A Dose of Science About Drug Dosing and Off-Label Uses

03/17/2008 08:18 AM |

Two articles in the NY Times -- one about the discussion of off-label uses for Zyprexa and another accusing drug companies of launching meds at a higher dose than necessary -- are devoid of scientific context.

The failure to report on off-label uses without describing the process of arriving at them and the fact that most are the product of trying to solve a clinical problem is a consistent and glaring gap in reporting. And burying the science only empowers trial attorneys and federal prosecutors who are constantly prodded by Senator Grassley to use the threat of prosecution to shake down drug companies for settlement fees.

With respect to the allegation that Avastin, Herceptin, Cerazyme, etc., are overdosed on purpose is completely without merit. Dosing is -- by the nature of clinical trials -- one size fits all. Achieving an appropriate dose in the real world goes on all the time and hitting the right dose -- as the warfarin genetic labeling effort suggests -- is a matter of genetic variation and other factors that cannot be integrated into drug development. And consider this: in some instances changing the timing and dosing of certain drugs can be regarded as off-label use and therefore subject to prosecution and tort lawyer litigation.

When Avastin was being developed it's initial "failure" in early trials was -- according to Judah Folkman who pioneered angiogenesis drugs -- linked directly to the fact that the FDA wanted every patient to get the same dose even though he believed varying dosing to a number of criteria -- would have led to better and more precise outcomes.

Many drugs don't work in most people at the marketed dose. The failure of HMOs not to provide coverage of the most expensive and innovative medicines should have nothing to do with dosing. The right dose for the right patient at the right time for the best outcome is the goal of any doctor. The Critical Path leading to personalized medicine or tailored treatments reflects the commitment of companies and the FDA to move away from the one-size fits all approach.

The media continues to ignore the underlying science shaping medicine and it leads to the arrogant notion that prosecutors and policy analysts can strip doctors of their discretion about how to prescribe and use medicines to advance the health of their patients.

http://www.nytimes.com/2008/03/16/business/16gaucher.html?pagewanted=1&_r=1&ref=todayspaper

http://www.nytimes.com/2008/03/15/business/15drug.html?scp=1&sq=berenson&st=nyt  Read More & Comment...

The Tainted Veil

03/17/2008 07:51 AM |

Last August I commented on the Lou Dobbs program that it was unlikely that Congress would take FDA reform seriously “until there were dead bodies.”

Unfortunately, I was right.

On Friday, in the shadows of tainted Heparin, the Senate passed a budget resolution to give the F.D.A. an additional $375 million, a 20 percent increase over this year.

Some representative quotes on this issue from an article by Gardiner Harris in today’s edition of the New York Times:

“Congress has a responsibility to close the glaring gaps in food and drug safety that have begun to overwhelm the F.D.A.,” Senator Edward M. Kennedy, Democrat of Massachusetts.

“F.D.A. needs a serious infusion of resources and strong leadership dedicated to reforming the agency,” said Representative Henry A. Waxman, Democrat of California.

And, of course, everyone’s favorite FDA expert, Representative Rosa DeLauro, Democrat of Connecticut, “I don’t want to throw money at an agency that doesn’t have the infrastructure to carry out its mission.”

Some top agency officials are simply “incompetent,” she added, and real change can occur only with a new administration.

Really, a new administration? Note to Representative DeLauro – the head of every center at the FDA is a career government employee. At the FDA, an agency of roughly 10,000, there are fewer than 10 “political” appointees. Does Ms. DeLauro, the chair of the House appropriations subcommittee with authority over the agency, believe that Dr. Janet Woodcock is “incompetent?” What about CBER’s Dr. Jesse Goodman – widely considered one of the finest scientists in government?

And then, of course, there’s the usual ranting from our favorite Sheep in Wolfe’s Clothing.

Here’s a link to the complete article:

http://www.nytimes.com/2008/03/17/health/policy/17fda.html?scp=2&sq=gardiner+harris&st=nyt

Alas, the title of the article says it all –“Tainted Drugs Put Focus on the F.D.A.”

And it isn’t even a done deal.   Read More & Comment...

