To Sir, with Love

03/23/2009 03:35 PM |

Well, if not love then at least respect.  Significant respect.

I had lunch today with Sir Michael Rawlins (Chairman, National Institute for Health and Clinical Excellence) in his office today.  Finger sandwiches were served – but the conversation was meaty.

Rather than sharing any particulars of a private conversation (Chatham House rules, you know), I will say that we were of a mind on many things -- not the least of which is the need for better tools for clinical effectiveness research.

My only “ask” was for Sir Michael to consider traveling to the U.S. to speak at a Center for Medicine in the Public Interest conference on the future of clinical effectiveness.  He readily agreed.

Watch this space for more details.

While waiting in the NICE lobby, I picked up a brochure entitled, “How to Change Practice.”  There is much in it to debate, but one thing must be stipulated – the quote at the bottom of page 4:

“Change is not made without inconvenience, even from worse to better.”

The words (via theologian Richard Hooker, 1554-1600) are right, but it’s frightening that NICE should choose to quote from Hooker, who is (arguably) best known for his belief in the doctrine of “Justification by Faith.”

But I digress.

In the meantime, have a look at this new op-ed (from the Newark Star-Ledger), "President Obama, health care and "comparative effectiveness research."

Here are the concluding paragraphs to whet your wonkish appetite:

“Another way to make sure comparative effectiveness research is used properly is to follow the Food and Drug Administration's lead in creating a Critical Path Initiative for CER. The FDA's current Critical Path Initiative aims at using the latest scientific advancements to modernize the process through which treatments are turned from laboratory discoveries into useable medical technologies.”

“This model would be just as helpful in creating a modernized comparative effectiveness research program. By utilizing the most up-to-date scientific knowledge, treatment potency could be assessed in a manner that gives the utmost attention to the genetic, clinical, and demographic factors that affect how different patients react to different treatments.”

“President Obama is right to see the potential benefits associated with comparative effectiveness research. As he moves forward with his plan, however, it's imperative that he also be aware of the serious risks that this research poses.”

  Read More & Comment...

Blumenthal's Soros Connection

03/20/2009 06:07 PM |

Why did all the press releases about David Blumenthal, who will run the health IT shop over at HHS, ignore the following:

Blumenthal is also head of an organization called The Institute on Medicine as a Profession (IMAP) which according to it's website "aims to set forth a vision for professionalism in the 21st century and to promote that vision through research and policy initiatives. "

IMAP received a $7.5 million grant from George Soros who made his money in part from wrecking currencies. IMAP is part of a new venture called The Prescription Project, which is funded by Community Catylst, which in turn is funded by the same group that funds the liberal Families USA which also receives money from Soros. The Prescription Project is being funded by the Pew Charitable Trust to the tune of $6 million but is also linked to the Prescription Access Litigation Project through its affiliation with Community Catalyst. That project is comprised of the largest tort lawyers suing drug companies for a variety of reasons.

The Prescription Project is designed to end companies from having any contact with doctors or patients whatsoever. As the project notes: "Public and private payers spend billions of dollars a year on prescription drugs. When these payers rely on information from industry marketing campaigns rather than unbiased scientific studies, the result is higher cost and poorer quality."

Maybe we will only connect to doctors by computer using messages screened for commercial content and judge consistent with materials produced by the Federal Comparative Effectiveness Coordinating Council.
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Run Jesse Run!

03/20/2009 12:48 PM |

Jesse Goodman, the well-respected CBER director is getting a new job.  Actually, two new jobs.  He’s been promoted to be FDA’s Chief Medical Officer and will also serve (as the agency’s only representative) on the Federal Coordinating Committee on Comparative Effectiveness – where his ability to think big, think smart, and think fast will be a tremendous asset.

Jesse is a smart guy, a nice guy, a key player in the FDA’s Critical Path Initiative – and a heck of a tennis player.

It's good news for Dr. Goodman -- and better news for the public health.

Congratulations Jesse. 

  Read More & Comment...

The Sharfstein Shudder

03/19/2009 12:26 PM |

Unnamed "lobbyists" say one thing -- I say, let's give the guy a chance.

Here's what CongressDaily has to say:

Drug industry is wary of Obama's pick for FDA deputy

By Anna Edney, CongressDaily

Food, pharmaceutical and medical device groups have lauded President Obama's pick to lead the Food and Drug Administration, but his selection for second in command is giving the drug industry heartburn.

Industry insiders describe their colleagues as cautiously optimistic about FDA Administrator-nominee Margaret Hamburg, a former New York City health commissioner who works at a nuclear nonproliferation think tank, and nervous in varying degrees about Baltimore City Health Commissioner Joshua Sharfstein.

"Hamburg will be focused on the food supply and creating regulation of tobacco, and to some degree it's expected Sharfstein will have a certain amount of autonomy on pharmaceuticals and medical devices," one lobbyist said.

