President-Elect Obama

11/05/2008 06:15 PM |

Elections are like baseball games.  To quote Jackie Robinson:  "It (a baseball box score) doesn't tell how big you are, what church you attend, what color you are, or how your father voted in the last election. It just tells what kind of baseball player you were on that particular day."   

Barack Obama's election as President tells us a lot about what kind of ball player he was.  The next four years will be a reflection of his leadership, his self-confidence and response to events.  And nothing else. Now let's stop the thumb sucking and get down to business.
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The Morning After

11/05/2008 02:25 PM |

It’s Wednesday.  I woke up.  I shaved and drove to work.  My EZPass still worked. 

It’s Wednesday and Barack Obama is our President-Elect. 

Please note the possessive – “our” – because he will shortly be the President of the United States.  The whole United States.  Red states and blue states. He’s our president regardless of political affiliation or policy position.  It also means he’s obligated to listen to the opinions of all Americans – not just those who agree with his agenda.

Specifically, his healthcare agenda.  To that point:

It’s Wednesday and drug importation is still an unsafe, unsound idea.

It’s Wednesday, Part D is still a resounding success and the Non-Interference clause is still a good idea.

It’s Wednesday and the VA formulary still contains less than 65 percent the nation's 300 most-popular prescription drugs.  

It’s Wednesday and the tools for proper healthcare technology assessment (comparative effectiveness) still need to be redefined and reconfigured from cost-based to patient-centric measurements.

It’s Wednesday and the FDA is still under-funded.

It’s Wednesday and industry-supported CME is still working.

It’s Wednesday and incremental innovation vis-à-vis the development of new medicines is still misunderstood.

It’s Wednesday and there’s still no such thing as a “me-too” medicine.

It’s Wednesday and direct-to-consumer advertising is still a valuable consumer education tool.

It’s Wednesday and the pipeline is still dry. – although not as dry as some think.

It’s Wednesday and we still haven’t adequately addressed the unintended consequences of communicating early safety signals.

It’s Wednesday and Reagan/Udall Foundation funding remains hostage to political posturing.

It’s Wednesday and DSHEA is still a disaster.

It’s Wednesday and Americans still cannot buy health insurance competitively across state lines.

It’s Wednesday.  Tomorrow’s Thursday – which means the weekend is within sight.  Let’s take that opportunity to sit back and reflect on all the work we need to do – together – to reform American healthcare for all of us and with all of us as partners.

That’s change we can all support.

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Hands Off Our Healthcare!

11/04/2008 07:49 PM |

DIdn't find out about Proposition 101 -- Freedom of Choice in Healthcare Act --   in Arizona until yesterday...

http://www.medicalchoiceforaz.com/about/

Here's a movement worth spreading nationwide...


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Run of the Mill

11/04/2008 07:47 PM |

Per my recent blog, "Jeremy Bentham for FDA Commissioner, " this comment from a former FDA colleague -- who we'll refer to as "Dr. John Stuart Mill" ...

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Jeremy Bentham for FDA Commissioner?

11/04/2008 06:53 PM |

Remember Utilitarianism?  It’s the philosophy based on the principle of utility -- that the moral worth of an action is solely determined by its contribution to overall utility. And the poster boy of the Utilitarian School is Jeremy Bentham.  According to Bentham, “It is the greatest good to the greatest number of people which is the measure of right and wrong.”

If this sounds distressingly familiar it should.  It’s the philosophical foundation that underpins both NICE (the National Institute for health and Clinical Excellence) and HTA (healthcare technology assessment).

These philosophical musings are the result of a new and important article by Robert Jones (a retired Glaxo Wellcome executive and former member of EFPIA's economic policy committee from 1994 to 2006, and its chairman from 1994 to 2001).

