Blowing Up the Critical Path

07/03/2008 12:21 PM |

The 14-2 vote to add years to the time patients will get new diabetes drugs to search for potential CV risks is a direct attach on the Critical Path.  Long term studies are not needed when new biomarkers and predictive systems can be developed.  But of course, that won't pass muster with the dimwits who followed Nissen off the Critical Path in a 14-2 vote or the  media or pols who construed the choice as follows:

Diabetes drugs should face tougher safety standards that could cost manufacturers millions but protect patients from unforeseen heart risks, a government panel has recommended.

The Critical Path is all about determining who should get what drug based on predictive markers... Nissen, the media and the pols are all about fearmongering.  Test 'em all. 

"The majority of the panel said drug companies could begin safety testing before they submit drugs to the FDA, and finish the studies after the drugs are on the market. The testing would take an estimated five to seven years to complete, and likely cost tens of millions of dollars."

Oh really? And which patients will you expose to the additional risk while being treated to diabetes?  Or the so-called risk since it is unclear if there is a risk at all or which patients are at greater risk.  This is the result of Tabloid Medicine driving out good science and medical progress.

Meanwhile Nissen made this incredibly ignorant statement:

FDA is operating under ''the irrational belief that lowering blood sugar using virtually any pharmacological means will produce'' better results for patients."

Actually, that is what Nissen said -- we already have enough drugs to do the job.  The FDA has never practiced medicine but has data showing that reductions in blood sugar do keep people alive longer.  Nissen care to dispute that?

The danger of course is that this brutalization of medical science will spread to other diseases....Will the grownups at the FDA do the right thing and strike a balance for science?

''The fallacy here is that we will never know everything we'd like to about a drug before it goes on the market,'' Dr. Ray Woosley, president of the Critical Path Institute in Tucson, Ariz., said in a phone interview Tuesday. ''If we held up drugs until we did know everything a lot of people would die.''

www.nytimes.com/aponline/health/AP-Diabetes-Drugs-Heart-Risks.html  Read More & Comment...

Knowledge is Dour

07/02/2008 08:17 PM |

Finally!  We're addressing a serious flaw in our healthcare system -- too much CME.

Pfizer, according to the Wall Street Journal. “hoping to temper criticism that it's improperly influencing doctors, is eliminating direct financial support for medical-education courses that are offered by third-party companies.”

"The reason we're not going to directly support them has to do with mitigating the perception of a conflict of interest, if a direct payment is going from a company like Pfizer to them," commented Cathryn Clary, vice president of U.S. external medical affairs.

Okay, so let’s get this straight – this is being done not because anything was amiss or non-compliant or because there’s too much CME going on out there – but because of political pressure.

Senator Chuck Grassley, ranking member of the Senate Finance Committee, said in a written statement: "My goal is to strengthen the system by shedding light on the financial relationships that exist between industry and medical doctors, medical education programs, medical journals, and medical research. … Public scrutiny can do a lot to bring about necessary reforms."

But what it’s brought about is less CME -- fewer opportunities for physicians to hone their skills.

And this is a victory for who?

  Read More & Comment...

When Nissen Loved Vytorin

07/02/2008 02:16 PM |

From a Forbes article in 2003...

Pharmaceuticals
Statin Makers Bet Big On Imaging Technique
Matthew Herper, 11.10.03, 1:01 PM ET

ORLANDO, FLA. - Trying to get a leg up in the $22 billion market for cholesterol medicines, drug companies increasingly are turning to an imaging technique that allows researchers to see how much plaque is building inside arteries. Several of the biggest players are funding major research studies, and--in an unusual twist--many of these clinical trials are being run by the same cardiologist: Steven E. Nissen.

In retrospect, we realize that it is not unusual at all just...business as usual. 

www.forbes.com/2003/11/10/cx_mh_1110merck.html  Read More & Comment...

Nissen Auditions for FDA Commissioner

07/02/2008 01:09 PM |

If anyone in Washington who covers the FDA was paying attention yesterday to Steve Nissen's "compromise" on how to regulate new diabetes drugs they got an idea of how new drug development would fare under Nissen if he had more control over the FDA or became commissioner:

From today's WSJ:

"Cardiologist Steven Nissen of the Cleveland Clinic said the FDA should require companies to prove their drugs don't raise risks of cardiovascular disease before they are approved.

