Category Archives: Genomic medicine

“Turning the Tide” on HIV/AIDS

In advance of the upcoming XIX International AIDS Conference, the International AIDS Society and the University of California, San Francisco, have issued the “Washington D.C. Declaration,” a nine-point action plan aimed at broadening global support for “Turning the Tide” of the AIDS epidemic.

Everyone is urged to sign the Declaration.

It calls for:

1) An increase in targeted new investments;
2) Evidence-based HIV prevention, treatment, and care in accord with the human rights of those at greatest risk and in greatest need;
3) An end to stigma, discrimination, legal sanctions, and human rights abuses against those living with and at risk for HIV;
4) Marked increases in HIV testing, counseling, and linkages to services;
5) Treatment for all pregnant and nursing women living with HIV and an end to perinatal transmission;
6) Expanded access to antiretroviral treatment for all in need;
7) Identification, diagnosis, and treatment of tuberculosis;
8) Accelerated research on new tools for HIV prevention, treatment, vaccines, and a cure;
9) Mobilization and meaningful involvement of affected communities.

Turning the Tide is the theme of this year’s biennial conference, which will take place July 22-27 in Washington.  It is expected to draw 25,000 attendees, including HIV professionals, activists, politicians, and celebrities. Sir Elton John will open the conference and Bill Clinton will close it. A large delegation of U.S. members of Congress will participate, and Bill Gates will moderate a session. An enormous “Global Village” outside the D.C. Convention Center will be open to the public. “If you haven’t been, it’s a conference like no other,” conference cochair Dr. Diane V. Havlir said at a press briefing.

The recent optimism regarding HIV/AIDS stems from major advances in knowledge regarding prevention of partner transmission with early patient treatment, pre-exposure prophylaxis, and male circumcision as HIV infection prevention (new data will be released at the meeting), all of which are viewed as breakthroughs  in the fight against HIV/AIDS. “So we have now in our hands the tools. The question is how do we combine those tools together, and how do we roll them out,” said Dr. Havlir, professor of medicine at the University of California, San Francisco, and chief of the HIV/AIDS division at San Francisco General Hospital.

Dr. Diane V. Havlir / Photo by Miriam E. Tucker

Monday’s plenary session will include an address from Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, on “Ending the HIV Epidemic: From Scientific Advances to Public Health Implementation.” Other plenary topics during the week will include viral eradication, vaccines, TB and HIV, and HIV/AIDS in specific populations including minorities, women, youth, and men who have sex with men. On Friday, there will be a plenary talk that may be of particular interest to the primary care community, “The Intersection of Noncommunicable Diseases and Aging in HIV.”

Plenaries and other conference sessions will be webcast at http://globalhealth.kff.org/aids2012.

-Miriam E. Tucker (@MiriamETucker on Twitter)

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A Younger Kennedy’s Mental Health Crusade

Patrick J. Kennedy is no longer in Congress, but he’s still campaigning passionately on behalf of mental health. In a plenary talk at the annual meeting of the American Association for Geriatric Psychiatry (AAGP), the former democratic congressman from Rhode Island described his recent mission: An organization he founded called One Mind for Research, which “brings together the science, technology, financial resources, and knowledge required to create an unprecedented understanding of brain disease.” Its goal is to increase the investment in research by $1.5 billion each year for the next 10 years and to achieve a minimum 10% reduction in the cost of brain disease per year.

Courtesy of AAGP

The initiative was launched last May 25th on the anniversary of his uncle John F. Kennedy’s “Moonshot” speech, at the suggestion of his cousin Caroline. He said he told her at the time, “Great, instead of going to outer space, we’ll go to inner space!”

On a more serious note, Mr. Kennedy drew a parallel between President Kennedy’s focus on civil rights as a moral issue and the cause of the mentally ill, telling the audience of psychiatrists “What you all do in the field of mental health is to help lessen the marginalization of too many Americans…I think we have a historic opportunity now, with the implementation of the Mental Health Parity Bill and the [Affordable Care Act] to break down the segregation of mental health from overall health.”

