Matt Herper on the FDA's Avandia Data Desert

07/27/2007 08:52 AM |

http://www.forbes.com/business/2007/07/26/glaxo-avandia-fda-biz-cx_mh_0726glaxo.html

Or why the blockbuster model of drug development and data collection is over.  Read More & Comment...

The Nissen Effect

07/27/2007 07:41 AM |

I am adding a PS to my post. Vioxx was yanked by Merck because a pain killer was shown in a RCT to have a relative risk of MI events of 1.92 (rofecoxib 1.50 events vs placebo 0.78 events per 100 patient years). The results from the first 18 months of the APPROVe study did not show an increased relative risk of adverse cardiovascular events. All the problems cropped up after. And still both the FDA and Canadian Health advisory panels recommended returning Vioxx to the market for many patients under some conditions. In each case panelists believed that uncontrolled pain was a greater risk than the absolute risk of a heart attack from long term use associated with any NSAID.

In Avandia's case, we have no clear cut evidence of MI in any long term data except in the insulin population that doctors tend not to give Avandia to in the first place. So for the FDA to say Monday's meeting is not about Nissen is misleading. It is all about Nissen. It would not be meeting July 30 if not for his end run with his "study." More to the point, the FDA the failed to ask if uncontrolled glucose levels was a greater risk than the absolute risk of a heart attack from long term use associated with any oral diabetes drug.

That's the Nissen effect.  Read More & Comment...

Have I Been Misreading the FDA?

07/26/2007 10:41 PM |

Gardiner Harris has GSK all but sued...no big surprise there since the trial attorneys have been putting together their game plan for months. But Avandia off the market?

Maybe I and others are fighting an uphill battle and Avandia will get creamed. Certainly the number crunchers take a "take no chances" approach to the TZDs which would mean depriving people of use of these drugs based on a fear of uncertainty which is in turn based on a lack of data. I think in this environment that might be enough to crush the TZD's into a purgatory. What is disgusting is the double standard -- accusing the FDA of not acting fast enough when it is apparent that the process of constructing long term trial and evaluating it takes a long time and raising second guessers and sloppy studies from Nissen and Graham to heroic standards.

For what it's worth here are comments from other reviewers that sparked hope that the FDA might, just might, show some cojones....

"Finally, the observation that longer term studies in the meta-analysis had similar risks between rosiglitazone and comparators highlights the importance of looking to these long-term controlled studies to confirm this finding..."

and in a nod that some folks in the FDA know the value of a real world studies compared to churning claims data (that's you, long suffering Dr. Graham)....

"The interim results (mean followup of 3.75 years) from RECORD show that 6% of
patients in the rosiglitazone group and 11% of patients in the metformin +
sulfonylurea group have been switched to insulin.
The protocol does not specify the rationale for discontinuing rosiglitazone upon
initiation of insulin, but the most likely explanation is that combination
rosiglitazone and insulin therapy is contraindicated in the European Union.
Exposures to rosiglitazone may be longer than exposures to the comparator
drugs (metformin and sulfonylurea), because rosiglitazone-treated patients can
be treated with three oral anti-diabetic agents before switching to insulin whereas
the non-rosiglitazone treated patients initiate insulin upon failing dual
combination therapy.


This amendment was added because some patients
strongly expressed reluctance to initiate insulin therapy. The protocol does not discuss how study personnel should manage other CV risk factors during the course of the study (e.g., blood pressure, lipids, and the use of aspirin). Because this is an open-label trial, differential management of these CV risk factors in the rosiglitazone and non-rosiglitazone treated patients could bias results."

In other words, insulin and Avandia combos were being avoided in the real world to begin with. As for the other risks, it would appear they are manageable by physicians but they may never get the chance and neither may GSK.

The killer is not the drug, its the politics of uncertainy. It's the risk of lawsuits and the limited tolerance of risk which I predict will drive up overall death due to diabetes if the SSRI policy by fear model applies here.

