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FDA Warning for the Leader of Consumer Market for Personal DNA Sequencing: Part 4

Posted in Biomarkers & Medical Diagnostics, Cardiovascular Pharmacogenomics, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Genome Biology, Genomic Testing: Methodology for Diagnosis, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical R&D Investment, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Stem Cells for Regenerative Medicine, Technology Transfer: Biotech and Pharmaceutical, tagged 23andMe, Anne Wojcicki, Cancer - General, DNA, DNA microarray, DNA Sequencing, Food and Drug Administration, Full genome sequencing, genetic testing, Genomic, Illumina, Margaret Hamburg, mutation, Nucleic acid sequence on January 13, 2013| 9 Comments »

Consumer Market for Personal DNA Sequencing: Part 4

Reporter: Aviva Lev-Ari, PhD RN

Word Cloud by Daniel Menzin

This Part 4 of the series on Present and Future Frontier of Research in Genomics has been 

UPDATED on 12/6/2013

23andMe Suspends Health Interpretations

December 06, 2013

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Direct-to-consumer genetic testing company 23andMe hasstopped offering its health-related test to new customers, bringing it in line with a request from the US Food and Drug Administration.

In letter sent on Nov. 22, FDA said that 23andMe had not adequately responded to its concerns regarding the validity of their Personal Genome Service. The letter instructed 23andMe to “immediately discontinue marketing” the service until it receives authorization from the agency.

According to a post at the company’s blog from CEO Anne Wojcicki, 23andMe customers who purchased their kits on or after Nov. 22 “will not have access to health-related results.” They will, though, have access to ancestry information and their raw genetic data. Wojcicki notes that the customers may have access to the health interpretations in the future depending on FDA marketing authorization. Those customers are also being offered a refund.

Customers who purchased their kits before Nov. 22 will have access to all reports.

“We remain firmly committed to fulfilling our long-term mission to help people everywhere have access to their own genetic data and have the ability to use that information to improve their lives,” a notice at the 23andMe site says.

In a letter appearing in the Wall Street Journal earlier this week, FDA Commissioner Margaret Hamburg wrote that the agency “supports the development of innovative tests.” As an example, she pointed to its recent clearance of sequencing-based testsfrom Illumina.

She added that the agency also understands that some consumers do want to know more about their genomes and their genetic risk of disease, and that a DTC model would let consumers take an active role in their health.

“The agency’s desire to review these particular tests is solely to ensure that they are safe, do what they claim to do and that the results are communicated in a way that a consumer can understand,” Hamburg said.

In a statement, 23andMe’s Wojcicki says that the company remains committed to its ethos of allowing people access to their genetic information. “Our goal is to work cooperatively with the FDA to provide that opportunity in a way that clearly demonstrates the benefit to people and the validity of the science that underlies the test,” Wojcicki adds.

SOURCE

http://www.genomeweb.com/blog/23andme-suspends-health-interpretations

UPDATED on 11/27/2013

FDA Tells Google-Backed 23andMe to Halt DNA Test Service

VIEW VIDEO

http://www.bloomberg.com/news/2013-11-25/fda-tells-google-backed-23andme-to-halt-dna-test-service.html

FDA Letter to 23andME

23andMe, Inc. 11/22/13

Department of Health and Human Services	Public Health Service Food and Drug Administration
	10903 New Hampshire Avenue Silver Spring, MD 20993

Nov 22, 2013

Ann Wojcicki

CEO

23andMe, Inc.

1390 Shoreline Way

Mountain View, CA 94043

Document Number: GEN1300666

Re: Personal Genome Service (PGS)

WARNING LETTER

Dear Ms. Wojcicki,

The Food and Drug Administration (FDA) is sending you this letter because you are marketing the 23andMe Saliva Collection Kit and Personal Genome Service (PGS) without marketing clearance or approval in violation of the Federal Food, Drug and Cosmetic Act (the FD&C Act).

This product is a device within the meaning of section 201(h) of the FD&C Act, 21 U.S.C. 321(h), because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body. For example, your company’s website at http://www.23andme.com/health (most recently viewed on November 6, 2013) markets the PGS for providing “health reports on 254 diseases and conditions,” including categories such as “carrier status,” “health risks,” and “drug response,” and specifically as a “first step in prevention” that enables users to “take steps toward mitigating serious diseases” such as diabetes, coronary heart disease, and breast cancer. Most of the intended uses for PGS listed on your website, a list that has grown over time, are medical device uses under section 201(h) of the FD&C Act. Most of these uses have not been classified and thus require premarket approval or de novo classification, as FDA has explained to you on numerous occasions.

Some of the uses for which PGS is intended are particularly concerning, such as assessments for BRCA-related genetic risk and drug responses (e.g., warfarin sensitivity, clopidogrel response, and 5-fluorouracil toxicity) because of the potential health consequences that could result from false positive or false negative assessments for high-risk indications such as these. For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist. Assessments for drug responses carry the risks that patients relying on such tests may begin to self-manage their treatments through dose changes or even abandon certain therapies depending on the outcome of the assessment. For example, false genotype results for your warfarin drug response test could have significant unreasonable risk of illness, injury, or death to the patient due to thrombosis or bleeding events that occur from treatment with a drug at a dose that does not provide the appropriately calibrated anticoagulant effect. These risks are typically mitigated by International Normalized Ratio (INR) management under a physician’s care. The risk of serious injury or death is known to be high when patients are either non-compliant or not properly dosed; combined with the risk that a direct-to-consumer test result may be used by a patient to self-manage, serious concerns are raised if test results are not adequately understood by patients or if incorrect test results are reported.