Referencing his own struggles with substance abuse, depression and bipolar disorder and his role in Congress as chief sponsor of the parity bill, Mr. Kennedy decried the current insurance reimbursement system as being “wholly inadequate” for treating chronic mental conditions. “If we treated diabetics the way we treat alcoholics and addicts, we’d be waiting till we were cutting off their toes and they’d lost their eyesight before we paid for treatment,” he said, to applause.

He was equally emphatic regarding the politics involved in securing funding for One Mind’s 10-year plan. “If you consider how much money we put into neuroscience today compared to the burden of [mental] illness, any CEO in the country would be kicked out of their job for not doing enough research…it just doesn’t compute,” he said, again to applause.

He acknowledged there would be challenges. “I can’t tell you we’re going to be successful, but at least I’m going to do my part to see that we try something different.”

The AAGP plenary session was supported in part by an educational grant from Lilly USA, LLC.

-Miriam E. Tucker (@MiriamETucker on Twitter)

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H5N1: Keep That Genie in the Bottle

Throw out a hint of some meaty research and say “Don’t Ask! Don’t Tell!”  You might as well draw a map to the Christmas cache and tell the kids, “Don’t follow this trail!”

The U.S government seems to be engaging in the worst kind of this delusion by asking the journals Science and Natureto withhold the methodology sections of two important papers on H5N1 viral mutation.

Michele G. Sullivan/Elsevier Global Medical News

The papers, one by University of Wisconsin-Madison veterinary virologist Yoshi Kawakoa and one by Dr. Ron Fouchier of Erasmus Medical Center in Rotterdam, Netherlands, detail their work on avian flu H5N1 mutation. Each describes genetic engineering that created a new strain almost 100% lethal to ferrets — generally considered the best animals to model a human respiratory infections.

Presumably, Drs.  Kawakoa and Fouchier conducted their experiments with the goal of helping to protect mankind against the virus’ inevitable change. But the National Science Advisory Board for Biosecurity sees a dark side. The agency’s official plea to both journals suggests that publishing “the  methodological and other details … could enable replication of the experiments by those who would seek to do harm.”

Their concern is not unfounded: It goes without saying that an individual, or even  a country, could use this with evil intent.  A weaponized bird flu with a 90% or higher mortality rate would make the anthrax letters of  2001-2002 look like a scuffle in a kindergarten sandbox.

But is censoring going to keep this knowledge hidden?

Scientific discoveries almost always build upon prior knowledge in a long, nearly unbroken, chain of meticulous research. Researchers publish long strings of studies on the same topic, each one evolving just slightly from the last. Others with a passion for the same topic climb on board as well, so that eventually everyone benefits.

A clear representation of this? At least some of the research that so troubles our government has already been disseminated.

Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold). Courtesy the Centers for Disease Control and Prevention

Last year, Dr. Kawakoa described his lab’s creation of an H5N1 mutation almost universally lethal to ferrets.  The study describes his work with the two most virulent forms of H5N1, both isolated from humans and both with a human kill rate of up to 80%. Dr. Kawakoa and his colleagues manipulated the genes in both to create a novel virus that appeared even more lethal, killing all of the intranasally inoculated ferrets.

The paper not only identifies the genes — hemagglutinin (HA) and nonstructural protein (NS) — but the method of reverse engineering and  the modifications’ chromosomal positions. Its purpose was not to create a super-pandemic among humans, but to identify the genes and loci that most contribute to H5N1’s uniquely dangerous potential.

His new paper, according to the National Institute of Health’s  comment,  shows “that  the H5N1 virus has greater potential than previously believed to gain a dangerous capacity to be transmitted among mammals, including perhaps humans.”

Last September, Dr. Fouchier presented his now-to-be-edited work at the Fourth ESWI Influenza Conference. During an oral presentation, he described work that resulted in some potent H5N1 mutations. According to the conference daily, the researchers infected ferrets with the new H5N1, also formed by plasmid reverse engineering and also manipulating hemagglutinin.  The infected ferrets died, but didn’t transmit the virus.

