Genome (DNA) Sequencing/Analysis

Discussion in 'Men's Health Forum' started by Michael Scally MD, Jul 23, 2010.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Direct-To-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices
    U.S. GAO - Direct-To-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices


    In 2006, GAO investigated companies selling direct-to-consumer (DTC) genetic tests and testified that these companies made medically unproven disease predictions. Although new companies have since been touted as being more reputable--Time named one company's test 2008's "invention of the year"--experts remain concerned that the test results mislead consumers. GAO was asked to investigate DTC genetic tests currently on the market and the advertising methods used to sell these tests. GAO purchased 10 tests each from four companies, for $299 to $999 per test. GAO then selected five donors and sent two DNA samples from each donor to each company: one using factual information about the donor and one using fictitious information, such as incorrect age and race or ethnicity. After comparing risk predictions that the donors received for 15 diseases, GAO made undercover calls to the companies seeking health advice. GAO did not conduct a scientific study but instead documented observations that could be made by any consumer. To assess whether the tests provided any medically useful information, GAO consulted with genetics experts. GAO also interviewed representatives from each company. To investigate advertising methods, GAO made undercover contact with 15 DTC companies, including the 4 tested, and asked about supplement sales, test reliability, and privacy policies. GAO again consulted with experts about the veracity of the claims.

    GAO's fictitious consumers received test results that are misleading and of little or no practical use. For example, GAO's donors often received disease risk predictions that varied across the four companies, indicating that identical DNA samples yield contradictory results. One donor was told that he was at below-average, average, and above-average risk for prostate cancer and hypertension. GAO's donors also received DNA-based disease predictions that conflicted with their actual medical conditions--one donor who had a pacemaker implanted 13 years ago to treat an irregular heartbeat was told that he was at decreased risk for developing such a condition. Also, none of the companies could provide GAO's fictitious African American and Asian donors with complete test results, but did not explicitly disclose this limitation prior to purchase. Further, follow-up consultations offered by three of the companies failed to provide the expert advice that the companies promised. In post-test interviews with GAO, each of the companies claimed that its results were more accurate than the others'. Although the experts GAO spoke with believe that these tests show promise for the future, they agreed that consumers should not rely on any of the results at this time. As one expert said, "the fact that different companies, using the same samples, predict different directions of risk is telling and is important. It shows that we are nowhere near really being able to interpret [such tests]." GAO also found 10 egregious examples of deceptive marketing, including claims made by four companies that a consumer's DNA could be used to create personalized supplement to cure diseases. Two of these companies further stated that their supplements could "repair damaged DNA" or cure disease, even though experts confirmed there is no scientific basis for such claims. One company representative even fraudulently used endorsements from high-profile athletes to convince GAO's fictitious consumer to purchase such supplements. Two other companies asserted that they could predict in which sports children would excel based on DNA analysis, claims that an expert characterized as "complete garbage." Further, two companies told GAO's fictitious consumer that she could secretly test her fiance's DNA to "surprise" him with test results--though this practice is restricted in 33 states. Perhaps most disturbing, one company told a donor that an above average risk prediction for breast cancer meant she was "in the high risk of pretty much getting" the disease, a statement that experts found to be "horrifying" because it implies the test is diagnostic.

    To hear clips of undercover contacts, see U.S. GAO - Direct-To-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices.

    GAO has referred all the companies it investigated to the Food and Drug Administration and Federal Trade Commission for appropriate action.

    Attached Files:

    Last edited: Mar 29, 2012
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests: Misleading & Deceptive

    Commentary calls for regulation of direct-to-consumer gene testing.

    McGuire AL, Evans BJ, Caulfield T, Burke W. Regulating Direct-to-Consumer Personal Genome Testing. Science 2010;330(6001):181-2. Regulating Direct-to-Consumer Personal Genome Testing -- McGuire et al. 330 (6001): 181 -- Science

    Bloomberg News (10/8, Lopatto) reports that, according to a commentary published in the journal Science, "gene testing companies, such as 23andMe Inc. and DeCode Genetics Inc., should be regulated, because consumers may make wrong medical decisions based on inaccurate or misinterpreted results," particularly since "more than 90 percent of results aren't seen by an outside reviewer before being sent to the consumers." Unfortunately, "misinterpretation of the data may cause harm to consumers who take action on their own, said the scientists who wrote the commentary." Bloomberg News points out that the Food and Drug Administration is currently reviewing the genetic tests to determine the best way to monitor them for quality and safety.

    Consumer Gene Tests Should Be Regulated for Accuracy, Scientists Say
    Consumer Gene Tests Should Be Regulated for Accuracy, Scientists Say - Bloomberg

    By Elizabeth Lopatto
    Oct 7, 2010

    Gene testing companies such as 23andMe Inc. and DeCode Genetics Inc. should be regulated because consumers may make wrong medical decisions based on inaccurate or misinterpreted results, scientists said.