There Will Be Blood: Part II

03/14/2008 08:56 AM |

Here's a link to a a video that shows how atherosclerosis happens. This arterial tour gives you a graphic view of how unhealthy habit and genes can conspire to clog the major routes that supply blood to the heart and back again. No butter with your popcorn when watching this movie. Steve Nissen makes a cameo appearance as an avenging LDL molecule..(Not really.)

Read Full Story



  Read More & Comment...

When is an industry trial not an industry trial?

03/14/2008 06:25 AM |

The Center for Medicine in the Public Interest (the think tank home of drugwonks.com) is part of a transatlantic public policy institute consortium on the future of healthcare technology assessment (HTA). One of the member organizations, the German Institut fur Unternehmerische Freiheit (the Institute for Free Enterprise) held a seminar in Berlin yesterday entitled, "Cost Pressures on the German Health System -- Is Health Technology Assessment the Solution?"

One of the speakers was Dr. Christian Behles, Director and Professor of Drug Regulatory Affairs at the University of Bonn and an advisor to the German government.

Professor Behles pointed out that while IQWiG casts a suspicious eye on industry-designed pharmaco-economic studies, they use industry-sponsored RCTS as the basis of their comparative effectiveness findings.

He also noted that these RCTS were not designed to be used for head-to-head comparisons -- further reinforcing the recent comments made by NICE's Sir Michael Rawlings in front of the British House of Commons that HTA "is not based on empirical research."

In other words, IQWiG embraces industry-sponsored RCT data that was not designed to be used comparatively, while rejecting industry-sponsored data that was specifically designed to show the value of a new innovative medicine.

When is an industry study not an industry study? It seems that, for IQWiG, the answer is "when it's convenient."

It's interesting to note that the title of Professor Behles' presentation was, "HTA and Political Interference -- the Case of Germany's IQWiG."  Read More & Comment...

ODAC Jumps Off Padzur's Railroad and Refuses to Join Media Circus

03/13/2008 04:47 PM |

The best part of the ODAC meeting was when the committee as a whole dismissed Richard Padzur question -- designed to prop up an increasingly suspect coverage decision by CM -- asking to slap a one-size fits all dosing limit on ESAs. To quote one panelists: "This is silliness." Other comments could be characterized as dismissive.

In general the panel appeared perturbed that the FDA essentially did not provide it with either an objective or complete picture of the overall risks and benefits of ESA use in chemotherapy. The same goes with Padzur's lame attempt to misconstrue his negative opinion of the nature of quality of life data because most of it is observational study as the final word on the subject. He fooled the media who failed to look deeply into the data but not practicing oncologists on the panel.

Of course the media had all but predicted the demise of ESAs and is treating the ODAC decision as some sort of upset. Read the CNN.com piece below. You can just feel the shock and disappointment....Ultimately companies and doctors will have to work together to come up with more patient-centric data on who the drugs work for. If they had done this in the first place, the generalized concerns about safety could have been mitigated. Let's hope they do so going forward.

The committee did the right thing by swatting away Padzur's thinly veiled attemtp to manipulate them into affirming CMS' wrongheaded coverage decision. It did the right thing by giving doctors flexibility and recommending limiting use in areas where no benefit seems to exist.

http://money.cnn.com/2008/03/13/news/companies/amgen/?postversion=2008031316  Read More & Comment...

ODAC Live

03/13/2008 01:16 PM |

The committee voted against restricting the use of ESAs to small cell lung cancer.

Question 2--Should FDA require that product labeling be modified? Please address each of four potential approaches to mitigating risks through revised labeling separately.

a. To date, only clinical trials in small cell lung cancer have reasonably excluded an increased risk for death among patients receiving ESAs. Trials have demonstrated an increased risk of death and/or tumor promotion in head/neck, non-small cell lung cancer, breast (neoadjuvant and metastatic settings), lymphoid malignancies, and cervical cancers. Tumor types, other than those listed above, have not been adequately studied. Should the current indication be modified to restrict use only to patients with small cell lung cancer?

Vote: YES-- 6 NO-- 8

Question 2--Should FDA require that product labeling be modified? Please address the following potential approaches to mitigating risks through revised labeling.

b. Vote: The PREPARE trial demonstrated decreased relapse-free and overall survival in breast cancer patients receiving neoadjuvant chemotherapy. The risk/benefit assessment is different for patients receiving neoadjuvant and adjuvant chemotherapies than for patients with metastatic or incurable cancers. Should the current indication be modified to include a statement that ESA use is not indicated for patients receiving potentially curative treatments?