The team then let the virus do its own thing,  just moving it repeatedly from a sick ferret’s nose to a healthy nose without tinkering – the way a virus would naturally mutate by adapting to each new host.  Dr. Fouchier found a new H5N1 with new mutations: It became an airborne form after 10 transmissions, suggesting that avian flu can mutate within one species, rather than requiring a “mixing bowl” animal, like a pig.

“This virus is airborne and as efficiently transmitted as the seasonal virus,” the paper quoted Dr. Fouchier as saying. “This is very bad news, indeed.”

The meeting wasn’t secret. Journalists were there, and some even wrote about it. New Scientist ran a piece about the research, as did Scientific American.

If this much information is already out there, might it just be possible that a “rogue scientist” could come up with much, much more? And is the National Science Advisory Board for Biosecurity really suggesting that only two scientists in all the world have so advanced this virus?

It might even be possible that there are labs in other countries working on the same thing. And that some of those countries might want to suppress important findings — holding them close the vest to “protect” the populace.

We wouldn’t want that now. Would we?

—Michele G. Sullivan

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SABCS: Paging Biomarkers STAT

Image courtesy of NIH (public domain)

The CLEOPATRA, BOLERO-2, and AVEREL trial results generated a lot of excitement (and confusion) in San Antonio at the annual Breast Cancer Symposium. Since the results were finally released,  these trials have been hot topics.  There’s good reason.

In the CLEOPATRA trial, the addition of pertuzumab to trastuzumab and docetaxel in previously untreated patients with HER2-positive metastatic breast cancer extended progression-free survival (PFS) by 6 months compared with trastuzumab and docetaxel alone. In BOLERO-2, the combination of everolimus and exemestane extended PFS by 4 months (local review) and by 7 months (central review) in women with ER-positive, HER2-negative breast cancer that is refractory to non-steroidal aromatase inhibitors. In AVEREL, the addition of bevacizumab to trastuzumab and docetaxel in women with HER2-positive, locally recurrent metastatic breast cancer also improved PFS — by 2.8 months (local assessment) and by 2.9 months (central assessment).

This is all great news but biomarkers to identify the patients who actually benefit the most from these new regimens would be even better news. All three presenters at one press conference — Dr. Luca Gianni, Dr. Gabriel Hortobaygi, and Dr. Jose Baselga — stressed the need for these tools. All three of these trials involved exploratory components to assess potential biomarkers to predict response.

“The common theme … of our three studies is that we have a challenge with the development of new drugs in identifying biomarkers that will determine which is the group that can be enriched and will derive the lion’s share of the benefit of adding drug X,” said Dr. Hortobaygi. “None of our new drugs in this panel has such a biomarker as yet. There is much work being done in all three studies to try to identify biomarkers that will help us to do that,” he said.

“That continues to be one of the major challenges for bevacizumab. We did not have a biomarker that can tell us that we can treat less than 100% of patients to observe the benefit. I think that most of us on this panel believe that most of these drugs provide benefit to a subset of patients and not to everybody. That is an ongoing challenge and we really need to invest in and redouble our efforts, so that we can develop those biomarkers,” he added.

Dr. Gianni told me that a biomarker for bevacizumab seriously could help with drug development. “If there was a biomarker, this combination could become very, very promising and would deserve analysis, head to head with other very active treatments in the case of HER2-positive disease.”

Image courtesy of NIH (public domain)

Dr. Howard A. Burris III told me that it makes sense based on what we already know that not every patient will benefit from the same treatments. “We know that not all ER-positive women are the same. The BOLERO-2 trial looked at adding the mTor inhibitor everolimus to exemestane in patients with ER-positive breast cancer. [However], you’ve got patients that have 10% ER overexpression and some that have 100%. Then you’ve got groups of patients who relapsed after the adjuvant therapy, so they didn’t have a long-lived response, and some that have had d great response in the metastatic setting. Those patients are not at all alike,” he said.

