The Public Health and 'Avandiagate'

07/15/2010 02:12 PM |

Here's Steve Nissen's take on the 20-12 recommendation of the FDA advisory committee to keep Avandia on the market:

“Effectively, this drug is gone.”

U.S. sales of the drug have plunged from $2.2 billion in 2006 to $520 million last year because of fears generated largely by Nissen.  Meanwhile Actos, made by Takeda, the company Nissen has consulted for, has seen sales of it's product soar from $1. 9 billion in 2006 to $3.4 billion last year. 

I think they got their money's worth.

Whether patients did is another matter.  During the same time, the combined number of scrips for TZDs declined overall by 40 percent and scrips for oral diabetes agents fell by 20 percent.  (I am going to double check this figure..)   Did cardiovascular events among diabetics decline  by 25 to 43 percent as might be predicted?  No. 

While there was an effort to depict Avandia's problems as a matter of deadly risks purposely hidden by GSK the issue was really two-fold.  First, the fact that the FDA had to react to the risks of Avanda as framed by Nissen rather than the overall risk and benefits of each drug in the class in the context of treating diabetes and all it's complications.  It had to focus on heart risks and whether surrogate endpoints were reliable, etc.  all of which were issues framed to undermine confidence in the FDA and shift power to Nissen and outside or rogue forces.  Second, and only after wading through this thicket, was the FDA able even to carry out it's public health responsibility and provide the advisory committee with that task.  To that end,  Commissioner Hamburg's leadership on this issue, along with the stewardship of Drs. Woodcock, Temple, Jenkins and DelPan should be applauded.  And once again David Graham demonstrated why he is best suited for getting coffee in the FDA's division of psychopharmacology..


The big question is whether the treatment and management of diabetes is better off after the fearmongering.

More people have diabetes and fewer people are taking drugs.  Is that a good thing?

Maybe Nissen should worry more about patients instead of his publicity and his bank account.






  Read More & Comment...

Twenty to Twelve and All is Well

07/15/2010 07:19 AM |

The vote ended up not even being that close. Ten panel members voted to keep Avandia on the market but with serious revisions to its label as well as possible restrictions on its sale. Seven voted to simply add further warnings to the drug’s label. Three voted to allow further sales without change. Twelve members voted for market withdrawal.

By my count that’s 20-12 for.

Here’s how that was reported in the Washington Post:

“There is sufficient evidence to be concerned that the diabetes drug Avandia increases the risk for heart attacks and strokes compared with other medications used to treat the common condition, but insufficient evidence that the drug increases the risk for death, federal advisers concluded Wednesday.”

Can you imagine how the mainstream media would have reported the vote had it been 20-12 against?  It would most likely have been something like:

“A consensus of expert FDA advisors strongly called for the recall of the controversial diabetes drug Avandia.”

What does 20-12 mean?  For those screaming for Avandia’s recall it means a considerable set back.  To the FDA it means that it’s time to acknowledge the adcomm’s thoughtful advice and get to work making a decision based on sound-science and the public health.

To most Americans it means that it’s almost time for lunch.

  Read More & Comment...

Three Little Words

07/14/2010 09:16 AM |

Ah, those three little words that we hear so infrequently but that mean so much ...

Robust internal debate.

Reading the coverage of yesterday's Avandia adcomm, you'd think  the FDA professsional staff never disagreed with each other and lived in perfect regulatory harmony.  Nothing could be further from the truth.  Also, statements like "Avandia has split the agency in two" is just laughable -- considering the issue exists in one division of one center.  But, hey, hyperbole sells.

Robust internal debate.  It's healthy and it's the rule rather than the exception -- media reports to the contrary.

Kudos to Peggy Hamburg who, once again, reminds everyone that the science is the only thing that counts.

And science, as those who know understand, is plenty contentious enough.
  Read More & Comment...

PhRMA's Dear John

07/13/2010 09:28 AM |

Pharmaceutical Research and Manufacturers of America (PhRMA) today announced that John J. Castellani will assume the role of President and Chief Executive Officer effective September 1, 2010. Mr. Castellani joins PhRMA after more than nine years as President and CEO of Business Roundtable, a leading association of corporate chief executive officers. He will succeed former PhRMA President and CEO Billy Tauzin, who transitioned to a role as senior advisor earlier this year.  Read More & Comment...