Your company submitted 510(k)s for PGS on July 2, 2012 and September 4, 2012, for several of these indications for use. However, to date, your company has failed to address the issues described during previous interactions with the Agency or provide the additional information identified in our September 13, 2012 letter for(b)(4) and in our November 20, 2012 letter for (b)(4), as required under 21 CFR 807.87(1). Consequently, the 510(k)s are considered withdrawn, see 21 C.F.R. 807.87(1), as we explained in our letters to you on March 12, 2013 and May 21, 2013.  To date, 23andMe has failed to provide adequate information to support a determination that the PGS is substantially equivalent to a legally marketed predicate for any of the uses for which you are marketing it; no other submission for the PGS device that you are marketing has been provided under section 510(k) of the Act, 21 U.S.C. § 360(k).

The Office of In Vitro Diagnostics and Radiological Health (OIR) has a long history of working with companies to help them come into compliance with the FD&C Act. Since July of 2009, we have been diligently working to help you comply with regulatory requirements regarding safety and effectiveness and obtain marketing authorization for your PGS device. FDA has spent significant time evaluating the intended uses of the PGS to determine whether certain uses might be appropriately classified into class II, thus requiring only 510(k) clearance or de novo classification and not PMA approval, and we have proposed modifications to the device’s labeling that could mitigate risks and render certain intended uses appropriate for de novo classification. Further, we provided ample detailed feedback to 23andMe regarding the types of data it needs to submit for the intended uses of the PGS.  As part of our interactions with you, including more than 14 face-to-face and teleconference meetings, hundreds of email exchanges, and dozens of written communications, we provided you with specific feedback on study protocols and clinical and analytical validation requirements, discussed potential classifications and regulatory pathways (including reasonable submission timelines), provided statistical advice, and discussed potential risk mitigation strategies. As discussed above, FDA is concerned about the public health consequences of inaccurate results from the PGS device; the main purpose of compliance with FDA’s regulatory requirements is to ensure that the tests work.

However, even after these many interactions with 23andMe, we still do not have any assurance that the firm has analytically or clinically validated the PGS for its intended uses, which have expanded from the uses that the firm identified in its submissions. In your letter dated January 9, 2013, you stated that the firm is “completing the additional analytical and clinical validations for the tests that have been submitted” and is “planning extensive labeling studies that will take several months to complete.” Thus, months after you submitted your 510(k)s and more than 5 years after you began marketing, you still had not completed some of the studies and had not even started other studies necessary to support a marketing submission for the PGS. It is now eleven months later, and you have yet to provide FDA with any new information about these tests.  You have not worked with us toward de novo classification, did not provide the additional information we requested necessary to complete review of your 510(k)s, and FDA has not received any communication from 23andMe since May. 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 PGS’s uses and consumer base without obtaining marketing authorization from FDA.

Therefore, 23andMe must immediately discontinue marketing the PGS until such time as it receives FDA marketing authorization for the device. The PGS is in class III under section 513(f) of the FD&C Act, 21 U.S.C. 360c(f). Because there is no approved application for premarket approval in effect pursuant to section 515(a) of the FD&C Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the FD&C Act, 21 U.S.C. 360j(g), the PGS is adulterated under section 501(f)(1)(B) of the FD&C Act, 21 U.S.C. 351(f)(1)(B).  Additionally, the PGS is misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because notice or other information respecting the device was not provided to FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k).

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific actions you have taken to address all issues noted above. Include documentation of the corrective actions you have taken. If your actions will occur over time, please include a timetable for implementation of those actions. If corrective actions cannot be completed within 15 working days, state the reason for the delay and the time within which the actions will be completed. Failure to take adequate corrective action may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.

We have assigned a unique document number that is cited above. The requested information should reference this document number and should be submitted to:

James L. Woods, WO66-5688

Deputy Director

Patient Safety and Product Quality

Office of In vitro Diagnostics and Radiological Health

10903 New Hampshire Avenue

Silver Spring, MD 20993

If you have questions relating to this matter, please feel free to call Courtney Lias, Ph.D. at 301-796-5458, or log onto our web site at www.fda.gov for general information relating to FDA device requirements.

Sincerely yours,

/S/

Alberto Gutierrez

Director

Office of In vitro Diagnostics

and Radiological Health

 Center for Devices and Radiological Health

SOURCE

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2013/ucm376296.htm

Cancer Diagnostics by Genomic Sequencing: ‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

Symposia

http://aaas.confex.com/aaas/2013/webprogram/start.html

Personal Genetics: An Intersection Between Science, Society, and Policy

Saturday, February 16, 2013: 8:30 AM-11:30 AM

Room 203 (Hynes Convention Center)

On 26 June 2000, scientists announced the completion of a rough draft of the human genome, the result of the $3 billion publicly funded Human Genome Project. In the decade since, the cost of genome sequencing has plummeted, coinciding with the development of deep sequencing technologies and allowing, for the first time, personalized genetic medicine. The advent of personal genetics has profound implications for society that are only beginning to be discussed, even as the technologies are rapidly maturing and entering the market. This symposium will focus on how the genomic revolution may affect our society in coming years and how best to reach out to the general public on these important issues. How has the promise of genomics, as stated early in the last decade, matched the reality we observe today? What are the new promises — and pitfalls — of genomics and personal genetics as of 2013? What are the ethical implications of easy and inexpensive human genome sequencing, particularly with regard to ownership and control of genomic datasets, and what stakeholder interests must be addressed? How can the scientific community engage with the public at large to improve understanding of the science behind these powerful new technologies? The symposium will comprise three 15-minute talks from representatives of relevant sectors (academia/education, journalism, and industry), followed by a 45-minute panel discussion with the speakers.

