Monday, February 24, 2014

Genetic Testing Lab Position Statement


To show your support of this position statement, please send an e-mail with your intent, and affiliation to danielle.bonadies@yale.edu

Since the patents on the BRCA1 and BRCA2 genes (associated with hereditary breast and ovarian cancer) were overturned in mid-2013, the options for BRCA testing have exploded. Many laboratories are offering comprehensive, quality testing at ~50% of the previous cost. This competitive marketplace has many benefits to patients, providers and researchers, but we have also seen some laboratories beginning to use manipulative tactics to secure their profits in this volatile field. Genetic counseling centers have reported receiving pressure from clinicians to use specific laboratories for testing, learning that these clinicians are receiving financial incentives or hefty speaker's fees from these laboratories. The conflict of interest is clear. We have reports of other laboratories threatening to siphon-off referring clinicians if their laboratory isn’t used.

Below please find the full text on a “Genetic Testing Lab Position Statement” that pledges we, the ordering clinicians, will continue to make laboratory and testing choices based on what is in the best interest of our patients and will not be swayed by political, personal or financial gain.

This is also an opportune time for patient organizations, clinical organizations and insurers to show their support of laboratories that will fully share past, current and future data in open databases that serve research and patient care.

Please pass this on to your family, friends, colleagues, patients and contacts within your networks.


Genetic Testing Position Statement
Cancer Genetic Counseling Program Yale School of Medicine/Yale Cancer Center
New Haven, CT February 2014


With the emergence of new testing technologies and the 2013 Supreme Court decision banning gene patenting, the available cancer genetic testing options and the laboratories offering testing have expanded exponentially and are likely to continue to do so. As providers we have a responsibility to our patients to make the best decisions regarding which laboratory to use and which tests are most appropriate based on what is best for the patients. Our decisions will not be swayed by political, personal and/or financial gain.

Whenever possible (1), we will choose a laboratory based on these four criteria:


1. Quality: Is the test being offered accurate and comprehensive compared to what else is on the market?

2. Time: How long will the patient have to wait for his or her test results?

3. Cost: Will our patient’s insurance carrier cover this test at this laboratory?

4. Open Access: Has this facility pledged to Free The Data? Whenever possible we will choose laboratories that have pledged to make all of their past, present, and future gene data publicly available in order to allow this important information to be freely accessible to all clinicians and researchers, to further the advancement of medical knowledge and to best serve patient care. We will not support laboratories that hoard data.

To avoid any real or perceived conflicts of interest, we will not accept gifts (including trips, speaking stipends, stock options), funding, personal or financial support from testing laboratories. We pledge to update our laboratory choices over time as these choices evolve, choosing the best option for our patients and clinical research.

As clinicians, insurance plans, patient groups, and professional organizations nationwide begin to decide which laboratories to use in this quickly evolving marketplace, we ask that they join us in this pledge.

1. Laboratory choices must sometimes be based on insurance plan regulations, test availability, or the lab’s previous experience with a rare familial mutation.


 Genetic Testing Lab Position Statement.pdf -


Position Statement Signed By:


Clinicians:

Ellen T. Matloff, MS, CGC, Yale Cancer Genetic Counseling

Danielle C. Bonadies, MS, CGC Yale Cancer Genetic Counseling

Karina L. Brierley, MS, CGC, Yale Cancer Genetic Counseling

Rachel E. Barnett, MS CGC, Yale Cancer Genetic Counseling

Niki Lovick, MS CGC, Yale Cancer Genetic Counseling

Michelle Ernst, MS CGC, Yale Cancer Genetic Counseling

Jennifer Doherty, MS, CGC, Yale Cancer Genetic Counseling

Amanda Lamb, ScM, CGC, Maine Medical Center

Nisha Isaac, MS, CGC, University of Maryland St. Joseph Medical Center

Sayaka Hashimoto, MS, LGC, Nationwide Children's Hospital and Ohio State University

Kristin DePrince Mattie, MS, MD Anderson Cancer Center at Cooper

Cathleen McCann, MS, CGC, Sarasota Memorial Healthcare System

Paul B. Dorsey, MS, Legacy Genetic Services

Catie Beattie, MS, CGC, Casey Eye Institute

Peggy Cottrell, MS, CGC, Regional Cancer Center

Jessica Adsit, MS, CGC, Legacy Center for Maternal Fetal Medicine

Amie M. Blanco, MS, LCGC, UCSF Cancer Risk Program

Carrie Fagerstrom, MS, CGC, Randall Children's Hospital at Legacy Emanuel

Melanie Hardy, MS, CGC, Henrico Doctors’ Hospital

Allen E. Bale, MD, DNA Diagnostic Lab, Yale University

Robert Pilarski, MS, LGC; MSW, LSW, Ohio State University Cancer Genetics Program

Christina Dupre, MS, CGC, New England Ob/Gyn Associates

Lauren Ryan, MS, LCGC, UCSF Cancer Risk Program

Meagan Farmer, MS, CGC, University of Alabama at Birmingham

Robert Cook-Deegan, MD, Institute for Genome Sciences & Policy and Sanford School of Public Policy at Duke University

Carol Guthrie, MD Spokane Breast Center, Columbia Medical Associates

James P. Evans MD, PhD, Bryson Distinguished Professor of Genetics & Medicine, Editor-in-Chief; Genetics in Medicine, University of North Carolina at Chapel Hill

Robert Nussbaum, MD, Division of Medical Genetics, University of California, San Francisco

