Swedes say genetics can help tailor treatment

Do benefits outweigh privacy implications?

Members of a Swedish research team say physicians may one day use genetic tests to determine how well a drug will treat a patient’s condition long before they write the first prescription to treat it.

Doctors say there is a great need to be able to preview how a patient will respond to a drug. And the benefits that could come from such tests far outweigh the risks to society, such as genetically stigmatizing some patients as difficult to treat.

At the recent Ninth European Meeting on Hypertension in Italy, the researchers from Uppsala University and Eurona Medical AB announced they could identify a genetic marker in 31 of 102 patients, which they believed would indicate a good response to ACE inhibitors.

Results of the study

Seventy-three percent of these patients had successful drug therapy, defined as a reduction of diastolic blood pressure by more than 10 mmHg or reaching a level below 90 mmHg. In the remaining patients who did not have this ACE inhibitor responder signature, 42% still had positive results.

Lead researcher Hans Lithell, MD, PhD, says his team is beginning with ACE inhibitors and hopes to be able to develop similar techniques for other classes of drugs like beta-blockers, diuretics, angiotensin II inhibitors, and calcium channel blockers.

"Today, doctors start treatment quite blindly," says Lithell, professor of geriatrics at Uppsala University. "Nobody knows any characteristics of which drug to start with."

In general, Lithell says, doctors know how to match up drugs and the conditions they treat. But on an individual basis, one patient may do well on a drug while another person with the same condition will not. Lithell says his team is working out a way to recognize genetic patterns — or polymorphisms — in patients that are related to favorable responses to particular types of drugs. "Our first study is with ACE inhibition," he says. "There is that relationship there."

Whether Lithell’s study is a breakthrough or another step in the direction of a test is not certain, says Jay N. Cohn, MD, professor of medicine at the University of Minnesota in Minneapolis. But those steps need to be made. He says physicians must be able to apply the findings of large clinical trials to their individual patients in their own practices.

Some patients don’t have average response

When large clinical drug trials become available, they show the trends of how patients responded to the treatment. "But everyone within the trial doesn’t benefit," Cohn says. Doctors just can’t get a copy of the published study and be able to tease out how individuals did.

Genetic tests like Lithell’s may be what doctors need, or perhaps the answer lies elsewhere, such as determining physiologic markers, Cohn says. Researchers may be able to look at the physical state of a blood vessel and be able to determine how it will respond to drugs. But the important thing, he stresses, is that researchers keep looking for the tests that will help doctors improve the care they give to patients. Working with genetic testing, however, leads to these questions:

-How should physicians counsel patients when test results return?

-What will different interest groups such as insurers do with the information?

"I don’t think we should slow down the search for genetic markers for response because they will have social implications," Cohn adds. "Social issues have to be addressed as they develop."

"The general notion has been we’re already going down this road," says William Fassett, PhD, MBA, a pharmacy ethicist and incoming dean of the school of pharmacy at the University of Washington in Seattle. Scientists are mapping the human genome. Doctors already have genetic tests that are markers for diseases like Tay-Sachs, he adds, so the need for counseling and the protection of privacy are not new concepts.

At one extreme, Fassett says, people may fear advances in genetics will lead to constant scrutiny. Each hair or flake of skin someone sloughs off and leaves behind could betray the privacy of the owner. But the other side of the story holds the promise of how doctors may be able to help patients.

"The need to be able to test drugs is so great that people will want that," Fassett says. "You’re not going to stop the science."

The question to address is not how to control the science, Fassett explains, but how to use the information scientific research provides.

A good example is how Americans have been struggling with the use of personal credit reports and financial information. At any time, there are plenty of people who can get access to these personal records if they are willing to do some research and spend some money. Consumers can’t do much about that, he says. But Congress can pass laws that protect an individual’s rights by adding explanations to the report or note when it is being contested and why. Genetic testing may lead to similar measures for medical files.

Lithell notes his test isn’t like the extreme that Fassett describes — where tissue samples taken from patients are studied for all sorts of personal information. Rather, it’s more like a blood test that looks for particular blood types, then discards the sample. The only trait the laboratory would be looking for would be the response to a particular drug. But even so, others say it will bring its own set of responsibilities.

"It’s just what we are dealing with now," says Bill Allen, JD, assistant professor for the Program of Medical Ethics, Law and Humanities at the University of Florida College of Medicine in Gainesville.

Allen notes things can get a bit tangled when determining how the law protects patients’ privacy of genetic information. In Florida, for example, genetic information is considered to be private, unless a patient gives consent for others to use it.

But insurers may be getting permission when new subscribers sign a general waiver that is often required to join a health plan. (Such a waiver often can act as a blanket permission statement to gain access to personal files.) It’s a good idea to understand what members are permitting their insurers to see when they sign this statement, he says.

How protective are state laws?

There is another wrinkle: Under the Employ-ment Retirement Income Security Act (ERISA), state laws that protect individual genetic information may not apply to people who are self-insured or get their coverage through the large companies that insure their own employees and often use an insurer as a third-party administrator. Allen says when it comes to protecting the privacy of genetic information, "the state laws are not a huge significance."

There is protection under federal law, says Philip Reilly, MD, JD, president and CEO of the Eunice Kennedy Shriver Center in Waltham, MA, a research facility for developmental disabilities and mental retardation, and an editor of The Gene Letter. People are protected through the Health Insurance Portability and Accountability Act of 1996, he says, which keeps insurance companies from using genetic material as a basis for rejecting people who are switching health plans.

Lithell’s test doesn’t set off any alarms, he says, mostly because doctors need to have such tests to tailor care. He adds that he speaks with insurers all the time. They tell him theyll avoid using information as a basis for their underwriting because the controversy "and political hot water" isn’t worth the money they could save.

Federal legislators are also working on other bills this summer that contain provisions for keeping medical information private.

No rejections, but maybe coercion

Allen notes that consumers should realize having such genetic tests could change the way insurance plans are structured. Companies may not use genetic information to keep people out of the plan but still could use it as a basis for coercion. Members who take the test and use the drugs that are indicated by the results may be rewarded with lower copayments.

Today, medical ethics needs to follow the relationship between doctor, patient, and insurer, Allen says. The trick is to come up with a system the gives the payer a legitimate voice without breaking down the relationship between doctor and patient.