Organizer:

Peter Yang, Harvard University

Co-organizers:

Brenna Krieger, Harvard University

and Kevin Bonham, Harvard University

Discussant:

James Thornton, Harvard University

Speakers:

 

Ting Wu, Harvard University

Personal Genetics and Education

Mary Carmichael, Boston Globe

The Media and the Personal Genetics Revolution

Brian Naughton, 23andMe Inc.

Commercialization of Personal Genomics: Promise and Potential Pitfalls

Mira Irons, Children’s Hospital Boston

Personal Genomic Medicine: How Physicians Can Adapt to a Genomic World

Sheila Jasanoff, Harvard University

Citizenship and the Personal Genomics

Jonathan Gitlin, National Human Genome Research Institute

Personal Genomics and Science Policy

THIS IS A SERIES OF FOUR POINTS OF VIEW IN SUPPORT OF the Paradigm Shift in Human Genomics

How to Tailor Cancer Therapy to the particular Genetics of a patient’s Cancer

‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities PRESENTED in the following FOUR PARTS. Recommended to be read in its entirety for completeness and arrival to the End Point of Present and Future Frontier of Research in Genomics

Part 1:

Research Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine

http://pharmaceuticalintelligence.com/2013/01/13/paradigm-shift-in-human-genomics-predictive-biomarkers-and-personalized-medicine-part-1/

Part 2:

LEADERS in the Competitive Space of Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment

http://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer-personalized-treatment-part-2/

Part 3:

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research

http://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical-research-part-3/

Part 4:

The Consumer Market for Personal DNA Sequencing

 

Part 4:

The Consumer Market for Personal DNA Sequencing

How does 23andMe genotype my DNA?

Technology and Standards

23andMe is a DNA analysis service providing information and tools for individuals to learn about and explore their DNA. We use the Illumina OmniExpress Plus Genotyping BeadChip (shown here). In addition to the variants already included on the chip by Illumina, we’ve included our own, customized set of variants relating to conditions and traits that are interesting. Technical information on the performance of the chip can be found on Illumina’s website.

All of the laboratory testing for 23andMe is done in a CLIA-certified laboratory.

Once our lab receives your sample, DNA is extracted from cheek cells preserved in your saliva. The lab then copies the DNA many times — a process called “amplification” — growing the tiny amount extracted from your saliva until there is enough to be genotyped.

In order to be genotyped, the amplified DNA is “cut” into smaller pieces, which are then applied to our DNA chip, a small glass slide with millions of microscopic “beads” on its surface (read more about this technology). Each bead is attached to a “probe”, a bit of DNA that matches one of the approximately one million genetic variants that we test. The cut pieces of your DNA stick to the matching DNA probes. A fluorescent signal on each probe provides information that can tell us which version of that genetic variant your DNA corresponds to.

Although the human genome is estimated to contain about 10-30 million genetic variants, many of them are correlated due to their proximity to each other. Thus, one genetic variant is often representative of many nearby variants, and the approximately one million variants on our genotyping chip provide very good coverage of common variation across the entire genome.

Our research team has also hand-picked tens of thousands of additional genetic variants linked to various conditions and traits in the scientific literature to analyze on our genotyping chip. As a result we can provide you with personal genetic information available only through 23andMe.

Genetics service 23andMe announced some new cash in the bank today with a $50 million raise from Yuri Milner, 23andMe CEO Anne Wojcicki, Google’s Sergey Brin (who also happens to be Wojcicki’s husband), New Enterprise Associates, MPM Capital, and Google Ventures.

With today’s new funding also comes the reduction of the price of its genome analysis service to $99. This isn’t special holiday pricing (as 23andMe has run repeatedly in the past) the company tells me, but rather what its normal pricing will be from now on.

This move is overdue, at least as far as 23andMe’s business model is concerned. Just yesterday TechCrunch Conference Chair Susan Hobbs told me she was waiting for another $99 pricing deal to buy the Personal Genome Analysis product. Sure 23andMe has experimented with various pricing models, including subscription, since its founding in 2007, but had been at an official and prohibitive $299 price point until today. It’s also apparently been rigorously beta-testing various price points in the past couple of weeks, at some point experimenting with some lower than $99.

For comparison, the company’s original pricing began at $999 and offered subscribers just 14 health and trait reports versus today’s 244 reports, as well as genetic ancestry information. Natera, Counsyl and Pathway Genomics are also in the genomics space, but they work by offering their services through doctors rather than direct to consumer.

Since the company’s launch five years ago, it’s had 180K civilians profile their DNA, and representative Catherine Afarian tells us that, post-price drop and funding, its goal is to reach a million customers in 2013. This is a supremely ambitious goal considering it wants to turn an average user acquisition rate of 36K per year into one of 820K in one year alone.

But Afarian isn’t fazed and brings up how the company once sold out 20k in $99 account inventory on something called “DNA Day.” “Once we can offer the service at $99 it means the average American will buy in,” she said.

That $299 was too pricey, according to Hobbs, but $99 might be just right. She said the $99 price point, which yes, is less than an iPhone, was the main factor in her decision to buy in. “23andMe is more ‘nice-to-know’ information rather than ‘need-to-know’ information. It’s nice to know your ancestry. It’s more of a need to know that you are predisposed genetically for a type of cancer, so that you may take precautionary measures,” she said, implying that the data given by 23andMe isn’t necessarily vital medical information, or actionable when it is. While 23andMe can give you indicators about certain disease risks, it doesn’t close the loop, as in tell you what to do to prevent these diseases.