Erin Ash, MS, CGC, Bennett Cancer Center of Stamford Hospital

Cristina Ruiz, MS, CGC, Advocate Center for Breast Care, Oak Lawn, IL 

Kelli Mayfarth, MS, CGC Health-Quest Hospital System, New York

Tricia Z. Page, MS, CGC, JScreen at Emory University

Kory Jasperson, MS CGC, Huntsman Cancer Institute

C├ęcile Skrzynia, MS, CGC, Cancer and Adult Genetic Counseling, UNC Chapel Hill

Kim Brussow, MS, LCGC, Good Samaritan Hospital

Jessica Chowns, MS, CGC, Parkview Health

Melissa Dempsey, MS, Parkview Health

Kathy Christiansen, RN, BSN, OCN, Cancer Prevention and Hereditary Cancer Risk Program, Methodist Estabrook Cancer Center

Marjan Champine, MS, LCGC, Huntsman Cancer Institute

Shawnia Ryan, MS, CGC, Providence Genetics Clinic

Lindsay Conant, MS, LCGC, Oregon Health & Science University


Shelly Levin, MS, LCGC,  Kaiser Permanente Medical Group


Amy K Krie, MD, Medical Oncologist, Clinical Director Avera Breast Program

Brittany Burnett, MS, LCGC, Sharp Healthcare, San Diego, CA 

Community Members and Advocacy Groups:

Genetic Alliance

Kirsten Dooley, Yale Cancer Genetic Counseling

Lisa M Guzzardi, BRCA Advanced, Facebook Group

Marly Canuck Wietzke, Vancouver, BC, Canada

Nicki Boscia Durlester, Founder, Beyond the Pink Moon, Facebook Group

Pamela Morris Watt, CT

Tracy Dunbrook, CT

Cathy Corman, MA

Katie Behr, CT

Andrea Downing, Activist, Patient Advocate

Amy Byer Shainman, The BRCA Responder, BRCA Health Advocate, Co-Administrator of The BRCA Sisterhood on Facebook

Victoria Costello, Genetic Counseling Graduate Student, Sarah Lawrence

Leslie Kellman, NY

Marlene Kuma Gutierrez, CA

Rochelle Bernold, CT

Emily Kelley, Community Manager, Young Previvors Facebook Page

Teri Smieja, Co-author of Letters to Doctors, The BRCA/HBOC edition, Co-creator BRCA Sisterhood Facebook Group.

RaeAnn Kragenbring, Genetic Counseling Graduate Student, Sarah Lawrence

Mary Carpenter

Katherine Lambertson, Fellow, Genetic Alliance

Robin Baslaw, CT

Kate Berges, CT

Jessica DiGiovanna, Genetic Counselling Graduate Student, Mount Sinai

Peter Grudberg, CT

Terry Stoller, CT

Jill Holdren

Joanna Rudnick, Independent Documentary Filmmaker Read more!

Monday, January 13, 2014

After 23andMe, Another Personal Genetics Firm Is Charged with False Advertising

Original post by Dina Fine Maron on Scientific American, 1/11/14

It sounded like a miracle of science and convenience: swab your cheek and drop the saliva sample in the mailbox and GeneLink Biosciences, a personal genetics company, would analyze your DNA and send back nutritional supplements customized to your personal genome. The regimen, the company promised, was good for diabetes, heart disease, arthritis, insomnia and other ailments. The Federal Trade Commission (FTC), however, thought it sounded like false advertising and brought a lawsuit against the company, charging its claims were misleading and not founded in sound science.

The case is the latest in the continuing controversy over personal DNA testing services. Two months ago the U.S. Food and Drug Administration warned 23andMe to stop selling its personal genetics testing kits because the company failed to prove its tests worked and the agency worried about the public health consequences of inaccurate results. The GeneLink case, the FTC’s first against a personal genomics company, could serve as a shot across the bow to other similar businesses. Under the terms of a proposed settlement announced on January 7, Orlando, Fla.–based GeneLink agreed to stop making unsubstantiated health claims. The settlement, which would only take place after a 30-day public comment period and a final decision from the FTC, would keep GeneLink and its former subsidiary, foru International, from making any future claims that their products can impact the course of disease unless such claims are supported by two double-blind, randomized control trials—the gold standard of medicine. A violation of that agreement could lead to fines.

“What we’re alleging is that [GeneLink’s] claims got ahead of the science,” says Carolyn Hann, a lead attorney on the case for the FTC’s Bureau of Consumer Protection. “By taking action against GeneLink and foru we were trying to indicate to this industry we were aware of the claims being made and we wanted the industry to understand where we stand on these issues,” she says. The FTC could not comment on whether other cases against genetic companies are in the offing. Although the commission opened investigations into two other genetic firms in the past, both cases were closed before action was taken, in part because the outfits were no longer going to market their products in the U.S.

GeneLink and its former subsidiary, now an independent company, had claimed that they were sending cheek swab samples to a third-party laboratory for analysis of genetic variations called single nucleotide polymorphisms (or SNPs). The companies claimed they could examine specific SNPs that affect nutritional health and aging and then offer personalized nutritional supplements and skin health products. “Any claims at all that one can look at those SNPs or other SNPs and make any meaningful recommendations for nutrition, cosmetics or anything along those lines are just entirely unfounded and entirely without any scientific merit,” says geneticist James Evans, editor in chief of the journal of the American College of Medical Genetics and Genomics.

The heart of the controversy was GeneLink’s claims that its custom-blended supplements could help compensate for aging or mitigate health issues such as heart disease and arthritis.

Under this lawsuit the FTC also charged that GeneLink failed to adequately protect consumer’s personal data, including contact information, Social Security and credit card numbers, and genetic data. According to FTC documents, GeneLink and foru had obtained genetic information from nearly 30,000 consumers since 2008. The proposed agreements would force the firms to set up comprehensive information security programs to protect such consumer data in the future and to assign at least one employee at each company to oversee that program. The corporations would also be required to receive initial regular external audits to check that the information is secure. The FTC cannot file criminal charges, only civil suits.

