Diffusion and Use of Genomic Innovations in Health and Medicine Workshop Summary (2008) / Chapter Skim
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4 Translation of Genomic Technology at the Clinical Level
4 Translation of Genomic Technology at the Clinical Level
Pages 47-64
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From page 47... ...
Berg, M.D., M.P.H. University of Washington Primary care is of growing importance in the translation of genomic innovations, and genomic innovations will achieve a bigger foothold in this country only if they penetrate into primary care, Berg said.
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From page 48... ...
It has to improve clinical outcomes that patients would notice and care about when compared to current practice. For example, changes in laboratory values are usually not enough in primary care because the patient expects to actually experience improvement with a new test or innovation.
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From page 49... ...
Furthermore, the decision-making process needs to be specified as explicitly as possible. Another process characteristic is that the guideline needs to focus on clinical outcomes -- that is, not simply on intermediate outcomes such as laboratory tests or knowledge, but on actual clinical outcomes that patients or families would notice and care about.
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From page 50... ...
There are precedents in providing reliable advice, such as the United States Preventive Services Task Force, which evaluates preventive interventions. The Centers for Disease Control and Prevention (CDC)
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From page 51... ...
Introducing a Genomic Innovation to Clinical Practice Steven Shak, M.D. Genomic Health There has been a great deal of discussion about recent genomic innovations and the question of whether there is adequate evidence to validate their clinical utility.
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From page 52... ...
During the 1990s, however, new technologies such as gene expression assays were developed that now allow careful measurement and quantification of individual genes in a tumor in order to better understand individual differences. Genomic Health chose to optimize a new technology for quantitative analysis of gene expression for use with tumor blocks.
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From page 53... ...
In the past, this material was not considered useful for conducting molecular studies, but scientists at Genomic Health undertook an effort to look at RNA in tumor blocks in a precise and quantitative way and, after two years of effort, developed an assay system that enabled them to do so. This was important for two reasons.
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From page 54... ...
It was to meet this challenge that Genomic Health applied the principles of drug development to the process of developing a diagnostic test. In particular, the company applied the principle of doing multiple studies with a logical sequence and rigor at each step, essentially analogous to the phase I, phase II, and phase III drug development trials.
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From page 55... ...
, Genomic Health conducted two clinical-validation studies to test that particular assay independently in a prospective way on archival tissue from well-defined cohorts. The first study was performed in collaboration with NSABP to examine the Recurrence Score in the landmark NSABP B-14 clinical trial.
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From page 56... ...
These methods and procedures include specimen eligibility, reagent qualification, instrument validation, controls and calibrators, and linearity, precision, and reproducibility. In the case of Genomic Health's clinical validation study, it took 6 to 9 months to finalize the assay format and show its analytical performance.
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From page 57... ...
In defining the conceptual framework for evaluation of clinical effectiveness, it is important that the focus be on transparency and putting breast cancer patients first. There is a need for studies that establish clinical utility by showing directly, or by inference, that use of the test will improve outcomes and spare toxicity and health care resources.
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From page 58... ...
Shak to comment on infrastructure development within National Institutes of Health (NIH) -funded research, given that Genomic Health was able to take advantage of data that had been collected from randomized controlled trials (RCTs)
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From page 59... ...
The example of using stored tumor blocks to ask a question about a therapeutic intervention that was not anticipated illustrates the value of biobanking. For that particular example, the concerns were lessened because the later research addressed precisely the issue that the original samples were collected to address -- that is, improved outcomes for breast cancer patients.
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From page 60... ...
Shak responded that the company probably spent somewhere between $50 million and $100 million over about 7 years to arrive at its current situation. Genomic Health is now working on colon cancer and has been able to take advantage of some of the lessons learned with Oncotype DX, so some things are less costly.
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From page 61... ...
Burke responded that it is important to properly align reimbursement incentives. One questioner noted that Shak described paying close attention to what the providers and patients viewed as clinical utility, which in this situation was avoiding the unnecessary use of chemotherapy.
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From page 62... ...
What is impressive about the reclassification studies is that one could compare the incremental benefit due to use of Oncotype DX with the benefits from a conventional tool and link that to an outcome known from a randomized controlled trial, albeit one that had been conducted in the past. Although this study approach does not fit easily into the clear conceptual boxes of indirect and direct evidence, the evidence appears more direct, the speaker said.
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From page 63... ...
There are many areas in clinical practice that desperately need better quality research. Shak commented that one thing that might help is if one moves on to other innovations when the early data on a particular innovation do not look compelling.
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From page 64... ...
It is not reasonable for insurers to require multi-center randomized controlled prospective trials if they are not paying for them, the speaker continued. Who will pay for these trials?
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