Ignorance is not Bliss

07/13/2010 09:11 AM |

It’s got to be more than just “sign here.”  And it’s about time.

The IOM report on ethical and scientific issues in post-marketing drug safety studies could very easily get lost in the frenzy over you-know-what. That would be a shame because its real value lies in an intelligent and thoughtful outline of how to restructure informed consent. And in our age of the digitally empowered healthcare consumer, this is welcome news

"When a substantial amount of information indicating that a drug to be studied may involve serious safety risks has already accumulated, there are heightened obligations to ensure that potential participants understand the risks posed by study enrollment," the IOM Committee on Ethical and Scientific Issues in Studying the Safety of Approved Drugs says in a letter report.

The IOM says the emphasis given to risk information in the informed consent process should increase with the severity of risk and the level of certainty about the causal connection between a drug and the adverse outcome. "At a minimum, risks that should be disclosed should include any black box warnings, the 'major statement' currently listed in television advertisements, any adverse event findings of an FDA advisory committee, and a summary of evidence from published peer-reviewed studies."

The committee notes that in addition to verbal disclosures and written consent documents, there is a growing set of additional tools, such as videos and interactive electronic presentations that can enhance potential study participants' understanding of risks they may face.

Bravo.

"Whatever efforts are employed to communicate with potential participants, it is key that they include information that is useful to participants about where the weight of the evidence falls with regard to serious risks and the level of confidence that experts have in drawing conclusions about the risks," IOM says.

Potential study subjects should understand how treatment they will receive in the study differs from the current standard of care. "This is particularly crucial in cases in which medical practice has shifted away from prescribing the study drug because accumulating evidence from passive surveillance, observational studies and small trials or meta-analyses suggests that another therapy is as effective and has a more favorable safety profile," IOM says.

And, of course, FDA must assure that the post-marketing study is appropriately designed to answer the public health questions at issue and minimize risk to participants. Risks should be judged acceptable by FDA, data safety monitoring boards and institutional review boards and the study and subjects should be continuously monitored. As always – but it’s certainly worth repeating.

“Ignorance is never better than knowledge”

-- Enrico Fermi

  Read More & Comment...

Hamburg v. Nissen

07/12/2010 10:14 AM |

Make no mistake, the Avandia brawl has nothing to do with science, except that in no instance have the anti-Avandia forces -- and that's what they are -- presented any evidence of a biological mechanism explaining why there might be a higher risk of heart problems.  After pouring through the the 700 pages of additional data about Avandia and combining it with clinical outcomes from BARI-2 and ACCORD study -- both finding no heart risk associated with the drug  --  the choice about whether to use Avandia boils down to clinical judgment and the needs of the individual patient.

As a commentary in this week's Biocentury suggests, the FDA's public hearing on Avandia being held this week is stacked in favor of Steve Nissen and David Graham, the two most public and vociferous critics of the drug.   Something tells me that forces within and outside the FDA are seeking to force FDA commissioner's Peggy Hamburg's hand.

If the advisory committee votes to pull Avandia it will be hard for the FDA not to concur.  And that will be the beginning of the end of the FDA's science-based regulatory authority, at least under this administration.  It will mean that that marauders who react to any safety signal can run to the media and members of Congress to slow down or delay a product's approval or kill it's sales.   It's means that meta-analysis, which has become a powerful data dredging tool for generating risks and diverting attention from benefits by producing spurious statistical association will triumph over biologically based outcomes. 

Fearmongering requires new and unexpected risks.  It must eliminate efforts to individualize treatment based on risks and benefits. 

Nissen and Graham along with their fellow travelers on the one side.  Dr. Hamburg and the FDA's future is on the other.  

The decision on Avandia will decision which way regulatory science and the FDA will go for years to come.
  Read More & Comment...

Please don't hold the Mayo

07/12/2010 07:42 AM |

One of the more interesting subtexts surrounding King James’ move to Miami is the negative economic impact it will have on the economy of Cleveland specifically and the Ohio in general. 

A similar subtext (albeit one that has been entirely ignored) is the negative economic impact the State of Michigan will experience following the University of Michigan’s recent announcement that it will ban any industry-sponsored CME.