Click here to see the original post from Scientific American

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Thursday, January 2, 2014

U.S. Preventive Services Task Force Finds Benefit in Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer for Small Group of High-Risk Women


WASHINGTON, D.C. – December 24, 2013 – The U.S. Preventive Services Task Force (Task Force) today published its final recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. The Task Force recommends that women with family members who have had breast, ovarian, tubal, or peritoneal cancer talk with a health care professional to learn if their history might put them at risk for carrying a BRCA mutation. Women who screen positive should receive genetic counseling and, if indicated after counseling, BRCA testing. Additionally, for the vast majority of American women (90 percent), who do not have a family history associated with an increased risk for the inherited mutations, the Task Force continues to recommend against genetic counseling and testing.

One important step in preventing BRCA-related cancer is helping women understand their risk. Mutations in the BRCA1 and BRCA2 genes, which are present in 0.2 to 0.3 percent of women, are just one of many factors that can increase a woman’s risk for developing breast and ovarian cancer. Women with these potentially harmful mutations can have up to a five times greater chance of developing breast cancer, and BRCA mutations can also increase a woman’s lifetime risk for ovarian cancer to as high as 40 percent.

“Too many American women and families are faced with the challenge of dealing with cancer diagnosis and treatment. We have great hope in the science of genomics to improve screening practices and even prevent some cancers,” says Task Force chair Virginia Moyer, M.D., M.P.H. “At this point, the evidence shows that most American women will not benefit from genetic counseling or the test for gene mutations in BRCA1 and BRCA2. For women who have a family history that might be associated with an increased risk for these mutations, we found that some may benefit from in-depth genetic counseling that thoroughly reviews their family history and, if indicated and after weighing the pros and cons of BRCA testing, receiving the test.”

Current tests work best for women at a high risk for developing cancer, but the test alone does not always provide a definitive answer. There are some harms of testing; results are often inconclusive and many women could be burdened with the uncertainty of whether they are—or are not—at an increased risk for cancer. Inconclusive genetic testing leads many women to choose to take powerful medications or undergo major surgery to reduce their risk for developing cancer. Unfortunately, most will not benefit from these interventions and may needlessly suffer great harm, especially because they were never at increased risk to begin with. Therefore, the Task Force continues to recommend against routine genetic counseling and BRCA testing in women without a strong family history of cancer.

“Evidence still shows that there are serious, negative consequences that could result from testing women who are at low risk for BRCA mutations. The BRCA test works best for women who have reviewed their family history of breast or ovarian cancer and the pros and cons of the screening test with a trained professional,” says Dr. Moyer. “We hope further research will improve the ways genomic science can help women and their doctors understand their risk for cancer.”

The Task Force’s final recommendation statement is published online in Annals of Internal Medicine, as well as on the Task Force Web site at www.uspreventiveservicestaskforce.org. A fact sheet that explains the recommendation statement in plain language is also available. A draft version of this recommendation was available for public comment in April 2013.

The Task Force is an independent, volunteer panel of national experts in prevention and evidence-based medicine that works to improve the health of all Americans by making evidence-based recommendations about clinical preventive services such as screenings, counseling services, and preventive medications.

Contact: Ana Fullmer at Newsroom@USPSTF.net / (202) 350-6668

Click here to read the original bulletin by The U.S. Preventive Services Task Force
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CMS Cuts Reimbursement for BRCA1/2 Testing by 49 Percent; Analyst Downgrades Myriad Shares

Original post on GenomeWeb, 12/30/13

NEW YORK (GenomeWeb News) – The Centers for Medicare and Medicaid Services updated its reimbursement level for BRACA testing at $1,438 for 2014, a slash of nearly 49 percent from a previous level of $2,795.

As a result, investment bank Mizuho Securities today downgraded its rating on Myriad Genetics' shares to Hold from Buy and cut the price target on the company's stock to $24 from $36.

In morning trading on the Nasdaq on Monday, shares of Myriad fell 16 percent to $20.18.

In a document filed with the US Securities and Exchange Commission today, Myriad said CMS posted a National Limit Amount of $1,438.14 for CPT code 81211, which covers a test for the full sequencing of the BRCA1 and 2 genes, and for CPT code 81214, which covers a full sequencing of only the BRCA1 gene. No payment rate was set for CPT code 81216, which covers a test for the full sequencing of the BRCA2 gene.

The payment rates for 81211 and 81214 become effective "on or after" Jan. 1, 2014, CMS said.

CMS has opened a public comment period through Jan. 27, 2014, "[a]s the public has not had the opportunity to provide comment on the new NLA for 81211," Myriad said, adding it plans "to address a number of both substantive and process concerns" during the comment period.

"It is unclear why CMS has not valued the BRCA 2 gene in the 81211 code," the Salt Lake City-based company said. "It is also unclear how CMS arrived at the 81211 payment rate within the requirements of the federal gapfill regulations."

In September CMS posted an NLA for Myriad's BRACAnalysis test of $1,449 for the remainder of 2013, suggesting that that rate would last into 2014. Two Medicare contractors, however, quickly said that they had committed an error in setting the $1,449 figure.

In its new BRCA1/2 NLA document posted on Friday, CMS cited the decision by the US Supreme Court in June that invalidated certain claims on patents covering the BRCA1/2 genes held by Myriad. Before the SCOTUS decision, Myriad was the only laboratory offering BRCA testing, but since the judgment a number of firms, including Quest Diagnostics, Laboratory Corporation of America, and BioReference Laboratories' GeneDx business, have launched their own tests.

Medicare's Administrative Contractors (MAC) have received pricing data from the labs offering BRCA testing, and "[b]ased on the new information, the MACs submitted pricing information for CPT code 81211 that resulted in an NLA of $1,438.14," CMS said.