    The tests are promoted as providing information about a person’s likelihood to develop a wide range of traits and conditions, from excessive ear wax to cancer and Alzheimer’s disease. More than 90 percent of results aren’t seen by an outside reviewer before being sent to the consumers, according to a commentary in the journal Science.

    The U.S. Food and Drug Administration is reviewing the tests, and the Government Accountability Office said in July that the companies were misleading consumers by providing unclear or conflicting information. Misinterpretation of the data may cause harm to consumers who take action on their own, said the scientists who wrote the commentary. In one study, 40 percent of Alzheimer’s patients reported increasing their medications after getting the tests, the authors said.

    “The first step is transparency, for consumers to have access to accurate information,” said Amy McGuire, an associate professor of medicine and ethics at Baylor College of Medicine in Houston who was an author of the commentary, in a telephone interview.

    One difficulty in regulating these tests, also made by Pathway Genomics Corp. and Navigenics Inc., is that they combine genetic traits that don’t have a health-care impact, such as a proclivity to be a fast runner, with more serious medical information, such as prostate cancer risk, McGuire said.

    Breast Cancer Risk

    The authors said that some information, such as ancestry, may not have medical consequences and should only be checked to make sure that it’s accurate. Other assays, such as those that measure breast cancer risk, should only be performed with counseling from a health-care professional, the authors wrote.

    “Clearly with medical information with important health implications, patients need to be able to attain that information in an environment where their options are laid out,” McGuire said. “And someone can help understand not just what does that result tell you, but what does it mean in the context of other risk factors.”

    Pathway Genomics announced in May that it intended to sell its kits in Walgreen Co.’s retail stores, which sparked an effort by the FDA to monitor the testing companies. Walgreen shelved the plan after the FDA opened a review, saying the gene tests were medical devices. The tests work by collecting a person’s saliva and analyzing DNA from the spit sample in a lab.

    FDA Review

    “This paper presents some interesting options for the oversight of DTC testing,” said Erica Jefferson, a spokeswoman for the FDA, in an e-mailed statement. The paper’s approach may not be the best option, and the FDA is developing a way to monitor these tests, with the goal that direct-to-consumer tests be safe and effective when used without guidance from a health- care professional, she said.

    Brenna Sweeny, a spokeswoman for Foster City, California- based Navigenics, and San Diego-based Pathway Genomics didn’t immediately return a call requesting comments.

    Edward Farmer of DeCode referred comment to previous statements by Kari Stefansson, executive chairman and president of research for DeCode. Stefansson said in June that DeCode welcomes regulation by the FDA.

    ‘Entirely Confident’

    “While 23andMe is entirely confident in its own reports developed in conjunction with physician and scientific advisers, the company is in discussions with the FDA regarding an improved regulatory framework for genetic testing,” said Ashley Gould, general counsel for the Mountain View, California-based company, in an e-mailed statement. “23andMe believes new regulations should provide transparency across the industry so that consumers know what they are getting from the services they choose.”

    The FDA should review all tests before they come to market, today’s editorial said. Less risky ones, such as those that trace ancestry or susceptibility to extra earwax, could be subject to a light review and a national registry to disclose uncertainty.

    Groups such as GeneTests, a website that displays genetic information, and the National Institutes of Health should play a role in making sure information from testing companies about methods and accuracy is publicly disclosed, said McGuire and her colleagues in the editorial.

    Professional Review

    More risky tests, such as those for Huntington’s disease or cancer, should be reviewed by a health-care professional, the scientists said. Involving a doctor or nurse would limit access to tests because it would make them more expensive. There would still be a chance that patients would be unnecessarily treated if the reviewers weren’t properly trained, the authors said.

    Ira Loss, an analyst with Washington Analysis, said consumers don’t know how accurate test results are without any independent assessment.

    “I’m not surprised an editorial like this is being published,” Loss said in a telephone interview today. “There’s a very strong sense in the medical community that the more serious genetic information shouldn’t arrive in an envelope, particularly if there’s a bad message to be delivered.”
    Last edited: Oct 8, 2010
  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests: Misleading & Deceptive

    Direct-to-consumer genomewide profiling to assess disease risk provides information about a person's genetic risk of 20 to 40 common polygenic diseases. The tests simultaneously genotype approximately 500,000 variant bases of a person's DNA. Consumers can purchase these tests, currently priced between $400 and $2,000, on the Internet. Consultation with a health care provider is not a prerequisite. Proponents argue that providing this type of information directly to consumers may result in improved compliance with health-screening practices and more healthful lifestyle choices. Skeptics assert that such testing has the potential to cause harm, including anxiety and increased use of unnecessary and expensive screening and medical procedures. The clinical validity and utility of these tests have not been demonstrated, and given their cost, many observers argue that their sale raises consumer-protection issues.

