Labels, Lawyers, and Logic

10/27/2008 01:19 PM |

In today’s Wall Street Journal, reporter Alicia Mundy begins her article on Wyeth v. Levine as follows:

“For nearly a century, Americans have been able to sue drug companies for deaths or injuries caused by medicines. Now the pharmaceutical industry and other big businesses are hoping the Supreme Court will sharply curb that right.”

That’s her opinion and she’s entitled to it – but it should really appear on the op-ed page.

Here’s my opinion -- When product manufacturers provide fraudulent information to FDA, or deliberately withhold information about safety problems associated with their products, preemption doesn’t offer them protection and they can and should be held accountable.

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.

For more on the issue of “Labels, Lawyers, and Logic,” see here.

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.

The problem is that the current liability system doesn’t reward lawyers who focus on these real public health concerns. Instead, the most experienced and well-financed law firms know that the biggest payouts regularly go to those who take advantage of the FDA’s best efforts to promote the safe and effective use of medications and medical technology. More and more often, these “mass tort” firms specialize in taking a new product warning label or withdrawal decision by the FDA, and view it as a signal to go forward with all guns blazing. Their bullets, unfortunately but not unpredictably, hit multiple innocent targets and result in a wounded American health care system.

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Who's the Healthcare IT Girl?

10/27/2008 12:58 PM |

From the Boston Globe:

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David Brooks Prescription for Health Care Reform: The Hamilton Project?

10/26/2008 07:21 PM |

http://www.nytimes.com/2008/10/26/opinion/26brooks.html?hp

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


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Going to the Matt for Personalized Medicine

10/24/2008 11:13 PM |

From the educated pen of Matt Herper at Forbes.

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."
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Science Fiction: FDA Under President Obama

10/24/2008 08:03 PM |

In the drape measuring department there has been a lot of chatter and speculation about who will do what to the FDA if Obama gets elected, which in my mind is still not a given. 

However rumor has it that Rosa DeLauro, who has been stonewalling on the funding for the Reagan Udall Critical Path Institute, has been asked to write the transition plan for the Department of HHS by the Obama camp.  I can only imagine what that has in store for FDA given her Stone Age view of "Industry involvement = biomarkers =  unsafe drugs". 

As for names floating around to replace Andy von Eschenbach....How does FDA Commissioner David Graham sound?  When I heard this from a contact who told me that Graham was mentioned not once but three times, I nearly choked on my supply of Vioxx.  A Graham nomination would trigger mass resignations and protests at FDA and would send a signal that Obama or whoever he appointed at HHS was clearly in the pocket of the trial attorneys and drug safety nuts....

And speaking of suck-ups in pursuit of power...

Airdate: 10/1 - Health care policies
11AM Case Western University Cardiovascular Medicine Chair Dr. Steven Nissen, M.D. for Obama-Biden

Nissen has also given Obama about $3300 in campaign contributions in 2008
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Bogus and False Reports

10/23/2008 06:04 PM |

From Factcheck.org

In a TV ad and in speeches, Obama is making bogus claims that McCain plans to cut $880 billion from Medicare spending and to reduce benefits.

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Gems on REMS

10/23/2008 01:19 PM |

Next Tuesday and Wednesday (in collaboration with FDA News and United BioSource), the Center for Medicine in the Public Interest is sponsoring the "Risk Management and Drug Safety Summit."  Topic A:  REMS.

Here's a link to the agenda. 

A few thoughts in advance.

Many have looked at the FDAAA language on REMS and seen it as an ill-advised green light for the FDA to inject itself into the practice of medicine. 

While I agree that REMS does indeed represent an expansion of the FDA's mission, I do not agree that it is ill advised.  REMS is the responsible extension of the FDA's mission of safety and efficacy into the new realm of safe use.  As previously discussed in this space ("A Potent FDA Double Feature") the FDA's role in educating both patients and providers on the safe use of approved therapies is a logical and approprite third leg of the agency's mission. 

The first real move into this space was the FDA's change in the warfarin label.  As Dr. Caroline Wright (Foundation for Genomics and Population Health) wrote:

“Just a month after the label for the blood-thinning drug warfarin was updated to explain that genetic variation in specific genes influences how patients respond to the drug, the US Food and Drug Agency (FDA) has approved the first genetic test for warfarin sensitivity.