Vote: YES--11 NO--2
The current indication should be modified to say that it should not be used in the adjuvant setting.



c. Vote: Although increased tumor promotion and/or decreased survival have been demonstrated in several tumor types, adverse findings have been duplicated in two malignancies-breast cancer and head and neck cancer Should the current indication be modified to include a statement that ESA use is not indicated for patients with breast and/or head & neck cancers? (If yes, please specify breast and/or head & neck cancer).

Vote: YES--9 NO--5
Modified to say that ESA use not indicated for metastatic breast and head and neck cancers.  Read More & Comment...

Evidence-Based Medicine Takes a Flying Leap

03/13/2008 08:07 AM |

http://www.bmj.com/cgi/content/full/327/7429/1459?eaf


Hazardous journey
Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials

Gordon C S Smith, professor1, Jill P Pell, consultant2

1 Department of Obstetrics and Gynaecology, Cambridge University, Cambridge CB2 2QQ, 2 Department of Public Health, Greater Glasgow NHS Board, Glasgow G3 8YU

Correspondence to: G C S Smith gcss2@cam.ac.uk

Abstract

Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge.

Design Systematic review of randomised controlled trials.

Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists.

Study selection: Studies showing the effects of using a parachute during free fall.

Main outcome measure Death or major trauma, defined as an injury severity score > 15.

Results We were unable to identify any randomised controlled trials of parachute intervention.

Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.

I am sure CBO's Peter Orzag, who has been pushing comparative effectiveness as a way to reduce costs by denying access to new technology will be the first to volunteer....  Read More & Comment...

How many economists does it take to screw in a lightbulb?

03/13/2008 07:06 AM |

If the lightbulb is meant to shine a light on the value of new healthcare-related technologies in the context of healthcare technology assessment (HTA) -- then the answer is "one."

And the "one" is Dr. Frank Lichtenberg of Columbia University.

According to Frank, for HTA to yield valid decisions in practice, it is necessary to have reliable estimates of:

ΔCOST
ΔQALY
and VSLY (Value of a Statistical Life Year)

And his main point is that the devil is in the details.

He believes that incorrect estimates of some or all of these key inputs are often used:

ΔCOST is frequently overestimated
ΔQALY and VSLY are frequently underestimated

And due to these estimation biases, health technologies that are truly cost-effective may often be rejected as cost-ineffective.

Per the recent debate over the utility of new cancer treatments, he makes a very interesting point -- that even though, over the past 30 years, the U.S. Mortality Age-Adjusted Rates for cancer have remained relatively constant -- (leading to such mainstream media headlines as Fortune Magazine's "Why have we made so little progress in the War on Cancer?” and NEJM articles like "The effect of new treatments for cancer on mortality has been largely disappointing” -- the often ignored reality is that 5-year relative survival rates, for all cancer sites, have increased from 50.1% in 1975 to 65.9% in 2000.

For more specifics on both the economic impact of new treatments and their impact on cancer survival, please see the paper that Dr. Lichtenberg wrote for the Center for Medicine in the Public Interest in 2007:

Click here:

http://www.cmpi.org

Then go to the heading "Reports" and click on "Value of Cancer Drugs."

Lichtenberg cites two crucial studies, pointing out how health care economists must seriously reconsider the outdated estimates of a QALY:

Viscusi and Aldy: The value of a statistical life for prime-aged workers has a median value of about $7 million in the United States

Viscusi, W. Kip and Joseph E. Aldy, “The Value of a Statistical Life: A Critical Review of Market Estimates Throughout the World,” The Journal of Risk and Uncertainty, 27:1; 5–76, 2003.

and

Murphy and Topel: The value of a life year is $373,000.

Murphy, Kevin M., and Robert H. Topel, “The value of health and longevity,” Journal of Political Economy, 2006.

Attention must be paid. Hello NICE. Hello IQWiG. Hello Senators Baucus and Conrad.