"Companies are clearly going to get more scrutiny."

The drug industry is viewing the dual picks, as one FDA lawyer put it, as a "power-sharing agreement."

Obama emphasized food safety when he announced the selections of Hamburg and Sharfstein, likely keeping in mind the string of deadly foodborne illness outbreaks in recent years. Hamburg's public health and bioterrorism background make food safety a natural fit. She is a senior scientist at the Nuclear Threat Initiative, which publishes Global Security Newswire, a National Journal Group affiliate.

Sharfstein, on the other hand, has a long and sometimes contentious history with the pharmaceutical industry.

"Anyone who spent their career under Henry Waxman ...," said one lobbyist, trailing off with a shudder.

Sharfstein worked under the now-House Energy and Commerce chairman from July 2001 to December 2005, a Waxman spokeswoman said.

Waxman has been tough on drug companies, particularly given several scandals involving contaminated drugs or unheeded warnings in the recent years. Sharfstein has carried the torch on many of his former boss' public health priorities, ranging from cracking down on medication use for illnesses not approved by FDA to criticizing pharmaceutical companies for gifts handed out to physicians.

Sharfstein led the Obama transition team's FDA evaluation and was thought by many to be a shoo-in for the top post at the agency. He raised warning bells as well that led the agency to re-evaluate the safety of cough and cold medicine use for children.

The pediatrician could play a key role implementing 2007 FDA legislation that set up a system for pharmaceutical companies to assess risks associated with their products and come up with a plan to mitigate those risks -- hence the term risk evaluation and mitigation strategy, or REMS. The law affords FDA the discretion to determine how stringent a product's REMS should be, and the drug world fears potentially burdensome REMS could become the norm.

"I think companies are really nervous based on his track record," an industry insider said.

Peter Pitts, co-founder of the Center for Medicine in the Public Interest and a former FDA associate commissioner for external relations, argued the drug lobby's fears are unfounded.

"I don't think you'll see more strident regulations," Pitts said. "I think you'll see a more effective way to use existing regulations."

He anticipates FDA will experience an influx of resources this year that will have the underfunded agency running smoother and more efficiently.

One lobbyist called the new funding on the horizon "a blessing and a curse," adding, "With that money, the question is: What type of additional oversight or regulatory burden [is] not going to be put on just pharma-companies but biotech and medical device companies as well?"

Waxman is a leader in trying to move legislation that would grant FDA the authority to oversee tobacco, a bill Sharfstein worked on with the chairman, as well as his most recent legislation that would allow FDA to approve generic versions of biologic drugs.

  Read More & Comment...

Comparative Ignorance on Prostate Cancer Screening

03/19/2009 03:29 AM |

In case you missed it, here is what the Fritz Schroder who ran the European Randomized Study of Screening for Prostate Cancer said about the results of the study published today in the New England Journal of Medicine:

By initially screening men 55 to 69 years with the PSA marker and offering regular follow up, this led to an increase in early detection. Deaths due to metastasized disease were then reduced. Exact data showedthat on average for every 1,408 men screened, 48 had cancer diagnosed and received treatment, resulting in saving one life. Screening took place on average every four years with a mean follow-up over nine years. The cut-off value was a PSA level of 3.0 ng/ml or more. Men with this reading were then offered a biopsy.

The study shows that PSA screening delivers a 20% reduction in mortality from prostate cancer. This provides decision makers on screening policies with important new data on the effectiveness of PSA testing in preventing deaths.

Did you miss that? I sure did. I am sure you did too. Know why? Because the New England Journal of Medicine, the New York Times, USA Today, etc, all ignored the findings and ran with this:

"The PSA blood test, used to screen for prostate cancer, saves few lives and leads to risky and unnecessary treatments for large numbers of men, two large studies have found."

Mortality Results from a Randomized Prostate-Cancer Screening Trial  (The New England Journal of Medicine)

"The findings, the first based on rigorous, randomized studies, confirm some longstanding concerns about the wisdom of widespread prostate cancer screening. Although the studies are continuing, results so far are considered significant and the most definitive to date ..."

Continued Here

"What the European study tells us is that, if you are a man who chooses screening, you are 47 times more likely to be harmed by screening than to have your life saved," said Dr. Otis W. Brawley, chief medical officer of the American Cancer Society.

Where to begin?

Unnecessary and harmed by screening?

What is Brawley thinking? Does the ACS really pay him to say things to reduce prostate cancer survival rates? Does he realize that urological oncology has learned how to segment and stage prostate cancers based on risk and PSA velocity? That the number of cancers detected that undergo watchful waiting have increased even as the more dangerous tumors can be removed successfully to increase overall life expectancy at ever age and that this is possible because of the increase in early and widespread detection in combination of better treatment?