“Its [utility] depends on your genetic data,” said Afarian when I asked her about the usefulness of the product. “If you’ve got a Factor 5 that puts you at risk for clotting, you might want to invest in anti-clotting socks. [And] there’s always something about themselves that people didn’t know.”

Hobbs said eventually that she wouldn’t buy it, but only because she was looking into more exact lineage information for her little girl, and you need a Y chromosome in all DNA tests to show paternal lineage. Afarian also countered this hesitation, saying that what makes 23andMe unique is that it’s not only looking at just your Y or your mitochondrial DNA, but also your autosomal DNA, which does show some patrilineal information for females who lack that precious Y.

While still sort of a novelty, the potential for 23andMe goes beyond lineage and hopefully that extra $50 million will go further than keeping the price low and into research. The company hopes that a million users will result in a giant database of 23andWe genetic info that can be used to spot trends, like which genes mean a higher risk of diabetes/cancer, etc. Which is great if it happens but for now remains a pipe dream for 23andMe/We.

http://techcrunch.com/2012/12/11/23andnotme/

12/13/2012 @ 5:23PM |6,471 views

What Is 23andMe Really Selling: The Moral Quandary At The Center Of The Personalized Genomics Revolution

This week, 23andme, the personalized genomics company founded by Anne Wojcicki, wife of Google co-founder Sergey Brin, got an influx of investment cash ($50 million). According to their press release, they are using the money to bring the cost of their genetic test down to $99 (it was previously $299) which, they hope, will inspire the masses to get tested.

So should the masses indulge?

I prefer a quantified self approach to this question. At the heart of the quantified self-movement lies a very simple idea: metrics make us better. For devotees, this means “self-tracking,” using everything from the Nike fuel band to the Narcissism Personality Index to gather large quantities of personal data and—the bigger idea—use that data to improve performance.

If you consider that performance suffers when health suffers then a genetic test can been seen as a kind of metric used to improve performance. This strikes me as the best way to evaluate this idea and leads us to ask the same question about personalized genomics that the quantified self movement asks about every other metric: will it improve performance.

Arguments rage all over the place on this one, but the short answer is that SNP tests—which is the kind of DNA scan 23andme relies upon— don’t tell us all that much (yet).  They analyze a million genes out of three billion total and the impact those million play in long term-health outcomes is still in dispute. For example, the nature/nurture split is normally viewed at 30/70—meaning environmental factors play a far more significant role in long-term health outcomes than genetics.

Moreover, all of the performance metrics used by the quantified self movement are used to for behavior modification—to drive self-improvement. Personalized genomics isn’t there yet. As Stanford University’s Nobel Prize-winning RNA researcher Andy Fire once told me, “if someone off the street is looking for pointers on how to live a healthier life, there’s nothing these tests will tell you besides basic physician advice like ‘eat right, don’t smoke and get plenty of exercise.’”

And even with more well-regarded SNP tests, like the ones that examine the BRCA 1 and 2 markers for breast cancer—which  . NYU Langone Medical Center bioethicist Arthur Caplan explains it like this, “Say you test positive for a breast cancer disposition—then what are you going to do? The only preventative step you can take is to chop off your breasts.”

So if prevention is not available the only thing left is fear and anxiety. Unfortunately, in the past few decades, there have been hundreds of studies linking stress to everything from immunological disorders to heart disease to periodonitic troubles. So while finding out you may be at risk for Parkinson’s may make you feel informed, that knowledge isn’t going to stop you from developing the disease—but the resulting stress may contribute to a host of other complications.

This brings up a different question: if personalized genomics can’t yet help us much and could possibly hurt us—where’s the upside?

Turns out there’s a big upside: Citizen science. SNP tests are not yet viable because we need more info. 23andme talks about the “power of one million people,” meaning, if one million take these tests then the resulting genetic database could lead to big research breakthroughs and these could lead to all sorts of health/performance improvements.

This is what 23andme is really selling for $99 bucks a pop—a crowdsourced shot at unraveling a few more DNA mysteries.

And this also means that the question at the heart of the personalized genomics industry is not about metrics at all—it’s about morals: Should I risk my health for the greater good?

http://www.forbes.com/sites/stevenkotler/2012/12/13/what-is-23andme-really-selling-the-moral-quandary-at-the-center-of-the-personalized-genomics-revolution/

You can browse your data for all of the variants we test using the Browse Raw Data feature, or download your data here.

before you buy (59) »

What unexpected things might I learn?

How does 23andMe genotype my DNA?

Can I use the saliva collection kit for infants and toddlers?

getting started (20) »

When and how do I get my data?

How do I collect saliva samples?

How long will it take for my sample to reach the lab?

account/profile settings (20) »

Which Ancestry setting in My Profile should I choose?

How do I use Browse Raw Data?

What do the options under the “Account” link in the upper right-hand corner control?

product features (145) »

I know that a particular person is my relative. What’s the probability that we share a sufficient amount of DNA to be detected by Relative Finder?

What is the average percent DNA shared for different types of cousins?

How does Relative Finder estimate the Predicted Relationship?

research initiatives (8) »

What do I get in return for taking surveys?

What is your research goal?

