with the model under which the P-value is calculated. We present a logically unflawed solution to the problem of establishing (approximate) compatibility of an observed genotype distribution with HWE. The test is available in one- and two-sided versions. For both versions, we provide tools for exact power calculation. We demonstrate the merits of the new approach through comparison with the traditional chi(2) goodness-of-fit test in 2x60 genotype distributions from 43 published genetic studies of complex diseases where departure from HWE was noted in either the case or control sample. In addition, we show that the new test is useful for the analysis of genome-wide association studies. |
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