Warfarin is the most widely used anti-coagulant medication in the world, prescribed to over 2 million people a year to prevent blood clots, heart attacks and strokes. Patients can display markedly different responses to the drug, so doses vary enormously between individuals. Achieving the correct dose is critical, as patients who receive too high a dose are at risk of severe bleeding, whilst those who receive too low a dose may remain at risk of life-threatening blood clots.

The Nanosphere Verigene Metabolism Nucleic Acids Test detects particular variations in two genes, CYP2C9 and VKORC1, which are involved in the metabolism and mechanism of action of warfarin respectively. Specific variants of these genes are identified from a patient sample by hybridization to sequence specific probes (oligonucleotides) attached to a microarray. These are subsequently detected using the Verigene System which measures light scattering from gold nanospheres tethered to another complementary oligonucleotide. Depending upon the genotype, patients can then divided into slow, fast or normal warfarin metabolisers and their doses adjusted accordingly.

FDA states that it cleared the test based on a broad range of published literature together with the results of a study, conducted by the manufacturer, on hundreds of DNA samples. ‘In a three site study, the test was accurate in all cases where the test yielded a result, although 8% of the tests could not identify which genetic variants were present.’ Although the Nanosphere test is not intended as a stand-alone tool to determine optimum drug dosage but to be used alongside clinical evaluation and other tools to determine the best treatment for patients, this approval underlines the FDA’s ongoing commitment to personalised medicine."

It's important to note that when the FDA announced the warfarin label change the agency (and Larry Lesko in particular) came under attack from critics who asserted that this was the FDA, inappropriately, telling doctors how to practice medicine.

What some see as mission creep, others see as responsibility in our new age of more precise diagnostics.

The concept of "safe use" as an integral part of the FDA's 21st century mission and the REMS concept (as refined via FDAAA) as one of many tactics to achieve better patient care is contentious.

And crucial.

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Kidding Us on Uninsured Children

10/22/2008 06:43 PM |

Three percent of all children under the age of 19 lack insurance at some point during the year according to a study release in JAMA this week.

But what do the numbers really say?

"However, the Rochester team found that kids from families with annual incomes at 200 percent to 400 percent of the poverty level ($38,000 to $76,000) are now just as likely to be uninsured as children from poorer families. "

76K and you can't or won't add your kid to your health plan? In NJ, the cost of adding two kids to your individual HMO health plan (and this is the most expensive place in the nation to do so) is $400 a month. Not cheap but still....

Moreover, why can't we provide middle class Americans, single parents, kids starting out, with less expensive health care coverage. Am I missing something? Why not a monthly fee of $100 to cover primary care, prescription drugs and catastrophic health care costs?

Read article here
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Joe The Plumber, Dan The Doctor and the McCain Health Care Plan

10/22/2008 06:26 PM |

When it comes to making the tax system more progressive,  truth be told, no one does more in one fell swoop in that regard than John McCain.

At least that was the point I made at a debate I participated in at Columbia University Medical Center on which health care proposal was better for America: McCain's or Obama's?

According to a report by the Lewin Group, the Obama plan -- which seeks to preserve employer based insurance -- does so by shoving about 52 million Americans into publicly funded health plans.  It pays for that transition by cutting the reimbursement of doctors by at least 25 percent compared to what they get from private insurers, raising about $300 billion in taxes and cutting insurance premiums through price controls.  I ignore the estimated savings from health IT and disease management because it's all based on articles published by people like me.  

In essence, the Obama plan is preserving the tax exclusion for employer based insurance, which favors the rich.  As the Center for Health Transformation's Jim Frogue noted several years ago: "Under the current tax code, workers whose employers contribute to their health coverage have that amount excluded from income and payroll taxes. Most employees are not aware of this (which is why Obama is able to portray the McCain health plan as a tax increase).  Yet it amounts to a significant and, incidentally, highly regressive tax break--the higher one's tax bracket, the bigger the subsidy. According to the Lewin Group, a leading econometrics consulting firm, families earning $100,000 per year average $2,638 in tax subsides, but those under $15,000 get an average subsidy of only $79."
http://www.heritage.org/research/healthcare/EM740.cfm 

26 million Americans will get private coverage under the McCain plan and 12 million of those will be able to shop for health insurance that is cheaper than the $12000 a year policy Obama and Biden believes is the "right" amount of coverage.  And that coverage will be available with guaranteed issue conditions but shorn of expensive mandates that many people who are indifferent to risk but price sensitive do not want. 