The Fighting Wolverines currently receive about $1,000,000 in such services.  And in cash-strapped Michigan that ain’t chump change when libraries are being shuttered and teachers are losing their jobs.

And for what larger purpose?  The U-M's intent in banning industry funding for CME is "to dispel the risk or appearance of conflict of interest.”

It will also result in less CME for the university systems physicians. The school expects the number of CME courses to decline "somewhat" as a result of the new policy.

(According to the ACCME, the university produced 499 separate CME activities last year, reaching more than 130,000 physicians.)

"Somewhat less" CME is not acceptable.  Does the university system expect the taxpayes of Michigan to make up the difference -- so that they can exult in their political correctness?

Since an important aspect of healthcare reform is about lowering costs, how will similar moves by other large public universities (motivated not by public health but by "perceived conflicts") be justified?

Speaking of Cleveland, in the January 2010 issue of Academic Medicine (Adad. med. 2010; 85:80-84), four researchers from the Cleveland Clinic published a paper entitled, "The Effect of Industry Support on Participants of Bias in Continuing Medical Education."  The purpose of the study:  "To obtain prospective evidence of whether industry support of continuing medical education affects perceptions of commercial bias in CME."

The method:  "The authors analyzed information from the CME activity database (346 CME activities of numerous types; 95,429 participants in 2007) of a large, multi-specialty academic medical center to determine whether a relationship existed among the degree of perceived bias, the type of CME activity, and the presence or absence of commercial support."

The study's conclusion?  "This large prospective analysis found no evidence that commercial support results in perceived bias in CME activities.  Bias level seem quite low for all types of CME activities and is not significantly higher when commercial support is present."

The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) have adopted a new policy regarding the disclosure of conflicts of interest. Here's the key paragraph:

"There is no inherent conflict of interest in the working relationships of physicians with industry and government.  Rather, there is a commonality of interest that is healthy, desirable, and beneficial.  The collaborative relationship among physicians, government, and industry has resulted in many medical advances and improved health outcomes."

What a unique perspective -- a "commonality" rather than a "conflict" of interest.

We should all pay attention to our nomenclature.  It's not about "conflict of interest" -- it's about (as Secretary Sebelius correctly says) "interest."  And having an "interest" is not necessarily a bad thing -- as long as you're transparent about it.

When it comes to CME and "interest," we need to weigh it against benefit.  And, as with drugs and devices, we must consider the "safe use" of industry-sponsored CME. 

"The best interest of the patient is the only interest to be considered."

William Mayo, MD

 

  Read More & Comment...

Arizona Duo on Repeal

07/09/2010 11:48 AM |

Congressman Jeff Flake (R,AZ) from CMPI on Vimeo.

  Read More & Comment...

Peggy Pronounces

07/08/2010 02:40 AM |

Two important pieces of news from our friends at BioCentury:

Hamburg opposes separate safety reviews

FDA Commissioner Margaret Hamburg told BioCentury she opposes separating postmarket safety oversight from new drug reviews, a policy Rep. Rosa DeLauro (D-Conn.) and Sen. Chuck Grassley (R-Iowa) are promoting. DeLauro recently announced plans to attach a report instructing FDA to create an independent postmarket drug safety office to an appropriations bill.

"We need to strengthen the integration of safety and efficacy throughout the lifecycle of medical products," Hamburg said. "It would be a mistake to further separate and stovepipe safety and efficacy." Hamburg said she is considering organizational changes to better integrate safety and efficacy oversight. In addition, she said FDA needs to "strengthen safety science, and that's why I've asked the Institute of Medicine to do a report [on postmarket safety studies], and our Science Board will be undertaking a study about safety science at FDA"

Hamburg supports releasing complete response letters

Releasing information about negative decisions on drug applications could benefit drug developers and advance scientific progress, FDA Commissioner Margaret Hamburg said Tuesday at a conference on drug development. An FDA transparency working group's draft proposals include publicizing redacted versions of complete response and refuse to file letter.

"We don't publish information when we don't approve a drug as to why we don't approve it, but that information clearly could have broad value," Hamburg said at the meeting, sponsored by Friends of Cancer Research, Ewing Marion Kauffman Foundation, Council for American Medical Innovation and others. Companies might oppose public release of information about rejection of their application, but "those same companies can recognize there are benefits if everyone opens up and does the same,” she said.