I am adding a PS to my post. Vioxx was yanked by Merck because a pain killer was shown in a RCT to have a relative risk of MI events of 1.92 (rofecoxib 1.50 events vs placebo 0.78 events per 100 patient years). The results from the first 18 months of the APPROVe study did not show an increased relative risk of adverse cardiovascular events. All the problems cropped up after. And still both the FDA and Canadian Health advisory panels recommended returning Vioxx to the market for many patients under some conditions. In each case panelists believed that uncontrolled pain was a greater risk than the absolute risk of a heart attack from long term use associated with any NSAID.

In Avandia's case, we have no clear cut evidence of MI in any long term data except in the insulin population that doctors tend not to give Avandia to in the first place. So for the FDA to say Monday's meeting is not about Nissen is misleading. It is all about Nissen. It would not be meeting July 30 if not for his end run with his "study." More to the point, the FDA the failed to ask if uncontrolled glucose levels was a greater risk than the absolute risk of a heart attack from long term use associated with any oral diabetes drug.

That's the Nissen effect.  Read More & Comment...

FDA Reviewer Rips Nissens

07/26/2007 02:55 PM |

I refer to Section 5.2 of the review of study which looks at the Nissen study:

N&W used the Peto method to compute odds ratios and confidence intervals. Trials with zeros in both arms are excluded from the analysis when using this approach as well as other approaches, such as the exact test used by this reviewer. In cases where only a few studies are excluded (as for MI where 4 studies
were excluded), the impact is minimal but when about half the trials are excluded (as is the case for the CV mortality endpoint in both N&W’s database and in the GSK database) there may be a greater impact on the results.(my emphasis...that's called withholding evidence.)

The latter point is illustrated with the database provided by GSK. This reviewer performed several analyses of the mortality data (both CV and all-cause; overall event rates less than 0.3%) and the results clearly show that the analytical approach can change non-significant results when including all the data (p>0.3) to borderline significant results when just considering those studies with at least one death (third
row of Table 3.1.2). The results for analyses using a continuity correction of 0.5 in each cell of those trials with zeros in either one arm or both arms are particularly striking with odds ratios close to one. "

This reviewer thinks that these results demonstrate the problems with any meta-analytic technique when data is extremely sparse and suggest that performing additional analyses may be warranted under these circumstances."

For the table and full discussion please go to:

http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-00-index.htm  Read More & Comment...

Fresh from the FDA Dockets

07/26/2007 12:33 PM |

This from the Glaxo data submission. I can bet you won't see this reported anywhere else:


Using real world data from real world patients... this is clinical, not claims data...

"In the monotherapy cohorts, there were 12,440 users of rosiglitazone, 16,302 of
pioglitazone, 131,075 of metformin, and 48,376 of sulfonylureas. For the combined
endpoint of myocardial infarction plus coronary revascularizations, the hazard ratio forrosiglitazone versus pioglitazone was 0.97 (95%CI 0.78 – 1.20), indicating essentially no difference between these thiazolidinediones. Both agents had somewhat less favorable outcomes than metformin, and both had somewhat better outcomes than sulfonylureas. In the dual therapy cohorts, there were 37,906 users of rosiglitazone in conjunction with metformin or sulfonylureas and 27,415 users of pioglitazone in similar combinations. Outcome rates in the rosiglitazone users versus the pioglitazone users were similar in combination with both metformin (HR 0.97, 95%CI 0.81 – 1.17) and sulfonylureas (HR 1.12, 95%CI 0.89 – 1.41). No combination with rosiglitazone or pioglitazone was meaningfully different in terms of outcomerates from a metformin-sulfonylurea combination.

The incidence of a combined endpoint of myocardial infarction and coronary
revascularization in users of rosiglitazone appears to be nearly the same as in users of pioglitazone, metformin and sulfonylureas. There is strong evidence against the
proposition that rosiglitazone in particular is associated with as much as a 40 percent
increase in risk. As in previous analyses of observational data in the US, the results
from the monotherapy and the dual-therapy comparisons, though not individually
significant, are consistent in suggesting that the risk of CHD events in patients using
thiazolidinediones may lie between the risks associated with sulfonylureas (higher
incidence) and metformin (lower incidence)."

http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-00-index.htm (Appendix D)  Read More & Comment...