What is 23andMe Research?

https://customercare.23andme.com/categories/20021003-faqs

https://customercare.23andme.com/home

REFERENCES

http://www.foundationmedicine.com/diagnostics-publications.php

http://www.coriell.org/media-center/publications

Http://www.coriell.org/assets/pdfs/gronowski_etal_coriellinstitute_clinicalchemistry2011_humantissuesinresearch.pdf

http://scholar.google.com/scholar?start=10&q=Gene+Mutation+Aberration+%26+Analysis+of+Gene+Abnormalities&hl=en&as_sdt=0,22&as_vis=1

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Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1

Posted in Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiovascular Pharmacogenomics, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Interviews with Scientific Leaders, Medical and Population Genetics, Metabolomics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Proteomics, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Scientist: Career considerations, Stem Cells for Regenerative Medicine, Technology Transfer: Biotech and Pharmaceutical, tagged Aviva Lev-Ari, Cancer - General, Clinical trial, DNA, DNA Sequencing, Full genome sequencing, genetics, Genomic, Personalized medicine, University of Texas MD Anderson Cancer Center on January 13, 2013| 13 Comments »

Author & Curator: Aviva Lev-Ari, PhD, RN

Cancer Diagnostics by Genomic Sequencing: ‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

How to Tailor Cancer Therapy to the particular Genetics of a patient’s Cancer

THIS IS A SERIES OF FOUR POINTS OF VIEW IN SUPPORT OF the Paradigm Shift in Human Genomics

‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

PRESENTED in the following FOUR PARTS. Recommended to be read in its entirety for completeness and arrival to the End Point of Present and Future Frontier of Research in Genomics

Part 1:

Research Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine

Part 2:

LEADERS in the Competitive Space of Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment

http://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer-personalized-treatment-part-2/

Part 3:

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research

http://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical-research-part-3/

Part 4:

The Consumer Market for Personal DNA Sequencing

http://pharmaceuticalintelligence.com/2013/01/13/consumer-market-for-personal-dna-sequencing-part-4/

 

Part 1:

Research Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine

 

In Part 1, we will address the following FIVE DIRECTIONS in Genomics Research

• ‘No’ to Sequencing Patient’s DNA, ‘No’ to Sequencing Patient’s Tumor, ‘Yes’ to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

• Sequencing DNA from individual cells vs “humans as a whole.” Sequencing DNA from individual cells is changing the way that researchers think of humans as a whole.

• Promising Research Directions By Watson, 1/10/2013

• Disruption of Cancer Metabolism targeted by Metabolic Gatekeeper

• Molecular Analysis of the different Stages of  Cancer Progression for Targeting Therapy

First:

Predictive Biomarkers and Personalized Medicine

No to Sequencing Patient’s DNA, No to Sequencing Patient’s Tumor, Yes to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities

 

MD Anderson Research

targeted agents matched with tumor molecular aberrations.

Molecular analysis

Patients whose tumors had an aberration were treated with matched targeted therapy, compared with those of consecutive patients who were not treated with matched targeted therapy

Results

40.2% – 1 or more aberration.

In 1 aberration , matched tx higher response rate  27% vs 5%

Longer time ot treatment failure  TTF 5.2 vs. 2.2

Longer survival  13.4 vs. 9 months

Pt. w/1 mutation (molecular aberrationMatched targeted therapy associated with longer TTF vs. prior systemic therapy 5.2 vs. 3.1

matched therapy was an independent factor predicting response superior to TTF

Conclusion

Not randomized study, and patients had diverse tumor types and a median of 5 prior therapies,  results suggest that identifying specific molecular abnormalities and choosing therapy based on these abnormalities is relevant in phase I clinical trials

Clin Cancer Res. 2012 Nov 15;18(22):6373-83. doi: 10.1158/1078-0432.CCR-12-1627. Epub 2012 Sep 10.

Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative.

Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul S, Naing A, Janku F, Luthra R, Ye Y, Wen S, Berry D, Kurzrock R.

Source

Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. atsimber@mdanderson.org

http://www.ncbi.nlm.nih.gov/pubmed?term=22966018

 

Opinion by Dr. Pierluigi Scalia, 1/11/2013.

The fact of using nanotechnology in order to target and treat abnormal cancer cells and tissues adds a powerful weapon towards eradicating the disease in the foreseeable future. However, focusing on weapons when we still have not found a reliable way to build that personalized “shooting target” (Cancer Fingerprinting) still constitutes, in my opinion, the single most relevant barrier to the adoption of Personalized treatments.

http://pharmaceuticalintelligence.com/2013/01/09/nanotechnology-personalized-medicine-and-dna-sequencing/

Ritu Saxena’s interview

http://pharmaceuticalintelligence.com/2013/01/07/personalized-medicine-gearing-up-to-tackle-cancer/

Other studies supporting this perspective

 

p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias

 

Chromosome aberrations in solid tumors

 

Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis

 

Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors

 

Clonal analysis of delayed karyotypic abnormalities and gene mutations in radiation-induced genetic instability.

 

Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgVH status and …

 

Detection of aberrations of the p53 alleles and the gene transcript in human tumor cell lines by single-strand conformation polymorphism analysis

 

Genetic aberrations detected by comparative genomic hybridization are associated with clinical outcome in renal cell carcinoma

 

VH mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia

 

Microarray gene expression profiling of B-cell chronic lymphocytic leukemia subgroups defined by genomic aberrations and VH mutation status

 

… nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations

 

Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations

[DOC] Pax 6 Gene Research and the Pancreas

 

Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in human malignancies

Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p.

Cytogenetic analysis of soft tissue sarcomas: recurrent chromosome abnormalities in malignant peripheral nerve sheath tumors (MPNST)

Radiation-induced genomic instability: delayed cytogenetic aberrations and apoptosis in primary human bone marrow cells

SOURCES

Search:

Gene Mutation Aberration & Analysis of Gene Abnormalities

http://scholar.google.com/scholar?start=20&q=Gene+Mutation+Aberration+%26+Analysis+of+Gene+Abnormalities&hl=en&as_sdt=0,22&as_vis=1

Second:

Sequencing DNA from individual cells vs “humans as a whole.”