“I think we’re going to find that there isn’t this one size fits all and I think that the closer we get to this idea of having a panel — where you’re going to find out what the various overexpressions are for these patients — the clearer we’re going to be about who should get what.” Dr. Burris is the chief medical officer and the director of drug development at the Sarah Cannon Research Institute in Nashville.

“The primary toxicity, interestingly, for many of the new biologics is the financial toxicity. So it’s perfectly acceptable to give a relatively expensive therapy to the 10% of that it’s going to benefit greatly. The shame is that you can’t treat 10 patients to help that one patient who will benefit most. Somewhere in between is a societal decision,” Dr. Burris said.

“I think we’ve got to get closer to the idea that when a woman gets her original biopsy or surgery that you learn everything you can about that patient; then, at the time of relapse — if that’s unfortunate enough to occur –- if possible get a biopsy to see what’s changed; but if not, at least your first attempt in treating that relapse is going to be in the right direction. Identifying who’s the group at highest risk for relapse or who needs to stay on therapy longer are all going to be factors that are going to be important going forward,” said Dr. Burris.

Dr. Gianni noted that it’s easy to envision that these regimens potentially could be used earlier in the disease progression for women with breast cancer, who are identified by a biomarker to respond well to one of these regimens. It makes sense that these regimens could be used earlier for women identified by a biomarker to respond well to one of these regimen, he said.

Kerri Wachter

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At 25 Years, NIAMS Celebrates Progress, But Has a Long Way to Go

It’s been 25 years since the establishment of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and great strides have been made in diagnosis, treatment, and management of numerous conditions, “but you ain’t seen nothing yet,” said Dr. Francis Collins, director of the National Institutes of Health.

Opportunities for medical research have never been as great as they are today, said Dr. Collins, who gave the welcome address for NIAMS’ 25th anniversary at the NIH campus in Bethesda, Md.

Although prominent researchers in the field agreed that research has come a long way in the past 25 years, they stressed that there is still a long way to go. Currently, the molecular basis for 4,000 diseases is known, said Dr. Collins. “But we have effective treatment for only 200.”

In broad strokes, the day-long event touched on the past, present, and future of major diseases of bones, joints, muscles, and skin – including muscular dystrophies, osteoporosis, rheumatoid arthritis, and lupus – through panels and discussion involving prominent researchers, physicians, and patient advocates.

“These diseases are chronic, crippling, and common,” said Dr. Stephen Katz, director of NIAMS, in his opening address. “They affect every family in the United States.”

Among the attendees were many researchers and clinicians who said they felt loyalty and appreciation for receiving funding from NIAMS at some point in their career. For some, the progress in the past 2 decades was quite tangible.

“Public investment in osteoporosis research has really changed how we take care of the patients,” said Dr. Sundeep Khosla, president of the American Society for Bone and Mineral Research. Dr. Khosla, professor at the Mayo Medical School, Rochester, Minn., recalled a time more than 2 decades ago when calcium, vitamin D, and estrogen were the only options he could offer to patients with osteoporosis.

A few years later, bisphosphonates became available, then came anabolic drugs, and now more drugs are in the pipeline. Patient diagnosis also has advanced, he said. Although he agreed that the field still has a long way to go, he was optimistic about more progress. “Who knows what will happen in the next 25 years?” he asked.

There was talk of individualized therapy, balancing research and treatment, and a closer collaboration among scientists, all in the spirit of bringing better diagnosis and treatment to patients.

“We’re in a different world from when all we had was aspirin,” said Dr. Daniel Kastner, a scientific director at the National Human Genome Research Institute. “But what we really want is a cure. And we’re not there yet.”

Naseem S. Miller (@ReportingBack)

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Can You Keep a Secret … at Medical Meetings?