USA Today: We Spread Fear, You Decide

07/26/2007 10:25 AM |

Here's Rita Rubin summing up the data on Avandia. Maybe she missed the risk of cancer associated with other diabetes drugs.
"A study in the August issue of the journal Diabetes Care concludes that the class of drugs to which Avandia and Actos belong may double heart failure risk. The authors analyzed clinical trials, observational studies and case reports. ?Everyone (who takes the drugs) is at risk,? says co-author Curt Furberg, a Wake Forest University medical epidemiologist who sits on the FDA?s Endocrinologic and Metabolic Drugs panel."

Of course Rita ignores a study in Diabetes care showing no difference in all cause mortality or all the info on Avandia now available for the adcomm hearing. More important, she ignores an even greater threat from oral diabetes drugs.....cancer.

http://www.usatoday.com/news/health/2007-07-25-avandia-fda_N.htm?csp=34

Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin
Samantha L. Bowker, MSC1,2, Sumit R. Majumdar, MD, MPH1,3, Paul Veugelers, PHD2 and Jeffrey A. Johnson, PHD1,2


OBJECTIVE—Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer.

RESEARCH DESIGN AND METHODS—This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided.

RESULTS—We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 ± 1.9 years (means ± SD). The mean age for the cohort was 63.4 ± 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1–1.6]; P = 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5–2.4; P < 0.0001).

CONCLUSIONS—Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.

Gee, we don't know do we? But that's because we don't have USA Today/Nissen/Furberg peddling this panic. Maybe because these are generic drugs perhaps, no Big Pharma to attack?

http://care.diabetesjournals.org/cgi/content/abstract/29/2/254?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&minscore=5000&resourcetype=HWCIT  Read More & Comment...

Comparative Effectiveness: Compared To What

07/26/2007 10:17 AM |

Can anyone provide any examples of where comparative effectiveness was used to pay a higher price for a new product or treatment in any government run health system. And where are the follow up studies or studies that compare effectiveness of care conducted according to comparative effectiveness recommendations vs patient-centered care.
Where are the protections that permit doctors to practice medicine as they see fit? Where is the evidence that comparative effectiveness research has not led to government taking over the practice of medicine?  Read More & Comment...

AHRQ Angels

07/26/2007 10:00 AM |

"Mr. Dingell (for himself, MR. RANGEL, MR. STARK, and MR. PALLONE) introduced the following bill; ..."

Thus begins SCHIP legislation so dangerously flawed that it's hard to know where to start.

But since we have to start the debate somewhere, let's start with Sections 904-906.

Sec. 904. Comparative effectiveness research. Establishes within the Agency of Healthcare Research and Quality a Center for Comparative Effectiveness Research to conduct research on the outcomes, effectiveness, and appropriateness of health care services.Also establishes an independent Comparative Effectiveness Research Commission to set priorities and ensure credibility for the Center’s work. It also establishes a Comparative Effectiveness Research Trust Fund, initially funded through the Medicare trust fund, to support the work of the Center and the Commission.

Translation: DERP on a national level courtesy of the AHRQ Angels. Evidence-based medicine without any good evidence. General population studies inappropriately used something they were not designed for --comparative effectiveness

Sec. 905. Implementation of health information technology (IT) under Medicare. Requires CMS to develop a plan to implement a health information technology system for Medicare.

Translation: A system akin to many in the EU (i.e., NICE) where reimbursement decisions are made on a cost-based, rather than a patient-centric matrix.

Sec. 906. Development, Reporting, and use of health care measures. Requires the Secretary to designate a single national entity to coordinate development of health care measures

Translation: The next step towards price controls and choice controls -- not to mention a further slide towards the enshrinement of practice variation over patient variation.

No matter how you cut it, evidence-based medicine based on bad evidence is bad medicine. This language disintermediatesphysicians, hurts patients and helps nobody other than payors (both public and private).

How about this -- let's keep our eye on the prize and reauthorize SCHIP for the population it has always been intended to serve, our nation's neediest children.  Read More & Comment...