"At present, it is our understanding laboratories are offering the CPT code 81211 test for prices that range from approximately $900 to $2,900. As CPT code 81214 is similar to CPT code 81211, the additional comment period will apply to both CPT codes 81211 and 81214," CMS added.

Mizuho analyst Peter Lawson today downgraded Myriad's shares following the reimbursement cut, saying that although Medicare accounts for only 10 percent of Myriad's BRCA revenues, "CMS pricing has increased the fear that private payors may also cut pricing."

While the reimbursement rate may increase after the public comment period, "we are cautious on that outcome," Lawson said.

Leerink Swann analyst Dan Leonard added that even if BRCA testing reimbursement is increased, any increase will not take effect until after April 1, 2014. "[T]hus, the lower payment rate for 81211 will occur at least through" March 31, 2014, he said in a research note.

He maintained a Market Perform rating on Myriad's shares with a $25 price target.

Click here to see the original post on GenomeWeb

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Wednesday, December 4, 2013

Class Action Law Suit Filed Against 23andMe

Original post on Forbes by Dan Munro, 12/2/13

That didn’t take long. Quite literally about 5 days from the date of the FDA’s warning letter to 23andMe (11/22) and the filing of a class action law suit in the Southern District Court of California (11/27).

While the merits of the legal case are best suited for legal interpretation and debate, the damage to the marketing of general purpose Personal Genome Services (by 23andMe or any other company) could be significant. As stated in the filing:

“NATURE OF THE ACTION”

1. This proposed class action alleges that 23andMe, Inc. (“Defendant”) falsely and misleadingly advertises their Saliva Collection Kit/Personal Genome Service (“PGS”) as providing “health reports on 240+ conditions and traits”, “drug response”, “carrier status”, among other things, when there is no analytical or clinical validation for the PGS for its advertised uses.

2. In addition, Defendant uses the information it collects from the DNA tests consumers pay to take to generate databases and statistical information that it then markets to other sources and the scientific community in general, even though the test results are meaningless.

3. Despite Defendant’s failure to receive marketing authorization or approval from the Food and Drug Administration (“FDA”), Defendant has slowly increased its list of indications for the PGS, and initiated new marketing campaigns, including television advertisements in violation of the Federal Food, Drug and Cosmetic Act (“FDC Act”).

It’s that second bullet point that’s at the very heart of the FDA filing and subsequent debate. Are the test results “meaningless?” Absent the scientific rigor of an FDA process – how do we as consumers know?

In light of all the recent publicity, several stories have also surfaced that call into question that exact point.

The point is that if I cannot trust 23andMe to tell me much of value about my risk factor for Celiac, or my ability to digest dairy products or coffee, or to get my son’s results right, can I trust it for anything? What should I do if it tells me that I am at higher risk of developing Alzheimer’s or lung cancer? The answer is … not lose any sleep about it.” Bernard Munos – Forbes Contributor – 11/29/2013 (23andMe: A Fumbling Gene In It’s Corporate DNA)

“I sent a support request to 23andMe including my research and conclusions (this would be called a “bug report” in software engineering). After a few days of waiting, 23andMe confirmed the bug and apologized. So the bug was not inside of me, but in the algorithm. An algorithm can be fixed easily, unlike my genetic code.” Lukas F. Hartmann – 11/26/2013 (Why 23andMe Might Have The FDA Worried: It Wrongly Told Me I Might Die Young)

The controversy extends further back too. This was filed in April of 2011:

My suggestion is that unless you have a specific reason behind your motivation, don’t bother with genetic testing services, especially if you’re not of European ancestry and you’re under the age of 30. I can see how it may be useful as a preemptive measure for people with a family history of a debilitating disease, or for people who are seeking out long-lost relatives. But for the rest of us, the money is probably better spent towards a gym membership, more fruits and vegetables and health/life insurance. And not having to worry for the rest of your life about something that may or may not happen to you? That’s priceless. Elly Hart – Night Editor, Allure Media (Why 23andMe Genetic Testing Is A Waste of Time and Money)

Ms. Hart also points out a legal dilemma that has yet to be tested. The Genetic Information Nondiscrimination Act (GINA – 2008 here) specifically prohibits the use of genetic information in health insurance and employment. GINA has no such applicability to Disability or Life Insurance as noted by this repetitive 23andMe disclaimer: “GINA does not cover life or disability insurance providers” (8 occurrences here).

All of which is why the FDA was correct in issuing their warning. It’s one thing to believe in the false hopes and misleading promises of dietary supplements. It’s something else entirely when an email arrives warning you of a serious health condition or genetic risk lurking in your DNA. For anything beyond ancestral curiosity, personal genetic data definitely needs the full rigor of scientific review and accuracy.

Click here to see the original article on Forbes.com


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Tuesday, December 3, 2013

Ask Well: Genetic Testing for Breast Cancer

Original post by Roni Caryn Rabyn, NYTimes, 11/27/13

Some Israeli doctors want Israel to conduct a national screening campaign to test all Jewish Israeli women of Ashkenazi descent for harmful genetic mutations that heighten the risk of breast and ovarian cancer. The debate is detailed in the article, “In Israel, a Push to Screen for Cancer Gene Leaves Many Conflicted.”

Most American Jews are Ashkenazi, meaning their families originated in Eastern and Central Europe and they may be wondering if they should seek genetic testing.

Here are answers to some questions about genetic testing for the three common harmful mutations in the BRCA1 and BRCA2 genes.

Q: I’m an Ashkenazi Jewish woman. Should I be tested for the mutations in the BRCA1 and BRCA2 genes?
A: If you have been diagnosed with breast or ovarian cancer or have a family history of breast or ovarian cancer, you may want to be tested for one of the mutations in the BRCA1 and BRCA2 genes that are common among Ashkenazi Jews. Knowing your carrier status may help you evaluate your future risk and can be useful information for other family members. If you have cancer, the information can help shape treatment and alert you to other risks (such as a heightened risk for ovarian cancer if you have breast cancer).

