Latest Drugwonks' Blog
I am still colelcting my notes and my thoughts and will report on what the various speakers (including the FDA's Janet Woodcock, Jane Axelrad) had to say. In the meantime, let me commence this reportage with my own opening remarks:
When I told my wife -- who is not in this line of work -- that I was chairing a conference on REMS, she asked me what I was doing at an event about rapid eye movement.
A common question I get about REMS is – how is it different from what we used to call RiskMAPS? I see two main differences. The first, obviously and importantly, is that REMS has actual legislative language. And that’s an important detail – but it’s one-dimensional.
While I agree that REMS does indeed represent an expansion of the FDA's authority, I do not agree that it is either ill advised or an over-extension of the agency’s purview.
Their latest attempt to muddy the waters of FDA labeling authority comes in the form of internal FDA documents that, Waxman staffers claim, show career officials oppose agency regulations that weaken consumers' ability to sue drug makers.
Here’s one quote they’re using to make the case for “the FDA doesn’t believe in preemption" ...
"Much of the argument for why we are proposing to invoke preemption seems to be based on a false assumption that the FDA approved labeling is fully accurate and up-to-date in a real time basis," the report quoted Dr. John Jenkins, who oversees FDA's new drug reviews, as saying. "We know that such an assumption is false."
Nobody ever claimed that any FDA label is fully accurate. Such an assumption is indeed false – but nobody has ever said different. What supporters of preemption do say is that the FDA carefully considers the scientific evidence relating to any proposed warning, as well as the public health consequences of including or omitting particular language from drug labeling or advertising. Those who support preemption believe that a drug’s FDA mandated label deserves deference from courts and juries applying state tort law.
John Jenkins is right. But that doesn’t make preemption wrong.
The next “smoking gun” statement comes via Jane Axelrad, an associate director for policy at the agency, who wrote: "We rarely find ourselves in situations where sponsors want to disclose more risk information than we think is necessary," she said. "To the contrary, we usually find ourselves dealing with situations where sponsors want to minimize the risk information."
Jane’s right too. But that doesn’t change the argument for preemption. Of course drug companies would prefer to minimize risk information – and they make their arguments based on sound science. Sometimes the FDA agrees, other times they do not.
Labeling can and must be a valuable tool for improving and protecting America’s health. That’s the law. The FDA is concerned that current labeling practices are in direct counterpoint to the principle objective of current regulations, to facilitate a doctor’s ability to “rationally prescribe” any medical product approved by the FDA. Rational prescribing occurs when a health care professional orders an approved prescription drug or biological product in circumstances where the risk/benefit profile of the product is optimal. The FDA’s most potent weapon in the battle for accurate, timely, “rational,” prescribing is clear, approved labeling.
The FDA’s legal and legislative authority over labeling for prescription drugs and biological products is plenary. The Federal Food, Drug, and Cosmetic Act establishes mandatory and prohibited labeling content and manufacturers have no choice but to comply with these requirements. Less obvious, but equally important, is the principle that the Act also constitutes a “ceiling.” In other words, a manufacturer cannot add risk information to labeling unless the FDA has specifically granted its permission.
The FD&C Act clearly gives the FDA the authority to decide whether or not a product, when used properly, is safe, effective, and properly labeled. A product, used as described in FDA-approved labeling, should be considered safe and effective throughout the United States. Preemption is a well-recognized doctrine of constitutional law derived from the Supremacy Clause and analyzed by the Supreme Court in several cases. Federal law preempts state law here because FDA intends for federal regulation to be exclusive and preemption does not exceed statutory or constitutional limitations.
The “leaked” documents being aggressively peddled to the media change the sound legal and public health argument for preemption not a whit. What it does show is that there is a robust and collegial debate within the agency on this matter. Taking these conversations out of context, as is now being done by members of Mr. Waxman’s staff, just shows how desperate they are – and how weak their intellectual arguments.
"Honest differences are often a healthy sign of progress. "
-- Mahatma Gandhi
But – and it’s a big but -- NICE, the National Institute of Clinical Excellence, is expected to introduce a big increase in the threshold to assess whether such treatments for relatively rare conditions are cost-effective.
In other words, NICE is going to even further restrict access to critical care – particularly for cancer patients.
Alan Johnson, the health secretary, told the Daily Telegraph at the weekend he wants "a fair system that doesn't deny people essential treatment unduly.”
Welcome to “benevolent government healthcare.”