Is Second Best the Best We Can Do?

07/26/2007 08:23 AM |

Please have a look at this brief essay in the July edtion of Nature Biotechnology.

The topic is FDA advisory committies and conflicts of interest -- a topic that regular readers of Drugwonks are most familiar with.

Here's a link:

http://cmpi.org/archives/2007/07/settling_for_second_best.php

You'll find some tough questions about the infamous $50,000 limit. For example, does that also include dollars earned by adcomm members who have served as expert witnesses in court trials against pharmaceutical firms?

Or what about fees that are earned but later contributed to a charity?

Anyone come to mind?  Read More & Comment...

Anti-Semitism at the British Medical Journal

07/25/2007 11:08 PM |

The BMJ is running a poll asking readers to vote whether medical schools and other academic institutions should boycott Israeli institutions.

BMJ is thus complicit in advancing anti-Semitism. If JAMA called for a boycott of Iranian or Palestinian or Cuban academics and medical researchers it would be pilloried in the MSM. Here at home, the BMJ pro-boycott poll (and you don't run such a poll unless you are promoting it) gets no mention. Double standard. You bet.

Here is a link to an article in the Jerusalem Post about the bastards at BMJ.

http://www.jpost.com/servlet/Satellite?apage=2&cid=1184766044837&pagename=JPost%2FJPArticle%2FShowFull

And here is a link to the ADL's anti-boycott campaign. The petition states "These highly politicized and blatantly biased attacks violate the basic tenets of journalistic and academic objectivity and disregard key facts of the complex Arab-Israeli conflict. Singling out Israel for boycott while ignoring the brutal human rights abuses occurring everyday in countries like Sudan, Zimbabwe and Iran isn't activism -- it's anti-Semitism."

We encourage drugwonk followers to click and take a stand against the BMJ and other outlets that offer safe haven to hatemongers.

http://www.adl.org/boycott/  Read More & Comment...

Personalized Medicine for Mental Illness

07/25/2007 06:08 PM |

Drugwonks congratulates Genomas CEO Gualberto Ruano, a champion of personalized medicine, for the receipt of a NIH grant support his pathbreaking research on the development of a gene test for drug induced metabolic disorder and atypicals.

http://www.courant.com/business/hc-bizadd2-0723,0,133185.story?track=rss

Also http://www.genomas.net  Read More & Comment...

Add Cancer to the Laundry List of Statin Scares

07/25/2007 05:52 PM |

We have mentioned the increased risk of ALS and greater violence attributed to statins that lower LDL.

http://online.wsj.com/article/SB118314239102053337.html?mod=googlenews_wsj

http://archinte.ama-assn.org/cgi/content/abstract/164/2/153

It wasn't too long that someone would run an statistical correlation "showing" that statins are association with cancer. Not a specific cancer mind you. Just cancer.

http://www.cbsnews.com/stories/2007/07/24/health/webmd/main3092265.shtml

Would someone please create a federal program to give epidemiologists something constructive to do? Better yet, how about medical journals imposing a ban on running articles that do nothing to generate mechanistically informed hypotheses but everything to run articles that the average reporter can understand once it has been pre-digested by a PR firm by said medical journal?

PR for medical journal ok but PR for new medicines, not ok?  Read More & Comment...

Clueless Uwe Reinhardt

07/25/2007 05:30 PM |

World reknown health care expert Reinhardt complains to the WSJ that he cannot get his extremely large and supple brain around the question about why we stupid Americans don't like socialized medicine:

"Why do I never hear any Republican political candidate, or the editorial page of the Journal for that matter, openly advocate the abolition and privatization of the VA health system? Why are even the staunchest American conservatives, and the veterans themselves, so protective of the VA health system, if socialized medicine is so bad?"

One explanation may be that the VA health system is generally viewed among health-policy experts as the cutting edge in the smart use of electronic information technology and of quality control in health care. The Journal itself featured an article on this point on its front page some time ago. In a peer-reviewed research paper published in the Annals of Internal Medicine (December 21, 2004), researchers of the RAND Corp. reported that the quality of care received by VA patients scored significantly higher overall than did comparable metrics for patients in the rest of the U.S. health system."