While some Israeli doctors want to expand testing and make it routine, general practice in the United States has not encouraged genetic testing for individuals who are cancer-free and don’t have a family history.

But for Ashkenazi Jews, the bar for genetic testing is not as high as for the general population, said Dr. Susan M. Domchek, executive director of the Basser Research Center for BRCA at the University of Pennsylvania’s Abramson Cancer Center.

“If you’re Jewish, we have a low threshold for testing,” Dr. Domchek said. “If you have an aunt who had breast cancer at 51 and you want testing, that’s O.K.”

Keep in mind that the odds of testing positive are fairly low — only one in 40 Ashkenazi Jews, or 2.5 percent, carry the mutation. That is higher than the rate in the general population, in which fewer than 1 percent carry these mutations, but it means you have a 97.5 percent chance of testing negative.

Remember that a family history includes relatives on both sides of the family, including your father’s side.

“People ignore the father’s side of the family, and they shouldn’t,” said Dr. Domchek. “Women will come to us and say there’s no family history, but actually the dad was Ashkenazi Jewish and the dad’s mother had breast cancer at 40 – that’s a significant family history.”

Q: What if I don’t know much about my family history?
A: Many Ashkenazi Jews have limited information about their family because they lost relatives in the Holocaust. Others come from small families that don’t provide a lot of clues, and families everywhere become estranged and keep secrets. One reason Israeli doctors want to do broad-based screening of Ashkenazi Jewish women is so that individuals are not dependent on family members for information.

Nevertheless, Dr. Domchek emphasized that there is still some uncertainty about what it means if a woman tests positive for a mutation and no one in her family has had cancer. Research is trying to resolve questions about what the risk is in these cases. “It’s a challenge to give an individualized risk assessment,” she said.

If you are concerned because you have limited information about your family, genetic counseling may help clarify whether you should pursue testing.

Q: What does the test consist of? How much does it cost? Will insurance cover it?
A: The genetic test is a blood test, often accompanied by genetic counseling. Testing for the three specific BRCA1 and BRCA2 mutations common among Ashkenazi Jews generally costs between $300 and $500 for all three. Insurance coverage varies and may be more likely to pick up the cost if the individual has a clear family history of breast or ovarian cancer. Genetic testing of men who do not have cancer is generally not covered, Dr. Domchek said.

Q: What does a positive result mean?
A: A woman who tests positive for a mutation will be given a range of risk for developing breast cancer and ovarian cancer during her lifetime that takes her family history into account, but assessing individual risk is a challenge, Dr. Domchek said. “If the only history is a mother who developed breast cancer at 55 and the mother has four sisters and no one else has cancer of any sort,” then the woman’s risk will be deemed lower than if several of her aunts have cancer, she explained.

While about 12 percent of women in the general population will develop breast cancer at some point in their lives, 55 percent to 65 percent of women with a harmful BRCA1 mutation and around 45 percent of those with a harmful BRCA2 mutation will develop breast cancer by age 70, according to the National Cancer Institute. While about 1.4 percent of women in the general population will develop ovarian cancer, some 39 percent of carriers of a harmful BRCA1 mutation and 11 percent to 17 percent of carriers of a harmful BRCA2 mutation will develop ovarian cancer by age 70.

Q: What factors should I weigh when considering prophylactic surgery?
A: Choosing prophylactic surgery is a difficult and highly personal decision. Many doctors emphasize the importance of removing the ovaries, because the mutations increase the risk of ovarian cancer, which is harder than breast cancer to detect at an early stage. Israeli physicians urge women to undergo ovary removal as soon as they have had their children, preferably by the age of 40. Removing the ovaries also reduces the risk of breast cancer considerably.

The choice of whether to have a prophylactic double mastectomy is complex. Close monitoring and surveillance of the breasts with frequent magnetic resonance imaging scans and clinical breast exams is another option, doctors say. Over time, however, doctors say many women tire of the constant checkups, especially if they are called back for frequent biopsies and some eventually opt for mastectomies as a result.

Both oophorectomy and mastectomy are difficult operations that have serious side effects. Breast reconstruction often leads to infections and other complications and many women are disappointed by the look and feel of their new breasts. Removing the ovaries robs women of important hormones and plunges them into menopause overnight, leading to hot flashes, reduced sex drive and heightened risks of heart disease and bone loss. Hormone replacement treatment or other medication is often required.

Click here to read the original post from the NYTimes
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Monday, December 2, 2013

Genetic Testing Should Adhere to Medical, Not Business, Ethics: FDA's Regulation of 23andMe Is a Welcome Move for Consumers

Original post by Karuna Jaggar on HuffPost Business, 12/1/13

This week the Food and Drug Administration (FDA) issued a warning letter to the direct-to-consumer genetic testing company 23andMe, demanding that it immediately stop marketing and selling its DNA testing service until it receives approval from the agency tasked with regulating medical tests and devices. In what has widely been called a "scathing" letter, the FDA said that 23andMe had failed to show that "the firm has analytically or clinically validated the [23andMe Saliva Collection Kit and Personal Genome Service] for its intended uses" and expresses concern "about the public health consequences of inaccurate results from the P.G.S. device."

It sounds temptingly light-hearted to find out about the percentage of genes you share with a Neanderthal, your earwax type, or why you love Brussels sprouts while others can't stand them. But 23andMe's test doesn't stop there. It claims to provide health reports on some 254 diseases and conditions. Some of the information the company provides, based on the saliva you send them, includes how your body may metabolizes certain pharmaceutical drugs, an individual's carrier status, and risk of disease such as Parkinson's, schizophrenia, sudden cardiac arrest, scoliosis, and Amyotrophic Lateral Sclerosis (ALS). Hardly light-hearted and recreational given the potentially life-altering implications of such information.