What's troubling is that Cong. Carolyn Maloney wants to do randomized trials to compare autism rates between groups of kids vaccinated with thimerosal preserved shots compared to those without.
Of course this is the handiwork of David Kirby and other anti-vaccine freaks who know they can tease out of any data the slightest link and build their case in court. The scientific community should say "no" to this pseudo-experiment.
http://invivoblog.blogspot.com/
Lest anyone forget, Light tried to pass himself off as an adviser to President Bush in powerpoint presentations he made in support of price controls and drug importation by virtue of becoming an on-line member of some Republican donor's circle.
Here's the story of LIght's slimeballing, his willful spreading of a lie and how on-line members of the unhinged anti-pharma army ran with the rumor that Light's personal attack was being "silenced."
Read more here
If you visited the Web site of the student-run Harvard Health Policy Review last week, you would be greeted with the words "Access forbidden!"
On Monday, rumors soon began circulating on the pharmaceutical blogs Pharmagossip and Gooznews that a higher authority had pulled the plug on access after the journal published a scathing attack in September on three Harvard professors who edit the Journal of Health Economics and serve as faculty advisors to the Review.
Not true, Review editor-in-chief Kevin Huang told The Scientist. While the dispute led one Harvard economist, Richard Frank, to resign from the journal's advisory board, the decision to temporarily take the Web site down was made by student editors. "When the article broke," says Huang, "I really had no idea what was going on." The article had been handled by a senior editor, and he wanted read it and discuss it with the group. "Now, when I look at the situation, it was really one-sided, and as a journal, we do want to be balanced." (The Review is not peer-reviewed.)
The disputed article, "Ethical Standards for Healthcare Journal Editors: A Case Report and Recommendations," was written by Donald Light of the University of Medicine & Dentistry of New Jersey and Rebecca Warburton of the University of Victoria. It vividly describes their frustration trying to publish a critique of a 2003 estimate of drug development costs in the Journal of Health Economics.
That estimate, published in the JHE by Joseph DiMasi at the Tufts Center for the Study of Drug Development and two colleagues, put the price for bringing a new drug to market at $802 million. But Light and Warburton wanted to argue that DiMasi's team had worked off of pharmaceutical funding since the mid-1970s. Plus, they believed the team relied upon unverifiable data, and made questionable assumptions. Instead of publishing their letter, Light and Warburton allege, JHE editors defanged their critique and were overly generous with space granted for the original authors' response. Light and Warburton demanded an additional rejoinder, and only achieved their goals after threat of legal action. "The editors of JHE violated, in our opinion, almost every ethical standard established for editors," they write, "Yet they remain accountable to no one."
Light told The Scientist he chose to vent his tale in the Review because "It seemed like an interesting journal and it was on their own turf." He felt his sharply worded critique was important because "The DiMasi results continue to be cited by journalists, policy-makers, congressional bills, and by reports by the Department of Commerce protecting the American market from lower drug prices in other countries."
JHE editor Thomas McGuire told The Scientist that Light and Warburton's accusations are "far-fetched" and "bullshit," and says he was initially glad to accept the Light and Warburton article but wanted to scrub it of "personal attacks" against DiMasi.
A major point of contention sprang from the journal's standard policy for handling conflicts-of-interest: Although the Tufts Center is openly funded with drug money, authors only need to disclose direct sources of project funding. McGuire felt that questioning DiMasi's "motives" and emphasizing this potential conflict was unfair in light of the journal policy. "[Light] has been quite personal in his attacks on the original authors and on me, and it was clear he was on a mission here," said McGuire, who does not accept money from drug companies.
Light also asserted that McGuire gave DiMasi et al the "last word." But McGuire contended that is standard practice when authors respond to a published study.
Even so, JHE editors felt that many of Light's claims were reasonable. The assertion that the drug data are unverifiable, for instance, had been noted by editor Richard Frank in an editorial that accompanied the original DiMasi et al paper. "I think there are some real conflicts-of-interest out there," Frank said, "I don't have a problem with trying to insist on disclosure." He added that he also made cuts to the DiMasi reply that he felt were personal.
The JHE editors are in discussion with the Review about publishing a reply or posting their response online.
As for Light, he appears to be spreading the Harvard censorship rumor. In an October 18th email sent to a colleague and obtained by The Scientist,Light wrote, "Someone, it seems -- the Harvard University Administration? -- has decided to protect its three full professors who censored critics of the pharmaceutical industry by blocking out all access to the case and the evidence."