    Studies of the psychological, behavioral, and clinical effects of genetic-risk disclosure for single diseases have generally been small and have yielded somewhat mixed findings. The Scripps Genomic Health Initiative was designed as a longitudinal cohort study to measure the effects of direct-to-consumer genomewide scans. Subjects purchased a commercially available genomewide risk scan at a subsidized rate and underwent Web-based standardized assessments at baseline and during follow-up, with the aim of gauging changes in anxiety level, diet, exercise, test-related distress, and use of screening tests. The paper revealed that "five to six months after receiving the test results, people were no more likely to exercise or reduce their dietary fat intake,"

    Even if patients are not disturbed by the results of direct-to-consumer genome-wide profiling, experts are worried that the results may not be valid. There is concern whether the data given to patients is accurate to patients. This study was not intended to assess whether the tests had clinical validity or were clinically useful. An undercover investigation of 15 DTC genetic testing services by the U.S. Government Accountability Office found "'egregious examples of deceptive marketing, in addition to poor or nonexistent advice from supposed consultation experts," according to the medical journal The Lancet.

    Bloss CS, Schork NJ, Topol EJ. Effect of Direct-to-Consumer Genomewide Profiling to Assess Disease Risk. New England Journal of Medicine;0(0). MMS: Error

    BACKGROUND The use of direct-to-consumer genomewide profiling to assess disease risk is controversial, and little is known about the effect of this technology on consumers. We examined the psychological, behavioral, and clinical effects of risk scanning with the Navigenics Health Compass, a commercially available test of uncertain clinical validity and utility.

    METHODS We recruited subjects from health and technology companies who elected to purchase the Health Compass at a discounted rate. Subjects reported any changes in symptoms of anxiety, intake of dietary fat, and exercise behavior at a mean (±SD) of 5.6±2.4 months after testing, as compared with baseline, along with any test-related distress and the use of health-screening tests.

    RESULTS From a cohort of 3639 enrolled subjects, 2037 completed follow-up. Primary analyses showed no significant differences between baseline and follow-up in anxiety symptoms (P=0.80), dietary fat intake (P=0.89), or exercise behavior (P=0.61). Secondary analyses revealed that test-related distress was positively correlated with the average estimated lifetime risk among all the assessed conditions (?=0.117, P<0.001). However, 90.3% of subjects who completed follow-up had scores indicating no test-related distress. There was no significant increase in the rate of use of screening tests associated with genomewide profiling, most of which are not considered appropriate for screening asymptomatic persons in any case.

    CONCLUSIONS In a selected sample of subjects who completed follow-up after undergoing consumer genomewide testing, such testing did not result in any measurable short-term changes in psychological health, diet or exercise behavior, or use of screening tests. Potential effects of this type of genetic testing on the population at large are not known.

    (Funded by the National Institutes of Health and Scripps Health.)
  4. Millard Baker

    Millard Baker Member

    Re: Direct-To-Consumer Genetic Tests

    What are your thoughts about the "personal genome service" form 23andme - founded by wife Google founder - which in a way seems like an extension of google's goal to index EVERYTHING
  5. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests

    FDA panel advises caution on personal genetic testing
    Doctors should supervise the ordering and interpreting of tests that are directly marketed to patients, the panelists agree.
    Genetic testing: FDA panel advises caution on consumer genetic tests -

    Genetic test makers defend technology before FDA
    FDA weighs risks and benefits of disease-predicting genetic tests at 2-day meeting
    Genetic test makers defend technology before FDA - Yahoo! Finance

    2011 Meeting Materials of the Molecular and Clinical Genetics Panel
    2011 Meeting Materials of the Molecular and Clinical Genetics Panel
  6. Structure

    Structure Member

    Re: Direct-To-Consumer Genetic Tests

    Pacific Biosciences (PACIFIC BIOSCIENCES | Pacific Biosciences) has long claimed that their technology will bring us the $100 direct sequencing of a person's entire genome, in a matter of hours. They just went public last year (PACB). Their stock has been pretty steady at between $15 and $16 a share.

