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1236 volume 15 | number 11 | november 2009 nature medicine

Did you have an ‘aha’ moment that led you to public policy in genetics?Sort of. It came through talking [in July] with Kathy Hudson, the former director and founder of the Genetics & Public Policy Center. I began to appreciate this bigger question that I think all clinicians and individuals in the field should be asking: ‘What are the policy implications of what we’re doing?’

Why is it important to ask that question?There are many new discoveries coming out of genomic research, but there is a very low barrier to validating genetic tests. Clinicians and patients need to be aware of the issues around how tests get to market.

How do genetic tests come to market in the US?We have a two-path system: genetic tests developed in-house by a clinical laboratory or genetic test kits developed and sold by a manufacturer. The former, known as ‘laboratory developed’ tests don’t require FDA [US Food and Drug Administration] approval, but the latter, called ‘test kits’, do.

The vast majority of genetic tests are laboratory developed. The result is that the end user does not know what level of scrutiny has been given to that particular test, since it has not gone through the FDA.

Why doesn’t the FDA regulate ‘laboratory developed’ genetic tests?FDA has jurisdiction over laboratory-developed tests, but they have chosen not to exercise enforcement up to this point. Instead, the Center for Medicare and Medicaid Services regulates clinical labs under a division called ‘CLIA’, which looks at the labs to make sure they’re doing tests correctly.

Would the system work better if the FDA applied the same level of scrutiny to all genetic tests?Yes and no. It makes sense to develop a scrutiny system based on risk. Specifically, tests for higher-risk conditions, such as breast cancer or cystic fibrosis variants, would receive more scrutiny than those for lower-risk conditions, such as type 2 diabetes. Any test result that requires a patient to face a significant clinical management decision should receive more scrutiny because there is more associated risk.

Would a genetic test registry help?We have called for the development of a mandatory test registry so that there’s clear and transparent information available to the end user about what tests are available, who’s doing it, what the performance of that test is in that laboratory, what’s the clinical validity of that test supporting its use and what’s known and not known about it.

Straight talk with…Joan ScottAs advances in genetics continue to flow from the laboratory into the clinic—and, increasingly, into courts—it’s crucial

to parse the influence of gene-based technologies. The Genetics & Public Policy Center (GPPC) launched in 2002 to do

just that. Located within the Johns Hopkins Berman Institute of Bioethics in Washington, DC, its staff monitors advances

in human genetics, including genetic testing, and their translation into clinical medicine. The GPPC staff also advises

decision-makers on developing sound policies. In September 2009, Joan Scott was named the new director of the

Genetics & Public Policy Center. Scott spoke with Genevive Bjorn about the twists and turns of using information from the

double helix.

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Q & a

nature medicine volume 15 | number 11 | november 2009 1237

Before joining the GPPC, you worked as a genetic counselor from 1978 to 1998. How has genetic testing changed in your view?Historically, the kinds of genetic tests that were available were for relatively rare, but very highly penetrant, conditions. For example, with Huntington’s disease, if you have the genetic variant, that variant has a very high risk of being associated with a clinical manifestation of the disorder. In other words, there’s a direct correlation between having the genetic variant and having the disease.

Now we’re beginning to identify gene variants that are much more common in the general population but confer much lower risks for a wider range of diseases, such as diabetes, heart disease and arthritis.

Or there may be three or four variants related to a particular condition that you’re testing for at the same time. Basically, we have a lot more information now but know less what it all means.

Testing for variants has been in the news lately, specifically direct-to-consumer genetic tests. Both the UK and US are considering tighter regulations of them. What’s at the heart of the controversy?There are a wide variety of genetic tests that are available directly to consumers, and part of the confusion is that all genetic tests get lumped together. Some tests, such as for cystic fibrosis or Huntington’s, have very high validity because the associated risks are well known. Then there are other genetic tests sold to consumers that have less clinical validity but seem to satisfy people’s curiosity. There’s a type of test that will tell people about their ancestry, which some people may find fascinating, but it’s not necessarily clinically useful today.

Do you have concerns about direct-to-consumer genetic tests?The most suspect tests purport to identify a defect and then sell something to fix it. For instance, you can buy a test to see if there are problems with your metabolism or the way you metabolize certain nutrients, and, if so, the message is that you should change diet. These results are often followed with the sales pitch: ‘I have a particular nutrient supplement that will help that’.

It’s not to say that genes don’t play a role in how you metabolize, and eventually it may be very useful information down the road. But, currently, what we know about some of these variants means they have questionable clinical validity and certainly questionable clinical utility. Plus, some of these tests are very expensive, up to $1,200 a pop.

However, there are genetic variations clearly involved in how people metabolize foods and drugs. Variants can affect metabolic pathways, and some of these tests may tell us a lot about basic biology.

What about placing additional regulations on direct-to-consumer genetic tests?Organizations such as the American College of Medical Genetics and the American Medical Association think patients should only get genetic tests through a healthcare provider. But it’s not a one-size-fits-all system. There are many types of genetic tests that are perfectly appropriate for individuals to access directly, such as type 2 diabetes and heart disease. Having more info about themselves could motivate people to change behavior.

How might risk-based assessment of genetic tests actually work?For example, tests currently offered direct to consumer for a high-risk condition, such as cystic fibrosis, do not come with automatic [follow-up by] a healthcare provider. With risk-based assessment, this test might be automatically kicked up into a higher risk category that FDA would monitor more closely.

You worked for a genomics company before coming to GPPC. Given the vagaries of private enterprise, who’s best suited to hold the vast amounts of genetic information coming from test results and samples?It’s okay for private companies to hold samples as long as they make known their policy about what happens to the sample and obtain informed consent. The customer should be able to opt out and still receive services.

The UK Biobank works as a national repository for genetic information. Are there any comparable biobanks in the US, and what purpose do they serve?Policymakers are considering a national US biobank. But at the moment the only active US equivalent comes in the form of smaller longitudinal cohort studies. There are also a number of biobanks and genomic repositories across the country.

The importance of these kinds of data is that they allow us to link genetic information about individuals to medical information and then track it over time.

How is GPPC involved with these longitudinal studies?We’ve been evaluating what people think about participating in these large longitudinal cohort studies, what their concerns are and what they would expect in return for participating.

What have you found?There are two broad categories of people. Some people are very willing to participate in these kinds of medical research studies for altruistic purposes. They want to help advance what we know about diseases

to foster treatments and cures. And then there are individuals who are interested in participating because they think they may learn something about themselves. Most people don’t

expect much more in return, apart from some safeguards put into place to insure that the data was handled ethically, appropriately and with privacy.

Going forward, what is your vision for the GPPC?The issues I just mentioned are still very important for the center. Personally, as a clinician, I also have interests in other areas. Specifically, I want to know how this new genomic information is going to impact health care.

How do you propose finding this out?By asking a lot of hard questions. I want to know: what do people do with this information that comes from genetic tests? Do people change health behaviors? Does it really improve health outcomes in the long run to get these kinds of test results? What’s the overall cost to the healthcare system in order to access and utilize this information effectively?

Do you have any hints now at answers to these questions?No, not really. We have a dearth of data when it comes to the use of some of this new genetic information in daily clinical practice.

What might be the role of genetic testing in health care reform in the US?I can only speculate that it would be helpful to have information about cost effectiveness and value added for various genetic tests. At the end of the day, what we should be keeping our eye on is how this information improves health outcomes.

“I want to know how this new genomic information is going to impact health care.”

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