Oh, and did he read the methodology section of the study which controlled for mortality caused by treatment? Guess not.

Read More

Now let's turn to Kolata who's article is as balanced as the Dreyfus Affair. The American study likely understates the impact of screening because the design is biased against minorities who would have higher detection rates of cancers that progress faster and have an oversampling of asymptomatic patients whose slow growing tumors are likely to have a a good prognosis. This bias was further compounded in the American study because the treatment rates in the untreated group were about the same as those in the treatment group:

The other half of the men on the trial were offered “usual care” - meaning ‘whatever their health insurers considered appropriate’. Crucially, this meant that the control group for the study contained men who could also potentially be screened for prostate cancer.

"According to this analysis, over half of men in the ‘unscreened’ group actually received some form of prostate cancer screening (compared to over eight-out-of-ten men in the ’screened’ group)."

In the US trial, some men who were in the unscreened group actually ended up having a PSA test - probably as part of their health insurance or because of suspected prostate cancer symptoms.This may have significantly affected the results, by cutting deaths from prostate cancer in this group, and reducing any differences the trial was designed to show."

Finally, both studies took a one size fits all approach to screening and to PSA levels. In fact, PSA use and levels in the real world are tailored to family history, age and race. Increasingly, algorithms that combine clinical data, PSA levels and other markers such as fusion genes and sarcosine, a metabolite found in urine can be used to more precisely determine whether prostate cancers were benign, localized or agressive.

Read More

Here is info on the PSA Test

So the take away is this: to make policy or impose reimbursement from one clinical trial or even several is fool hardy. To dictate clinical practice and ration screening based on press releases or sound bites is irresponsible.

Then again both the NY TImes and the American Cancer Society are desperately seeking to show the flag on comparative effectiveness. They have done the job well on prostate cancer screening. At the expense of cancer patients and medical progress.
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My Daughter's Battle With AHRQ

03/18/2009 06:55 PM |

The folly of comparative effectiveness reviews
By Robert M. Goldberg

Comparative effectiveness—which is supposedly the “science” of comparing two treatments for the same illness and determining which one provides the best outcome for the least amount of money—is something that at least on the surface should be a process we can all agree on.   Who wouldn’t want to use baking soda in warm water for an upset stomach instead of a four-dollar pill?  
 
But these homely comparisons are not why a collection of interests—including insurance companies, managed care plans, government bureaucrats, advocates of single-payer health plans and experts from government-run health systems from Canada, Britain and Australia—have spent millions lobbying for the inclusion of $1.1 billion to create a government run agency to conduct comparative effectiveness studies.  And it is not because, as the advocates for this mega-agency promise ( with a budget  exceeding  the Food and Drug Administration’s allocation on regulating new drugs, vaccines and devices) any decisions would be legally binding on doctors, Medicare, Medicaid or any health plan that would be regulated under Obamacare.   In fact,  Britain’s  National Institute for Health and Clinical Excellence (NICE) has no authority to control what doctors do or what its National Health Service (NHS) pays for.    (The managed care lobby, America’s Health Insurance Plans or AHIP, supports giving a comparative effectiveness agency such authority.)
 
Yet, the NHS now obliges itself to follow NICE comparative effectiveness decisions.  And so doctors and patients have to wait years for NICE judgments or more accurately for NICE to say that paying for drugs for osteoporosis, Alzheimer’s, arthritis and cancer just isn’t worth it.  Even worse, the whole comparative effectiveness decision-making process now overshadows everything.   Any evidence, biological or otherwise that does not go through the government comparison mill lacks “kosher certification” and is regarded as not authoritative.   To express pain, pose scientific questions, challenge questionable or sloppy assertions, one must become part of the bureaucratic apparatus or the parasitic lobbying necessary to obtain a “seat at the table.” The establishment of such an agency is dangerous if not done with great humility and humanity. My opposition is based not only on this concern but my experience on how it grinds human life into dust. 
 
Several years ago my daughter battled bulimia.  She was hospitalized three times for one month or less.   Her discharge had nothing to do with treatment success.  It had everything to do with her managed behavioral health plan following the logic of the comparative effectiveness review of the Agency for Healthcare Research and Quality (AHRQ) which will be responsible for turning the $1.1 billion into more reports.  Or rather, it was how such reports are written and used that gave the insurer the running room to toss Sara and others like her out of the inpatient setting irrespective of whether they were clinically ready.  
 
For instance, an AHRQ technology assessment, “Management of Eating Disorders,” published in 2006 concluded that the evidence for the effectiveness of combination of treatments for bulimia remains “weak.”   It also went on to note that “few factors were found to be consistently related to outcomes.”
 