Genetic testing is complex and raises a wide range of medical, ethical, and scientific issues. And no one knows this better than the families who have cancer-linked mutations on the BRCA1 or BRCA2 genes, commonly known as the "breast cancer genes." Some mutations of the BRCA genes are known to increase people's risk of breast, ovarian, and other cancers. Other mutations of the BRCA genes don't increase people's risk of these cancers. And we haven't yet learned what some other rare BRCA mutations mean for a person's future risk of disease.

Until this summer, one company, Myriad Genetics, held an exclusive patent on the human BRCA genes. This monopoly meant that Myriad offered the only commercially available test for BRCA mutations, the test was expensive, you could not get a second opinion, and Myriad held exclusive rights to develop new tests and targeted therapies related to the BRCA genes.

When Breast Cancer Action joined a group of geneticists, researchers, physicians, and women with family histories of breast and ovarian cancer to file suit in 2009 with the ACLU against Myriad Genetics, not only were we challenging one company's right to patent the human BRCA1&2 genes, we were taking a stand to ensure that more women had access to potentially life-saving information about their inherited risk of cancer. An additional benefit of ending Myriad's monopoly is that new companies could offer new and better tests, utilizing advances in technology. During the years when Myriad held an exclusive monopoly on the human BRCA genes, rapid technological advances meant that the cost of genetic sequencing dropped dramatically, yet Myriad doubled the cost of their BRCA test over this same time frame. And indeed, the very day that the U.S. Supreme Court ruled in our favor in June, approximately half a dozen companies announced they would begin offering BRCA testing for a fraction of the cost.

Some people have drawn a link between the BRCA case and 23andMe's test by applauding direct-to-consumer companies for making people's genetic data accessible to them for just a couple of hundred dollars. And there are those who argue that the FDA's move to block one direct-to-consumer company's genetic testing is a move to block people's right to discover their own genetic information. Yet, the truth is that these companies, including 23andMe, go beyond genetic sequencing by offering interpretation of your test results. And this is where some of the most complex ethical, medical and scientific issues emerge--in understanding what our genes mean.

The truth is that we still understand very little about how our genes interact with our environment, and our individual choices, to impact our health. Despite the many advances in genomics, we still don't understand much about genomics at a most basic level. Even some of the most well-studied genes, such as the BRCA 1 & 2 genes discussed above, don't tell a person if she'll get cancer. After all, some women with these mutations never get cancer, and we don't know why.

Most genes are not nearly so well understood as the BRCA genes. We simply don't have the scientific evidence to know what mutations of most genes mean. Yet, direct-to-consumer companies like 23andMe are willing to make interpretive claims about some of these genes, despite the high risk of false positives and false negatives.

The FDA is asking 23andMe to demonstrate that its medical service is analytically and clinically validated. Validation includes both the analysis of people's saliva samples to conduct genetic sequencing and also the interpretation of these results to predict future risk of disease. While there are standard protocols followed by most labs that enable them to conduct DNA analysis, a number of studies have demonstrated that different clinical validation methods of different direct-to-consumer companies means that the same person can get different results from two different labs. A person may be told by one lab that they are at increased risk for disease and the same person may be told by another lab they are at below average risk of the same disease.

This problem of inadequately validated claims of clinical significance cannot simply be solved by saying these tests, like those offered by 23andMe, are for entertainment purposes only. 23andMe is making bold claims about a person's medical future, risk of disease, and responses to particular drugs. And the basis of 23andMe's claims, these predictions, must be subjected to rigorous scrutiny, peer review, and yes, FDA regulation.

While no one company should hold a monopoly on genetic testing, we also can't assume that every new test is a good test. All genetic testing should be properly validated to ensure the methods of testing and interpretation fulfill the intended purpose and provide meaningful and accurate information. Medical data ought to be shared with open-access databases for the benefit of scientific and medical advances. Testing should be accompanied, both before and after testing, with independent genetic counseling. And corporate marketing practices should not overpromise the benefit of genetic testing or drum up people's fear of disease.

Arguably, the primary compensation that consumers give to companies like 23andMe is access to their genetic and family histories. With nearly half a million people having given 23andMe their DNA and their family history, we must address issues of privatization of genetic material. Indeed, others have addressed the fact that 23andMe has used its vase database of genetic and family history to get a patent on "gamete donor selection based on genetic calculations". We need not focus on the controversy about "designer babies" which ensued, to see that 23andMe is using its customers' biodata and familial information to launch new business products, again with vast moral, medical, and scientific implications.

The key lessons we learned from Myriad monopoly on the "breast cancer genes" are not only that genetic testing is fraught with moral and medical complexity but also that, as a medical service, genetic testing must adhere to medical rather than business ethics. Public health and patient protection should come before company profit. And this week the FDA has taken a welcome stand to protect public health by insisting that what is clearly a medical service be regulated as such. While we continue, as a society, to sort out how to use genetic information to best serve the public's health, I am glad to see this move to regulate genetic testing according to medical rather than business ethics.

Click here to read the original article from HuffPost Business

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Wednesday, November 27, 2013

Here’s why the FDA is targeting 23andMe

Original story on medcitynews.com by Christina Farr, 11/26/13

Monday morning, federal regulators issued an enforcement action against 23andMe, a popular Silicon Valley-based genetic testing startup.

Community forums and news sites across the web exploded with debate, with most people rallying to 23andMe’s defense. The company’s ample support-base claims that the Food and Drug Administration is over-regulating, and is stifling innovation.