Hamburg told BioCentury that disclosures would describe the reasons for a rejection. They also "would obviously speak to the adequacy of data in certain instances, but more significantly, that certain approaches might not be effective or certain kinds of molecular entities have certain toxicities, and that could have relevance beyond a particular application." FDA would not release commercial confidential information "without industry's explicit permission," she said.

  Read More & Comment...

Robert Butler's Legacy

07/07/2010 06:17 PM |

Robert Butler MD died this week of leukemia at the age of 83, full of projects and brimming with new constructs for future research.   I was a junior at SUNY Buffalo when I read "Why Survive? Being Old in America.”   What I found striking about the book what Butler’s ability to deconstruct aging as a product of disease, not of getting old, which he argued was society’s convenient way of not investing time and money into understanding the biological processes that characterized “getting old.” 

Butler’s contribution to science and society has been two-fold.  Through his  establishment of the National Institute on Aging he developed a focused program of biomedical research and epidemiological studies to establish precisely which diseases had the most impact as we age and provided clinicians and academic scientists tools for preventing the onset of conditions once considered a natural part of getting old.  This change in clinical practice, bolstered by the research Butler supported has done more to improve life expectancy and increase well-being in the United States than anything else we have done. 

Second,  Butler has combined this push for science-based prevention with a sustained search for molecular markers of ‘aging’, or more accurately, of the molecular factors that contribute to cellular breakdown and wear and tear.   And recently, genetic analysis has shown that  “extreme longevity is associated with a select group of genetic markers.”   Yet people who live long lives also have similar levels of a large set of disease-associated genetic risk factors as people do not, including risk factors for Alzheimer's, diabetes, and cardiovascular disease.   The question is now what are those factors that make longer life possible and how do they regulate other diseases. 

These and other issues are being studied now because Robert Butler made aging his life’s purpose.  Irving Kristol observed: You have to know one big thing and stick with it. The leaders who had one very big idea and one very big commitment. This permitted them to create something. Those are the ones who leave a legacy.

Robert Butler leaves many big legacies.  Our nation, our world is better and living longer and healthier as a result.

An excellent tribute to Dr. Butler can be found here:  tinyurl.com/26ph5s9

 

  Read More & Comment...

Barrasso on Berwick

07/07/2010 01:46 PM |

  Read More & Comment...

The IRS and health care

07/07/2010 01:29 PM |

  Read More & Comment...

The Berwick Bypass

07/07/2010 11:30 AM |

The President's decision to make a recess appointment to install Donald Berwick at CMS, thereby bypassing Senate confirmation hearings, has less to do with the romance with the NHS I originally revealed in my American Spectator article and more to do with what would likely to be embarrassing revelations about Berwick's finances in his last year as CEO of the Institute for Healthcare Improvement and  that it appears that he and his closet associates are part of a closed loop of cash and influence that will now control the nation's healthcare system.  I will be reporting more on this later.


  Read More & Comment...

CME: To Be or Not to Be

07/06/2010 06:56 PM |

  Read More & Comment...

Rationing As a Budgeting Strategy

07/06/2010 02:40 PM |

Secretary Katherine Sebelius on the evils of private sector rationing in 2009:

"It's private insurers who often are telling their clients that, "No, you can't get this recommended treatment that the doctor has made"; "No, you can't get this drug"; "No, you're not going to be able to stay in the hospital an extra day"; "No, you're not going to get this because we're concerned about costs."

HHS solution to the fact that Congress has underbudgeted money for temporary insurance coverage for people with pre-existing conditions in state run high risk pools:

The Obama administration has not ruled out turning sick people away from an insurance program created by the new healthcare law to provide coverage for the uninsured.

Administration officials insist they can make changes to the program to ensure it lasts until 2014, and that it may not have to turn away sick people. Officials said the administration could also consider reducing benefits under the program, or redistributing funds between state pools. But they acknowledged turning some people away was also a possibility.

“There’s a certain amount of money authorized in the statute, and we will do our best to make sure that that amount of money insures as many people as possible and does as much good as possible,” said Jay Angoff, director of the Office of Consumer Information and Insurance Oversight at the Department of Health and Human Services (HHS). “I think it’s premature to say [what happens] when it’s gone.”