Image courtesy of Flickr user velo_city (CC)

Tuesday morning I sat through the late-breaker session at the annual meeting of the American Society of Hypertension.  The last two oral abstracts were based on work from the International Consortium for Blood Pressure Genome-wide Association Studies (GWAS), whose goal is to identify genetic variants in known and novel genes that influence blood pressure in the general population. In the first talk, Dr. Mark Caulfield discussed the consortium’s methodology and the indentification of 29 single nucleotide polymorphisms (SNPs) associated with blood pressure — 16 of which were at novel loci.

In the second talk, Dr. Daniel Levy discussed the development of a genetic risk score that incorporated all 29 alleles identified in the GWA and the score’s associations with several blood pressure-related clinical outcomes (such as target organ damage and cardiovascular events).  Before doing so though, he asked everyone in the audience to refrain from photographing the slides or recording the presentation due to an upcoming publication of the study.

As a reporter, I don’t consider myself bound by such requests for secrecy.  If it’s presented in a public forum, it’s fair game in my book. 

My question is to physicians, many of whom are now quite well-published themselves, thanks to everyman’s news outlets — blogs and social media.  Would you refrain from discussing the study in a widely-read (or completely unknown) blog or online forum?  Are you going to scoop reporters, who comply with the request? Do you think that such requests slow medical research?

We really want to know what you think.

Kerri Wachter

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Whose Rights Are at Stake?

The Supreme Court heard arguments Tuesday in support of the 2007 Vermont statute limiting the release of the information detailing which drugs doctors prescribe. This information is maintained by pharmacies, which sell it to data-mining agencies, that in turn sell it to drug companies, for marketing purposes. Patient information is excluded from the data, doctor’s information is not.

Under the Vermont law, this information can be released only with the consent of the doctor. However, once data collection firms like IMS Health and interested parties like Pharmaceutical Research Manufacturers of America, challenged the statute, the issue became a question of free speech.

In the case of Sorrell v. IMS Health Inc., data-mining firms claim they have First Amendment rights to buy and sell the information for their marketing use.

However, the state’s attorney’s office likened the release of the confidential information to disclosing a doctor’s tax returns, patient files, or a competitor’s business information, arguing that First Amendment rights in the case apply to protecting doctor’s information. But since the information is given away to parties including insurance companies, journalists, and law enforcement, the court wasn’t too convinced.

” … just don’t tell me that the purpose is to protect their privacy,” said Justice Antonin Scalia. “[A doctor's] privacy isn’t protected by saying you can’t sell it but you can give it away.”

Justice John Roberts said Vermont is trying to reduce health care costs by “censoring” information doctors hear about brand-name drugs, with the intent that they will prescribe more generics, a measure Justice Scalia added was a restriction on free speech.

Vermont Assistant Attorney General Bridget Asay responded that “the purpose of the statute is to let doctors decide whether sales representatives will have access to this inside information” on the prescribing habits of physicians.

Attorneys general of several states, the federal government, AARP, medical associations, privacy groups, and the New England Journal of Medicine have filed briefs in support of the Vermont statute, according to a brief by Cornell (N.Y.) University Law SchoolThe National Association of Chain Drug Stores, the Association of National Advertisers, the Associated Press, and Bloomberg have filed in support of the data mining firms.

In an age in which personal data can mined through social networks and search engines, this case could set the precedent concerning how much personal information can be used for marketing. A decision is expected by June.

 Tell us what you think. 

–Frances Correa (@FMCReporting on Twitter)

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Genetic Diseases Lurk in All Prospective Parents

A woman and a man with no personal or family history of a severe, recessive, childhood-onset genetic disease still face a roughly 1 in 1,500 chance of giving birth to a child affected by a severe, genetic disease simply due to the chance pairing of mutations that each parent unknowingly carries.

Genetic screen result showing deletion causing Lesch-Nyhan syndrome/courtesy Stephen Kingsmore and Science Translational Medicine

Will those odds motivate prospective parents to get themselves screened before conceiving a child, to learn whether they each carry a recessive mutation in the same gene?

It’s a choice that parents-to-be may soon face, thanks to a wide-ranging carrier screening test reported today by researchers at the National Center for  Genome Resources in Santa Fe and their associates.