It was the process of taking the opinion of a group of health care consultants that evidence was “weak” and giving it the imprimatur of government authority that allowed health plans to limit coverage for eating disorders, claiming they are psychological instead of biological or truly measurable.   This happened even without a law linking reimbursement to an explicit recommendation.  

In fact, the reasons that “factors” are not “related to outcomes” have nothing to do with the implication that longer treatment is ineffective.  The “technology assessment” never states what is well known: that the disease is still not well understood.  Worse, it never acknowledges that the 30 day or less discharge contributes to the problem.  When Sara was discharged she found herself fighting the urge to binge or purge the sense of shame and drive to perfection common among people with bulimia was amplified and was, sadly, reinforced by parents anxious to avoid a relapse or doing anything wrong.  
 
Sara was discharged the first time after she did not binge or purge in a controlled setting for a few days in a row.  Twice more she was discharged not because she was able to get control of her illness but because her blood pressure had been stabilized. Similarly, one of her friends at her eating disorders program had a perforated stomach from so much vomiting. Against the medical advice of her doctor, her insurance company kicked her out after a week because her heart rate was “normal.”   
 
In 2007, Magellan, Aetna and Blue Cross and Blue Shield, three groups leading the push to expand AHRQ’s reach (and whose comparative effectiveness centers would do much of AHRQ's work) were sued.  Susan Pisano, the spokeswoman for AHIP, said “there is no research that shows that longer treatment produces better results. In today's environment, the real question has to be: What does the evidence show?" I wonder where she got that excuse. 
 
Advocates of comparative effectiveness claim that studies will be used differently here than in Britain.  That’s a lie.  In every other setting in the United States, comparative effectiveness reviews have been used to restrict access to new drugs or deny coverage to life-saving treatment more often than not.  Comparative effectiveness research as currently construed is not about what’s best for people.  It’s about saving money for political purposes.  Don’t take my word for it.  Ask my daughter.  Read More & Comment...

Healthcare Reform Quote of the Week

03/18/2009 12:25 PM |

Here's what Representative Henry Waxman (D, CA) told the American Medical Association the other day: "We all know that we have to get costs under control, but the way to do that is not to tell physicians what they can and cannot do or put them in a position where they cannot put the needs of their patients first.”

 

Mr. Waxman said this publicly at the AMA’s National Advocacy Conference.

 

Further:

 

“Don’t let anyone tell you that what I’m interested in is socialized medicine.  I flatly tell you that is not the case … I am not interested in trying to put a public plan in place that would drive out competition.”

 

Thanks for that – but just what does Mr. Waxman define as “socialized medicine?”

 

We’ll see soon enough.

 

Good quotes from Mr. Waxman – but the winner of the drugwonks healthcare reform quote of the week (yes, even though it's only Wednesday) goes to Senator Ron Wyden (D, OR):

 

"Nobody disputes the fact that there's going to be some startup costs."

 

Thank you Senator Wyden.

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Is Comparative Effectiveness Comparison Shopping?

03/17/2009 05:21 PM |

A nice piece on comparative effectiveness by Ceci Connolly of the Washington Post.  No pun intended.  Nice in that it underscores the limits of comparative effectiveness and it's link to consumer choice rather than top down directives. 

However, there are limits that Connolly's piece did not discuss and which likely will be silence by the IOM panel which is stacked with people who believe that the one size fits all, literature review, take it or leave approach of comparative effectiveness is the key to  universal coverage.  This (with some rare and sensible exceptions) is a panel of patronage appointees intended to suppress responsible, science based alternatives to evaluating treatment effects.  I will have much, much more on this subject in a forthcoming post.  But for instance, don't expect the IOM panel, which is stacked to simply implement an AHRQ agenda that they have developed and receive millions from to address the following issues:

Which drug or treatment works best for an individual based on a variety of factors including genetic variation, co-morbidity, life style preference, stage of life? 

Moreover, will comparative effectiveness force additional studies before a product is paid for?  If so, that will inevitably delay access, raise prices or reduce rates of innovation.  And if trials have to be randomized for each subpopulation the cost goes higher still. 

The drug effectiveness review studies conducted by DERP fail to control for subpopulations and the literature they look at themselves exclude adjustments for severity of illness, genetic variation, etc.   So most "studies" show no difference in drugs for a particular illness when in fact there are substantial variations, particularly in the areas of depression, schizophrenia, hypertension. 

Therefore, shouldn't money be spent on tools for personalized medicine instead of one-size fits all guidelines?  Read More & Comment...

Career Advice

03/17/2009 11:48 AM |

Sources inside the Obama administration assure me that they have no plans to bifurcate food/tobacco from drugs/devices.  In other words, Commissioner-designate Hamburg and proposed Principal Deputy Commissioner Sharfstein will act as a team in addressing the direction of the FDA as a totality.