Here is Dr. Lichtenberg's presentation on these issues -- spelled out and supported by both facts and examples:

Download file

If the devil is in the details (and it is) -- it's time for a deep dive beyond simplistic and self-serving "comparative effectivess."  Read More & Comment...

ESAs Under the Gun and Off the Critical Path

03/12/2008 12:22 PM |

After reading the FDA's documents prepared for the ODAC review of ESAs I am struck by how primitive and incomplete the brief about the safety problems associated with the anemia drugs are and how short-sided the FDA is in how to assess risk and benefit of the drugs going forward.

1. The FDA memo ignores quality of life benefits and it's risk management of the drug ignores the opportunity to use electronic medical records and observational studies to determine which dose works for what patients. It rewrites the standard for demonstrating quality of life to require randomized controlled trials to demonstrate such benefits....



2. The FDA memo ignores patient preferences and would radically limit the freedom of doctors to prescribe drugs based on their real world experience as opposed to the results of clinical trials focusing on higher than label doses.

3. The FDA ignores the fact that there are no randomized clinical trials assessing the impact of transfusion on survival or mortality.

4. Rather it cites the decline in transfusion-related infections even though the principle reason for using ESAs in chemo-related anemia was to reduce fatigue and sustain hemoglobin levels more efficiently in tandem with newer and more powerful cytotoxic agents/regimens.

5. The FDA ignores the fact that requiring RCTs to establish safety would entail studies of such power that doing so will be nearly impossible. Imposing this standard on all drugs would eliminate many drugs from regular use.

The fix is in. To a large extent the companies have themselves to blame for not tracking the risk and benefits of these medicines more consistently. However denying access to patients who feel better on the drug and who know the relative and absolute risks associated with their use is wrong. And it sends a message to companies that efforts to demonstrate risks and benefits in the post market consistent with the Critical Path will be rejected. The FDA's use of unsophisticated arguments and models in pressing for ESA restrictions underscores that trying to create a patient-centered pathway is simply not worth it. And if it isn't, how serious can the agency be about Critical Path and including patient preferences in its evaluations?
http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4345b2-00-FDA-index.htm  Read More & Comment...

Acronyms of Denial

03/12/2008 04:48 AM |

I am currently "on the road" in Europe with Dr. Frank Lichtenberg of Columbia University. We're speaking on the topic of healthcare technology assessment (HTA). We've already spoken in Brussels (cold and wet) and Rome (sunny and fattening). Today we are in Berlin.

When it comes to health care there are a lot of acronyms. When it comes to cost-containment strategies the main ones are:

HTA: Healthcare Technology Assessment

EBM: Evidence-Based Medicine

CER: Comparative Effectiveness Research

RUM: Rational Use of Medicine

But no matter the acronym, these are all cost-based practices designed to reduce costs and restrict patient care. They are acronyms of denial.

Today, Healthcare Technology Assessment is a short-term, short-sighted, politically-driven policy that results in one-size-fits-all medicine. And while it may provide transitory savings in the short-term, current HTA strategies result in a lower quality of care that result in higher health care costs over time.

Restrictive formularies and health care systems that deny patients access to the right medicine in the right dose at the right time but pay for more invasive and expensive procedures later on have their priorities upside down.

So why is the current HTA model enjoying such wide support? Because it drapes a veil of pseudo-science around the blunt instrument of one-size-fits-all price controls. Consider what Sir Michael Rawlings of NICE said about comparative effectiveness in front of the British House of Commons:

“It is not based on empirical research, there is no empirical research anywhere in the world, it is really based on the collective judgment of the health economists we have approached across the country. It is elusive."

IQWiG in Germany claims that it makes its decisions based on "international standards." But such "standards" do not exist. Nice try though.

HTA, as it is currently designed, places into conflict the short-term budgeting dilemmas of governments elected for relatively short periods of time with the ever-lengthening life spans of its electorate.

HTA is a creature not of health care professionals, but of economists being paid by governments (aka: "payers"). Hardly a group of disinterested academics.

HTA is widely based on the concept of “patient variation,” that the same care should be applied to every patient suffering from the same disease based on evidence derived from RCTs.

In other words, if one medicine is effective for 40% of the target population and another drug within the same therapeutic category if also effective for 40% of the population – but we cannot (because of the design of these RCTs) clinically predict which 40% will respond to either treatment – what kind of evidence is that?