Under the McCain plan, as I noted, the amount employers contribute will be counted as wages and will be taxed at the marginal tax rate as Obama notes.  But it will also, as the Lewin study notes, lead to an increase in wages and overall greater tax subsidies overall at every tax bracket with most of the tax subsidies going to Americans in the lowest income brackets.  Of course, those in the higher brackets will be able to bank increased wages in tax free HSAs, IRAs ,etc.  to offset tax liability. 

And under the Obama plan Dan the Doctor will get paid less, pay more taxes and get sued more often and more successfully.  Under McCain, doctors will be able to compete and serve patients directly outside of government controls. 

I think there is considerable openness to other approaches to making health care convenient and affordable in both camps.  At least I hope so.  Because the effort to herd people into a glorified version of SCHIP or Medicaid -- or simply giving everyone an HSA -- will fail. 

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Orszag's Good Behavior

10/21/2008 05:48 PM |

Does  Peter Orzag have a new gold standard for comparative effectiveness:  comparing established treatments like antidepressants to placebos and finding placebos just as effective....
http://www.cbo.gov/doc.cfm?index=9887
Let's take a step back.

In his powerpoint presentation Orszag has a slide stating:

"As we seek to improve the efficiency of the health sector, let’s learn some lessons from economics."

He shows some slides that automatic enrollment in 401Ks leads to higher participation in 401k plans than when it's voluntary.  As if that's an earth shattering discovery.

Then a slide purporting to show that the placebo effect is almost as strong as antidepressants, angina pectoris treatment, knee surgery and exercise. 

Then a slide showing that once a day dosing and frequent doctor-patient interventions increase compliance with medication regimens

What are we to derive from this?

I think Orszag is trying to underscore the importance of psychological and behavioral differences in determining responses to treatment, not that placebos are better. 
That is, individual responses have to be taken into account to maximize value and improve outcomes.  Establishing who is risk averse and why is part of this process.  So too is genetic response to medicine.  All are important. 

That is, measuring the personal is critical to comparative effectiveness.   Finding ways to promote patient-centered care is crucial.  More to the point, perhaps Orszag is seeking to drive comparative effectiveness towards value-based medicine based on personalized health care information which in turn is generated by a critical path for comparative effectiveness. 

Thank  you Dr. Orszag. 
 
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Silence is Leaden

10/21/2008 12:55 PM |

The always savvy Jim Edwards has a thoughtful and important article in this week’s edition of BrandWeek.  Its title, “Why Pharma Fears Social Networking,” says it all.

Almost.

Edwards writes that, “Although a majority of marketers have embraced online social media and user-generated content efforts, one industry is conspicuously not taking advantage of the gold rush: pharmaceuticals.”

His use of the term “gold rush” defines the scope of the article.  He’s talking about Pharma and social networking in terms of marketing and sales.  Well, it is BrandWeek after all. But there's so much more to Pharma and social networking than just marketing.  But I'll get to that in a minute.

Jim continues, “Marketers fear that user-generated content will include complaints about injuries caused by their drugs’ side effects. The law requires these “adverse events” to be reported to the FDA. The FDA’s adverse-event databases are regularly combed by lawyers looking for potential class-action suits. Thus, drug marketers have stuck with a decidedly Web 1.0 model, in which customer interaction is kept to an absolute minimum.”

Indeed.  And what a truly 21^st century malaise it is – being “decidedly Web 1.0” in a 2.0 world.  A digital dilemma if ever there was one -- worse even than restless leg syndrome.

But Edwards believes that, “This head-in-the-sand approach may be about to change. A debate is raging in the drug business as to whether companies should adopt a Web 2.0 strategy. On one side are digital agencies telling companies that online customers generate far fewer adverse event reports than drug companies might expect.  On the other side are brand managers, whose every published word must survive a thicket of in-house lawyers, some of whom aren’t Internet savvy. The pressure for drug companies to evolve is growing.”

And I am quoted as follows:

“Drug companies need to begin embracing ways to look for adverse events instead of hoping they don’t stumble across them. I think the attitude of ‘there’s safety in ignorance,’ or active ignorance, is no longer actionable or responsible.”

Looking for the early adaptor? The BrandWeek article calls out Johnson & Johnson for specific kudos.  

