The Health, Wellness & Beauty Pages

June 16, 2010

• JUNE 9, 2010 By AMY DOCKSER MARCUS

Hospital Study Shifts Protocol to Inform Its Participants of Worrisome Test Results

Children’s Hospital Boston, breaking with scientific convention, has designed a new genetic research project so information gleaned from DNA submitted by patients and their families can benefit not only science, but potentially participants themselves.

No decisions have been made on what will be passed on to families, but research has already identified genes associated with conditions such as autism, diabetes and obesity. Families who learn they are at genetic risk might seek medical intervention sooner. Others may adopt lifestyle changes to try to lower their risk.

In most large-scale genetic research, people contribute genetic information knowing they will receive neither payment nor personal results. One big reason is the concern among researchers and medical ethicists that people would be confused or alarmed by the information, which isn’t always well-understood even by geneticists. Some genes confer increased risk for disease, for instance, but that doesn’t mean someone will definitely get sick.

But the Boston project, at one of the nation’s leading pediatric hospitals, comes at a time when researchers are starting to confront whether more medical information should be shared with participants in genetic studies. New technologies allow researchers to run many genetic tests at the same time, revealing potentially important health information about individuals.

“We plan to follow these families for years,” said Kenneth Mandl, one of the principal investigators on the Gene Partnership Project. “In order to ask people to spend more time with this project, we felt we needed to give them something back.”

One of the project’s goals is to pinpoint the genetic causes of a range of childhood diseases by seeing how lifestyle and environment interact with genetic risk over time. But a key notion is that researchers will be in regular communication with participants. Families will be told of relevant clinical findings regarding their genetic information, as well as clinical trials or other research studies applicable to them.

Investigators have already collected several hundred DNA samples from children, their siblings and parents. The hospital plans to start recruiting in the next several weeks from the roughly 60,000 children seen every year at the hospital’s emergency room. The goal is to collect 10,000 DNA samples every year and ultimately to make gene testing part of routine health care at the hospital. Families participate at no cost.

The hospital has invested about $10 million from federal grants, donations and hospital funding, and is working to raise an additional $50 million over the next three years.

The Gene Partnership Project is one of a growing number of genetic databases around the country, many collecting DNA from people with specific diseases. Typically the samples, usually blood and saliva, are housed at academic medical centers or hospitals, and researchers interested in studying different diseases submit proposals requesting samples from the databanks. Any findings are usually published in scientific papers but not returned to participants.

Isaac Kohane, one of the principal investigators, said his involvement grew out of an autism study he did with another co-investigator, Louis Kunkel. The research revealed that two children in the study might have leukemia. Under the terms of the study, the researchers weren’t supposed to give clinical information back to the patients. But such so-called incidental findings are increasingly common as researchers use more sophisticated genetic testing.

“I lost two nights of sleep over what to do,” Dr. Kohane said. The researchers realized after retesting that the finding was a false positive, but they started talking about ways to communicate clinically relevant information to participants.

Children’s Hospital Boston gets permission from parents but also explains the project and gains assent from children ages 7 or older, then again at age 13. If the child doesn’t want to participate at any stage, the DNA is destroyed. At age 18, participants must give consent to continue to participate, said Ingrid Holm, who is one of the co-investigators of the Gene Partnership.

When investigators find genetic information they believe should be shared, a special oversight board including geneticists, ethicists and advocates weighs whether the data are scientifically valid enough to share with interested families. One of the issues is whether the findings require some kind of intervention, such as medical treatment or a lifestyle and dietary change.

Patient data are anonymous, but the families can be contacted through a secure electronic-messaging system.

Jessica Freier of Newton, Mass., whose 11- and 9-year-old sons are seen at the hospital’s developmental-medicine clinic, said, “I had hesitation about my kids’ genetic information being in a database. I wasn’t sure how much I wanted on record.” She said she agreed to do it because she thinks the database may help develop “best practices for treating kids.”

Her 11-year-old son had many questions for the genetic counselor. “He wanted to know how they store it and what they can harvest from it,” she said.

Other projects are considering such steps but are still wrestling with the issue of how to share results in a meaningful way that might allow people to prevent or treat diseases.

Hakon Hakonarson, director of the Center for Applied Genomics at Children’s Hospital of Philadelphia, says the pediatric biobank at the hospital has DNA from more than 100,000 people, including over 60,000 children. Currently, participants receive no genetic results.