That being said, the issue of whether or not food safety and security remains inside the FDA or becomes its own agency within HHS remains as contentious as ever, with Representative Waxman and Representative DeLauro agreeing to disagree.

Mr. Waxman (D-CA) believes that the "first step on the legislative path" should be shoring up food safety and finding ways to prevent further incidents. According to the Pink Sheet, “Waxman did suggest that he would entertain the concept of a bifurcated agency in the future. Once reforms are passed and implemented, he suggested Congress could consider "whether a reorganization is necessary" for food safety enforcement.”

But Representative Rosa DeLauro, (D-CT), the chair of the House Agricultural Appropriations Subcommittee which oversees FDA's budget, has introduced the Food Safety Modernization Act, which would move some divisions out of FDA and form a Department of Health and Human Services agency for food safety. The bill, H.R. 875, has 40 co-sponsors.

That being said, a dangerous bifurcation that must be avoided at all costs is a differentiation in the vision for the future of the FDA between appointees and career staff.  Drs. Hamburg and Sharfstein should listen and learn from the agency’s senior staff – most specifically as to how the agency can be both regulator and colleague with the industries it regulates.  A fine line to walk -- but a journey worth the effort.

Exhibit A:  The Reagan/Udall Foundation and the Critical Path Initiative.

After all, the FDA must work to both protect and advance the public health.

A shared vision, crafted together will succeed. 

Unity, yes.  Bifurcation, no.

Yes we can.
  Read More & Comment...

Stark Mad

03/17/2009 04:35 AM |

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Taxing Benefits

03/16/2009 10:48 AM |

During the election, candidate Obama called candidate McCain’s proposal to tax employer-provided health benefits “the largest middle-class tax increase in history.” Today President Obama is sending signals that he would support the same idea.

Representative Pete Stark (D, CA) says it's a "stupid idea."

According to the New York Times, such a tax could raise $3.6 trillion over a decade to help “expand coverage to the 46 million uninsured Americans.”

(The complete New York Times article – worth a read – can be found here.)

Except when you take an honest look at who is being inappropriately included in that 46 million (4.1 million now eligible for government benefits via expanded SCHIP + 12 million already eligible for government programs but not signed up + 10 million illegal aliens, + 10 million Americans “opting out” = 32 million) it really comes out to about 14 million uninsured Americans.

$3.6 billion (over 10 years) + the President’s proposed $634 billion “down payment” (over 10 years) divided by 14 million uninsured.  Talk about healthcare inflation!

(And this isn't counting the dollars allocated via the stimulus package that provides unemployment insurance-eligible Americans and their families with government health insurance as part of their benefits.)

For more on miscounting the uninsured, see “Sasquatch Care.”

Another thing the candidate Obama was against but now supports seems to be drug importation.  Can support of government price controls be far behind?
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Uncle Sam, MD? Not So Fast.

03/13/2009 01:36 PM |

According to Douglas Schoen (formerly a pollster for President Bill Clinton) and Scott Rasmussen (president of Rasmussen Reports, an independent national polling company), “It is simply wrong for commentators to continue to focus on President Barack Obama's high levels of popularity, and to conclude that these are indicative of high levels of public confidence in the work of his administration”

Relative to healthcare reform, they find that a majority of Americans aren’t so keen after all to have their Uncle Sam become Uncle Sam, MD:

“There is no real appetite for increasing taxes to pay for an expanded health-insurance program. Less than half would support such an idea, which is 17% less than the percentage that supported government health insurance when Bill Clinton first considered it in March of 1993.”

(Their complete opinion piece in today’s edition of the Wall Street Journal can be found here.)

The conclusions reached by Schoen and Rasmussen are completely in line with a poll fielded by the Center for Medicine in the Public Interest last October.

The CMPI survey was of “Millennial” voters (18-28 years old) -- often portrayed as the new “driving force” in American politics.  When millennial voters were engaged on the issue of health care reform they had some very strong – and often contradictory – opinions a -- particularly when it comes to issue of “universal care.”

The national public opinion poll of young voters (the result of 1001completed interviews with adults 18-28 years of age who are registered to vote) shows limited acceptance for the potential consequences of greater government control over health care.

While millennial voters report to strongly support the need for reform and the concept of “universal care,” when asked if they are willing to pay higher taxes to pay for a government-run health care system, their level of support swiftly turns in the opposite direction.

Millennial voters are strongly against government-care that results in longer wait times to see a health care provider, limits to the types of treatments and medicines they can access, and the potential for the government to interfere in the decision making and relationship between doctor and patient.

Some germane findings:

* A majority (51 percent) were not in support of any health care reforms that could raise their personal tax burden;

* Sixty-two percent said they would not support any health care reforms that could increase wait-times to see a doctor or the availability of treatments and medicines; and,

* Millennial voters were also equally unsupportive (62 percent) of health care reforms that would increase the role of the government regulation and oversight in doctor-patient decision-making.