Sequencing DNA from individual cells is changing the way that researchers think of humans as a whole.

The ability to sequence single cells meant that researchers could take another approach. Working with a team at the Chinese sequencing powerhouse BGI, Auton sequenced nearly 200 sperm cells and was able to estimate the recombination rate for the man who had donated them. The work is not yet published, but Auton says that the group found an average of 24.5 recombination events per sperm cell, which is in line with estimates from indirect experiments2. Stephen Quake, a bioengineer at Stanford University in California, has performed similar experiments in 100 sperm cells and identified several places in the genome in which recombination is more likely to occur. The location of these recombination ‘hotspots’ could help population biologists to map the position of genetic variants associated with disease.

Quake also sequenced half a dozen of those 100 sperm in greater depth, and was able to determine the rate at which new mutations arise: about 30 mutations per billion bases per generation3, which is slightly higher than what others have found. “It’s basically the population biology of a sperm sample,” Quake says, and it will allow researchers to study meiosis and recombination in greater detail.

SOURCES:

http://www.nature.com/news/genomics-the-single-life-1.11710#/genome

Nature 491, 27–29 (01 November 2012) doi:10.1038/491027a

http://pharmaceuticalintelligence.com/2012/11/05/every-sperm-is-sacred-sequencing-dna-from-individual-cells-vs-humans-as-a-whole/

 

Third:

Promising Research Directions By Watson, 1/10/2013

The main reason drugs that target genetic glitches are not cures is that cancer cells have a work-around. If one biochemical pathway to growth and proliferation is blocked by a drug — the cancer cells activate a different, equally effective pathway.

Watson advocates a different approach: targeting features that all cancer cells, especially those in metastatic cancers, have in common.

A protein in cells called Myc. It controls more than 1,000 other molecules inside cells, including many involved in cancer. Studies suggest that turning off Myc causes cancer cells to self-destruct in a process called apoptosis.

cancer biologist Hans-Guido Wendel of Sloan-Kettering. “Blocking production of Myc is an interesting line of investigation. I think there’s promise in that.”

Personalized medicine” that targets a patient’s specific cancer-causing mutation

Watson wrote, may be “the inherently conservative nature of today’s cancer research establishments.”

http://pharmaceuticalintelligence.com/2013/01/09/the-cancer-establishments-examined-by-james-watson-co-discover-of-dna-wcrick-41953/

 

Opinion by Dr. Stephen Willliams, 1/11/2013

Kudos to both Watson and Weinstein for stating we really need to delve into tumor biology to determine functional pathways (like metabolism) which are a common feature of the malignant state ( also see my posting on differentiation therapy).

http://pharmaceuticalintelligence.com/2013/01/09/the-cancer-establishments-examined-by-james-watson-co-discover-of-dna-wcrick-41953/

http://pharmaceuticalintelligence.com/2013/01/03/differentiation-therapy-epigenetics-tackles-solid-tumors/

Fourth:

Disruption of Cancer Metabolism targeted by Metabolic Gatekeeper

Figure’s SOURCE:

Figure brought to my attention by Dr. Tilda Barlyia, 1/10/2013

http://blogs.nature.com/spoonful/2012/12/metabolic-gatekeeper-provides-new-target-for-disrupting-cancer-metabolism.html

Author: Yevgeniy Grigoryev

In the 1920s, the German physiologist Otto Warburgproposed that cancer cells generate energy in ways that are distinct from normal cells. Healthy cells mainly metabolize sugar via respiration in the mitochondria, switching only to glycolysis in the cytoplasm when oxygen levels are low. In contrast, cancer cells rely on glycolysis all the time, even under oxygen-rich scenarios. This shift in how energy is produced—the so-called ‘Warburg effect’, as the observation came to be known—is now recognized as a primary driver of tumor formation, but a mechanistic explanation for the phenomenon has remained elusive.

Now, researchers have implicated a chromatin regulator known as SIRT6 as a key mediator of the switch to glycolysis in cancer cells, a finding that could lead to new therapeutic modalities. “This work is very significant for the cancer field,” says Andrei Seluanov, a cancer biologist at the University of Rochester in New York State who studies SIRT6 but was not involved in the latest study. “It establishes the role ofSIRT6 as a tumor suppressor and shows that SIRT6 loss leads to tumor formation in mice and humans.”

SIRT6 encodes one of seven mammalian proteins called sirtuins, a group of histone deacetylases that play a role in regulating metabolism, lifespan and aging. SIRT1—which is activated by resveratrol, a molecule found in the skin of red grapes—is perhaps the best known sirtuin, but several of the others are now the focus of active investigation as therapeutic targets for a range of conditions, from metabolic syndrome tocancer. Just last month, for example, a paper in Nature Medicine demonstrated that SIRT6 plays an important role in heart disease.

Six years ago, a team led by Raul Mostoslavsky, a molecular biologist at the Massachusetts General Hospital Cancer Center in Boston, first showed that SIRT6 protects mice from DNA damage and had anti-aging properties. In 2010, the same team established SIRT6 as a critical regulator of glycolysis. Now,reporting today in Cell, Mostoslavsky and his colleagues have shown that SIRT6 function is lost in cancer cells—thus, definitively establishing SIRT6 as a potent tumor suppressor.

In the latest study, the researchers showed that mouse embryonic cells genetically engineered to lackSIRT6 proliferated much faster than normal cells, growing from 5,000 cells to 200,000 cells in three days. In contrast, SIRT6-expressiong cells grew at less than half that rate over the same time period. When injected into adult mice, these SIRT6-deficient cells also rapidly formed tumors, but this tumor growth was reversed when the scientists put SIRT6 back into the cells.