He said he personally would “like to give information back because that would be the right thing to do.” His biggest concern is that the samples are collected for research, not for making medical decisions. “We do not want to misinform anyone,” Dr. Hakonarson said.

 

By Jennifer Evans 1:12 pm  April 5, 2010

So it was a natural move for him to ship off his own genetic code for analysis. He wanted to experience first-hand how behavior can change based on personalized information about the risks for disease.

By Aaron Rowe February 18, 2010  |5:00 am 

Read More http://www.wired.com/wiredscience/2010/02/getconference/#ixzz0k4k7eWJS

March 16, 2010

This article has been updated to include comments from the ACC meeting.

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – Genetic testing for variants related to Warfarin treatment response decreased hospitalization rates by almost one third in a prospective study of patients at sites across the country, according to research being presented today at the American College of Cardiology’s scientific session in Atlanta.

Researchers from Medco Health Solutions, the Medco Research Institute, and the Mayo Clinic led the comparative-effectiveness study, which looked at the utility of genetic testing for improving the safety and effectiveness of the widely prescribed blood thinner Warfarin (marketed as Coumadin by Bristol-Myers Squibb and Jantoven by Upsher-Smith). The research was funded by Medco and the Mayo Clinic’s Center for Individualized Medicine.

Warfarin dosing can be challenging given variable drug response between individuals and a narrow therapeutic range for the drug: doses that are too high or too low can lead to bleeding or clotting complications, respectively. Consequently, the US Food and Drug Administration requires a black box warning on Warfarin labels outlining such risks and recommending close patient monitoring.

Last month the FDA also updated Warfarin labeling to include genetic testing recommendations as well. As GenomeWeb Daily News sister publication Pharmacogenomics Reporter reported in February, the labeling now refers to a table outlining recommended doses for individuals depending on their CYP2C9 and VKORC1 genotype information.

For the current study, which began in July 2007, researchers enrolled patients from 49 states who were insured by dozens of health plan sponsors managed by Medco.

Using Medco’s integrated medical and pharmacy claims systems, the team compared 896 individuals who received genetic testing for CYP2C9 and VKORC1 genes early in their Warfarin treatment with 2,688 control individuals, selected from the same group of health insurance sponsors the previous year, who had received treatment without genetic testing.

Patients participating in the study ranged from 40 to 75 years old, with an average age of 65 years old. Around 60 percent of participants in the study and controls groups were men. Genetic testing for the study was performed at the Mayo Clinic, which also gave doctors guidelines for applying genetic information to drug dosing and management.

The researchers found that those in the genetic testing group were 28 percent less likely to be hospitalized for bleeding or thromboembolism — and 31 percent less likely to be hospitalized for any reason — than individuals in the control group, based on medical claim data.

“These results show that we can greatly reduce hospitalizations, and their significant costs, by making genetic testing routine early in a patient’s therapy with warfarin,” lead author Robert Epstein, Medco’s chief medical officer and president of the Medco Research Institute, said in a statement. “If it costs a few hundred dollars for the genetic test but avoids the $13,500 hospital bill, it very quickly pays for itself.”

However, according to a review presented at the ACC meeting by Mandeep Mehra, chief of cardiology at the University of Maryland Medical Center, the design of the Medco/Mayo study did not sufficiently account for the fact that physicians, aware that their patients were being genotyped as part of a clinical trial, may have followed those patients more closely, leading to better outcomes.

While Epstein acknowledged that physicians knew their patients were being genotyped, he also said the fact that physicians in the Mayo/Medco study may have followed their patients more closely because of genetic testing shouldn’t be a mark against the clinical utility of the intervention.

“If, in fact, receiving genotyping information helps the physician pay closer attention to the patient, like make them do more INRs because it points out the person has a rare genotype and needs to be tracked closer, I don’t think that’s a bad thing,” he said.

Down the road, researchers reportedly plan to look at the cost-benefit profile of warfarin genetic testing.

For information about genetic testing that is affordable and can help you determine some of your genetic predispositions, please visit DNAistheWay.net

---

Turna Ray contributed additional reporting for this article from the ACC meeting. A detailed article on Medco’s presentation and Mehra’s review can be found on Pharmacogenomics Reporter.