A few points courtesy of Mr. Jones:

“Over the past 20 years or so, stakeholders in the medicines purchasing process have been grappling with the difficult problem of identifying value in prescription medicines. In the early 2000s there emerged a consensus that the way forward was through objective, methodical assessment of value by a cluster of techniques generically called "health technology assessment" (HTA); and this has apparently become the mechanism of choice as a procedure by which new medicines can establish prices and enter markets – a choice not only of purchasers but also of the suppliers, the pharmaceutical industry, which has expressed support for the ideas behind HTA for something over 20 years. Yet in taking this position the industry has perhaps paid insufficient attention to two vital strategic possibilities:

i. that systematised value assessment would not simply serve the interests of a free-market competitive contest but might tend to be captured by regulatory agencies which have predominantly purchaser-side responsibilities; and
ii. that the need to satisfy pre-established criteria of value could in due course have profound effects on the dynamics of a private-industry innovation system.”

And:

“Efficient public purchasing is a desirable goal. But as HTA processes in many countries – including the UK – often arrive at a point awfully close to rationing, it is the status of rationing as a means of delivering purchasing efficiency which needs examination. The role of NICE in the UK is instructive here.”

And relative to our friend Jeremy Bentham:

“The more serious point from which NICE suffers is an external failure to comprehend the utilitarian logic on which it operates (a failure of comprehension which NICE seemingly has little idea how to correct). NICE is often held to be an example to the world of enlightened drug policy administration. In fact, it is a peculiarly British institution, operationally tuned to British public policy objectives, and its procedures would be of uncertain temper if applied in other jurisdictions.”

“At the root of its operations is a Benthamite approach to health benefits. For NICE, value equates to social utility, the optimisation of which informs all of its judgements. Some of NICE's decisions may seem cruel in human terms, and ill-advised in public relations terms, but there is an arid logic to them which can usually be seen at work.”

“NICE's decision to withhold approval of donepezil from patients with mild Alzheimer's disease, on the grounds that an insufficiently high percentage of patients would benefit, while the drug was approved for patients who had progressed beyond the mild stage, was widely ridiculed. Why, it was asked, do we not allow the drug to do some good when patients are still enjoying some quality of life, rather than restricting it to use when a poor and declining quality of life can be only marginally reversed?”

To view Mr. Jones' full commentary, click here.

Utilitarianism isn’t a one-dimensional worldview.  Consider Bentham’s comment that,

“It is vain to talk of the interest of the community, without understanding what is the interest of the individual.”

If there’s a better statement of support for 21^st century HTA based on patient-centric rather than cost-based tools, I like to hear it.

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Legal Side Effects

11/04/2008 01:21 PM |

From today's Wall Street Journal:

Legal Side Effects

Diana Levine's story is gut-wrenching. It's also the sort of case that makes bad law, which is why Monday's Supreme Court oral argument in Wyeth v. Levine is important for consumers and drug development in America.

A professional guitarist who suffered from migraines, Ms. Levine went into a clinic in April 2000 for an injection of Phenergan, an antinausea drug produced by Wyeth Pharmaceuticals. The clinic administered the drug by what the label described as the "preferred" method -- "deep intramuscular injection." When that didn't help her symptoms, the clinic injected another dose directly into her arm -- a technique known as "IV push." As the label warned, this was dangerous. If Phenergan is accidentally injected into an artery instead of a vein, gangrene can quickly set in and lead to amputation. To avoid this, the drug's label described in detail how to administer an intravenous injection.

Even so, the worst happened. Gangrene set in and Ms. Levine lost her right hand and forearm. She sued the clinic, which settled the case. But then she sued Wyeth in Vermont state court. She argued that Wyeth should have warned health-care providers never to attempt IV-push injection because "other, safer methods" were available. She won, and the Vermont Supreme Court upheld the $6.7 million verdict.

In Wyeth v. Levine, the issue is whether a drug company that had sought and received all the necessary approvals from the Food and Drug Administration, and had labeled that drug in accordance with FDA requirements, can still be held liable under state law. This is not a case about whether a drug company concealed evidence or other misconduct. The FDA-approved label for the drug specifically warned against the risk that became Ms. Levine's reality.