    Exactly how long it will be before they actually fulfill this promise is a matter of much speculation. However, they do have some pretty kick-ass technology, and it does work (although it isn't at the point where a genome is mappable with the constraints promised). See a video here: Pacific Biosciences

    When technology like this is mature, these other companies that rely on SNP-based genotyping will die off like the garbage that they are.
  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests

    Deflating the Genomic Bubble

    Evans JP, Meslin EM, Marteau TM, Caulfield T. Deflating the Genomic Bubble. Science 2011;331(6019):861-2. Deflating the Genomic Bubble

    “Soccer is the sport of the future in America … and it always will be.” This oft-quoted epithet poking fun at the promise of the “beautiful game” in the United States can seem uncomfortably apt when applied to genomic medicine. It's now been 10 years since humans deciphered the digital code that defines us as a species. Although it may be hard to overestimate the significance of that achievement, it is easy to misconstrue its meaning and promise. People argue about whether mapping the human genome was worth the investment. With global funding for genomics approaching $3 billion/year, some wonder what became of all the genomic medicine we were promised. It thus seems an appropriate time to take stock of whence the real benefits from genomic research may come and how best to attain a future in which genomics improves human health.

    Attached Files:

  8. Millard Baker

    Millard Baker Member

    Re: Direct-To-Consumer Genetic Tests

    There are a lot a reasons to be concerned about personal genetic testing - mainly the validity of results - but I think FDA impetus is a little too paternalistic... suggesting people can't handle the truth and that the information can only be filtered through a doctor.

    Reminds me of the aggressive pharma ads promoting drugs to consumers - advising them to request them from their doctors - since only your doctor can tell you if it is right for you. Problem is that the pharm reps have already told your doctor that the drugs are right for you. :D
  9. zkt

    zkt Member

    Re: Direct-To-Consumer Genetic Tests

    Then there was the "just say no to drugs" campaign.
    My question then and now still is: which ones?
    Last edited by a moderator: Mar 9, 2011
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests

    Brooks MA, Tarini BA. Genetic Testing and Youth Sports. JAMA: The Journal of the American Medical Association 2011;305(10):1033-4. Genetic Testing and Youth Sports, March 9, 2011, Brooks and Tarini 305 (10): 1033 — JAMA

    Genetic testing is becoming available to consumers for many applications such as ancestry exploration, future disease risk, and prenatal carrier testing. Now there is another option—sports performance from online genetic testing companies offering everything from single gene tests to multiplex testing of numerous purported sports performance genes. In the “winning is everything” sports culture, societal pressure to use these tests in children may increasingly present a challenge to unsuspecting physicians. The aim of this Commentary is to bring this issue to the attention of physicians, provide evidence regarding this testing, and encourage clinicians to advocate for young patients when necessary.


    As understanding of the human genome increases, more genetic variants will likely be implicated in sports performance. Although a number of genes are being marketed for sports performance, 1 the ?-actinin-3 ( ACTN3 [GenBank accession number M86407.1 ]) gene has received the most attention. Named the “speed gene,” ACTN3 produces ?-actinin-3, …

    CyGene. Optimum athletic performance DNA analysis.

    Attached Files:

  11. Millard Baker

    Millard Baker Member

    Re: Direct-To-Consumer Genetic Tests

    The UGT2B17 test is the best genetic test for athletes !

    (It's the genotype that allows them to use steroids (testosterone) and not get caught)
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests

    Last edited by a moderator: Jun 4, 2014
  13. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests

    FDA Panel Says Home Gene Tests Need MD Input
    Medical News: FDA Panel Says Home Gene Tests Need MD Input - in Genetics, Genetic Testing from MedPage Today

    GAITHERSBURG, Md. -- Certain types of genetic tests that are available for at-home use without a prescription should not be used without the involvement of a physician or genetic specialist, an FDA advisory panel recommended.

    So-called direct-to-consumer (DTC) genetic tests can provide information ranging from a whether a person is lactose intolerant, at risk of developing Alzheimer's disease, or likely to respond to a certain type of drug. After taking a quick blood or saliva sample in the privacy of one's own home, the test is mailed to a laboratory for interpretation and the person is later sent his or her results.

    But some of those results -- for example, a person's likelihood of developing heart disease -- are of limited utility without the involvement of a physician, agreed members of the FDA's Molecular and Clinical Genetics Advisory Panel, which wrapped up a two-day meeting on DTC testing on Wednesday afternoon.

    "I want any test that has a high predictor that a person will get a disease, I want that filtered through a physician," said panelist Valerie Ng, MD, PhD, a pathologist at the University of San Fransisco in Oakland, Calif.

    The panel wasn't clear on whether that would mean a physician would have to order the test, or if a physician would have to interpret the test, or both. That will ultimately be up the FDA to decide. The agency -- which may decide to make certain tests that are currently DTC available by prescription only -- isn't required to follow the advice of its advisory committees, but it often does.

    Physician involvement is not nearly as important for nutrogenetic tests that tell a person how their body processes a certain type of food, or for other less-serious genetic information, such as whether the person has thick earwax, the panel decided.

    Following the hearing, Alberto Gutierrez, director of the FDA's Office of In Vitro Diagnostics, told reporters that certain types of tests, such as nutrogenetic tests, might be appropriate for at-home use as long as the companies make truthful claims.