The team, led by Dr. Stephen F. Kingsmore, report their findings with a test that screens for mutations in 448 different genes that can each lead to a severe, recessive childhood disease. Five of these diseases already have preconception screens that are usually offered to selected, higher risk people: fragile X, cystic fibrosis, Tay-Sachs disease, Canavan disease, and familial dysautonomia. By applying a panel of state-of-the-art genetic-testing technology, Dr. Kingsmore and his coworkers expanded their screening net to include 443 additional genes and diseases, including 142 metabolic disorders, 122 neurologic defects, 46 genes that affect development, 45 with cutaneous presentations, etc. In an interview, he told me that while today’s report focuses on screening 448 genes, the actual total now possible has grown to 580 different genes and resulting disorders. I’m sure over time the list will grow even longer.

In the current paper they applied the 448-gene screen to 104 people, and found that each person carried, on average, 2.8 mutations. Although several subjects had known genetic disorders, correcting for this skewing still produced the estimate that any adult carries, on average, 2.8 recessive gene mutations even if they appear completely healthy and have absolutely no personal or family history suggesting they might be a carrier. In short, everyone harbors some genetic flaws hidden within their cells that can unexpectedly appear in their children if their partner contributes a mutation in the same gene.

Mathematically, a recessive, genetic-mutation burden of 2.8 per parent out of 448 genes works out to a 1 in 25,000 risk for having an affected child, but the actual risk is much higher because everyone has some genetic skewing that boosts the risk. For example, people with Northern European ancestry have a 2.5% rate of carrying a mutated cystic fibrosis gene. As a result, the overall risk for any seemingly healthy couple with no affected family members is one in 1,500.

With a risk as significant as that, Dr. Kingsmore and his associates call for making preconception genetic screening available to everyone, not just those with a pedigree that seems to put them at higher risk. They also noted that the tests they ran cost $378 per person, a price that could drop with higher volume. But the cost of testing also must include the added fees for test interpretation, results reporting, and genetic counseling.

—Mitchel Zoler (on Twitter @mitchelzoler)

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Remembering the Father of Erythropoietin

Biochemist Eugene Goldwasser, who had the drive and tenacity to spend more than 20 years isolating the first minute amounts of human erythropoietin, died at 88 last Friday, December 17. After Dr. Goldwasser and his lab staff isolated a few milligrams of the protein in 1977, he  eventually decided to collaborate with Amgen and in 1980 allowed them to start using some of his precious isolate to hunt for the gene. Amgen cloned the gene in 1985, and then began marketing the gene product as Epogen in 1989.

image courtesy of Flickr user with a hook

One of his colleagues at the University of Chicago, Dr. Donald Steiner, called Dr. Goldwasser’s isolation of erythropoietin a medical landmark similar in importance to the discovery of insulin. Although erythropoietin has gone through rocky times recently, with evidence of adverse effects curbing its use and dropping sales, the various marketed forms of  erythropoietin continued this year to tally billions of dollars in sales and substantial clinical benefits in patients with anemia.

I first learned of Dr. Goldwasser’s death in an obituary I read this morning, and subsequently I found several other pieces about him on the web. These include obits from the University of Chicago, The Chicago Tribune, The New York Times, and journalist Merrill Goozner, who wrote about Dr. Goldwasser’s work in a 2004 book on drug development. Also, a  remembrance by Dr. John Henning Schumann, a Chicago colleague and friend. Taken together, they sketch a committed, multi-faceted man motivated by a scientific challenge and a desire to help advance medical care.

For me, two nuggets from the write-ups standout. First is the vignette of of Dr. Goldwasser meeting a Japanese researcher in the lobby of Chicago’s Palmer House Hotel in 1975 to accept a modestly-sized box that inside held the dried concentrate of 2,550 liters of urine collected from patients with aplastic anemia. Over the next couple of years, Dr. Goldwasser and his associates purified from this gift a few milligrams of human erythropoietin, the first isolation of the human protein and a key step on the path toward cloning the gene and large-scale production.