(For further details on the CMPI poll, see “The Young and the Restless.”)

The CMPI poll and the findings of Schoen and Rasmussen demonstrate that all sides of the debate need to do a better job educating Americans about how various reform plans will impact the future of our healthcare system.

Nobody said it was going to be easy. 

  Read More & Comment...

Conflict of Interest For Thee But Not For Me

03/12/2009 07:27 PM |

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Pawlenty of Advice on Healthcare Reform

03/12/2009 06:26 PM |

To watch CMPI’s interview with Governor Pawlenty, click here.
  Read More & Comment...

NICE -- and Necessary

03/12/2009 01:01 PM |

SUTENT SIGNIFICANTLY INCREASES PROGRESSION FREE SURVIVAL FOR PATIENTS WITH ADVANCED PANCREATIC ISLET CELL TUMORS,
STUDY STOPPED EARLY

NEW YORK, NY, March 12 -- Pfizer Inc announced today that a phase 3 clinical trial of Sutent (sunitinib malate) has been stopped early after the drug showed significant benefit in patients with advanced pancreatic islet cell tumors, also known as pancreatic neuroendocrine tumors.

An independent Data Monitoring Committee (DMC) recommended halting the trial after concluding that Sutent demonstrated greater progression-free survival compared to placebo plus best supportive care in patients with pancreatic islet cell tumors.

“We are delighted by these findings which demonstrate that Sutent provides a benefit for patients with advanced, well-differentiated pancreatic islet cell tumors — a rare cancer with limited treatment options,” said Dr. Mace Rothenberg, senior vice president of medical development and clinical affairs for Pfizer’s Oncology Business Unit.  “These and previously reported phase 2 data contribute to the growing body of evidence indicating activity with sunitinib in patients with pancreatic islet cell tumors.”

Pfizer has notified clinical trial investigators involved in the trial and regulatory agencies of the DMC recommendations.  All patients in the trial will have the option to continue taking Sutent or be switched from placebo to Sutent.  The full data set from this trial is being analyzed and more details will be presented at an upcoming scientific meeting.

This phase III trial of sunitinib in patients with advanced pancreatic islet cell tumors was initiated based on the results of a earlier phase II trial published in the Journal of Clinical Oncology(July 2008).

In contrast to exocrine pancreatic adenocarcinoma, pancreatic islet cell tumors are rare, indolent tumors of the endocrine pancreas with an incidence of 5-10 per million worldwide annually.  Pancreatic islet cell tumors include insulinomas, glucagonomas and gastrinomas.  Current treatment options are limited.

Sutent is currently approved for both advanced renal cell carcinoma (RCC) and second-line gastrointestinal stromal tumor (GIST), based on efficacy and safety data from large, randomized Phase 3 clinical trials.  Sutent has played an important role in reshaping the treatment landscape for these two difficult-to-treat cancers.  To date, more than 38,000 patients globally have been treated with Sutent in the clinical setting and trials.

This is the second phase III Sutent trial Pfizer has stopped early on the recommendation of an independent data monitoring committee due to benefit.  In January 2005, a phase III trial in GIST was unblinded early when a planned interim analysis showed significantly longer time to tumor progression with Sutent compared to placebo.

  Read More & Comment...

A Sound Peg in a Care Shoal

03/12/2009 11:54 AM |

Commissioner Hamburg and Deputy Commissioner Sharfstein. Does this mean a partnership where one addresses the FDA’s food-side mission (Hamburg) and the other drugs and devices (Sharfstein)? Does it mean that the FDA will be under the thumb of Representative Henry Waxman? (Dr. Sharfstein was a former Waxman staffer.) Or does it mean that the FDA now has the political cover to remove the knife from its back and get back to work?

Will Dr. Sharfstein’s strong support of more robust OTC labeling help or hinder the FDA’s move towards a BTC (Behind-the-Counter) regulatory paradigm?

How will Dr. Hamburg address the dire state of food safety and security at an agency that gets dinged by our elected representatives – but for which Congress is slow to write a bigger check? Will Dr. Hamburg fight for an FDA food safety and security stimulus package? She certainly has the bona fides to do so.

And what about DTC? Will we see more letters (a perennial Hanukah wish from Mr. Waxman) or a move towards brighter lines from DDMAC?

And then there’s the question of REMS plans and complete response letters.

And biomarkers.

And guidance on off-label promotion.

And follow-on biologics.

And bioequivalence for generics.

And drug importation.

And comparative effectiveness for NDA submissions.

And companion diagnostics.

And 510(k) reform.

And greater international harmonization.

And the working relationship with the senior career staff at FDA.

And working relationships with industry and academia.

And, and, and …

Many questions. Few answers.