    Other tests, such as carrier screening tests -- which show whether a person is a genetic carrier of a condition and therefore has a risk of passing it on to their children -- may eventually require doctor involvement.

    "We're not going to be able to take one approach to all types of tests," Gutierrez said. "Some may not require a doctor at all and some might require that a qualified health professional be involved, and some might involve the doctor to order the test."

    "Most of the committee agrees that physician involvement is necessary," panel chairman John Waterson, MD, PhD, a geneticist at Children's Hospital and Research Center in Oakland, Calif., told MedPage Today after the meeting.

    The popularity of DTC tests increased exponentially following the completion of the Human Genome Project. Last year, the FDA informed companies selling the do-it-yourself genetic tests that they weren't in compliance with FDA regulations. That move led pharmacy giant Walgreens to shelve plans to stock a genome mapping kit. Some companies dropped out of the DTC game, and others have been working with the FDA to comply.

    Genetic testing companies believe it is an individual's right to have full access to their health information, while others who testified at the meeting felt that having too much medical information can be harmful, particularly if the information is incorrect, or if there's not much a person could do with the information.

    Jeremy Gruber, president of the Council for Responsible Genetics, a nonprofit organization founded to stimulate public debate on the social and ethical impacts of genetic technologies, said he thinks the FDA should better regulate DTC genetic testing companies in order to mitigate the harm that could be caused by the tests.

    "We believe that everyone should have access to their genome and allowed to sequence it if they choose," said Gruber. However, he added, "We must acknowledge that DTC testing can cause as much harm as good."

    Many people argue that knowing genetic predisposition to a certain disease -- particularly one for which there is no treatment, such as Alzheimer's -- adds no value and only serves to increase anxiety.

    However, that finding was disputed in a recent study published in the New England Journal of Medicine that found users of the at-home genetic tests did not have increased anxiety after their results were revealed.

    "The bottom line from actual studies, is that when people attempt to learn something, they are not upset by what they learn, even when the news is bad," said Mary Pendergast, a lawyer, industry consultant, and former FDA deputy commissioner. "Everyone's lives have trials and tribulations. We can handle it."

    >The panelists -- about half of of whom were medical doctors -- also questioned whether average consumers are sophisticated enough to understand their genome screening results, which is part of the reason a physician could be helpful. (However, most physicians aren't trained geneticists, so they can't be expected to be able to accurately interpret the results either, a few committee members pointed out.)

    But representatives from the companies that make the tests disagreed with the unsophisticated consumer argument and argued that people deserve to be able to have unfettered access their genetic information.

    Pendergast -- who delivered sharply worded testimony during the public hearing that elicited scattered applause from the audience -- accused the panel, and doctors in general, of being "paternalistic."

    "The medical profession has objected every time the FDA has tried to give tests directly to consumers," she said, providing home pregnancy tests as an example. "It's, frankly, medical paternalism -- the FDA trying to keep medical products from consumers 'for their own good.'"

    The panel also heard from witnesses who referenced a 2010 undercover investigation by the Government Accountability Office (GAO), which revealed that home genetic tests often provide incomplete or misleading information to consumers. For the GAO investigation, investigators purchased 10 tests each from four different direct-to-consumer genetic testing companies -- 23andMe, deCode Genetics, Pathway Genomics, and Navigenics -- and the interpretation of the results differed according to which company analyzed the results.
  14. sailing man

    sailing man Junior Member

    Re: Direct-To-Consumer Genetic Tests

    My concerns go further than the ability to understand the results, or the accuracy of the test. At the risk of sounding like one of the million “big Brother Is watching” I would worry if I found something which gave me a higher risk of some age related illness it could become feed for insurance companies to decline coverage. I would want a secure system much better than we see in the “mail in test” or doctor’s offices. A law to protect the person being tested would be a good start.
  15. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer Genetic Tests

    Pediatric Genetic Testing for Common Disease Risk

    As with other marketing efforts, the increasing availability of DTC genetic testing could create demand from patients for these tests within the primary care environment, including inquiries from parents directed toward their child’s pediatrician about the value of pediatric genetic testing for common disease risk. In anticipation of this, researchers conducted a survey to characterize parents who are most likely to be interested in such testing on their child’s behalf. Data for this study were collected through the Multiplex Initiative, a research project in which healthy adults were offered multiplex genetic susceptibility testing for themselves. Responses of a subgroup of parent participants are described. The following were their primary research questions: (1) What factors are associated with parents’ perceptions of the risks and benefits of pediatric multiplex genetic testing? and (2) Which factors are associated with parents’ willingness to test their child?

