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.
  Read More & Comment...

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.
  Read More & Comment...

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

  Read More & Comment...

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.
  Read More & Comment...

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.

  Read More & Comment...

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.
  Read More & Comment...

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.

  Read More & Comment...

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

  Read More & Comment...

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.”


  Read More & Comment...

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/
  Read More & Comment...

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.
  Read More & Comment...

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
  Read More & Comment...

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.

  Read More & Comment...

Who's the Healthcare IT Girl?

10/27/2008 12:58 PM |

From the Boston Globe:

  Read More & Comment...

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


  Read More & Comment...

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."
  Read More & Comment...

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
  Read More & Comment...

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.

  Read More & Comment...

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.

  Read More & Comment...