Again with the 2004 study (which by the way did not compare metrics with rest of the country, only a couple of other HMOs)

Perhaps Reinhardt hasn't read about the excellent care the VA is delivery to vets with mental illness and PTSD:

"The VA has seen its backlog of disability claims swell to 600,000 as soldiers return from ongoing wars, a logjam blamed for financial dislocation, despair and even suicides of vets. The suit says the claims system is "riddled with inconsistent and irrational procedures" that violate the due process rights of injured vets seeking care and compensation. For example, the VA employs the same officials both to challenge and judge claims.


"According to the suit, the biggest casualties of this bureaucratic morass are the unprecedented number of troops returning with PTSD, a mental disorder especially prevalent in soldiers stationed in Iraq and Afghanistan, where they're faced with multiple tours of duty, invisible battle lines and the "moral ambiguity of killing combatants dressed as civilians." The military says more than a third of the 1.6 million men and women who have served in Iraq or Afghanistan report mental health issues ranging from PTSD to brain injuries, yet only 27 of the nation's 1,400 VA hospitals have programs dedicated to treating PTSD. Worse yet, the complex process of applying for disability payments is especially daunting for these patients, who often experience memory lapses and disorientation."

http://news.yahoo.com/s/time/20070725/us_time/behindtheveteranslegalbattle  Read More & Comment...

Jacob's Ladder

07/25/2007 09:06 AM |

A letter from the current issue of The Economist penned by our friend and colleague Jacob Arfwedson:

Drug tests

SIR – Your leader on the reform of pharmaceutical regulations in America maintains that safety concerns must be addressed, but why assume that the government will do a better job than independent players (“From bench to bedside”, June 30th)? In the United States private agencies ensure quality assessment (including off-label use and risks missed by the government) in a speedier way than the Food and Drug Administration.

As Peter Pitts, a former associate commissioner at the FDA, has shown, there is no direct link between additional clinical trials and safer medicines. The length of the FDA approval process has doubled since the 1960s as have the financial costs since the late 1980s. Moreover, the number of clinical trials doubled between 1977 and 1995 and the number of patients tripled. Yet in the past 40 years the share of medicines withdrawn from the market has remained constant.

Jacob Arfwedson
Centre for the New Europe
Brussels

The rest of the story is that the science of clinical trials needs updating. If we want to truly move into the era of personalized medicine, we need adaptive clinical trials that can look more precisely at sub-populations.

"Traditional" clinical trials that demonstrate a 40% efficacy rate without even attempting to isolate which 40% is expensive in financial terms and only marginally helpful in helping physicians best treat their patients. It also plays into the hands of the Evangelists of Evidence-based Medicine and the Votaries of Me-Tooism. We must think about clinical trials in new ways. It's a crucial aspect of the Critical Path.  Read More & Comment...

And speaking of Wisconsin ...

07/24/2007 11:27 AM |

From today's Wall Street Journal

Cheese Headcases

When Louis Brandeis praised the 50 states as "laboratories of democracy," he didn't claim that every policy experiment would work. So we hope the eyes of America will turn to Wisconsin, and the effort by Madison Democrats to make that "progressive" state a petri dish for government-run health care.

This exercise is especially instructive, because it reveals where the "single-payer," universal coverage folks end up. Democrats who run the Wisconsin Senate have dropped the Washington pretense of incremental health-care reform and moved directly to passing a plan to insure every resident under the age of 65 in the state. And, wow, is "free" health care expensive. The plan would cost an estimated $15.2 billion, or $3 billion more than the state currently collects in all income, sales and corporate income taxes. It represents an average of $510 a month in higher taxes for every Wisconsin worker.

Employees and businesses would pay for the plan by sharing the cost of a new 14.5% employment tax on wages. Wisconsin businesses would have to compete with out-of-state businesses and foreign rivals while shouldering a 29.8% combined federal-state payroll tax, nearly double the 15.3% payroll tax paid by non-Wisconsin firms for Social Security and Medicare combined.