Edwards writes, “One company is attempting to prove it either way: Johnson & Johnson, which in March acquired Childrenwithdiabetes.com, a community site for parents of kids with diabetes. The site has open bulletin boards and even takes ads from competing companies. Joe Natale, vp-new media, said J&J monitors the site for adverse events and people who give incorrect medical advice, but aside from that anyone can post whatever they want. “The best way to destroy that community would be to in any way hamper or infringe upon the way they create content or share information. If [a company thinks] that every post for every user has to be reviewed and copy-cleared in advance, I will tell you not to waste your time.”

Here is the complete BrandWeek article..

There are legal issues – and they’re important.  There are marketing opportunities – and they’re exciting.  But what really matters is that social media is a terrific opportunity to help educate the various constituencies of American healthcare about all sorts of important issues.  Safety?  Sure.  But also safe use, compliance/adherence, and a host of others.

If safety is important (and it is very important), then pharmaceutical companies should seek out (rather than side-step) ways to uncover legitimate adverse events.  By not engaging in 21^st century digital expiscatoriation, industry leaves the FDA with little choice but to pursue its own well meaning (if questionably designed) communications vis-à-vis early safety signals.  Silence is leaden. The obvious lines between social media and traditional DTC are obvious and will be used by legislators and pundits intent on hoisting the industry with its own petard.  Pharma must lead, follow, or get out of the way.  Complaining is not an option.

And neither is avoidance.

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A Potent FDA Double Feature

10/20/2008 02:37 PM |

The Pink Sheet reports that, “FDA’s initiative to influence the safe use of dugs will kick off in the new year.”

According to Dr. Janet Woodcock, “FDA does not control the health care system, so our improving the use of marketed drugs, to a great extent, is going to involve influence rather than control,” by partnering with the growing patient safety movement, she said. “The vast majority of harm from approved drugs comes from misuse, inappropriate use … failure to use, abuse and medical mix-ups. There is just carnage out there, and we know that.”

“Influence rather than control” is a savvy and sophisticated concept -- one that many of our elected members of Congress could learn from.

This new "Safe Use" initiative is the patient-facing sibling of the agency’s “Safety First” pharmacovigilance progam. But it's more than that -- it's the FDA reasserting ownership of safety from those who would use it only as a malllet of fear.

And it’s a potent double feature.
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Healthcare v. Tort Bar

10/20/2008 02:09 PM |

Here is today’s house editorial from the Washington Times:

EDITORIAL: The FDA and junk science
Monday, October 20, 2008

There are many good reasons for the Supreme Court to uphold the authority of the Food and Drug Administration in determining what information should be included on the label describing the risks and benefits of a drug. A current case would challenge that authority, known as pre-emption, and hand it over to trial attorneys suing drug companies that, as part of any financial settlement, would be able to demand changes to the information a company would have to provide doctors and consumers.

Today's Op-Ed by Tomas Philipson notes that vaccine investment dried up after litigation costs in the wake of a successful lawsuit. But higher prices are not the only result of overturning pre-emption. Nor are they the most costly. The litigation that found pertussis vaccines "caused" Sudden Infant Death Syndrome was conducted without any scientific basis for such a link. This has spurred a whole industry of trial attorneys and doctors on the take who have been willing to concoct the conspiracy that vaccines or their ingredients "cause" autism or other brain damage. That in turn has allowed science to be hijacked in favor of what one observer has called "judgments based on anecdotes and speculation."

That observer was Marcia Angell, who, more than a decade ago, saw how fearmongering fed by courtroom antics and junk science shoved aside the FDA and caused a panic among women regarding silicon breast implants. It was a panic, as Dr. Angell noted back then, that had "no good scientific evidence for or against a link between breast implants and systemic disease of any kind."

Today, it is even easier to supplant science and replace it with a state of fear. Fake blogs, journalists working closely with trial attorneys, and doctors and scientists on tort-lawyer payrolls create and spread specious theories and crank out statistical associations without any real evidence of cause and effect. Panic spreads and is reinforced in court-proceedings. As one theory is knocked down, such as the measles vaccine causing autism, another one - thimerosal - springs up.