This morning (October 21), the Review posted a more heartening message on its Web site: "We have taken down our website temporarily to update it. We hope to have it up very shortly."
--Brendan Borrell
mail@the-scientist.com
Correction (October 22): In the original version of this story, we incorrectly referred to Merrill Goozner's blog as Goozner News. The blog's true name is Gooznews. The Scientist regrets the error.
Read New York Times Article here
In today’s Wall Street Journal, reporter Alicia Mundy begins her article on Wyeth v. Levine as follows:
And here’s former FDA Chief Counsel Dan Troy’s opinion:
“Judgments concerning the need for and formulation of statements in drug labeling and advertising are squarely within FDA’s statutory authority and expertise, and they deserve deference from courts and juries applying state tort law. The agency carefully considers the scientific evidence relating to a proposed warning, as well as the public health consequences of including or omitting particular language from drug labeling or advertising. FDA should not have to act to safeguard its control over the label each time a plaintiff brings a state law action challenging the absence of a particular warning in drug labeling. Where FDA repeatedly has reviewed particular drug labeling and advertising content, state courts and juries should not second-guess the agency’s scientific determinations. FDA’s legal authority over drug labeling and advertising is broad, and its expertise is unmatched. The agency’s decisions on the content of these communications deserve substantial deference from courts applying state tort law in product liability cases that challenge the adequacy of drug warnings.”
It should also be noted that the FDA has consistently stood behind the concept of preemption through both Republican and Democratic administrations – so any mention of “the Bush FDA pushing preemption” is just bad reporting.
Recently, the 3rd U.S. Circuit Court of Appeals ruled that federal law bars a suit alleging false-advertising claims under state law because the U.S. Food and Drug Administration has "exclusive authority" to regulate prescription drug advertising.
"To allow generalized state consumer fraud laws to dictate the parameters of false and misleading advertising in the prescription drug context would pose an undue obstacle to both Congress' and the FDA's objectives in protecting the nation's prescription drug users," U.S. Circuit Judge D. Brooks Smith of the Western District of Pennsylvania, wrote in his 51-page opinion in Pennsylvania Employees Benefit Trust Fund, et al. v. Zeneca Inc.
Further, U.S. Solicitor General Paul Clement issues an opinion to the U.S. Supreme Court supporting federal preemption, saying that FDA-approved drug labeling preempts state law.
Specifically, Clement disagreed with the Vermont Supreme Court’s ruling that a patient could sue Wyeth over the labeling of its anti-nausea drug Phenergan (promethazine). In the case of Wyeth v. Diana Levine, Clement opined that the state court, “erroneously interpreted” the law by saying the FDA’s approval of a drug label is only a “first step.” He also noted that federal law prohibits a company from unilaterally changing the FDA-approved label.
Clement writes, “If manufacturers were free to make unilateral changes to labeling the day after the FDA’s approval, based on information that was previously available to the FDA, the approval process would be greatly undermined and the agency’s careful balance of risks and benefits thwarted.
Press candidates on electronic medical records
Adopting health information technology will require the knowledge and resources of both the public and private sectors. But health IT will usher in a new era of medicine, improving communication among physicians, helping doctors discover health problems before they grow severe, and allowing medical staff to come up with personalized treatment options. Reforms like this hold enormous potential for reducing healthcare costs and improving the quality of life for millions of Americans without sacrificing valuable programs such as Medicare. Let's hope the candidates give them the attention they deserve.
PETER PITTS
The writer is president of the Center for Medicine in the Public Interest, and a former associate commissioner of the Food and Drug Administration.
Some of us hoped that by reforming his party, which has grown so unpopular, McCain could prove that he could reform the country.....
In some sense this whole campaign was a contest to see which party could reach out from its base and occupy that centrist ground. The Democratic Party did that. Senior Democrats like Robert Rubin, Larry Summers and Jason Furman actually created something called The Hamilton Project to lay out a Hamiltonian approach for our day. McCain and Republicans stayed within their lines. There was a lot of talk about earmarks. There was a good health care plan that was never fully explained. And there was Sarah Palin, who represents the old resentments and the narrow appeal of conventional Republicanism.
For those interested, the total number of articles Brooks wrote about the McCain health plan was zero. That's one less than the one he wrote fully explaining Hillary's single payer system...
http://select.nytimes.com/2007/09/18/opinion/18brooks.html
But let's go to the Hamlton project that lays out that Hamiltonian approach Brooks and other pastel Republicans hunger for. Medicare in particular.
