Evolution of Translational Omics Lessons Learned and the Path Forward (2012) / Chapter Skim
Currently Skimming:
6 Lessons from the Case Studies
6 Lessons from the Case Studies
Pages 163-182
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From page 163... ...
, a number of omics-based tests derived from this research have reached the market and are being used to manage patient care across a broad range of medical specialties and subspecialties. The purpose of the case studies was to examine the test discovery and development processes used in omics research and omics-based test development to help determine the criteria needed to effectively guide development of omics-based tests, and to consider the roles of the various responsible parties in test development (discussed in Chapter 5)
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From page 164... ...
METHODS Examination of what transpired in the development of the omics-based tests at Duke University was based on presentations to the committee, a panel discussion with Duke University researchers and administrators, documents provided by the National Cancer Institute and Duke University, and the peer reviewed literature. The Duke case study is illustrative of the more systemic challenges involved in the development of omics-based tests and the need for rigorous criteria for test development, and is discussed in more detail in Appendix B
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From page 165... ...
Oncotype DX Genomic Health Prognostic No www.oncotypedx.com/ "a 21-gene assay that provides en-US/Breast.aspx an individualized prediction of chemotherapy benefit and 10-year distant recurrence to inform adjuvant treatment decisions in certain women with early-stage breast cancer" (Genomic Health, 2011)
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From page 166... ...
Tissue of Pathwork Diagnostics Diagnostic Yes "The Pathwork® Tissue of Origin www.pathworkdx.com/ TissueOfOriginTest/ Origin Test is an in vitro diagnostic intended to measure the degree of similarity between the RNA expression patterns in a patient's formalin-fixed, paraffin-embedded (FFPE) tumor and the RNA expression patterns in a database of fifteen tumor types (poorly differentiated, undifferentiated, and metastatic cases)
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From page 167... ...
decision summary, if there is one, or if not, the company-proposed use and/or guideline recommendation. NOTE: ASCO = American Society of Clinical Oncology, FDA = Food and Drug Administration.
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From page 168... ...
Importance of a Well-Designed Development Plan As described in Chapter 2, an important aspect of test development is a well-designed development plan. Components of a test development plan include starting with a clinically meaningful question, developing a candidate test on a training set of specimens, locking down the candidate test, and employing rigorous test validation procedures.
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From page 169... ...
In Chapter 5, the committee recommends that journals and funders require the public availability of data, metadata, prespecified analysis plans, code, and fully specified computational models. The importance of data availability was highlighted in the OvaCheck case study, in which publicly available datasets enabled external researchers to uncover serious problems in experimental design (Baggerly et al., 2004)
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From page 170... ...
and private sources OVA1 No Initial raw data used to find a preliminary panel of biomarkers is available; raw data used to finalize the panel of biomarkers in the OVA1 test is unavailable; data on samples used to train the computational model are available in the 510(k) decision summary, but are not available in peer-reviewed literature AlloMap Yes The microarray data used to initially identify (Deng et al., biomarkers during the discovery phase of product 2006)
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From page 171... ...
Entity Involved? No Methodology used to derive and train Yes the computational model is not National Surgical Adjuvant available in sufficient detail to fully Breast and Bowel Project reproduce Yes Some of the details needed for Yes independent replication are unclear TRANSBIG, a Consortium of from the supplementary materials, but the Breast International Group inquiries about the computational model have always been answereda Yes Methodology used to derive and train No the computational model is not available Yes Methodology used to derive the Yes (PrecisionMed International computational model is not available housed specimens, Quest Diagnostics performed biomarker measurements, Applied Clinical Intelligence performed data analysis)
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From page 172... ...
Both tests developed as laboratory-developed tests (LDTs) had published computational models (Oncotype DX and Corus CAD)
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From page 173... ...
This second validation included the 63 primary validation samples plus samples from patients who had contributed samples to the gene discovery and/or diagnostic development phases of the study. Overlap of training and validation datasets can lead to a number of problems in test discovery and development, including overstatement of the accuracy of an omics-based test and incorrect error estimation (Leek et al., 2010)
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From page 174... ...
. As noted by Baggerly and colleagues and by McShane, the computational models developed by a Duke University lab were not locked down prior to use in the clinical trials (Baggerly, 2011; McShane, 2010)
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From page 175... ...
. However, in retrospect, the Duke IRB recognized that an IDE should have been obtained for the omicsbased tests because the tests were used to direct patient management in the clinical trials (FDA, 2011a)
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From page 176... ...
In the case of Oncotype DX, Genomic Health completed reverse-transcriptase polymerase chain reaction (RTPCR) analysis of the specimens used for clinical validation and supplied the results to the National Surgical Adjuvant Breast and Bowel Project, who conducted the analyses evaluating the association between recurrence score and clinical outcome.
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From page 177... ...
Corus CAD Prospective (not directing therapy -- trial was for development and validation) The development and validation pathways for Oncotype DX and MammaPrint offer some interesting comparisons.
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From page 178... ...
Clinical trials assessing clinical utility are important because they can inform how a test is used in practice. As described in Chapter 4, prospective trial designs in which biomarkers direct patient management (as in Figures 4-4 and 4-5)
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From page 179... ...
The involvement of investigators, institutions, funders, and journals is essential for ensuring good research practices and oversight of omics-based test discovery and development. A well-designed test development plan addresses a clinically meaningful question and employs rigorous test discovery, development, and validation procedures.
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From page 180... ...
510(k) Substantial Equivalence Determination Decision Summary Assay and Instrument Combination Template.
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From page 181... ...
2010a. NCI Address to the Institute of Medicine Committee on the Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials.
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From page 182... ...
Presented at Meeting 2 of the Commit tee on Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials, Washington, DC, March 30.
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