But this case is not just about Ms. Levine. It is about a drug-approval system that balances the risks of treatments against the risk of not being treated at all. And a jury, faced with a single sympathetic plaintiff, is in no position to rule on the correctness of those FDA judgments. The Supreme Court ruled as much in February in Reigel v. Medtronic, a similar case involving medical devices. Justice Antonin Scalia argued for the 7-2 majority in Reigel that a jury "sees only the cost of a more dangerous design, and is not concerned with its benefits; the patients who reaped those benefits are not represented in court."

Though the tort bar lost that case, Ms. Levine's lawyers are arguing that the relevant federal devices statute explicitly mentions pre-emption, while the drug statute does not. But this is a red herring. As Ms. Levine's lawyer admitted at oral argument, the question in Wyeth is not whether any state-law tort claim was pre-empted by FDA regulation. The question is whether, in a case in which the FDA has made one determination about safety, a state jury should be permitted to come to another. As Justice Scalia put it yesterday, "If you're telling me the FDA acted . . . irresponsibly, then sue the FDA."

Chief Justice John Roberts asked former Solicitor General Seth Waxman, who argued the case for Wyeth, whether this case could be distinguished from Reigel on these grounds. Mr. Waxman's response goes to the heart of this case: "A jury was asked to look at the same information [that the FDA had] and conclude that the precise language that the . . . FDA required Wyeth to use rendered that drug unreasonably unsafe." In other words, the jury is being asked to look at a situation where the worst has happened, and the risks have been realized, and to decide whether the FDA made the right call. This would all but guarantee that the drug companies would be sued whenever a known risk becomes actual in a particular case.

The U.S. drug approval system is imperfect, and the FDA makes mistakes -- most of which involve blocking or slowing drug therapies that could save lives. Congress created that system and asks drug companies to spend some $1 billion per drug and wait years to gain approval. It amounts to double jeopardy to say, even if you do all those things right, and disclose all the known dangers and label the drug as ordered by the FDA, that you can still get sued if something goes wrong because someone else made a mistake.

If a known and disclosed medical risk can still lead to a law suit, drug companies can literally be sued for anything. No doubt there are trial lawyers and Democrats in Congress who would prefer it that way. But if we want state juries second-guessing the FDA at every turn, let's pass a law in broad daylight so everyone knows whom to blame when drug innovation stops cold.

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The Nine Opine

11/04/2008 01:15 PM |

From today’s New York Times:

Justices Weigh Effect of F.D.A. Approval of Drug Labels on Suits in State Courts

By ADAM LIPTAK

WASHINGTON — It was supposed to be the term’s blockbuster business case, one that might put an end to thousands of state-court injury suits. But the argument in the Supreme Court on Monday, in the case of a Vermont musician who lost her arm after receiving an injection of an anti-nausea drug, quickly turned into a search for limiting principles.

The case, Wyeth v. Levine, No. 06-1249, concerns an implied form of the doctrine of pre-emption, which bars state lawsuits from people injured by products that met federal safety standards. The drug law at issue in the case says nothing about pre-emption, and the question before the court was whether the Food and Drug Administration’s approval of drug labels should knock out state lawsuits contending that the labels did not contain adequate warnings.

A broad endorsement of implied pre-emption based on regulators’ actions rather than on statements in laws enacted by Congress could shut down countless injury suits in cases involving not only drugs but also motor vehicles, household products, chemicals and agricultural products.

Several justices appeared open to the idea that pre-emption could follow from the F.D.A.’s approval of a drug label — but only if drug companies remained subject to lawsuits if they failed to disclose new information about potential risks. There was much discussion of what information should be considered new.

Other justices seemed prepared to allow pre-emption — but only if the drug agency had considered the particular risk before approving the label.