Here's what the "centrists" have in mind for the Medicare prescription drug benefit according to
"To encourage price competition and discourage adverse selection, Medicare should allow competition for exclusive contracts to sell the standardized plans in each Part D region. To address the stresses on the federal budget, prices paid for drugs purchased on behalf of beneficiaries previously covered by Medicaid should be reduced to near their former Medicaid levels. To limit the ability of manufacturers to name their prices of therapeutically unique drugs, a standby mechanism for establishing temporary administered prices should be developed."
If you go through the position paper, Frank and Newhouse, two smart people who know better in my opinion, recommend price controls on breakthrough drugs based on the same approach taken by NICE in England. And they would give one drug benefit management firm the right to sell "standardized" plans to by region. That's a backdoor for a national drug formulary and robbing seniors of choice. They argue such a change is needed to encourage price competition, but how will reducing the number of plans increase competition? As for adverse selection, are Frank and Newhouse blind to the emergence of tools to drive patients to the right drug based on clinical and genetic criteria. As Mark McClellan has noted http://www.brookings.edu/papers/2007/04useconomics_frank.aspx
Revolutionaries
Merck's Free Radical
Cancer drugs don't help 75% of the people who take them. Stephen Friend says he can use science to end the crapshoot
In the downtrodden drug industry, Merck cancer guru Stephen Friend may be one of the last great dreamers. His latest idea is one that would completely change the secretive and siloed way the pharmaceutical business fights cancer: create a giant, open-to-the-public database that will include every cancer drug and every patient and how that patient is doing. Track everything and over time we might be able to raise the abysmal success rate of treatment.
Friend, 54, has been a doctor who treated kids with cancer, an academic, an entrepreneur and a biotech chief executive. He helped develop a diagnostic test that predicts whether breast cancer will return after surgery. For five years he has been in charge of getting cancer drugs invented at Merck. Now 8 are in clinical trials, up from one, with 15 more preparing to enter trials. Friend is still unsatisfied. Why is it that, on average, three out of every four people who take a cancer medicine get lots of side effects but no benefit?
Researchers have been too willing to bet on hunches, he says, yet the technology to understand the complex biology of cancer is at hand. Spurred by Friend, Merck has spent billions on an arsenal of technologies for understanding how genes work. The resulting data stream is sent through the fastest supercomputer in the drug industry, a beast that consumes 64 kilowatts of power and is capable of 16 trillion calculations a second. Friend thinks he can accurately predict how groups of proteins in tumors work together and use that information to kill the cancer. He's trying to drag the secretive world of drug-discovery chemistry into the computer age.
The Friend way would take all the data collected each year from the thousands of cancer patients entered in trials, make it anonymous and put it into one database, preferably held by the government but definitely accessible to any physician or scientist. Right now those data are lost to the wind once the trial is over. But by keeping track of patients' genes, the genes in their tumors and what drugs they take, scientists will be able to discern patterns. Instead of trying drugs in order, from the ones that work most often to those that work least often, doctors will be able to pick the medicine that is most likely to help a particular patient. New medicines will get to market faster, along with diagnostic tests that will predict what will work. Friend predicts, somewhat optimistically, that prescribing decisions won't be based on "a promotional campaign." The database will decide.
"That future world is coming," says Friend. "And pharmaceutical companies can live in that world. If you develop the best drug and develop it for the right patient, all this does is get it to that right patient."
Merck has not done much so far to open its trial data to the world, nor have its rivals, but Merck has less to lose here and more to gain. It has fewer cancer drugs in human tests than Pfizer or AstraZeneca, and its shares have dropped by half this year. Friend is powering ahead, building a first stab at the big database with the H. Lee Moffitt Cancer Center in Tampa, Fla. Over the next five years every patient who walks through Moffitt's door will be asked to put genes and tumor samples in a database that will number 100,000 patients; 5,000 are already in. The database will provide information to the doctors doing research there and, eventually, to patients. If it turns out you have a gene that tells researchers what drug will work for you, Merck and Moffitt plan to let you know. Experiments that would have required weeks of thawing tumor samples now take a matter of hours.
"Right now most of medicine is based on a bunch of gray-haired guys who say, 'This is the way I do it and it seems to work,'" says Moffitt Director Bill S. Dalton. "We need to determine over time what is useful and what isn't. The only way to do that is to study 100,000 patients."