“Our study provides a proof-of-concept that inhibiting glycolysis in SIRT6-deficient cells and tumors could provide a potential therapeutic approach to combat cancer,” says Mostoslavsky. “Additionally, SIRT6 may be a valuable prognostic biomarker for cancer detection.”

Currently, there are no approved anti-glycolytic drugs against cancer. However, the latest findings indicate that pharmacologically elevating SIRT6 levels might help keep tumor growth at bay. And there’s preliminary data to suggest that the work will translate from the bench to the clinic: looking at a range of cancers from human patients, Mostoslavsky’s team showed that the higher the level of SIRT6 the better the prognosis and the longer the survival times.

SOURCE:

http://blogs.nature.com/spoonful/2012/12/metabolic-gatekeeper-provides-new-target-for-disrupting-cancer-metabolism.html

Fifth:

Molecular Analysis of the different Stages of  Cancer Progression: The Example of Breast Cancer 

Figure’s SOURCE:

The molecular pathology of breast cancer progression

Alessandro Bombonati1 and Dennis C Sgroi1,2* Journal of Pathology, J Pathol 2011; 223: 307–317

Published online 16 November 2010 in Wiley Online Library

(wileyonlinelibrary.com) DOI: 10.1002/path.2808

http://onlinelibrary.wiley.com/store/10.1002/path.2808/asset/2808_ftp.pdf;jsessionid=26C2C424E6948A5FAF3CBADBA385184A.d02t04v=1&t=hi26qzd4&s=a8a4aadb3fc6d448080c0ef3c67415b8277145aa

Post by Dr. Tilda Barlyia and Comments on   “The Molecular Pathology of Breast Cancer Progression”

http://pharmaceuticalintelligence.com/2013/01/10/the-molecular-pathology-of-breast-cancer-progression/

Conclusion

The Paradigm Shift in Human Genomics will follow the following FIVE DIRECTIONS:

• No to Sequencing Patient’s DNA, No to Sequencing Patient’s Tumor, Yes to focus on Gene Mutation Aberration & Analysis of Gene Abnormalities
• Sequencing DNA from individual cells vs “humans as a whole.” Sequencing DNA from individual cells is changing the way that researchers think of humans as a whole.

• Promising Research Directions By Watson, 1/10/2013

• Disruption of Cancer Metabolism targeted by Metabolic Gatekeeper

• Molecular Analysis of the different Stages of  Cancer Progression for Targeting Therapy

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PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity

Posted in Bio Instrumentation in Experimental Life Sciences Research, CABG, Cardiac & Vascular Repair Tools Subsegment, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Coagulation Therapy and Internal Bleeding, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, HTN, Interviews with Scientific Leaders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Origins of Cardiovascular Disease, PCI, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Stents & Tools, Systemic Inflammatory Response Related Disorders, tagged Conventional PCI, Dade-Behring, fibrinogen, MICHAEL WARD, myocardial infarction, University of California San Francisco on January 10, 2013| 12 Comments »

PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #13: PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity. Published on 1/10/2013

WordCloud Image Produced by Adam Tubman

 

Q&A Session between Dr. Michael Ward and Dr. Larry Bernstein presented for in our Research Category on 

Interviews with Scientific Leaders

Primary research:

Ang L, et al “Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention” J Am Coll Cardiol2013; 61: 23-34.

 

Question by DR. MICHAEL WARD

How ironic that an old diagnostic parameter should
reappear in the limelight of diagnostic predictors.

Of course, decades ago, doctors asked for “sed rates”, seeking to know if red cells, thought to be bound to fibrinogen, settled faster in a patient compared to a control subject’s blood. Fibrinogen has always been a diagnostic number in evaluating inflammatory results.

However, the diagnostic world, like the worlds of pharmaceuticals, medical devices, biologics, and other industries, always seek the ‘new kid on the block’ to differentiate themselves from the rest of the pack in the
marketplace.

So there was a binge (and still is) to seek new and exotic blood proteins that are surrogate markers for specific diagnoses or prognoses.

That is the irony, that in this case at least, fibrinogen has come full circle. Biology works in mysterious ways.

Answer by Dr. Larry Bernstein, MD, FCAP

Dear Dr. M.  Ward:

Doctors asked for “sed rates”, seeking to know if red cells, thought to be bound to fibrinogen, settled faster in a patient compared to a control
subject’s blood. Fibrinogen has always been a diagnostic number in evaluating inflammatory results.

You are quite right that physicians used “sed rates” as a measure of inflammation, and more in Lupus Erythematosis, Rheumatoid Arthritis, Nephritides, Systemic Sclerosis, and so forth.  The “sed rate” was not a part of the thinking about CVD, and PCI didn’t exist.  Recently, MI post-PCI has been defined as a type (NSTEMI?).

Yes. In principle, the sed rate is related to fibrinogen and red-cell aggregation.  I am not prepared to accept that a platelet count over 400,000 would make no contribution, even if many of the PCI related infarcts are within a range of 150-300,000.  I don’t know how much power there is in the discussion.  The role of tissue factor (plaque), and of platelets in hemostasis is undeniable.

The industry does look for every opportunity to seize on promising biomarkers.  The coagulation assays developed at Dade-Behring (Dade, Dupont Division; then Dade) were far better and more explanatory that the “sed rate”.  The sed rate measurement requires that you set up graduated tubes to watch the rate of sedimentation.  It is not a walkaway procedure.  Industry has been so good at introducing automation that led to high volume efficiency, that this led to the only part of hospital operations that had good accounting measures.  The long trip to reducing personnel, but of course the profiles were a piece of cake.  I continually reorganized to carve out services for immunology and toxicology, which took longer to get automated.