Given the justices’ interest in those refinements, the court seemed unlikely to rule broadly on the larger issues in the case: whether the agency and other federal regulators set minimum safety standards that states are free to augment or whether they make judgments about the optimal balance between risks and benefits that states must follow.

In February, however, an eight-justice majority of the court ruled, in Riegel v. Medtronic, that suits concerning injuries caused by medical devices were pre-empted by a 1976 federal law. But the underlying law in Riegel required pre-emption, in so many words; in the jargon, it involved “express pre-emption.”

The plaintiff in the case argued on Monday, Diana Levine, lost her arm after being injected with a Wyeth drug, Phenergan. The drug is safe, Ms. Levine’s lawyers said, when administered by intramuscular injection or by intravenous drip. But they said that efforts to inject the drug directly into a vein carry enormous risks.

A Vermont clinic used that third method, known as IV push, and apparently missed the vein. When the drug was exposed to Ms. Levine’s arterial blood, it caused swift and irreversible gangrene, requiring amputation of her arm below the elbow.

Ms. Levine settled with the clinic and sued Wyeth, saying the company should have added a warning telling doctors not to use the risky method.

Seth P. Waxman, a lawyer for Wyeth, said the company had provided “ample, lavish warnings” about the risks involved and left it to medical professionals to make the ultimate judgment about how to administer the drug.

Justices Samuel A. Alito Jr. and Ruth Bader Ginsburg both questioned the cost-benefit calculation that allowed the drug to be administered by IV push.

“On the benefit side of this you don’t have a life-saving drug, you have a drug that relieves nausea,” Justice Alito said. “On the risk side, you have the risk of gangrene.”

Justice Antonin Scalia said that what mattered was not whether the agency’s decision was sound but whether it had addressed the issue at all. “If you’re telling me the F.D.A. acted irresponsibly,” Justice Scalia told Ms. Levine’s lawyer, David C. Frederick, “then sue the F.D.A.”

Chief Justice John G. Roberts Jr. tried to boil down Mr. Frederick’s argument to a simple test. If the F.D.A had considered the risks involved in IV-push administration, Ms. Levine would lose; if the F.D.A. had not considered those risks, Ms. Levine would win.

Mr. Frederick said Ms. Levine would win under that analysis, saying the F.D.A. had never specifically compared the risks of methods of intravenous administration.

Mr. Waxman said he understood that “members of this court are concerned about applying a broad, vague or freewheeling analysis.” But Ms. Levine’s case, he added, is in the “heartland” of implied pre-emption, given that the jury had awarded damages for Wyeth’s failure to alter the very drug label the F.D.A. had approved.

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Last Inning of the Blame Game

11/04/2008 04:11 AM |

Paul Krugman is too busy trying to run up the score against the "unreasonable Republicans" ( those of us who are racist and reactionary according to the Nobel Spurious) to realize that after Election Day he will be playing defense.  So for instance, he will have to explain why denying employees the right to secret ballot and permitting voter intimidation in the workplace is "pro-labor legislation" and why a VA health system that consistenly cripples veterans and loses their medical records is a model for single payer healthcare.

Get ready Krug.  Spring training is nearly over.  http://www.nytimes.com/2008/11/03/opinion/03krugman.html?ref=opinion  Read More & Comment...

Oui Ministre

11/03/2008 03:02 PM |

At the recent Center for Medcine in the Public Interest conference, "Physician Disempowerment:  A Transatlantic Malaise," Francois Sarkozy, MD (yes, the brother of the guy who didn't really call Sarah Palin) presented a videotaped interview with the real French Minister of Health, Roselyne Bachelot.  Her topic, "The evolution of the practice of medicine."

To view the interview, click here.

And to view Dr. Sarkozy's PowerPoint presentation, click here. 

This issue is becoming ever more urgent when you consider today's news from the UK that NICE (the National Institute for health and Clinical Excellence) has extended until January its assessment of four kidney cancer drugs, none of which was deemed cost-effective in a draft appraisal issued in August .