And you only need one "study" to cause panic and launch a class-action lawsuit. (That and the visceral hatred of corporations Dr. Angell once found to be flimsy basis for silicon-breast-implant litigation.) But now Dr. Angell claims that the courts are the only avenue to establish the real risks of a drug because the FDA is merely a rubber stamp for drug companies. Forget the fact that the number of drug approvals have declined in the past few years and the number of late-stage drug flops has increased. So much for evidence.

Dr. Angell and the current editors of leading medical journals are willing to allow the trial bar to displace the FDA. This group is willing to forfeit the ability to target risk and benefit - where science is heading - and permit opinion and emotion to hold sway. As Dr. Angell noted, in the courtroom, the experts' opinions are the evidence. It would seem now that Dr. Angell and others have drug companies in their sights, their opinion (and overturning pre-emption) is all that matters.

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Prescription Shakedown Litigation Projection

10/20/2008 02:02 PM |

Fred Baron, the tort lawyer who helped write the book on how to attack Merck and Pfizer on COX-2 liability, rolled out heavy hitters in the Democratic party to lobby Biogen to grant him a compassionate use of Tysabri to treat his late stage multiple myeloma.

I hope and pray it works for his sake and everyone else's suffering with the disease including my boyhood friend's mom who has gone through every other drug for the disease but who has now relapsed.

"Biogen Idec is running an early-stage trial of the drug in multiple myeloma, but Baron doesn’t meet the criteria to participate.

Baron’s a prominent donor to the Democratic party, and many of his powerful friends, including Lance Armstrong and Bill Clinton, made appeals on his behalf. And the family agreed not to sue if anything goes wrong."

Gee, why didn't he think of that when it came to Celebrex which generated billions for Pfizer and also had anti-cancer properties that were being studied until Baron's tactics were deployed in lawsuits against the the product: Ironically, Tysabri was yanked from the market in the wake of the Vioxx withdrawal...

Pfizer, the world's biggest drugmaker, has reached a settlement in thousands of cases involving two prescription painkillers." The company announced Friday that "it had agreed to set aside $894 million to settle virtually all the lawsuits related to its withdrawn painkiller Bextra (valdecoxib) as well as a similar drug that remains on the market, Celebrex (celecoxib)," the New York Times (10/18, B2, Saul) added. The agreement "comes approximately one year after Merck announced a $4.85 billion reserve to settle litigation involving the similar painkiller Vioxx (rofecoxib)."

In 2004, Celebrex and Vioxx, "part of a class of drugs called Cox-2 inhibitors," were found "to increase the risk of heart attacks and strokes, especially in patients who took them steadily over long periods of time," the Los Angeles Times (10/20, Healy) notes. And, despite several trials that have shown that Celebrex may "offer a real prospect of preventing cancer," Pfizer "called off a number of clinical trials...and abandoned efforts to have the drug's cancer-prevention qualities recognized by the Food and Drug Administration" after "Vioxx was withdrawn from the market."

 

Note the amount of cash Pfizer had to fork over to various special interests in a decision that had nothing to do with with real risks of the drug, including the Prescription Access Litigation Project which is a limited liability corporation that funds and reports directly to Community Catalyst which also runs The Prescription Project.

"The Pfizer agreements...came after several pre-trial court rulings in the company's favor," according to Amy Schulman, Pfizer's general counsel. In one case, a district judge "who oversaw the federal cases in San Francisco" ruled that "there was insufficient scientific evidence that Celebrex caused heart attacks or strokes at the 200-milligram dose."

There is a certain degree of chutzpah requried to push for the off-label use of a drug to save your life when you have made millions perfecting a strategy employed by an organization that launches lawsuits based on the principle that off-label prescribing is inherently deceptive. I have to say I admire it and would do anything to keep living as well. As I said at the outset, I hope Baron responds and lives a long and healthy life. As for the Prescription Shakedown Project...that's another matter entirely...  Read More & Comment...

The Risk Swamp

10/17/2008 04:53 PM |

 Wither the FDA's Critical Path program?

Last we visited this topic, the Reagan/Udall Center remained mired in political treacle.

Little has changed.

My article in the October edition of The Journal of Medicine and Philosophy, “FDA and the Critical Path to Twenty-first century Medicine,” takes a look at what’s going on – and has already generated some interesting comments. (Names have been omitted to protect the honest.)

Some examples:

“The Critical Path is tied in knots.”
“There is a ray of light – in Europe.”
“The EU will be setting the scientific standards of the future.”
“It’s time to get the focus back to science rather than suspicion.”
“We must escape from the risk swamp.”