What’s a regulator to do? Their only alternative, as they see it, is to rely on cost-based comparisons. In other words, if two medicines are “equally effective” at 40% -- then they will opt to reimburse the one that costs less.

That isn’t evidence-based medicine. That’s bad medicine.

21st Century HTA models should reflect and measure individual response to treatment based on the combination of genetic, clinical, and demographic factors that indicate what keep people healthy, improve their health, and prevent disease. A rapidly aging society demands a new health care paradigm capable of providing for its needs in the 21st century. Equality of Care must be matched with Quality of Care.

The repercussions of choosing short-term savings over long-term results, of cost-based choices over patient-centric care, of “me-too” medicines over the right treatment for the right patient at the right time – are pernicious to both the public purse and the public health.

As Mark McClellan said, “Looking at a gigantic uniform solution for everything is never going to work.”

We're not at the end of this debate. We're not at the beginning of the end of this debate. But we are at the end of the beginning where at least we can all agree that this is not, and must not be exclusively a debate about saving money. It must be about patient care.  Read More & Comment...

Climbing the Peak of CDER Sinai

03/11/2008 06:04 PM |

After a national search for a new CDER director -- the best and the brightest was chosen.

Dr.Janet Woodcock is returning as full-time center director.

An overdue homerun for the FDA.  Read More & Comment...

But Let's Prevent Them From Working With Industry Anyways

03/11/2008 10:56 AM |

Leave it to the conflict of interest police to dig an even deeper hole for academic researchers and destroy American competitiveness: NIH funding is declining, restrictions on NIH researchers and NIH supported researchers are tighter than ever and now the conflict Kapos want to prohibit researchers from any sort of collaboration with drug companies or biotech firms.

A group of some of the most prestigious research groups in the country says that five years of flat budgets for the National Institutes of Health is threatening to deter an entire generation of young researchers. Scientists from UCLA, Harvard, Vanderbilt and four other research institutions say that the stagnant NIH budget is persuading young researchers to go into other careers or move to other countries which have proved more generous to biomedical research. To drive that point home, the report--"A Broken Pipeline"--profiles 12 young researchers engaged in groundbreaking work on stem cells, cancer and kidney disease and their difficulty finding new grants.

"This is a real problem, discussed at almost every meeting one attends on campus, that can't be simply dismissed," said Drew Faust, Ph.D., president of Harvard University. "This is about the investment that America is--or is not--making in the health of its citizens and its economy. Right now, the nation's brightest young researchers, upon whom the future of American medicine rests, are getting the message that biomedical research may be a dead end and they should explore other career options--and in too many cases, they're taking that message to heart. The president's latest budget proposal that calls for another year without an increase will only make the problem worse."

fiercebioresearcher.com

They live in a la-la- land where the government will just double NIH funding by raising taxes and -- according to the Soros-funded Institute for Medicine as Profession -- also add billions more to carry out drug development.

Why doesn't the media ever look at the implications of these ideas. I have always said, people like the folks at Healthcare Renewal, Sid Wolfe, Marcia Angell, Merrill Goozner, etc are willing to harm the public health en route to killing the private sector's role in drug development. If their conflict of inflict agenda is adopted -- which also opens doctors to the increased threat of lawsuits from trial attorneys -- they will have taken a strong stride towards that misanthropic goal....  Read More & Comment...

Disconnect on Drug Patents

03/10/2008 12:48 PM |

Two articles in the Wall Street Journal regarding the use, misuse and theft of drug patents...Of course all the drugs made by Thai-government run companies will be used for the poor and be of top quality....And none of them will ever make it onto the black market because there are SO many limits placed on selling inferior or bogus drugs to unsuspecting people in poor countries...



http://online.wsj.com/article/SB120515886199824251.html?mod=djempersonal

http://online.wsj.com/article/BT-CO-20080310-706680.html?mod=djempersonal  Read More & Comment...

Smokin Aces

03/10/2008 07:27 AM |

The House Energy and Commerce Committee's health subcommittee is scheduled to pick up Tuesday where it left off Thursday, discussing and possibly amending the tobacco-control legislation before certain passage. The full committee would then take up the bill, and passage there appears certain as well.