NICE, which "assesses" technology for the national health service in England and Wales, said that bevacizumab (Roche's Avastin), sorafenib (Bayer's Nexavar), sunitinib (Pfizer's Sutent) and temsirolimus (Wyeth's Torisel) did not represent the best use of NHS resources when used to treat advanced and/or metastatic RCC, despite acknowledging their clinical effectiveness in some settings and the narrow choice of other treatment options.

Is this what we want in the US?  Because this is what (at least in the current context) "comparative effectiveness" means.

What we need are 21st century assessment tools for a personalized approach to the "4 rights" -- the right medicine in the right dose for the right patient at the right time.  In other words, tools for patient-centric rather than cost-based comparative effectiveness.
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Opening Arguments

11/03/2008 01:57 PM |

Today the Supreme Court takes up Wyeth v. Levine. Many are calling it "the business case of the century."  And even though our century is still in its infancy -- it's hard to argue otherwise.  But preemption is more than just a legal argument -- it's an important public health issue.

Consider some of the arguments from the pages of the Journal of Life Sciences.

Attention must be paid.
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Imaginary Prescriptions For Health

10/31/2008 08:05 PM |

First we have the revelation that many doctors prescribe a real "nothing" for patients, in part because nothing is wrong from them (or us) but just want time and the "laying of the hands" from a healer. 
http://www.cnn.com/2008/HEALTH/10/30/ep.doctors.prescribe.placebos/

Next, rather than paying doctors for keeping people healthy or simply being there, health plans are -- even as legislative and ideological forces seek to eliminate the role of drug, biotech and device companies in discussing products with physicians -- filling the void with dollars and demands to swtich patients or start them on generic drugs.     Nothing wrong with generic drugs, they are saving Medicare billions, but ultimately we want to get to point where prescribing is based on value, not just cost.  But getting information about that will require close and open communication between everyone. 
http://ap.google.com/article/ALeqM5hsuaRf6mJu1lKskznFkkD9tHg6MAD944C4HG0

So you see, both power and knowledge abhor a vaccuum.   And it will be filled by those pushing a financial and political agenda, such as trial attorneys and the consumer groups that benefits from their largesse, medical quacks and shakedown artists (like Steve Nissen). 

How does this pentultimate preemption affect patients?

The most recent study from my former perch at the Center for Medical Progress at the Manhattan Institute (home to many solid Yankee fans!) tells the tale.  The analysis, conducted by Columbia University Frank Lichtenberg is entitled:

Alive and Working: How Access to New Drugs has Slowed the Growth in America’s Disability Rates

It concludes that "access to pharmaceutical innovations has been responsible for keeping large numbers of U.S. residents off disability rolls who otherwise would have joined them."

The study shows that if " the average vintage of drugs prescribed since 1995 and paid for by Medicaid had not become more recent, the rate of increase at which working-age people were classified as disabled would have been 30 percent higher than it actually was, resulting in 418,000 additional people receiving disability payments in 2004. Social Security benefits paid to this population would have been an additional $4.5 billion."

Are generics really the best value for Americans?  For millions of us, of course they are.  But to say it's better to prescribe generics in all cases is to suggest that the only valuable thing doctors do is not to prescribe new drugs... 

Better drugs (the right drug for the right person!), more time with doctors.  That's a much better bang for the buck than what the social engineers and health policy elite have in mind.
http://www.manhattan-institute.org/html/mpr_07.htm

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Preemptive Strike

10/31/2008 05:41 PM |

Today on CNBC's "PowerLunch" I debated the issue of preemption.

(I represented the "pro"/public health side of the argument.  The "anti"/tort lawyer argument was proferred by Brian Wolfman of Public Citizen.)

Here's a link to the segment. 