Keep those cards and letters coming.

Keep up the pressure.

And keep the faith.  Read More & Comment...

Generics are easy. Innovation is hard.

10/17/2008 01:02 PM |

Pfizer has announced plans to sell cheaper versions of its competitors' branded drugs when they lose patent protection. Greenstone, Pfizer’s generics unit (which it inherited in the 2003 acquisition of Pharmacia) has primarily sold copycat versions of Pfizer's own branded drugs when they lost patent protection, not other companies' drugs. (Pfizer's generics business is among the Top 10 generic companies by sales as measured by IMS Health.)

And they aren't alone in making more aggressive moves into the generics business. Novartis’ Sandoz unit is already a leader here, GSK is partnering with South Africa's Aspen Pharmacare Holdings, and Daiichi Sankyo is taking a majority position in India’s Ranbaxy.

According to David Simmons, general manager of Pfizer's new Established Products unit "We're always about innovation, and it will always be the lifeblood and sustaining element of Pfizer, but we don't see it as the be-all and end-all.”

Business is business, and Pfizer’s decision makes sense.  But, when the world’s largest pharmaceutical company says that innovation isn’t the “be-all and end-all,” there’s a much larger policy issue at stake – like the future of innovation.

Innovation is slow.  As any medical scientist will tell you, there are few "Eureka!" moments in health research. Progress comes step-by-step, one incremental innovation at a time. Companies more often profit by improving existing chemicals and making processes more efficient than by revolutionizing the whole field with new products.

Innovation is hard.  Today it takes about 10,000 new molecules to produce 1 FDA-approved medicine. And if that's not frightening enough, only 3 out of 10 new medicines earn back their research and development costs. And here's the kicker -- unlike other R&D-intensive industries, pharmaceutical investments generally must be sustained for over two decades before the few that make it can generate any profit.

Innovation is expensive.  In 2003, researchers at TuftsCenter for the Study of Drug Development estimated the costs to bring a new medicine to market to be $802 million, and others suggest that the total cost is closer to $1.7 billion

Innovation is under attack.  From accusations of the “me-too” variety, to crackpot schemes to replace pharmaceutical patents with a “prize” system, life for innovator pharmaceutical companies is rough and tough.  Israel Makov (formerly the Big Abba of generics giant Teva) once told me that he wasn’t really in the pharmaceutical business, but rather “in the litigation business.”

(PS/ If we don't think seriously about serious patent reform and towards more robust protection of data exclusivity we are going to seriously jeopardize the potential for new medicines -- at a time when science makes potential breakthroughs tantalizingly close.)

But innovation is important – and not just for pharmaceutical industry profits. Increases in life expectancy resulting from better treatment of cardiovascular disease from 1970 to 1990 have been conservatively estimated as bringing benefits worth more than $500 billion a year. In 1974, cardiovascular disease was the cause of 39 percent of all deaths. Today it is about 25 percent. Cerebrovascular diseases were responsible for 11 percent of deaths back then. In 2004 they caused 6.3 percent of deaths. Kidney diseases were linked to 10.4 percent of deaths and now they are associated with 1.8 percent. And that’s just for the United States.

As Harvard University health economist (and Obama healthcare advisor) David Cutler has noted: "The average person aged 45 will live three years longer than he used to solely because medical care for cardiovascular disease has improved. Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."

When innovator drug companies decide to play more aggressively in the generic drug world – that’s business, sound business.  When a senior executive at the world’s largest drug company says that innovation isn’t the “be-all and end-all” – that’s frightening, very frightening.

To borrow an over-used adjective from the world of global climate change -- we must protect "sustainable" innovation.

  Read More & Comment...

FDA Weaves a Web of Safety

10/16/2008 01:45 PM |

A worthwhile effort.  Hopefully this will be more than just a "must bookmark" for trial lawyers.