Then it's on to the House, where a bit more than half its members (220, to be precise) are co-sponsors of the bill. In the Senate, similar legislation has 56 co-sponsors – including Senators McCain, Clinton, and Obama.

Is cigarette smoking deleterious to America's health. Absolutely. Should Americans who currently smoke quit? Absolutely. Should the FDA regulate tobacco products? Absolutely not.

One major problem with the proposed legislation is that it sets a very high bar (both scientific and procedural) before the FDA could approve a claim of "modified risk." The impact here would be to reduce any tobacco company's ability (or, most probably, desire) to promote their brands that are lower in nicotine content or, indeed, to even develop such products.

Or consider this, adult smoking has been declining since 1997 due to a number of things including clean air laws, media campaigns, and youth access programs. And these victories were achieved on the state level. If FDA became the nation's tobacco czar, it would become difficult if not impossible (given today’s economic circumstances) to convince state legislators to continue to allocate the funds required for robust state-level tobacco control programs.

Then, of course, there's the question of both FDA resources and expertise. Let's take the latter first. What is the current level of FDA expertise in tobacco regulation? Zero. As far as resources are concerned, the FDA's tobacco program would be funded by user fees. And, considering the current state of FDA funding and staffing, you have to ask yourself if this is really the way we want to be going.

So, when you consider all of these issues, the answer to "Will FDA regulation of tobacco help to reduce tobacco use in America?" is very much an open one.

So for now, thank you for not regulating.

FYI -- the Center for Medicine in the Public Interest (the sponsor of drugwonks.com) does not accept funding from the tobacco industry.  Read More & Comment...

Something in the Water....

03/09/2008 03:52 PM |

Leave it to the mainstream media to pump out the ultimate scare: Big Pharma pollutes the water supply!!!!

AP probe finds drugs in drinking water

By JEFF DONN, MARTHA MENDOZA and JUSTIN PRITCHARD, Associated Press Writers

"A vast array of pharmaceuticals — including antibiotics, anti-convulsants, mood stabilizers and sex hormones — have been found in the drinking water supplies of at least 41 million Americans, an Associated Press investigation shows."

What no Viagra? What about OTC products? Is this some off-label use conspiracy?

"To be sure, the concentrations of these pharmaceuticals are tiny, measured in quantities of parts per billion or trillion, far below the levels of a medical dose. Also, utilities insist their water is safe."

Trillion? How about gazillion?


"But the presence of so many prescription drugs — and over-the-counter medicines like acetaminophen and ibuprofen — in so much of our drinking water is heightening worries among scientists of long-term consequences to human health."

Which scientists? I don't think AP could find one to comment...or at least one that wouldn't stop laughing long enough to do so.

"And while researchers do not yet understand the exact risks from decades of persistent exposure to random combinations of low levels of pharmaceuticals, recent studies — which have gone virtually unnoticed by the general public — have found alarming effects on human cells and wildlife."

Yes, truly alarming, especially when you claim we don't know the risks.

"We recognize it is a growing concern and we're taking it very seriously," said Benjamin H. Grumbles, assistant administrator for water at the U.S. Environmental Protection Agency."

Yes and so does I.M. Krankee assistant administrator for administrators at the EPA.

The evidence is overwhelming. The AP actually conducted a 5 month investigation.
Most significant:

"Anti-anxiety medications were detected in a portion of the treated drinking water for 18.5 million people in Southern California.A sex hormone was detected in San Francisco's drinking water."

Why am I not surprised. But no cocaine, pot or heroin? Are those drugs too?

The rest of the article breathlessly details the peril parts per trillion pharmaceuticals impose on the planet. It ends with this observation:

"We know we are being exposed to other people's drugs through our drinking water, and that can't be good," says Dr. David Carpenter, who directs the Institute for Health and the Environment of the State University of New York at Albany."

Very scientific judgment David. I know some people who should be drinking heavily...or have been. It's the birdbrains at AP who put this story together...

Read Article Here

  Read More & Comment...

Getting into DDMAC's PJs

03/07/2008 03:51 PM |

What constitutes a "complete and reviewable" submission for DDMAC review of a DTC ad?