Here are seven things for Dr. Hamburg and Dr. Sharfstein to consider:

1. A Strong, Science-Based FDA

Everybody benefits from an FDA that leads. This means the agency has to be out in front of every issue for which it is responsible. Every specific action the agency takes is an opportunity to speak to a larger public health issue. Vioxx, for example, was a missed occasion for the FDA to seize the day on the issue of drug safety. When the FDA confidently leads, other stakeholders follow with their expertise, resources and sense of duty. This is not a people-intensive proposition. But it does require the commitment and the skill to do it – and do it right and regularly.

2. The Reagan/Udall Foundation: A Partnership of Unequals

The FDA must be both regulator in protecting the public health and colleague in helping to advance it. This is a delicate balance and in the current political climate the agency gets no merit points for being seen as collaborating with those it regulates. The best way to do this is via the Reagan/Udall Foundation. Now that the election is over an immediate first step should be for the new FDA Commissioner to meet with Representative DeLauro and issue a joint announcement on moving forward with the work of the agency’s Critical Path program to develop the tools necessary for 21st Century pharmaceutical and medical device development and regulation. But FDA must be seen as leading rather than simply participating in the process.

3. Clarity vs. Ambiguity

Regulators often love ambiguity – because ambiguity is power. The problem is that such a philosophy can lead to regulatory dissonance – ranging from completed Phase III trials supported by the agency at advisory committee meetings and then derided by a division afterwards, to warning letters sent to companies over marketing materials that have been “pre-cleared” by DDMAC. If people want the various industries regulated by the FDA to follow the rules, there need to be as many bright lines as possible – and they need to apply to everyone equally. While a high degree of pragmatism will always be required, this is not an excuse for “I know it when I see it” regulation.

4. Information Management

The FDA’s information management system is dysfunctional. The FDA sits at the crossroads of vast amounts of information that is of vital use to both protecting and advancing the public health. –yet most of it is unusable. The new Commissioner should immediately appoint an IT Czar who, as her first order of business, should audit existing systems and draw up an information technology roadmap for the agency. A solid “taskforce of talent” is needed to address this tremendous opportunity. Solid information management systems will allow the agency to do its job better, faster, and less expensively. A solid public health triple play.

5. Food Safety and Security

The agency’s programs on food safety and security are failing. Resources at CFSAN (the Center for Food Safety and Applied Nutrition) are stretched drum tight. More money is certainly needed – but there is also a crisis in confidence that the agency knows what it’s doing – or that it cares. The issue of BPA (bisphenol A) is a good example. The FDA was purely reactive in its call for a review by its panel of experts. As a result, the agency was destined to have its judgment called into question whatever the decision. And this is precisely what happened. This further cements the general perception that the FDA doesn’t care and/or is beholden to the industries it regulates. The BPA issue was out there for a long time in a visible way. And the agency didn’t do anything. It didn’t lead, it followed. And the consequences shouldn’t have surprised anyone. A similar situation is brewing with melamine in baby formula. Further, there is a growing sense that CFSAN should be moved to its own independent status within HHS. Perhaps. But for this to proceed, serious thinking needs to go into two issues: (1) DSHEA and the regulation of dietary supplements as foods, and (2) the increasingly important issue of nutriceuticals and qualified health claims. Both are clearly FDA issues and should remain so.

6. Risk Communications

Rather than assuming the mantle of responsibility and proactively stepping forward with more regular and transparent risk communications programs, the FDA was driven by the winds of crisis. Today the agency has implemented certain programs (some required by FDAAA) that provide risk information – but without any context, rhyme or reason. The result is confusion among patients and physicians and a field day for the media. The unintended consequences have swamped the public health benefit. Senior agency leadership knows it – but what are they doing to address it? The answer is not clear. A good beginning would be for the FDA’s Risk Communications Advisory to look into the matter. This problem needs to be fixed as no one (not industry, not doctors, not patients,) is happy with the current state of affairs.

7. The Drug Label and the “Safe Use” of Drugs

Wyeth v. Levine notwithstanding, the drug label is the single most important piece of communications material the agency issues – and it isn’t working as well as it should. The New Physician Labeling Rule (January 2006) has had minimal impact for three main reasons: (1) It has not been widely adopted for products licensed prior to the rule (not a requirement, but an option), (2) There has been little agency out-reach to physicians and, (3) There has been no broader agency program on the issue of “safe use.” This last point will change in January when the FDA (via CDER – the Center for Drug Evaluation and Research) launches a more comprehensive “safe use” initiative. The agency must consider not just safety, efficacy and quality – but safe use as well. Not just drug safety, but patient safety. This makes perfect sense and gives the FDA the opportunity to speak not only to physicians, but to consumers as well. The program should be expanded to also include medical devices. It is a timely, important, and urgent opportunity and must be done with determination, creativity, and relentless passion. It must be the FDA on the offense for the public health. And the offense must never stop.