This employment tax is on top of the $1 billion grab bag of other levies that Democratic Governor Jim Doyle proposed and the tax-happy Senate has also approved, including a $1.25 a pack increase in the cigarette tax, a 10% hike in the corporate tax, and new fees on cars, trucks, hospitals, real estate transactions, oil companies and dry cleaners. In all, the tax burden in the Badger state could rise to 20% of family income, which is slightly more than the average federal tax burden. "At least federal taxes pay for an Army and Navy," quips R.J. Pirlot of the Wisconsin Manufacturers and Commerce business lobby.

As if that's not enough, the health plan includes a tax escalator clause allowing an additional 1.5 percentage point payroll tax to finance higher outlays in the future. This could bring the payroll tax to 16%. One reason to expect costs to soar is that the state may become a mecca for the unemployed, uninsured and sick from all over North America. The legislation doesn't require that you have a job in Wisconsin to qualify, merely that you live in the state for at least 12 months. Cheesehead nation could expect to attract health-care free-riders while losing productive workers who leave for less-taxing climes.

Proponents use the familiar argument for national health care that this will save money (about $1.8 billion a year) through efficiency gains by eliminating the administrative costs of private insurance. And unions and some big businesses with rich union health plans are only too happy to dump these liabilities onto the government.

But those costs won't vanish; they'll merely shift to all taxpayers and businesses. Small employers that can't afford to provide insurance would see their employment costs rise by thousands of dollars per worker, while those that now provide a basic health insurance plan would have to pay $400 to $500 a year more per employee.

The plan is also openly hostile to market incentives that contain costs. Private companies are making modest progress in sweating out health-care inflation by making patients more cost-conscious through increased copayments, health savings accounts, and incentives for wellness. The Wisconsin program moves in the opposite direction: It reduces out-of-pocket copayments, bars money-saving HSA plans, and increases the number of mandated medical services covered under the plan.

So where will savings come from? Where they always do in any government plan: Rationing via price controls and, as costs rise, waiting periods and coverage restrictions. This is Michael Moore's medical dream state.

The last line of defense against this plan are the Republicans who run the Wisconsin House. So far they've been unified and they recently voted the Senate plan down. Democrats are now planning to take their ideas to the voters in legislative races next year, and that's a debate Wisconsinites should look forward to. At least Wisconsin Democrats are admitting how much it will cost Americans to pay for government-run health care. Would that Washington Democrats were as forthright.  Read More & Comment...

Harry & Louise Redux

07/24/2007 08:48 AM |

Nearly 15 years ago, when then-First Lady Hillary Clinton proposed to restructure American health care in the image of the European and Canadian systems, most health insurance providers blasted her plan.

What a difference a few years make. Just last month, Senator Clinton and the very same insurers -- in their current incarnation as a trade group called America's Health Insurance Plans -- stood shoulder-to-shoulder in support of such a scheme. Their plan would give the federal government the power to determine what new medicines and services to cover based on budgetary considerations.

So what's changed? Not Senator Clinton -- she has always regarded government as the best arbiter of health care value.

It's the health insurers who have flipped, thinking the scheme will help them save a few bucks.

The model for this marriage of old foes is Britain's National Institute for Clinical Excellence (NICE), which employs comparative effectiveness studies in evaluating whether to pay for new and often expensive medicines.

More often than not, NICE recommends against using the new treatment because it's not "cost-effective" when compared to existing treatments.

That's why many Britons refer to NICE as "NASTY" -- "Not available, so treat yourself."

As health care costs have risen, many policymakers and insurance industry elites have declared that innovative and life-changing new treatments are not worth the price. What a disaster it would be for medical innovation if a narrow-minded focus on cost took precedence over new treatments, new drugs, and personalized health care decision-making.

Here's the rest of the story as reported in the Wisconsin State Journal:

http://www.madison.com/wsj/home/column/other/index/php?ntid=202448&ntpid=4

On Wisconsin!  Read More & Comment...

Not Lost in Translation

07/23/2007 08:49 PM |

What's on the minds of Turkish journalists covering health care ... counterfeit medicines.