    Tercyak KP, Alford SH, Emmons KM, Lipkus IM, Wilfond BS, McBride CM. Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk. Pediatrics:peds.2010-0938. Parents' Attitudes Toward Pediatric Genetic Testing for Common Disease Risk -- Tercyak et al., 10.1542/peds.2010-0938 -- Pediatrics

    Objective To describe parents' attitudes toward pediatric genetic testing for common, adult-onset health conditions and to identify factors underlying these attitudes.

    Participants and Methods Parents (n = 219) enrolled in a large, group-practice health plan were offered a "multiplex" genetic test for susceptibility to 8 common, adult-onset health conditions and completed an online survey assessing attitudes and beliefs about the risks and benefits of the test for their child, their willingness to consider having their child tested, and other psychosocial variables.

    Results Parents viewed the benefits of pediatric testing to outweigh its risks (positive decisional balance) and were moderately interested in pediatric testing. Variables associated with positive decisional balance included greater interest in knowing about gene-health associations in their child, anticipation of less difficulty understanding their child's genetic health risks, and more positive emotional reactions to learning about their child's decreased health risks (adjusted R2 = 0.33, P < .0001). Similarly, variables associated with greater parental willingness to test were being a mother (versus being a father), greater perceived risk of diseases in their child, greater interest in knowing about gene-health relationships in their child, anticipating less difficulty learning about their child's genetic health risks, anticipating more positive emotional reactions to learning about their child's decreased health risks, and positive decisional balance (adjusted R2 = 0.57, P < .0001).

    Conclusions As genetic susceptibility testing for common, adult-onset health conditions proliferates, pediatricians should anticipate parents' interest in testing children and be prepared to facilitate informed decision making about such testing.
  16. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer

    Banning Direct-To-Consumer (DTC) Ads Could Be Much Ado About Nothing
    Medical News: Banning DTC Ads Could Be Much Ado About Nothing - in Washington-Watch, Washington Watch from MedPage Today

    WASHINGTON -- Enacting a two-year moratorium on advertising new prescription drugs directly to consumers likely would have little effect on sales and costs of drugs, and could be bad for public health, a government report concludes.

    In recent years, a two-year moratorium on direct-to-consumer (DTC) ads following approval of a new drug has been proposed. The moratorium on advertising might allow more time for the drug's safety concerns to be revealed, but some patients might be harmed because they wouldn't know of a medication's availability in the absence of DTC advertising, according to an issue brief from the non-partisan Congressional Budget Office (CBO).

    Opponents of DTC advertising say that the ads might contribute to extra spending on drugs that would be passed on to consumers, insurers, and the federal government. Others also worry that DTC advertising might create widespread use of a drug beyond what the drug's benefits warrant.

    Among the brand-name drugs included in CBO's report, the average number of prescriptions written for new drugs with DTC advertising was nine times greater than for prescriptions for new drugs without DTC ads. However, DTC ads are usually only for blockbuster drugs -- which are generally those approved to treat common conditions that affect a large portion of the population. Drugmakers are much less likely to heavily advertise products that will only reach relatively few people.

    The number of prescriptions filled for some drugs might decrease because fewer patients would visit their doctors after seeing an ad on TV, according to the CBO report. However, obviously not every doctor writes a prescription for every patient who is requesting a certain drug, so perhaps not much would change, the report said.

    Also, drugmakers would compensate for not having DTC ads in the first two years of their product's introduction to the market by expanding their marketing efforts to physicians, the CBO report predicts.

    The costs for drugs that normally would be part of a DTC advertising campaign might increase, since less of the drug would be sold, the report said, although it didn't project a large increase.

    If such a moratorium banned drugmakers' ads from specifically mentioning a drug, pharmaceutical companies might air commercials that focus on a specific disease that their drug aims to treat and urge patients to seek medical treatment if they have the disease, the report predicts. That approach would work best for a disease for which there are drugs without close competitors, because a drug company would be banking on physicians prescribing their drug.

    The impact a moratorium would have on public health is unclear. On the one hand, fewer patients might be exposed to a new drug's side effects, but if fewer patients are taking a new drug, it might take a lot longer for those side effects to become apparent, the report said.

    Also, DTC ads do seem to spur some patients to visit the doctor to address an underlying disease, and that may become less prevalent if a moratorium were enacted.

    Concerns about prescription drug ads aimed directly at consumers have persisted since the late 1990s, when drug companies ramped up their DTC efforts. Prior to that, most pharmaceutical companies focused their marketing efforts directly at physicians.

    In 1999, the FDA finalized guidance that requires pharmaceutical companies to adhere to certain standards when advertising drugs to consumers: The ads must not be false, misleading, or lacking facts, and they must show a fair balance of the risks and benefits of the drug. In addition, pharmaceutical companies are required to submit promotional materials to the FDA when the drug ad airs.

