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Regulation of Predictive Tests
Pages 25-48

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From page 25...
... . The Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act brought the marketing of devices, including in vitro diagnostics, under FDA regulation (hereinafter, in this report, "companion diagnostic tests.")
From page 26...
... . He began his talk by pointing out that "in personalized medicine, the companion diagnostic really becomes key, because if you're going to be given a therapeutic, or you're going to be taking a clinical action based on the companion diagnostic, the diagnostic has to be right." The Medical Device Amendments of 1976 gave the FDA authority to regulate devices, including companion diagnostic tests, based on the amount of risk that is linked to the use of that device.
From page 27...
... In addition, the FDA regulates companion diagnostic tests by ensuring that all of the claims made on a diagnostic test's label are accurate and can be supported by evidence. The OIVD review of device performance is transparent with the reviews posted on the FDA website (FDA, 2009c)
From page 28...
... In contrast, FDA-approved companion diagnostic tests are generally developed by industry to be used in laboratories throughout the country, if not the world. FDA companion diagnostic "test kits" need to be more robust because anyone can buy the kit and perform the test, regardless of their expertise, Dr.
From page 29...
... Meyers said. CLIA has a lengthy list of requirements that ensures the analytic validity of the testing a laboratory performs, but CLIA does not regulate the clinical validity of a test, unlike the FDA's regulation of companion diagnostic tests.
From page 30...
... Meyers said. When a laboratory is going to implement an FDA-approved or -cleared companion diagnostic test, the laboratory must verify that the test's performance specifications are met.
From page 31...
... . This claim was supported with data generated by the company that devised the test, which showed that when individuals with follicular lymphoma are homozygous for a specific gene, they will have a 100 percent response rate to the drug, whereas those who are heterozygous or completely lack the gene will only have a 67 percent response rate (Figure 6)
From page 32...
... Mass also questioned the claim that laboratory-developed tests do not have to be reviewed by the FDA because they tend to not pose safety hazards. In the context of predictive tests, safety can be defined as the right patient getting the right drug, and the wrong patient not getting the wrong drug, he noted.
From page 33...
... Ms. Stack called for increasing clarity on both the regulation and reimbursement of predictive tests so venture capitalists, such as herself, can continue to develop innovative companion diagnostic companies.
From page 34...
... The current system makes no sense. Predictive tests are now in the clinic without FDA review, and FDA-reviewed companion diagnostic tests may be used for non-approved means.
From page 35...
... FDA reviews of tests are done using the same template for providing standard information on a companion diagnostic test as used by laboratories under CLIA, and the proficiency testing is basically the same for both laboratory-developed tests and FDA-regulated tests. One analysis found a 98.1 percent accuracy with samples sent to laboratories for proficiency testing for a broad range of genetic tests, most of which are laboratory developed (SACGHS, 2008b)
From page 36...
... Dr. Herbst added that "we're dealing with new information that changes maybe not the analytic validity of the test, but the clinical validity and ultimately probably the clinical utility." Dr.
From page 37...
... "As we began to have CAP proficiency testing, where your feet are put to the fire every 6 months, we've seen agreement go from 65 to 70 percent to close to 90 percent," he said.5 Ms. Javitt described a longstanding concern about the lack of mandatory proficiency testing for genetic tests because there is no specialty for them under CLIA.
From page 38...
... "We are missing huge chunks of information, and the quality of decisions depends a lot on the quality of information going into making those decisions," he said. The SACGT report recognized the need for more transparency in data collected on predictive tests, and recommended that genetic test developers be required to provide information on analytic validity, clinical validity, and clinical utility, said Dr.
From page 39...
... . The Twenty-First Personalized Medicine Coalition and the American Clinical Laboratory Association have also both supported the idea of registering laboratory-developed tests.
From page 40...
... "Sometimes some of the problems we see are due to the regulation not being fully enforced," she said. Consequently, SACGHS recommended that the gaps in the enforcement of existing regulations for analytic and clinical validity be identified.
From page 41...
... Neither laboratories nor manufacturers have the resources to assess the clinical utility of genetic tests, for example, by building on the CDC's Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative (SACGHS, 2008b)
From page 42...
... Two examples from EGAPP that highlight the need to do more translational research evaluating the clinical utility of predictive tests are the recent evaluations of (1) breast cancer gene expression profiles, and
From page 43...
... . EGAPP's evidence review found adequate evidence of the clinical validity of Oncotype DX and MammaPrint, but inadequate evidence of the clinical utility of Oncotype DX and no evidence of the clinical utility of MammaPrint.
From page 44...
... If the data do not indicate clinical utility, the predictive test should be taken off the market. Conceptually, such a registry would be more comprehensive than the registry of predictive tests proposed by SACGHS or SACGT.
From page 45...
... The off-label use of a questionably useful test also made the predictive test regulation appear inconsistent, Dr. Quinn said.
From page 46...
... Similar non-regulatory strategies for collecting and improving the clinical utility of predictive tests could be implemented.
From page 47...
... The FDA should be responsible for regulating analytical and clinical validity, but not clinical utility.


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