For a complete answer, see here:

http://www.fda.gov/cder/ddmac/submissions.htm

And for an insight into regulatory creep, consider this little codicil:

"Spokesperson verification – i.e., verification that a person who is held out as either being an actual patient or actual doctor is in fact a real patient or real doctor. Verification should consist of a signed statement from the spokesperson certifying that the claims they make in the piece about being a doctor/being a patient and actually prescribing or using the drug are accurate."

This is nothing more than a knee-jerk "PJ" ("Post-Jarvik") reaction. And DDMAC should know better. What does this have to do with fair balance or adequate provision? Nothing. What does it have to do with politics. Everything.

After all, what pharmaceutical company in their right mind would represent a "fake" doctor as a real one. Regarless of what you feel about the industry or DTC -- you must admit that the answer is -- none. That's why there have been precisely zero DDMAC actions on this front.

Verifiable? How about verifiably inane.  Read More & Comment...

No empirical basis for measuring comparative effectiveness

03/07/2008 11:33 AM |

Here's Sir Michael Rawlins, the director of NICE, exposing comparative effectiveness as a back of the envelope calculation that has hardened into a tool for rationing:

" It is not based on empirical research, there is no empirical research anywhere in the world, it is really based on the collective judgment of the health economists we have approached across the country. There is no known piece of work which tells you what the threshold should be. There have been ex cathedra statements. For example, the World Health Organisation says it should be somewhere around your GDP per person, but why the GDP per capita? It is elusive."

Who do you trust, your doctor or the collective judgment of health economists and their ex cathedra statements..... Policymakers who support comparative effectiveness as evidence-based are engaging in Orwellian Newspeak.

Read more of the sloppy methodology deployed by cost containers....
http://www.publications.parliament.uk/pa/cm200708/cmselect/cmhealth/uc27-i/uc2702.htm  Read More & Comment...

Just do it

03/07/2008 08:28 AM |

Straight shooting from the Washington Post editorial page. And we concur.

Some snippets:

"The FDA has been scolded about this yawning loophole in drug safety for over a decade but has not acted to fill it. Funding is the main problem."

We've been saying this for years and welcome the Post to the fold. Passage of FD Triple A is a giant step in the right direction -- but it is only a first step. Our elected representatives must stay focussed, tone down the rhetoric, and keep their eye on the prize. All of the wasted time and energy being spent trash talking biomarkers and posturing around the Reagan/Udall Foundation would be time and energy better spent addressing FDA's critical funding priorities.

"Without good data, there's no way to create an accurate, risk-based enforcement model, and no way for FDA officials to be held accountable."

It's not sexy -- but this is where the rubber meets the road. The FDA is at the intersection of life-saving data. Now is the time to make it happen via robust IT systems.

"The FDA very evidently needs more money, either through appropriations or user fees (which under current law can't be used for follow-up surveillance inspections). How much is unclear, since FDA officials won't say how much more in the way of money or inspectors is needed to carry out their expanding mission, claiming it's not their job to decide. We don't know whether their silence is attributable to their shyness or threats from the Bush administration. But when the safety of the American public is being risked by their financial inability to do their jobs, they need to speak up. That's the only way lawmakers -- who last year gave the FDA more money than the Bush administration had asked for -- can relieve FDA officials of their remaining excuses for nonperformance."

Yup.

Here's a link to the complete editorial:

http://www.washingtonpost.com/wp-dyn/content/article/2008/03/06/AR2008030603457.html

It shouldn't take tragic events, such as deaths due to counterfeit drugs, to make this happen. But if that's what it takes to get it done, then let's honor the victims by making real FDA reform a bipartisan public health victory.

Now.  Read More & Comment...

Junk Science and Austim: The Precautionary Principle Jackpot

03/06/2008 09:15 PM |

The National Vaccine Injury Compensation Program (NVIP) board voted to award a family monetary compensation in a case where the reviewers determined that the family was able to show -- not prove, not demonstrate on the basis of scientific evidence -- that it was not impossible to rule out that vaccines aggravated a rare mitochonrial disease (MD). MD is associated with systemic toxicity and nutrient starvation issues at the cellular level that can lead to developmental delays, brain damage and behaviors consistent with those found on the autism disorder spectrum.