    In 2008, spending on DTC advertising totaled $4.7 billion, which is nearly one-quarter of pharmaceutical manufacturers' $20.5 billion spent on all promotional activities, according to the CBO. The bulk of that money is aimed directly at doctors, including detailing, selling ads in medical journals, and sponsoring professional meetings.
  17. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer: Genome (DNA) Sequencing/Analysis

    A $1000 genome could be reached by 2013
    A $1000 genome could be reached by 2013

    Rothberg JM, Hinz W, Rearick TM, et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011;475(7356):348-52. An integrated semiconductor device enabling non-optical genome sequencing : Nature : Nature Publishing Group /

    The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.
  18. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer: Genome (DNA) Sequencing/Analysis

    The Future Is Now: 23andMe Now Offers All Your Genes For $999
    The Future Is Now: 23andMe Now Offers All Your Genes For $999 - Forbes

    Call it a dramatic sign of how far the field of genetics has come: Google-backed startup 23andMe is now offering consumers the ability to get their genes sequenced for $999. You can see the offer here, at least for a select few who will be selected on a first-come, first-serve basis.

    A quick note on terminology: a genome is all of the genetic information on your DNA. An exome is only those bits of DNA code that are known to be recipes for proteins, the functional building blocks and workhorses of the body. The rest of the genome may be important, but information is likely to be sparser. Right now, the exome is what we know about.

    What 23andMe is offering is to make people’s exomes available to them, and the DNA sequencer will go over their DNA 80 times (known as 80-fold coverage) to make sure that the genetic code is accurate. This is stunning because a year ago this would have cost ten times as much or more. 23andMe isn’t the first company to offer consumers exomes — that would be Knome, of Cambridge, Mass. — but still the low price is eye-popping. It’s also a lot more data than the DNA chips 23andMe has used up until now, which capture single-letter changes in genetic code scattered across the genome.

    Exome sequencing has already been used to great effect in medicine. See, for instance, this case I wrote about a year ago, or this one, in which sequencing the part of the exome that was on the X chromosome allowed scientists to figure out the cause of a genetic disease that was killing young boys in a Utah family.

    But, as science policy wonk Jonathan Gitlin wrote on Twitter, “for a consumer it still seems to have such marginal utility, especially at that price.” If there’s a medical need, 23andMe may not be the best way to serve it. If there’s not a real reason to look, there’s also nothing to look for.

    And as any investor in this space knows, right now there are doubts about how well the companies that sequence DNA are going to do in the short term as the bad economy could lead to shortfalls in research spending. Illumina, long the industry leader, has seen its shares drop 20% over the past year. Rival Life Technologies and upstart Complete Genomics are down 20%, too. Those of Pacific Biosciences of California, which makes a speedy but expensive machine, are down 75% from their year-ago peak. The science is marching on. The business model is still getting sketched out.
    Last edited: Sep 27, 2011
  19. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Re: Direct-To-Consumer: Genome (DNA) Sequencing/Analysis

    Experts Propose New Unified Genetic Model for Human Disease

    Common chronic diseases such as diabetes, coronary heart disease, stroke, neuropsychiatric illness (including schizophrenia, autism, and developmental disabilities), chronic respiratory disease, and cancer account for an overwhelmingly large fraction of mortality, morbidity, and health care expenditure (CDC - National Center for Health Statistics Homepage). These diseases disproportionately affect aging populations and burden the health care systems and economies of industrialized nations throughout the world. Understanding the underlying causes of such disorders is a key step toward enabling earlier and more precise diagnosis, prognosis, interventional therapy, and potentially prevention.

    Most common diseases are complex or multifactorial with both environmental and genetic contributions along with their nearly intractable interaction effects. In general, the environmental components are challenging to identify and quantitate. In contrast, as a result of the emergence of powerful genomic technologies, the analysis of the genetic components is becoming increasingly tractable and relatively inexpensive to investigate. These technical improvements have fueled a pipeline of discovery of the genes and variants that predispose to human maladies. The technical improvements have also impacted genetic diagnostics, as it is now practical to sequence an entire individual's genome for less than the cost of a comprehensive set of whole-body imaging scans. Furthermore, the cost of whole-genome sequencing is rapidly becoming less expensive than current clinically implemented “multigene panel testing“ for molecular diagnosis of disease traits with even modest genetic heterogeneity.

    In the past, focused, locus-specific, single-gene analyses have elucidated genetic etiologies for disease, but it is now emerging that whole-genome sequencing will produce a more complete assessment of genetic variation contributing to personal health. The genome of each individual contains the inherited contribution of common variants that segregate within the population, the inherited contributions of rare variants that emerged in recent history in the clan, the new combinations of such recently arising variants from both parents, and the new mutation contributions yielding the total mutational burden. Highly penetrant rare variants, and often de novo mutations, contribute medically actionable alleles to Mendelian disease and perhaps extremes of phenotypes in common disease. Common variants can contribute to medically actionable variants for pharmacogenomics traits.