Have a look and judge for yourself.
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Judicious Jane. Germane Janet. Bullish Bob. And other Gems on REMS

10/31/2008 11:58 AM |

Some memorable comments, questions, clarifications – and challenges from the recent Risk Management and Drug Safety Summit held at the National Press Club, October 28-29.

Janet Woodcock, MD, Director, CDER, FDA

“Safety means doing the right things for patients.”

“FDA must consider post-approval issues as part of a drug’s lifecycle.”

Dr. Woodcock also addressed the environment in which REMS exists.  She pointed out that there is a real difference between “headlines and help.”  In other words, REMS and other safety mechanisms can be viewed as either “headlines” about “unsafe” drugs or in a more appropriate context of “safe use.”

To this point she specifically discussed warfarin and abacavir – are these “dangerous drugs” or medicines that, with the appropriate diagnostic tools, can be used safely?  Two sides of the same coin.  Janet opts for “safe use,” while others (in the media and elsewhere) seem more predisposed to the other.

She also mentioned that the FDA’s Office of Surveillance and Epidemiology needs to hire “real experts” on “REMS issues” who can develop “predictable procedures and best practices.”

Per the agency’s forthcoming “safe use” program, Dr. Woodcock called for a public/private partnership to make the design and outreach of this important initiative more robust.

Laurent Auclert, MD, Head, Risk Management Plan Unit, Global Pharmacovigilance & Epidemiology, sanofi-aventis

Dr. Auclert began his talk by pointing out that “epidemiologists and statisticians must talk with each other.”  Everyone seemed to agree that this is both a good idea and an interesting sociological experiment.

He also considered the difference between RMPs in EU (“risk assessment”) versus REMS in the US (“risk minimization”).  A contentious proposition.

Jane Axelrad, JD, Associate Director for Policy, CDER, FDA

Jane pointed out that of the 15 post FDAAA REMS plans required by the agency, 12 were “MedGuide only.”  Her point was that the agency is using its REMS authority “judiciously.”

They don’t call her “Judicious Jane” for nothing.

She also reinforced the point made by Janet Woodcock that the FDA is trying to provide clarity to the process by developing both templates and clarity (per FDAAA) of classifications – and that the agency is preparing official guidance. 

Carmen Bozic, MD, Vice President, Drug Safety & Risk Management, Biogen Idec

Dr, Bozic presented the risk management plan for Tysabri (TOUCH -- TYSABRI Outreach: Unified Commitment to Health).  Fascinating stuff.  She called it “elaborate.”  A more appropriate adjective is “elegant.”

Robert Goldberg, PhD, Vice President and Director of Programs, CMPI

CMPI’s very own Bob Goldberg opined that ‘REMS may very well be a way to revive applications that once looked dead.” 

I hope so – and so do many others who look at the current “safety jihad (and jihadists) along with the current parched pipeline and wonder whatever became of the hoped-for miracles of the “biomedical century.”

Donald Therasse, MD, Vice President, Global Patient Safety, Lilly Research Laboratories

Don said what everyone was thinking, “The drug label must remain the central tool in risk minimization.”  And considering the current and heated debate over preemption, this is not only a timely comment – but a core and crucial one.  He also opined that, “REMS must complement rather than direct or impede the practice of medicine.”

John Ferguson, MD, Vice President & Global Head, Pharmacovigilance and Medical Safety, Novartis Vaccines & Diagnostics

John discussed REMS in the context of “string theory,” specifically outcomes, probability, and values (perceptions) – referring not to benefit and risk, but rather “composite benefit and composite risk.” He posed a disturbing question, “In an age of risk management – what happened to benefit.”  Indeed.

Cherif Benattia, MD, Vice President, Pharmacovigilance & Public Health, Vertex Pharmaceuticals

Cherif began by saying that we must shift the conversation “from information to communication and information.”  Sounds obvious – so why aren’t we doing it?  He also asked a disturbing question:

“Who should manage drug safety?  Lawyers?  Doctors?  The FDA?  State legislators?  Federal legislators?”