However, the majority of geneticists and medical professionals I’ve spoke with have sided with the Food and Drug Administration, arguing that many patients require genetic counseling after receiving DNA test results that point to a high risk of cancer and other life-threatening conditions.

One San Francisco-based neurologist, who asked to remain anonymous, told me that some of her healthiest patients — all 23andMe customers — have begun demanding unnecessary and expensive MRI tests for Alzheimer’s Disease. “23andMe’s test is creating chaos with people in their 20s and 30s,” she said. “They generate havoc and walk away.”

Indeed, in the event that this divisive case reaches the California courts, it may have far-reaching implications for the genetics industry and beyond.

23andMe: How it works

Google-backed 23andMe is among the first to market and sell an affordable DNA test directly to consumers rather than to care providers. The company is backed by Google and run by Anne Wojcicki, the soon to be ex-wife of the Google cofounder Sergey Brin.

On its website, 23andMe claims that it is “saving lives” by delivering clinical insights, such as your risk of developing breast cancer or Parkinson’s Disease. The company says in its marketing materials that it will provide “health reports on 254 diseases and conditions.”

23andMe also sends you information about your ancestral history and frequently describes this process in ads and blog posts as “empowering” and “fun.”

That’s all well and good, but the FDA is contending that 23andMe’s method of amassing DNA — its Saliva Collection Kit and Personal Genome Service (PGS) – is a class III medical device under the Federal Food, Drug, and Cosmetic Act. The device has not obtained proper regulatory clearance and is therefore misbranded under the law.

In its letter, originally issued on Friday, the FDA explains that the kit falls under the medical device category, as consumers could act on the results as a diagnosis — not just a prediction of risk. Regulators are concerned that a false positive from a 23andMe test could result in unnecessary surgery and that false negatives could lead to patients being less aggressive about screening for various health conditions.

The agency may have decided to take public action now, given that 23andme has begun testing various mutations of genes that indicate a woman might have a high risk of getting breast or ovarian cancer. A false positive on that test could cause a woman to undergo a needless mastectomy. And a growing number of women are requesting this test after hearing the news about Angelina Jolie’s surgery.

23andMe has 15 days to provide specific actions to address the issues raised by the FDA. At the time of this report, kits were still for sale on the company’s website.

Taking a stand

23andMe may choose to comply with the FDA, or it may argue that its PGS is not a medical device at all.

Lauren Fifield, a senior health policy expert predicts that the company will take a stand. “My gut tells me that the company isn’t challenging process but is instead challenging the very regulatory definition of what it is to be a device,” said Fifield, who works closely with startups, the FDA, and other federal health agencies in her role at Practice Fusion.

“What remains to be seen is whether the company and tech industry can convince the government that safety can be increased, or at least balanced, by innovation rather than set at odds,” she added.

23andMe is well funded, with an in-house legal counsel and policy team. The company has not responded to a request for an interview from any news publication, presumably as it convenes to determine a course of action.

In response to requests for information, 23andMe issued the following statement.

"We have received the warning letter from the Food and Drug Administration. We recognize that we have not met the FDA’s expectations regarding timeline and communication regarding our submission. Our relationship with the FDA is extremely important to us and we are committed to fully engaging with them to address their concerns."

Note the use of the term “expectations” rather than rules or requirements, which suggests that 23andMe is not convinced by the FDA’s arguments.

The FDA, meanwhile, made clear in dealings with the media that it is taking a hard line. This letter was not delivered out of the blue. The agency says 23andMe has dragged its feet despite “14 face-to-face or teleconference meetings, hundreds of email exchanges, and dozens of written communications” since 2009.

“Companies that receive warning letters have the opportunity to address the violations,” explained Erica Jefferson, a spokesperson with the FDA, in an interview with VentureBeat. “If the violations are not addressed to the satisfaction of the FDA, further actions may be warranted, including seizure or civil money penalties.”

It’s all about the messaging

This case is still developing, but one crucial lesson for health entrepreneurs is that the FDA pays a great deal of attention to messaging.

This rule of thumb doesn’t just apply to genetic testing. The FDA recently clamped down on a mobile medical app called uChek, pointing out that the company’s marketing was misleading. The agency is more inclined to take action if an app promises to deliver an alternative to a doctor’s visit.

To the agency’s credit, developers have found it far easier to avoid federal oversight. For reference, the FDA recently released its final guidance on how it intends to regulate mobile medical apps.

In this particular case, the FDA may have taken issue with 23andMe’s aggressive marketing tactics. The company recently hired a former Gilt Groupe exec as its president; since then, it has been advertising its test to consumers on social media and various television networks.

Consumers may not understand that the test is serious — not just a bit of fun — and that the results can indicate incurable or life threatening disease.

“When I started Navigenics (a 23andMe rival that was acquired by Life Technologies for an unspecified sum), we spent an enormous amount of time communicating shades of grey — and we did all this alongside regular meetings with the FDA,” said human geneticist and entrepreneur Dietrich Stephan in an interview.

“Engaging the FDA as a partner to bring the most robust and safe new type of test to market is “diagnostics 101,” he added.

Stephan told me about a family friend who ordered a 23andMe test on a whim. His mother felt compelled to take the test, after discovering that her son carried a genetic variant called BRCA, which indicates a high risk of breast and ovarian cancer. After the mother received a positive result, she ordered a double mastectomy despite protestations from friends and family.

Indeed, physicians I interviewed stressed that patients should not order a DNA test without regard to the consequences. Dr. Malcolm Thaler, a primary care provider at One Medical, said he would prefer to have a conversation with a patient before they order a test “to put the results in context” and explain the numbers in detail.

In the short term, we may seen 23andMe under pressure to more readily link consumers with genetic counselors and adapt its marketing campaigns to reflect the life-changing and potentially very serious nature of the results.

Is this a landmark case?