Here's an article that ran in one of that country's largest national daily newspapers, "Dunya"

http://cmpi.org/images/headlines/dunya_1407_pp.jpg

And, for those of you non-Turkish speakers, here's the translation ...

Counterfeit drugs are a major problem for our country, too

One of the most important factors that play a role in the prevention and treatment of diseases is undoubtedly drugs. When successfully treated, conditions such as hypertension are prevented from leading to strokes or heart attacks and drugs that provide effective treatment for diseases such as cancer, AIDS and Alzheimer’s also play a vital role.

Seen from this perspective, an expeditious introduction of new and effective (innovative) drugs for patients’ use does not increase healthcare costs; on the contrary, it is one of the most important factors that reduce healthcare costs. Countries that do not single out cost as a top criterion and take into consideration the overall benefit that a certain drug provides have a healthier social structure and are also able to control their total healthcare costs more easily. There is a large number of scientific studies that confirm the validity of this approach.

In our country, the cost of treatment is almost always viewed as identical to the cost of the associated drug. The rationale behind this approach is that “drugs” represent the measurable and avoidable aspect of basic healthcare costs. The government presents an approach whereby it directly prevents innovative drugs, which are relatively expensive due to their R&D costs, from being put at the service of society.

As a consequence, the number of saved lives decreases and, due to other healthcare expenditures, total healthcare costs inevitably increase. This governmental approach targets all pharmaceutical companies, local and foreign.

Delays in registration play a role in the rise of counterfeit drugs

The fact that innovative drugs have a higher price tag and are not reimbursed by the government has another important repercussion – the rise in counterfeit drugs. Two recent examples in our country presented a clear proof of this phenomenon. Counterfeit versions of two drugs, one for erectile dysfunction, the other for cancer treatment, were clandestinely released into the market. In his recent visit to Turkey, the former Associate Commissioner for External Relations at the American Food and Drug Administration (FDA), Mr. Pitts related his experience on counterfeit drugs. At a press meeting he organized at the Head Office of the Association of Research-Based Pharmaceutical Companies (AIFD), Pitts stated that the expeditious presentation of newly developed and safe drugs at the service of patients has become a priority throughout the whole world and emphasized that, thanks to this approach, patients have increased chances of surviving diseases such as cancer, MS and Alzheimer’s. Pitts pointed out that Turkey’s predominantly young population is a major advantage and that an expeditious introduction of effective drugs at the service of patients without much delay would allow chronic diseases to be treated in a timely manner which would potentially reduce heavier treatment costs down the line.

Buy your drugs only at pharmacies

However, the single most important issue that Pitts emphasized involved counterfeit drugs from China, Russia and South American countries and the damage they cause on human health. Pitts said that as counterfeit drugs provide significant profits, it has become increasingly difficult to fight them and that, in order to avoid counterfeit drugs, individuals must first be wary of environments where counterfeit drugs may be sold and they should not be swayed by the relatively inexpensive prices of these drugs.

Accordingly, it is very important to closely monitor each stage of the distribution channels, to place a barcode and identification on each drug package and to systematically implement as well as increase penal sanctions. Therefore, our most vital suggestions to protect ourselves from counterfeit drugs is to “purchase drugs from pharmacies and refuse to purchase drugs without barcodes”.

Nearly all cases of counterfeit drugs in our country up until now have resulted from drugs outside the official distribution channels. The proper approach that will fundamentally resolve the problem is to shorten the registration process for innovative drugs and expeditiously present them at the service of our citizens.

Ankara's Away!  Read More & Comment...

Nissen Says von Eschenbach "Whines" About Drug Approval Being Too Slow

07/23/2007 03:59 PM |

It is obvious Nissen tailors his remarks to the audience....so here he is talking trash about Andy von Eschenbach and Scott Gottlieb to an NPR crowd a while back...

Dr Steven Nissen, chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, was recently a member of a panel debating the topic of: "Government Science Panels: Fair and Balanced?" which was moderated by National Public Radio's Snigdha Prakash, and sponsored the Center for Science in the Public Interest on Aug. 2 2006.