The only use for sed rate now is for Temporal Thrombosis (?).

In the early days Yale NH Hospital had some 5 Perkin Elmer HPLCs to measure calcium.  Electrophoretic separation of isoenzymes was not helpful for managing patients.  The procedure was run batchwise once a day.  I was the first in CT to be running the immunoassay three times a day on the Roche COBAS Bio CFA., and Dupont put it on the ‘aca’.  A med tech could run it at 3 am  at Detroit Receiving, Bellevue, or Cook County, when the phone didn’t stop ringing for STAT results.

Physicians had expectations too.  So we had the progression from AST, LDH, and CK to isoenzyme MBCK, and then there were the cancer biomarkers – CEA, CA-125, PSA, with much to be discussed.

 

Q&A is derived from the following Article in

MedPage Today

Published: January 07, 2013

Fibrinogen Level Tied to Poorer PCI Outcomes

By Todd Neale, Senior Staff Writer, MedPage Today

Published: January 07, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

An elevated serum fibrinogen level predicted worse short-term ischemic outcomes among patients undergoing elective percutaneous coronary intervention after pretreatment with clopidogrel, researchers found.

Significantly higher levels of fibrinogen were seen in patients with periprocedural myocardial infarction (MI) defined by either creatine kinase-myocardial band (CK-MB) or troponin (P<0.02 for both), according to Ehtisham Mahmud, MD, of the University of California, San Diego, and colleagues.

Those relationships remained consistent after adjustment for several factors, including platelet function, which was not itself associated with periprocedural MI, the researchers reported in the Jan. 8 issue of the Journal of the American College of Cardiology.

“The results of the current study suggest that an elevated fibrinogen level…is related to significant platelet cross-linking and thrombus formation independent of residual P2Y12 receptor-mediated platelet activity during clopidogrel therapy,” they wrote.

Higher risk of ischemic cardiovascular events has been observed with both high platelet reactivity after thienopyridine treatment and elevated serum fibrinogen.

“As an acute phase reactant involved in the final common pathway of the coagulation cascade and essential component of platelet cross-linking in thrombus formation, fibrinogen possesses a clear biological mechanism for its adverse cardiovascular effects,” Mahmud and colleagues wrote.

In fact, high levels of serum fibrinogen have been shown to contribute to high platelet reactivity during clopidogrel treatment, resulting in uncertainty about whether insufficient platelet inhibition and elevated fibrinogen levels are independent or interactive risk factors for ischemic events.

To explore the issue, the researchers looked at data from 189 patients undergoing elective PCI who were pretreated with clopidogrel, defined as 75 mg daily for at least 7 days or a 600-mg bolus at least 12 hours before study enrollment. The mean age of the patients was 63.8 and most (74.1%) were male.

Nearly two-thirds (63%) had undergone a previous PCI, and 18% had undergone revascularization with coronary artery bypass grafting (CABG).

Baseline platelet function was measured using the VerifyNow P2Y12 assay. Markers of ischemic myocardial injury, including troponin and CK-MB, were measured every 8 hours after PCI until hospital discharge.

Periprocedural MI defined by troponin I or T occurred in 13.9% of patients. Those who had an MI had significantly higher levels of fibrinogen (363.1 versus 309.1 mg/dL, P=0.017).

The rate of CK-MB-defined periprocedural MI was 5.8%. Patients with that outcome also had elevated levels of fibrinogen (403.4 versus 313.5 mg/dL, P=0.007).

Both differences remained significant after multivariate adjustment that accounted for platelet function and other inflammatory markers.

The researchers found that a fibrinogen level of 345 mg/dL or higher — a cutoff identified as having optimal combined sensitivity and specificity for CK-MB-defined periprocedural MI — was associated with periprocedural MI defined by either troponin or CK-MB (P<0.04 for both).

Those relationships were stronger when systemic inflammation was low (C-reactive protein ≤0.5 mg/dL).

The platelet reactivity measurements were not associated with either definition of periprocedural MI, which is inconsistent with the findings from several smaller studies. The authors noted, however, that “the significance of these negative findings may be limited due to inadequate study power.”

In discussing the limitations of the study, the researchers pointed out that “the findings … do not provide insight into whether the relationship between high platelet reactivity and ischemic cardiovascular events demonstrated in previous studies is a direct one or mediated through the effect of serum fibrinogen.”

To get to the bottom of that, they wrote, “future studies relating platelet reactivity and adverse cardiac events should measure baseline fibrinogen.”

Mahmud has received clinical trial support from Accumetrics, Eli Lilly, and sanofi-aventis, and is on the speakers bureau for Medtronic. One of his co-authors is a consultant for Abbott Vascular, Boston Scientific, St. Jude Medical, Medtronic, and sanofi-aventis.

From the American Heart Association:

• ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention

Primary source: Journal of the American College of Cardiology
Source reference:
Ang L, et al “Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention” J Am Coll Cardiol2013; 61: 23-34.

---

Add Your Knowledge ™

Todd Neale

Senior Staff Writer

Todd Neale, MedPage Today Staff Writer, got his start in journalism at Audubon Magazine and made a stop in directory publishing before landing at MedPage Today. He received a B.S. in biology from the University of Massachusetts Amherst and an M.A. in journalism from the Science, Health, and Environmental Reporting program at New York University.

SOURCE:

http://www.medpagetoday.com/Cardiology/PCI/36734?goback=%2Egde_2184987_membe

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