The crux of the issue is that the FDA is still determining how it will regulate innovative health applications from Silicon Valley and other technology hubs. Health policy experts, like Practice Fusion‘s Fifield, believe this has the potential to be a “landmark case” if it goes to court.

Already, the public warning letter will serve as an important example and model for other startups.

“I’ll be watching how this case plays out,” said Heather Heine, an M.D. and founder of an early stage biotech company called Talking20. Heine doesn’t have such immense resources at her disposal as 23andMe to hire expensive consultants.

So Heine will keep a close eye on how 23andMe responds as she brings her company’s low-cost biomarker testing kit to market. “23andMe has the resources to push this envelope,” she said. “These resources allow them to be front-runners.”

Click here to read the original story on medcitynews.com
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Monday, November 25, 2013

F.D.A. Demands a Halt to a DNA Test Kit’s Marketing


Original article by Andrew Pollack, NYTimes, 11/25/13

In a crackdown on genetic testing offered directly to consumers, the Food and Drug Administration is demanding that 23andMe immediately cease marketing its main DNA service until it receives marketing clearance from the agency.

In a warning letter issued Friday and posted on the F.D.A.'s website Monday, the F.D.A. said that the company had failed to provide adequate evidence that its Personal Genome Service provided accurate results.

“F.D.A. is concerned about the public health consequences of inaccurate results from the P.G.S. device,” the agency said in its letter. “The main purpose of compliance with F.D.A.'s regulatory requirements is to ensure the tests work.”

23andMe, which is backed by Google and run by Anne Wojcicki, wife of the Google co-founder Sergey Brin, is perhaps the best known of the personal genome testing companies. Its service, which has been used by about half a million people, tells consumers whether they might be at a higher or lower risk of developing various diseases, among other things.

Whether such tests require F.D.A. approval and whether doctors must be involved in ordering such tests have been the subject of debate. 23andMe has long held that consumers are entitled to the information on their own DNA, though it has also been talking to the F.D.A. about how its tests could receive regulatory approval.

Ms. Wojcicki did not immediately respond to an email seeking comment and her company, which is based in Mountain View, Calif., had not yet responded on its website Monday morning.

The F.D.A. warning letter said the agency considered the Personal Genome Service a medical device that required approval.

The letter noted that 23andMe did apply for approval for some uses of the test in 2012. However, it said, the company did not provide the additional information requested by the agency, so the agency considered the applications to have been withdrawn.

The letter accused 23andMe of dragging its feet despite “14 face-to-face or teleconference meetings, hundreds of email exchanges and dozens of written communications” since 2009.

“However, even after these many interactions with 23andMe, we still do not have any assurance that the firm has analytically or clinically validated the P.G.S. for its intended uses, which have expanded from the uses that the firm identified in its submissions.”

The letter added, “Instead, we have become aware that you have initiated new marketing campaigns, including television commercials that, together with an increasing list of indications, show that you plan to expand the P.G.S.'s uses and consumer base without obtaining marketing authorization from F.D.A.”

What seems to have raised the most concern from the agency is 23andMe’s expansion into offering tests for mutations of genes that indicate a woman might have an extraordinarily high risk of getting breast or ovarian cancer. The F.D.A. said a false positive on that test could cause a woman to undergo a needless mastectomy.

The agency also seemed concerned about 23andMe’s expansion into testing of genetic variants to help predict people’s responses to drugs such as warfarin, a blood-thinning medication.

23andMe now sells its service, which also offers ancestry information, for $99. It is aiming to grow to 1 million customers by early next year. Part of its business plan is to use the information on its customers to perform biomedical research, such as finding genetic causes of diseases.

The F.D.A. first sent letters to 23andMe and some of its competitors in 2010, saying that regulatory approval would be required for the tests. Following that, some of the other companies stopped offering tests directly to consumers.

Click here to read the original article on The NYTimes
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Can 23andMe testing really enable you to be 'Healthy at 100'?


23andMe's Anne Wojcicki recently appeared on 'CBS This Morning' to discuss how personal genomic profiling can provide information to empower individuals to be "healthy at 100". After watching this segment, we are left wondering about several key issues:

- Does the type/quality of data obtained from 23andMe really give us enough information to be healthy at 100? While this might be the goal, we have yet to see evidence that demonstrates how this type of information can lead to better overall health. What measurable outcomes have shown that people can use this information to be “healthy at 100”? Or even healthier one year after learning the results? We would argue that our current knowledge of SNP analysis (the technology used by 23andMe) is insufficient to provide reliable estimates for disease risk. There have even been reports in which a sample from the same client was sent to several leading SNP-based companies for analysis, and the results included widely divergent risk estimates with companies reporting “above average,” “below average,” and “average” risks for the same condition in the same individual.

- Even if we can use SNP analysis to make accurate inferences about common disease risk, it is doubtful this information will be clinically useful in the majority of cases as most diseases are multifactorial and genetics is only one component contributing to risk. Wojcicki’s claim that this testing may have the power to allow a doctor to inform his patient he is “3 years away from being diabetic” is a gross overestimation of the power of this test. Are there data to show that SNPs are any better at predicting diabetes risk than an individual’s personal and family history, BMI, fasting blood sugar, diet and exercise habits?

- Wojcicki makes no mention of the limitations in this type of testing and does not reference other forms of genetic testing such as single gene tests, which often have defined risk associations and management recommendations. For example, it is entirely possible for a woman to receive a SNP-based result that states “low risk for breast cancer” and subsequently test positive for a genetic mutation, not included in 23andMe testing, that confers a risk of breast cancer of up to 85%.

- Beyond the vague and misleading information provided by 23andMe, there are also significant ethical ramifications that are not addressed. For example, 23andMe does not address the ethical issues around testing children for adult-onset disorders despite the field’s general recommendations against such testing.
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