Good luck Peggy. Good luck Josh.

Let’s get to work.

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Will Hamburg Lead Like Lederberg?

03/11/2009 09:44 PM |

Media accounts note FDA Commissioner-in-Waiting Peggy Hamburg's stint as NYC Public Health commissioner.

But to me her best credential was her long scientific association with Dr. Joshua Lederberg.

Dr. Lederberg cared about the FDA, the Critical Path, the swamping of 21st century science by junk science, fear mongering, the dumbing down of drug companies and reimbursement systems that discouraged innovation.

Great minds don't think alike. They are independent. But they also can withstand the political bluster in support of science and medical progress.

Josh Lederberg did this and more.

Let's hope Peggy Hamburg, whose scientific and public health credentials are excellent, does the same. Let's hope she supports the Janet Woodcocks, Bob Temples, Larry Lesko's and others who want to lead the FDA into a future of personalized and prospective medicine and food safety and not the fearmongers from in and outside the agency that want to bring it down because the hate the commercialization of medical knowledge.
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NHS: From Nanny State to "Show Me" State?

03/11/2009 11:57 AM |

Is comparative effectiveness entering a new "show me" state?

Bloomberg reports that,

"For two years, Pfizer, Inc. was quietly giving free doses of its expensive cancer drug Sutent as part of a campaign to help persuade the U.K. to pay for it. Last month, Pfizer finally won. The agency that advises the U.K.’s National Health Service decided the medicine extended the lives of patients enough to justify its cost, as long as the first course of treatment was free. The campaign wasn’t publicized by Pfizer or the U.K. and was revealed in interviews with government and company officials. The campaign cost Pfizer about 2.5 million pounds ($3.5 million) and gained the world’s biggest drugmaker an advantage over competing products made by Roche Holding AG, Bayer AG and Wyeth."

“It’s a relatively new phenomenon, and I think we’ll see more of it,” said Chris Brinsmead, president of the Association of British Pharmaceutical Industry.

The creative pricing arrangements lower the overall expense for the National Health Service and improve the ratio of cost to benefit that the National Institute for Health and Clinical Excellence uses to determine if a medicine should be covered. In all, drugs cost the nation 11 billion pounds annually, about 10 percent of the total health-care bill.

Johnson & Johnson’s blood-cancer drug Velcade won coverage in 2007 after the New Brunswick, New Jersey-based company said it would pay back the government for people who didn’t benefit. Patients get the first four doses of the 762.38 pound drug, then are tested to see if they’ve responded to the treatment. Those who improved continue with the drug. Johnson & Johnson provides a rebate of about 3,000 pounds for those who didn’t respond.

According to Sir Michael Rawlins, Chairman of NICE, “We’re meeting them partway.”

The complete Bloomberg story can be found here.

It's a creative approach based on outcomes -- a giant step towards recognizing the importance of personalized medicine the folly of basing reimbursement decisions on large-scale general population studies.
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Rotten Reuben

03/11/2009 02:12 AM |

No doubt this story will be all over the mainstream media tomorrow as another example of “tainted” industry-sponsored research.

Now this is a terrible case of ethics abuse – but trying to pin the rap on industry (in this case, Pfizer, Merck, and Wyeth) is quite a stretch.

But that won't stop politicians from trying.  After all, nothing like a little Pharma-bashing to get the electorate all hot and bothered. Case in point, Connecticut Attorney General Richard Blumenthal who commented that, “When the public and professionals rely on statements from purported experts with financial interests ... the public trust and credibility are at stake.”

Except that it wasn’t the funding that was the problem – it was the absence of ethics by a rogue anesthesiologist.

It’s also important to note that the majority of scientific fraud comes from non-industry sponsored research conducted by academic institutions -- a result of the “publish or perish” survival of the fittest paradigm.

Here’s the full story.

Take this Reuben off the menu.
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IOM Panel on Comparative Effectiveness Stacked With Rationing Proponent

03/11/2009 01:34 AM |

They include Mark Helfand who gets the bulk of the comparative effectiveness cash from the federal government, Joe Selby of Kaiser who also gets AHRQ money and Sean Tunis, another AHRQ recipient.  Not the least of whom is Alan Garber who compares placing a price tag on human life to putting prices on a menu.

Oh and he gets dough from AHRQ too. 

All support using comparative effectiveness studies like the one's AHRQ and HMOs pay them to do to justify saying "no."  All that many, so few people.  How do you spell conflict?  Mark McClellan stands alone a voice of sanity.

Garber wants us to believe that comparative effectiveness leads to higher prices for companies. How about ten solid examples Alan?  This from a guy who has spent his life slaving to restrict access to new technologies for the VA, Blue Cross and other insurers.

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