And that’s a good place to stop – but not for too long.

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Waxman Preempts The Facts By Redacting the Record

10/30/2008 06:16 PM |

If you read the article that Kevin Freking wrote for the AP, based on a report produced by Henry Waxman entitled.

And you would have missed this penultimate statement from the flurry of memos (I read them all) 

"I agree with the idea that we should preempt state requirements for labeling of drugs. It makes no sense for us not to have a federal system for labeling approved drugs that is based on a careful scientific review of the available data and a consistent application of labeling policies across products. I see this as a legitimate FDA area of involvement given our statutory authority over the drug approval process."

That was John Jenkins.  And not one of the memos take issue with the position that FDA should preempt state requirements, especially those dredged up from tort proceedings. 

The issue was and is about whether the FDA had enough control over labeling and safety monitoring in a coordinated fashion to produce the appropriate balance between risk and benefit, patient rights and company behavior.   The goal is to encourage companies to do more to make sure labeling reflects the most up to date science and is communicated clearly and quickly to patients and everyone else to improve the use of the product and public health.   The idea that FDA officials and their words are being twisted to promote a trial attorney agenda is disgusting beyond imagination...

Jenkins seeks a compromise which is now part of the fabric of the Critical Path and FDA authority under FDAAA:

"If we are going to go this route to protect sponsors, the appropriate balance in the favor of public health may be to give FDA more authority over labeling."

Which is exactly what has happened since 2003 when the memos were written.   Where oh where have the self-serving solons at JAMA and NEJM been the past five years.  They keep flogging VIoxx as an example of why tort lawyers should have control over labeoling.   But within the FDA Vioxx was and is regarded as a safe drug under certain conditions that no longer apply since the drug was withdrawn:

Jenkins again:

"Had Merck not decided to voluntarily withdraw the product it would have been necessary for them to make labeling changes to add warnings about ,the new findings. We probably would not have issued an approval letter on the labeling changes since we would not have had access to the full study report for review so we could evaluate the actual data that would be added to the labeling. So, we probably would have agreed to interim labeling and asked Merck to submit it as a CBE and we would have made more official determinations later after we reviewed the full study report. "

It was the withdrawal of Vioxx and the failure to work with the FDA to make labeling changes that triggered the "Vioxx scandal" and the ensuing mess.  Waxman wants us to believe FDA officials want more of the same instead of a science-based approach to label changes..  The Waxman report is all about manipulating the truth and is an example of how "facts" are treated in the courts that he and others would want to determine what is said about medicine and how it's practiced.
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REMS Creep

10/30/2008 03:55 PM |

I recently chaired the "Risk Management and Drug Safety Summit" (co-sponsored by the Center for Medicine in the Public Interest, FDA News, and United BioSource Corporation).  It was a content-rich experience.

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.

I can assure you that there will be no REMS sleep allowed during this event.

 
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.

The second, more important and contentious difference is the environment into which REMS was birthed – an environment in which there is growing realization that the 21^st century FDA must add a third leg to its mission of safety and efficacy – and that third leg is safe use.  The safe use of drugs.  And the formulation, implementation and communication of plans – REMS plans -- that will assist physicians and patients achieve better outcomes through the strategies and tactics devised therein.

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.”

“Influence rather than control” is a savvy and sophisticated concept -- one that many of our elected members of Congress could learn from, and one in which REMS plays an important role.

The FDA’s new "Safe Use" initiative is the patient-facing sibling of the agency’s “Safety First” pharmacovigilance program. But it's more than that -- it's the FDA reasserting ownership of safety from those who would use it only as a mallet of fear. I will not mention names.

That being said, there are those in industry and in the broader healthcare policy arena who look at REMS and don’t see GEMS.

Many have looked at the FDAAA language on REMS and see 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 authority, I do not agree that it is either ill advised or an over-extension of the agency’s purview.