Thus, under the very loose evidentiary standards of the NVIP under which a claim may have merit without proof of strong association or causation, the family won an award. That is all the family had to do was show that the vaccines were given around the time the mitochondrial disorder was aggravated.

Now the facts, ignored by the media and, it appears, the special masters reviewing the case:

1. Mitochondrial dysfunction may be one of the most common medical conditions associated with autism.

2. Autistic features are associated with MD. So are developmental delays.

3. There is a high frequency of biochemical markers of mitochondrial dysfunction namely hyperlactacidemia and increased lactate/pyruvate ratio in a small sample of autistic families. But there is no direct linkage between the two markers. (Am J Psychiatry. 2006 May;163(5):929-31. Lack of association between autism and SLC25A12.)

4.Instead, population studies show simply an association: definite mitochondrial respiratory chain disorder, suggesting that this might be one of the most common disorders associated with autism, about 7.2 percent in one study. (Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol. 2005 Mar;47(3):185-9.Click here to read)

5. There are no scientific studies documenting that childhood vaccinations cause mitochondrial diseases or worsen mitochondrial disease symptoms. In the absence of scientific evidence, the UMDF cannot confirm any association between mitochondrial diseases and vaccines.

But you don't have to bring science to bear in the NVIP, only a plausible basis for a claim which can be little more than a hypothesis that dramatizes risk. In the 1980s parents who sued for compensation for brain damage due to DTP vaccine won even though the did not prove an association and scientists said there was none. Sound familar?

So is this a "victory" for the vaccine-autism stalwarts. It was an ingenious approach taken by the parents and the autism fringe groups. They know the media and it's inability to assess the science and desire to portray suffering parents as triumphant over the government and vaccine companies. So my guess is it is. It is a loss for science and the public health.  Read More & Comment...

Ignorance, Bliss, and Gene Testing

03/06/2008 01:46 PM |

Can ignorance be bliss when it comes to information about your health? Is knowledge always power -- and can that power be abused? And what about the need for more robust FDA oversight of 21st centuty diagnostics?

Have a look at this article from today's edition of USA Today:

Companies cash in on checking your DNA for disease

By Rita Rubin, USA TODAY

Several new companies are betting consumers will be curious enough to shell out $1,000 or more to learn what diseases might lurk in their genes.

Using a half-teaspoon of saliva, collected at home and mailed to a lab, companies with catchy names such as de-CODEme and 23andME (for humans' 23 chromosomes) are selling the chance to peer into one's genome, the hereditary information encoded in DNA.

Q&A: What to know about testing your genes

The Genetics and Public Policy Center in Washington, D.C., has identified eight companies marketing a "personal genome service." They test for common gene variations linked to a higher risk of leading killers such as heart disease. Other firms market tests to detect genetic susceptibility to specific conditions; one for late-onset Alzheimer's is due this spring.


TEST: Tell if you're destined for Alzheimer's ... then what?
YOUR VIEW: Would you get tested for serious disease and live your life differently?

The tests raise a host of ethical and practical questions: Why should people be tested to see whether they're at risk for a disease they can't do anything about? What will they do with their results? What safeguards are in place to protect their privacy?

In The New England Journal of Medicine on Jan. 10, Harvard epidemiologist David Hunter, Muin Khoury of the Centers for Disease Control and Prevention and Journal editor Jeffrey Drazen called efforts to popularize genetic testing "premature." The diseases listed by test sellers involve multiple gene variations — many of which aren't yet known — that interact with each other and the environment, they say.

Linda Avey, who is co-founder of 23andMe in Mountain View, Calif., disagrees. "The debate is sort of over," she says. "There's so much interest and pent-up demand for this." Her firm charges $999 for a genetic profile. She won't say how many customers have paid for the test.

Among the more targeted tests, HairDX in Irvine, Calif., says for $149 it can tell men whether they're likely to start balding at 40 so they can "make the right decisions to preserve" their hair. Then there is Alzheimer's Mirror, which tests for the one known genetic risk factor for late-onset Alzheimer's.

"My big concern is that these tests are massively under-regulated," says Kathy Hudson, director of the Genetics and Public Policy Center. "There's nobody looking seriously at whether the claims these companies are making about the tests are accurate."  Read More & Comment...