From the FDA website:

FDA Creates Web Page with Drug Safety Information for Patients, Health Care Professionals
Comsolidates information in once access point

Consumers and health care professionals can now go to a single page on the U.S. Food and Drug Administration's Web site to find a wide variety of safety information about prescription drugs. The Web page, http://www.fda.gov/cder/drugSafety.htm, provides links to information in these categories:

• Drug labeling, including patient labeling, professional labeling, and patient package inserts;
• Drugs that have a Risk Evaluation and Mitigation Strategy (REMS) to ensure that their benefits outweigh their risks;
• A searchable database of postmarket studies that are required from, or agreed to by, drug companies to provide the FDA with additional information about a drug's safety, efficacy, or optimal use;
• Clinicaltrials.gov, a searchable database of clinical trials, including information about each trial's purpose, who may participate, locations, and useful phone numbers;
• Drug-specific safety information, including safety sheets with the latest information about the drug as well as related FDA press announcements, fact sheets, and drug safety podcasts;
• Quarterly reports that list certain drugs that are being evaluated for potential safety issues, based on a review of information in the FDA's Adverse Event Reporting System (AERS);
• Warning Letters, Import Alerts, Recalls, Market Withdrawals, and Safety Alerts;
• Regulations and guidance documents;
• Consumer information about using medications safely and disposing of unused medicines;
• Instructions how to report problems to the FDA through its MedWatch program;
• Consumer articles on drug safety; and
• The FDA's response to the Institute of Medicine's 2006 report on the future of drug safety.

"By placing Web links to these up-to-date resources on a single page, we're helping consumers and health care professionals find drug safety information faster and easier," said Paul Seligman, M.D., M.P.H., associate director of Safety Policy and Communication in the FDA's Center for Drug Evaluation and Research. "This type of communication is aimed at helping consumers and health care professionals make well-informed decisions about medication use."

Establishing such a Web page is one of the requirements of the Food and Drug Administration Amendments Act of 2007, and is among FDA's many efforts to address the safe use of drugs throughout their lifecycle.

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Groucho Marx and FDA Advisory Committees

10/16/2008 01:22 PM |

Well, duh.  A new report from the GAO (Government Accounting Office) FDA Advisory Committees: Process for Recruiting Members and Evaluating Potential Conflicts of Interest, found that “FDA employed many of the same recruitment and evaluation practices used by organizations previously identified by GAO as employing methods that could ensure an independent and balanced advisory committee.”

“… an independent and balanced advisory committee.”  Thank you.

But, according to the report, the FDA faces barriers when it comes to recruiting qualified advisory committee candidates without actual or potential conflicts of interest.  According to the GAO, “the agency may have been able to mitigate these barriers by expanding its outreach efforts,” since “the same leading experts that industry sought to conduct research” are those being recruited to serve on FDA advisory committees.

Does “mitigate” mean recruiting the second best and the almost brightest?  Not acceptable.

It reminds me of the old Groucho Marx quip , "I wouldn't join any club that would have me as a member."

  Read More & Comment...

Who's Life Is It Anyways?

10/15/2008 04:23 PM |

Tykerb is one of the newest tyrosine kinase inhibitors (TKI).  It interrupts the signaling pathway that produces a specific protein involved in the creation and support of cancer cell growth.  It is a small molecule drug that can target both HER 2 and HER 1 breast cancers.  Because it is a small molecule drug and not a large molecule it can also enter the brain where up to half of all late stage breast cancers spread.  Also, recent studies presented at the American Society of Clinical Oncology Breast Cancer Symposium on September 5, 2008. have shown that Tykerb can be used in combination with new gene profiling tests to tailor treatment to patients who would gain the most benefit and least risk:
http://community.breastcancer.org/forum/73/topic/721033

"Conclusions of the study had shown that Tykerb has antivascular activity superior to that of Nexavar. Avastin + Tykerb may be the first clinically-exploitable antivascular drug combination. High dose, intermittent 'bolus' schedules of Tykerb to coincide with Avastin administration may be clinically advantageous, even in HER2-negative tumors.

The system utilized for the study was a functional profiling assay, which may be used to individualize antivascular therapy. It can be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating microvascular cells in a variety of neoplastic and non-neoplastic conditions, for drug development, and individualized cancer treatment.

The cell-based assay can accurately sort drugs into categories of above average probability of providing clinical benefit on one hand and below average probability of providing clinical benefit on the other hand, based both on tumor response and patient survival."


And so how doth the comparative effectiveness institute known as NICE rule upon the value of Tykerb:
 

The Wall Street Journal (10/15, B2, Berton) reports, "GlaxoSmithKline PLC's breast-cancer drug Tyverb (lapatinib) shouldn't be eligible for reimbursement under the U.K.'s publicly funded healthcare system," the U.K.'s National Institute of Clinical Excellence (NICE) recommended on Tuesday. The company said that NICE, "which decides what treatments are made available free to U.K. patients, isn't recommending Tyverb's use by the National Health System. In its decision, NICE rejected the drugmaker's offer to bear part of the cost of the treatment."

