Genetic Testing

In today's NEJM there is an article regarding the use of genetic testing by Drs. Hamburg and Collins of the FDA and NIH respectively. It raises the issue regarding the use of these tests in the future for personalized medical treatment.

The authors state:

Genetic tests are not perfect, in part because most gene mutations do not perfectly predict outcomes. Clinicians will need to understand the specificity and sensitivity of new diagnostics. The agency's goal is an efficient review process that produces diagnostic–therapeutic approaches that clinicians can rely on and allows companies that invest in establishing the validity and usefulness of tests to make specific, FDA-backed claims about benefits.

Patients should be confident that diagnostic tests reliably give correct results — especially when test results are used in making major medical decisions. The FDA has long taken a risk-based approach to the oversight of diagnostic tests, historically focusing on test kits that are broadly marketed to laboratories or the public (e.g., pregnancy tests or blood glucose tests); such kits are sold only if the FDA has determined that they accurately provide clinically significant information. But recently, many laboratories have begun performing and broadly marketing laboratory-developed tests, including complicated genetic tests. The results of these tests can be quite challenging to interpret. Because clinicians may order a genetic test only once, getting the results right the first time is crucial.

There are reports of problems with laboratory tests that have not had FDA oversight: women were erroneously told they were negative for a mutation conferring a very high risk of breast cancer; an ovarian cancer test, marketed before the completion of an NIH-funded study,² gave false readings that reportedly led to the unnecessary removal of women's ovaries; and flawed, mishandled data underlying a test for Down's syndrome were discovered only days before the test was to go on the market. Through a process that includes opportunities for public input, the FDA will work to ensure the quality of key diagnostic tests, helping to protect patients and giving clinicians confidence that personalized medicine will lead to real health improvements.

In addition, the NIH will address the fact that there is no single public source of comprehensive information about the more than 2000 genetic tests that are available through clinical laboratories. On the recommendation of a federal advisory committee, the NIH — with advice from the FDA, other Department of Health and Human Services agencies, and diverse stakeholders — is creating a voluntary genetic testing registry to address key information gaps. Readily available information about these tests, including whether they were cleared or approved by the FDA, will help clinicians and consumers make informed decisions about using the tests to optimize health care. The registry will also support scientific discoveries by facilitating the sharing of data about genetic variants.

The issues regarding these tests can be characterized as follows:

1. Screening: The use to determine the predilection of an individual towards a certain disease. This is useful if and only if there is something that can be done to reduce mortality or morbidity. Just telling a person they may have a disease at some uncertain future date may be useless information and in fact harmful. Thus the mass genetic tests which seem commercially common may be resulting in harm rather than good.

2. Staging: There are millions of biopsies performed every year and the results sent to other physicians and in turn transferred in some manner to the patient. For example in a skin biopsy, if melanocytes have moved from the basal layer to the upper layers then this may be a sign for melanoma in situ. Thus what should one do? Standard practice is wide area excision but if one knew what pathways were activated in the cell one may have a better path to follow. Yet at this time such tests are not performed. The same could be said about cases of prostatic intraepithelial neoplasia, will it go to prostate cancer and if so will it be a virulent form? Knowing this via personalized medicine would save billions.

3. Treatment and Prevention: These steps are to some degree already underway.

Thus it is strange that we have the latter steps in progress and the initial high gain steps still at best in a formative stage. It would be useful for the FDA and NIH to look at a broader array of applying these new genetic personalized medical treatments.