    What emerges is a unified picture whereby previously distinct entities or categories of human diseases, chromosomal syndromes, genomic disorders, Mendelian traits, and common diseases or complex traits, can now be considered as part of one continuum, whereby common and rare variants including de novo mutations in the context of environmental influences result in perturbation of the biological balance of a restricted set of networks activating final common pathways that ultimately cause disease. Even though there may be many loci that contribute to interindividual inherited susceptibility of a phenotype in a population, in any one individual rare or common variants from just a few may be responsible for the trait (i.e., oligogenic inheritance). Extreme genetic heterogeneity and the contributions of new mutation may underlie some of the apparent complexity of complex traits.

    A unified genetic model for human disease breaks down the artificial boundaries between categories of human disease. It views all human disease categories including complex traits, Mendelian disease, genomic disorders, and even chromosomal syndromes as representing a spectrum of phenotypic manifestations reflecting the totality of pathogenic variants: ancestral alleles, those arising in recent ancestors (clan), unique combinations inherited from parents, and de novo variants. A full accounting of individual mutational load genome-wide and expansion of the current genocentric, locus-specific model opens the door to reinvestigation of classic problems in human genetics. These challenges include understanding the molecular basis of incomplete penetrance and variable expressivity of monogenic traits, clinical manifestations of “recessive alleles“ (i.e., weak semidominance), homologous allelic interaction and nonhomologous allelic interaction, and their effects on disease and health. This new synthesis is required to interpret the ecology of individual genomes in the context of complete individual genetic variation data, population genetics, and evolution.

    Genome-wide assays including whole-genome sequencing, copy-number arrays, and transcriptional profiling are among the current technologies that can be used to further explore and test the “genome-wide totality of pathogenic variants hypothesis.” These genome analysis methods can now generate a massive data flow, opening up to experimental exploration fundamental questions that have occupied the minds of generations of scientists and philosophers.

    Yet, such genome-wide experimental assays alone will be insufficient. Other challenges include: How many types of variants (repeat expansions, CNV between 100 and 500 bp, etc.) are we missing with current techniques? How will we validate the phenotypic effects of variants observed in a single individual or family? What analytical approaches should clinical genome sequencing projects adopt given the sheer complexity of some of the gene-disease associations described herein? How can we integrate disease risk emerging from common and rare variants in an individual genome? Can disease phenotypes be refined and redefined by molecular correlates such as gene expression, chromatin conformation, DNA methylation, and all of the other “omics? Can individual serial observation of molecular phenotypes, much as we currently do for routine lab measures such as glucose and lipids, show us stronger effects of underlying genetic variation that are otherwise poorly captured by cross-sectional studies and lead us to yet new models?


    Heat map and extended pedigree showing the conceptual relationship among de novo mutations leading to disease (red), recent mutations with moderate effects arising within a clan (yellow and green), and older common variants with small effects segregating in the population (blue). An individual's genetic disease risk emerges from the collection of variants he or she has inherited from both parental lineages of distant ancestors (typically common and of individually small effect), more recent ancestors (rare, but potentially larger effect), and de novo mutations.


    A Continuum for the Genetics of Human Disease - The square (center) represents genomic variation that can influence the different categories of genetic disease. The circles represent the overlapping categories of human disease with darker regions depicting intersection with greater overlap in the underlying genetic influences on these given disease categories. A unified model for human genetic disease proposes that all major categories of disease with genetic influence—Mendelian disease, common disease or complex traits, genomic disorders, and chromosomal syndromes—can be explained by variation in DNA sequence (SNV) or copy number (CNV) from a “wild-type” diploid state. Whereas trans-genetic interactions at a single locus (alleles) or between loci may contribute to Mendelian disease and complex traits, cis-genetic interactions can be important to phenotypic manifestations in genomic disorders (CNV) and chromosomal syndromes (segmental aneuploidy). Digenic and triallelic inheritance bridge Mendelian traits and complex disease; each represents an oligogenic inheritance model.

    Lupski James R, Belmont JW, Boerwinkle E, Gibbs RA. Clan Genomics and the Complex Architecture of Human Disease. Cell 2011;147(1):32-43.

    Human diseases are caused by alleles that encompass the full range of variant types, from single-nucleotide changes to copy-number variants, and these variations span a broad frequency spectrum, from the very rare to the common. The picture emerging from analysis of whole-genome sequences, the 1000 Genomes Project pilot studies, and targeted genomic sequencing derived from very large sample sizes reveals an abundance of rare and private variants. One implication of this realization is that recent mutation may have a greater influence on disease susceptibility or protection than is conferred by variations that arose in distant ancestors.

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  20. Michael Scally MD

    Michael Scally MD Doctor of Medicine