Second is the poignant story of how both the University of Chicago and Dr. Goldwasser failed to patent erythropoietin, allowing Amgen to become the owner of this very valuable franchise. The University’s omission sounds like an oversight, but for Dr. Goldwasser it was a conscious decision to sidestep the fortune he could have claimed.

“Gene never profited from his discovery, the way that scientists and inventors now clamor to patent everything in sight,” wrote his friend Dr. Schumann. “He believed that his discovery should be shared with the public; after all, the government had funded his research career–he figured the taxpayers ought to get the benefit of his discovery.”

It was an act that recalls a more innocent era in biomedical research. Filing for patents “was not generally done at the time,” said his University of Chicago colleague, Dr. Gary Toback, who added, “He was someone who took enormous delight in doing science.” Soon after Dr. Goldwasser’s death his son said: “He was first and foremost a scientist and he was gratified that he was able to make such a great contribution.” For a person like that, the thrill of having his 20+ year quest fulfilled and seeing the subsequent impact erythropoietin had on clinical practice must have been payback enough.

—Mitchel Zoler (on Twitter @mitchelzoler)

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Making Genotype a Routine Part of Drug Prescribing

Perhaps the boldest move to date to apply genotype information to drug prescribing, and to do it in a timely way to optimize the treatment a patient receives, launched in September at Vanderbilt University Medical Center in Nashville.

Vanderbilt physicians began routinely asking patients scheduled for coronary catheterization if they’d agree to have a small cell specimen genotyped using a commercially available chip that screens for 184 genetic polymorphisms that help determine the way a person metabolizes various prescription drugs. They decided to start with patients undergoing coronary cath, because many of these patients wind up getting a coronary stent and then require prolonged treatment with antiplatelet drugs, usually including clopidogrel. Some patients have a polymorphism in the gene for a protein involved in clopidogrel activation that impairs efficacy. Those patients either get a boosted clopidogrel dose or the pricier alternative, prasugrel. By mid November, 300 patients had undergone genotyping, with 10 poor metabolizers identified who received an alternate regimen.

image courtesy of Flickr user JaypeeOnline

Next up for expanding the program are patients scheduled for hip or knee replacement, because after surgery they’ll all go on an anti-coagulant drug, traditionally warfarin. Genotyping can help guide warfarin dosing during the first few days of treatment. (Since October, though, many patients began receiving dabigatran instead, an anti-coagulant that sidesteps the genotyping issue.)  Future patients to add to the genotyping list include those who are on or may soon start tamoxifen, azathioprine, 6-mercaptopurine, abacavir, codeine, or “virtually every antidepressant and most antipsychotics,” said Dr. Dan M. Roden, assistant vice-chancellor for personalized medicine at Vanderbilt and a driver and shaper of the program.

Although during rollout the program targets patients with a specific, imminent need for a certain drug, the broader concept is to have genetic information about variations in drug metabolism embedded in each patient’s medical record, so that it can automatically come into play whenever the patient gets prescribed a drug. “In the long perspective, it’s every 50-year-old,” because over the rest of ther lives they all stand a decent chance to receive some drug that carries a pharmacogenetic backstory, said Dr. Roden when I spoke with him last month in Chicago at the annual Scientific Sessions of the American Heart Association. Vanderbilt put “a huge amount of money into this,” he added, and it’s hoping to eventually persuade payers to foot the bill. So far Vanderbilt has supplied all the funding, because it believes this will improve outcomes and is also a great marketing tool.

A key element of Vanderbilt’s launch, which it says is the world’s first such program, was the careful wording of the alert that physicians get when their electronic pad identifies a patient with clopidogrel-activation deficiency. The pop-up’s text followed “a year of negotiations between lawyers, pharmacologists, pharmacists, and interventional cardiologists,” Dr. Roden said.

—Mitchel Zoler (on Twitter @mitchelzoler)

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