        The U.K.'s Telegraph (10/14, Smith) added that "trials of the drug...have shown it can reduce the size of a tumor by 60 percent and extend life by an average of two months, compared to standard treatment." But NICE "says it does not extend life by long enough to justify the extra cost."

As long as comparative effectiveness is conducted by the payor, for the payor and of the payor, the value of personalized medicine will be in the words of the Faber College's Dean Wormer:

"Zero, point zero." 

For a look at how NiCE conducts its comparative effectiveness work, take a look at this video: 

http://www.youtube.com/watch?v=xVdUsgYA_D4

 

  Read More & Comment...

Ode to a Canadian Physician

10/15/2008 01:15 PM |

At yesterday’s CMPI conference on the impact government-care has on physicians (in Europe, Canada, and the US), Brian Lee Crowley (President of the Nova Scotia-based Atlantic Institute for Market Studies) offered the following comments:

In summarizing the current state of the physician within the healthcare system in Canada I sought inspiration in poetry and was drawn to a poem by Elizabeth Barrett Browning, With apologies, I have somewhat modified her poem and entitled it:

Ode to a Canadian Physician

How do I disempower thee? Let me count the ways.
I disempower thee to the depth and breadth and height
My bureaucratic soul can reach, when some aspect of the health system escapes my
control.
For the ends of cutting my costs and using thy ideal Grace to shield me from the sting of
patient discontent.
I disempower thee to the level of everyman's
Most urgent healthcare need, by sun and candle-light, which are the pinnacle of the
technological sophistication thou art allowed.
I disempower thee freely, as men strive for “free” healthcare and end by merely
restricting access to thee.
I disempower thee purely, as they turn from specialists and hospitals in despair of finding
timely treatment there.
I disempower thee with a passion put to use
In my efforts to ingratiate myself with the electorate; Thank God for their childish faith.
I disempower thee with a loss of access to medical schools, thus ensuring that many will
never know the joys of thy tender care
I disempower thee with the breath,
Smiles, tears, and above all the income of all your life! --- and, if the Minister of Health
so choose,
I shall but disempower thee better if thou hast the temerity to prescribe a drug I judge too
costly, no matter how efficacious.

To reinforce his point in somewhat less poetic terms, Brian pointed to the following story that ran in the Canadian newspaper, the National Post, on August 06, 2008

MD uses lottery to cull patient list

In the latest jarring illustration of the country's doctor shortage, a family physician in Northern Ontario has used a lottery to determine which patients would be ejected from his overloaded practice.

Dr. Ken Runciman says he reluctantly eliminated about 100 patients in two separate draws to avoid having to provide assembly-line service or extend already onerous work hours, and admits the move has divided the community of Powassan.

Yet it was not the first time such methods have been employed to determine medical service. A new family practice in Newfoundland held a lottery last month to pick its caseload from among thousands of applicants. An Edmonton doctor selected names randomly earlier this year to pare 500 people from his heavy caseload. And in Ontario, regulators have heard reports of a number of other physicians also using draws to choose, or remove, patients, limit their prescribing to the state formulary, with sometimes extremely grave consequences for their patients.

Brian’s complete remarks can be found here.

Here is how he concluded his presentation:

Physicians surrendered great power to order their own professional lives and to act in the interests of their patients when physicians and hospital care was essentially taken under full political direction in the 1960s in a wave of ideological enthusiasm and economic ignorance. Despite the misgivings of some in the medical community, doctors largely embraced a public sector health care monopoly model, a monopoly that has only extended its tentacles and its centralising control in the intervening decades. Things are beginning to shift within the medical community, however, and the last two presidents of the Canadian Medical Association have been advocates of the private sector, a sea change of huge proportions. Like the wedding guest in Samuel Taylor Coleridge’s Rime of the Ancient Mariner, they have been traumatized by the brave new world of our health care system and are beginning to draw the policy conclusions that follow from that experience:

He went like one that hath been stunned,
And is of sense forlorn:
A sadder and a wiser man,
He rose the morrow morn.

Words for all of us to ponder on now -- rather than on the forthcoming post-election "morrow morn."

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