Read more here

Sounds like rationing to me, at least according to the definition used by Sec. Sebelius: "We will not allow these companies to insure only the healthy and leave the sick to suffer."

instead, the government will make that happen. 

  Read More & Comment...

Payer Proxy?

07/02/2010 08:28 AM |

California is the front line in the war over patient-centric care and cost-based controls.  And the present battle engagement is over Assembly Bill 1826 and “fail first/step therapy”

According to a report in the Sacramento Bee, insurance interests are lobbying state senators to reject the proposal.

“In letters, insurance associations and companies also contend that step therapy is a good idea because employees of health plans are often in a better position than patients' doctors to know the risks of drug interaction.”

Blue Shield of California also wrote, "step-therapy protocols also act as a check-and-balance to the cozy relationship that exists between many physicians and drug companies."

This from the industry that spiffs physicians with monetary incentives when they switch patients from innovator to generic medicines.

The group's letter says plans consult "expert opinion" and federal research, while many doctors lack a procedure to get "the latest information" about proper drug dosages.

All those in favor of disempowering physicians in favor of insurance companies signify by saying “Oy!”

The complete Sacramento Bee story can be found here.

  Read More & Comment...

Don't fix the blame, fix the problem

07/01/2010 03:58 PM |

From today's Wall Street Journal:

LETTERS

July 1, 2010

Finger-Pointing Doesn't Provide Care

The financial disaster that will befall doctors and the corresponding lack of access to care that will befall seniors if Congress fails to address scheduled cuts in Medicare ("Doctors Chafe as Medicare Cuts Loom," U.S. News, June 16) isn't a new problem. In fact, the president was only able to claim that his health-reform plan didn't add "one dime to our deficit" by ignoring $371 billion in spending needed to fix Medicare reimbursement rates.

Congressional Democrats claimed that the cost of fixing the Medicare payment formula shouldn't count as part of their health-care reform package because it was a problem they inherited. But now isn't the time to assign blame. Now is the time to solve the problem, for which we all will have to pay.

Peter Pitts

President

Center for Medicine in the Public Interest

New York City

(Mr. Pitts is a former associate commissioner for the Food and Drug Administration.)

  Read More & Comment...

Enter the Sandman

07/01/2010 03:50 PM |

video.nytimes.com/video/2010/06/30/sports/1247468158551/how-mariano-rivera-dominates-hitters.html
  Read More & Comment...

TMI

07/01/2010 01:52 PM |

Biosensors added to underpants

Using underpants to get to the biological bottom of things?  I encourage you to write in with your favorite application..
  Read More & Comment...

The Bard of Safety

07/01/2010 09:14 AM |

Now set the teeth and stretch the nostril wide.

A separate safety office? 

Hold hard the breath and bend up every spirit.

Report language in a House appropriations bill for FDA outlines the creation of an independent office within the agency to evaluate a drug's post-market safety profile.

Straining upon the start. The game's afoot.

According to Representative Rosa DeLauro (D, CT), who chairs the House Appropriations subcommittee, this new FDA office would (per the Pink Sheet) “avoid the potential for bias that arises when FDA staff who approve a drug are the same people who make decisions when a marketed drug's safety is called into question.”

This is a bad idea for many reasons, let me mention two:

(1)   How can you determine a drug’s “safety” without also understanding its real world concomitant benefit?

(2)   The more-than-implied accusation that FDA staff that worked on a drug’s ultimate approval cannot be trusted to view safety issues without “bias” is entirely untrue and highly insulting.  Who can be trusted?  FDA's own "Bard of Safety" -- David Graham? Shame. Shame.  Shame. 

Representative DeLauro did not provide specific language on a separate safety office during the subcommittee markup, but noted that she developed it with assistance from Senator Charles Grassley (R, IA), and Representative Maurice Hinchey (D, NY). Mr. Hinchey introduced H.R. 4816, the FDA Improvement Act of 2010, which would establish within FDA an independent Center for Post-Market Drug, Device and Biologics Safety and Effectiveness.

Once more unto the breach, dear friends, once more.

On the DDMAC front, the report calls for $3 million more for Abrams & Associates to review DTC materials and an additional $2 million for professional communications.

Depending on where you sit, that’s either too much or too little.

But when the blast of war blows in our ears,
Then imitate the action of the tiger

  Read More & Comment...