Dr Nissen spoke about the conflict-of-interest problems "evident at the highest levels of the FDA," the article says.

"For years," Dr Nissen said in describing FDA leadership, "we had an interim FDA Commissioner, Lester Crawford, who shortly after confirmation, abruptly resigns, apparently because he and his wife owned stock in regulated companies."

"Then the administration appointed Andrew Von Eschenbach as interim commissioner, creating another conflict," he noted.

"In his role as director of the National Cancer Institute," Dr Nissen said, "Von Eschenbach must seek FDA approval for human testing or approval of new cancer drugs, an obvious conflict."

But even worse, he said, "the administration appointed Scott Gottlieb as deputy commissioner."

"He came to this job with no regulatory experience, directly from Wall Street, where he served as a biotech analyst and stock promoter
"Between them, Drs. Von Eschenbach and Gottlieb have whined incessantly about the need to speed drug development."

"So while the American people worry about the safety of drug the top FDA leadership tells us we need faster drug approval."

Funny, I thought people cared about both. And for such a smart guy who wants to be FDA commish, the inability to conceive of faster drug approval and safer medicines being one in the same reflects scientific stupidity or political cupidity, or both. And for someone whose own studies have demonstrated excess mortality in the wake of promoting the stocks of companies he conducts research for, I would not be talking about putting profits before safety if I were him.  Read More & Comment...

Nissen's Nonsense

07/23/2007 02:19 PM |

I have decided to pull together the best of the blog commentary on Nissen's Avandia study:

From the Angry Pharmacist

http://www.theangrypharmacist.com/archives/2007/05/avandia_oh_why.html

From Respectful Insolence..

http://scienceblogs.com/insolence/2007/05/well_well_well_what_have_we_here_about_t_1.php

Kevin MD (who cites Medpage who cites but does not attribute my comparison of the WHI to Avandia risk)

http://www.kevinmd.com/blog/2007/05/avandia-and-heart-attacks.html

Dr. Kevin links to Nissen -- one day after making his Avandia > 9-11 tragedy with this ask and answer with Newsweek:

"Is there a case for prescribing Avandia? Are there some patients for whom the benefits outweigh the risks?

Again, I don’t think I want to go there. It’s important for me as a physician-scientist to put the data out there in a very neutral fashion, and not cast judgment about what people ought to do. We’re going to let everybody read our paper and make up their own minds. Obviously the FDA read our paper because they just issued a safety alert."

What a creep.

http://www.msnbc.msn.com/id/18789572/site/newsweek/  Read More & Comment...

NYT Swallows St. Steven's Sob Story

07/23/2007 10:46 AM |

Yes, Steve Nissen has sleepless nights about drug safety, particularly about the misuse of surrogate endpoints to approve drugs (which is why he has developed IVUS to develop a surrogate endpoint for drug approval).

And he compares Avandia's risk of death to that of 9-11 (though even his own meta-analysis did not estimate increased number of deaths only risk of having a heart attack sooner and not death).

He tells Diedtra Henderson of the Boston Globe he doesn't want to be FDA commissioner but tells the NYT he won't rule it out.

He uses the "I give all my money to charity" line but there is nothing about the fact the charities are his own research organizations and the Steven E Nissen Healthy Heart fund that doled out gym memberships and travel money to people at the ACC.

He is described as an "informal advisor to Congress" on drug safety. How about someone who coordinated with Congress to preempt the FDA's own analysis of Avandia in order stoke support for alternative FDA reform proposals. Who was working with Congressman Waxman and the NEJM to release his paper, supposedly told a Glaxo rep he was going to "destroy Avandia" but had the chutzpah to claim to the media he offered Glaxo the chance to co-author a paper.

Nissen's behavior with respect to Avandia and the increasing criticism that has been leveled at his "study" (if all the short term data showed a 40 percent increased risk, why is there no hint of it in long term studies like RECORD) were all neglected in the NYT study.

I predict that when all is said and done Nissen will be revealed as the Michael Nifong of medical research.

http://www.nytimes.com/2007/07/22/business/22nissen.html  Read More & Comment...