The database idea is taking root elsewhere. The U.S. government is funding a Cancer Genome Atlas, in order to figure out how a large database would work. The Multiple Myeloma Research Consortium has funded the collection of 1,900 patients' bone marrow samples that are being studied by the mit-Harvard Broad Institute, a genetic research center. New data from that effort will be available within months.
A megadatabase "could save me months or years of trying to collect patient information," says Oregon Health & Science University oncologist Brian Druker, who helped get Novartis' potent tumor-fighter Gleevec to the market. But he questions whether researchers understand cancer biology well enough for Friend's highly computational approach to pay off in the short term. "Over the long term the Merck strategy will be the winning strategy," says Druker. "But right now I don't think we're quite there."
Merck has spent the past few years trying to dig out of one of the toughest periods of its 120-year history. In 2003 several experimental drugs for various diseases failed, all at once. In 2004 the blockbuster painkiller Vioxx was yanked because it caused heart problems. Merck settled its Vioxx liability claims last year for $5 billion.
The stock recovered as eight drugs were approved in two years, but the revival was short-lived. Sales of its Vytorin cholesterol pill, produced with Schering-Plough, have crashed under doubts about its effectiveness at preventing heart attacks. Cervical cancer vaccine Gardasil has hit a growth wall, and the Food & Drug Administration rejected a promising cholesterol drug because Merck had not collected enough safety data.
Merck hopes fighting cancer is one way out of this funk. Friend was put in charge of Merck's cancer research efforts in 2003, two years after Merck bought the company he was running, Rosetta Inpharmatics. Friend had cofounded Rosetta in 1996 with Leland Hartwell, now director of the Fred Hutchinson Cancer Research Center in Seattle, and Leroy Hood, now president of the nearby Institute for Systems Biology. Like rival Affymetrix, Rosetta began selling tiny DNA chips that could be used to figure out how often cells were accessing their genes.
Merck bought Rosetta in 2001 for $620 million. Hood and Hartwell gave their shares to their institutions. Hartwell won the Nobel Prize six months later for other work. Friend made $10 million on the sale and built himself a solar-powered, off-the-grid house on Stuart Island.
The first fruits of Rosetta's technology began to emerge with a 2002 article in the New England Journal of Medicine. Dutch researchers using Rosetta's software found a particular pattern of genetic signals within breast cancer tumors that could predict whether or not the cancer would return after surgery. The test is not a significant product for Merck but was approved by the FDA in 2007. It and a similar test made by a rival, Genomic Health of Redwood City, Calif., are widely used to guide post-op treatment strategy.
Merck has been making big acquisitions to augment Friend's technology. In 2006 Merck spent $1.1 billion in cash to buy tiny Sirna Therapeutics, a leader in a field called RNA silencing, which uses small molecules to shut off genes. These molecules can't be used as drugs because the body destroys them. But they can be used in petri dishes to turn genes on and off to find out which are important.
This technology identified a gene last year called KRAS that predicts whether targeted cancer drugs like ImClone Systems' Erbitux will work in a given cancer patient. Clinical trials confirmed this finding this year, and it turned out that 40% of the patients who were receiving Erbitux were getting no benefit. In the past this would have hurt the chances for a drug like Erbitux, but the new test makes doctors more eager to use the drug when it makes sense. Eli Lilly is now buying ImClone for $6.5 billion.
Friend has identified three families of cancer drugs that he thinks his technology can accurately understand: drugs that destroy DNA; those that mess up cell division; and drugs that block some of the most important signals in cancer cells. Noticeably absent are drugs such as Genentech's $2 billion (annual sales) Avastin, which stanches tumor blood supply. These are too complicated to understand.
He's been buying the rights to drugs that fit his interests. In 2004 Merck bought Aton Pharmaceuticals for its drug Zolinza, used to treat cutaneous T cell lymphoma. In 2007 it pledged up to $1 billion for a cancer pill from Ariad Pharmaceuticals.
All of these bets are based on what Friend's giant computer tells him. "This is going to have to be the path taken by pharma in the future," says Hood of Friend's current work. "It's a gamble, but I think it's one that if Merck sticks with it, they'll win big."
Recently Friend took a detour on his way to a research conference in Chicago. He flew to Florida, rented a 1972 Chevy Chevelle and drove to Cape Canaveral to watch the space shuttle launch. He says it wasn't just that he wanted to recapture the feeling of the space race, when scientists were treated like heroes, but that he wanted to get a sense of a project that massive and complex. Creating a cancer drug is not that different.
"The puzzle's gotten big," he says of the cancer drug hunt. "But I think there is only one way to solve it."
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