REMS is the responsible extension of the FDA's mission of safety and efficacy into the new realm of safe use. The first real move into this space, if you think about it, was the FDA's change to the warfarin label. Warfarin is complicated to use because the optimal dose varies greatly among patients. With warfarin, if the dose is too strong the risk of serious bleeding increases and if the dose is too weak, the risk of stroke increases.

Via molecular diagnostics specifically called out in the amended FDA label, the health benefits and the resulting savings in health care costs generated by using personalized warfarin dosing decisions are estimated to prevent 85,000 serious bleeding events and 17,000 strokes annually – and that’s just in the

United States. And estimates predict the reduced health care spending from integrating genetic testing into warfarin therapy to be $1.1 billion annually.  And that’s the mid-range.

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.

In a recent paper, FDA Deputy Commissioner Randy Lutter said, “The Food and Drug Administration has a key role to play in facilitating the use of genetic information in drug therapies because it approves labels, and labels influence how doctors use drugs.”

It does not take even a small leap of faith to apply the philosophy of REMS to this trend of thought.

The concepts of "safe use" as an integral part of the FDA's 21st century mission and REMS as one of many tactics to achieve better patient care are contentious and crucial.  And it is that debate which brings us together today.

Later on this morning we’ll hear from Jane Axelrad, the associate director for policy at CDER.  Here’s what Jane had to say recently about REMS, “These safety plans allow patients to have continued access to certain medicines for which there are safety concerns that can be managed through appropriate use.”

Whether you say “appropriate” use or “safe” use – the principle is the same – making sure that the risk/benefit analysis of any given therapy is communicated in a lucid and (when required) strident manner. 

Sometimes that requires a label change.  Sometimes it requires a REMS plan.

But it will always require the active participation and leadership of the FDA in partnership with the pharmaceutical industry, physicians, and yes – even patients.  Because no safe use program will succeed without the secret ingredient of patient responsibility.

While some see REMS as mission creep, others see it as the natural and logical extension of FDA responsibility in our new age of more precise diagnostics and personalized medicine.

That’s how I see it and why the Center for Medicine in the Public Interest was pleased to be a co-sponsor of this conference.

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Fear of Five

10/30/2008 12:52 AM |

The anti-preemption crowd is running scared.

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

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Raising the bar and lowering the boom

10/28/2008 11:07 AM |

In what seems like an about-face, the British government says that it will now allow patients to pay privately for cancer drugs and other end-of-life treatments without having to meet the full cost of their NHS care if they choose to do so.

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.”


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Autism Anxiety Stoked By Both Campaigns

10/27/2008 06:59 PM |

The In Vivo Blog has a great post on how both campaigns are pandering to the "autism" vote such as it is and an honorable mention to Henry Waxman for standing up for science with regards to the autism-vaccine scare. 

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/
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Defaming Joe DiMasi (Part XXX)

10/27/2008 03:43 PM |

Donald Light (what an apt name for someone lacking scientific heft and what a disgrace that my tax dollars support in some way his position at the University of Medicine and Dentistry at NJ) continues to defame Joe DiMasi.....

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.
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The NYT Has An Evidence Gap

10/27/2008 02:55 PM |

Apparently the NYT thinks that an organization that evaluates medical devices for insurance companies and Medicare is less conflicted than the doctors seeking to help their patients. Does the NYT understand that head to head comparisons of most diagnostics and devices particularly for cancer have no use because of the increasingly personalized nature of treatment and the role such products play in seeking to increase the predictiveness and effectiveness of such technologies. Or that the only way to do so is not through randomized clinical trials but through clinical observation? Certainly insurance companies and ECRI (the comparative effectiveness outfit that works for insurance companies) would benefit from longer reviews before a product is paid for. But what about patients and doctors? Is there any evidence that delaying accessing to innovation for the sake of cost containment is any more efficient in finding the right treatment for the right patient than other patient-centered approaches developing knowledge?

Read New York Times Article here
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