Dr. Nissen said there are more than enough diabetes drugs on the market that lower blood-glucose levels, and now is the time for the FDA to raise its standards.

"Merely lowering blood-glucose levels in diabetes is too simplistic," Dr. Nissen said. "We must reduce the complications of diabetes, including cardiovascular disease."

online.wsj.com/article/SB121495996433621583.html

Dr. Nissen suggested that in addition to requiring more preapproval studies, companies should have large, long-term studies in place when a drug is approved to monitor whether the drug increases the risk of cardiovascular disease.

Why stop at diabetes drugs?  If you apply Nissen's logic to any illness "there are more than enough drugs" out there to treat everything under sun.  And since every drug has some cardiac risk, why not subject them all to increased long term clinical trials (that Nissen would conduct of course) to look at the problem. 

Let's set aside diabetes which is not just killing people here but worldwide.  And let's set aside Nissen's failure to acknowledge that by claiming there are more than enough drugs he is ignoring the fact that diabetes requires individualized treatment but that new medicines will be developed (we hope) around more particular and preventive approaches, etc., etc.  and that diabetes is not just a cardiovascular disease but part of a larger disorder that must be treated with as many tools as possible.   Would you want an FDA commissioner who would say "we have enough drugs for...."?  I am sure there are some who believe that, including Marcia Angell, but not many real physicians and scientists. 

I would love to see that statement thrown back at him.

Next, what are the implications of his approach to access to medicines for patients?

Here's what the lead medical officer who reviews diabetes drugs at the FDA said according to a reporting in Bloomberg News

"Conclusive evidence of cardiovascular benefit hasn't been established for any drug for Type 2 diabetes, despite several large, long-term trials," Hylton Joffe, lead medical officer in the FDA's Division of Metabolism and Endocrinology Products, told the FDA panel yesterday.

Requiring heart assessments, especially before FDA approval, would add years to drug development because it takes that long for damage to show up. There also are ethical and logistical questions about how to organize studies because patients don't want to be in a comparison group getting a dummy pill and usually require multiple medicines as their disease progresses, Joffe said."

www.nj.com/business/ledger/index.ssf
Frankly, I don't think Nissen -- who simply engaged in fearmongering over Avandia and drugs for ADHD -- couldn't care about the ethics of the matter. 

If Nissen were FDA Czar, here's what patients could expect:

Add years and billions to the cost of new drug development.
Say good-bye to the Critical Path.
Let millions of people who are dying of and suffering from any illness with a drug in development that may have a cardiac side effect that can be found in any amount of any correlation wait while some pet meta-analysis is verified.  So that includes drugs for:
Cancer
Alzheimer's
Schizophrenia
Parkinson's
HIV
Diabetes

And stem cell research of any kind...

I hope at least patients are paying attention. 

 



  Read More & Comment...

Springer Spaniels

07/02/2008 12:43 PM |

The following story courtesy of our friend and occasional colleague "Kerfuffle Kate" Rawson of the RPM Report:

FDA Steps Up Security for Advisory Committees 

By Kate Rawson

FDA advisory committee meetings are not supposed to be like episodes of the Jerry Springer show. And for good reason: One is a scientific discussion of the benefit-risk profile of new drug or indication. The other is a television tabloid talk show with topics in such poor taste that our own corporate content filters won’t even let us access the website.

But it was Springer-like behavior at a recent meeting (featuring a threatening rant by an apparently intoxicated speaker during the open public hearing) that led FDA to impose new security measures to protect the agency’s expert panelists. While FDA hasn’t made a formal announcement of the policy changes, Office of New Drug Director John Jenkins discussed the new procedures at the Drug Information Association’s annual meeting last week.

“We have put in place some new measures to help improve security at meetings,” Jenkins said. “If we anticipate that there may be an increased need for security at a particular meeting because it is a particularly controversial topic, we may have additional security procedures.”

Those procedures include:

1) Creating a physical barrier by roping off the committee from the public. The intent, Jenkins said, is “to put some separation between those who might become agitated in the audience and committee members.” (For taxpayers, it carries another benefit—preventing the public from sneaking pastries off the committee’s breakfast tray.)

 

2) Increasing the presence of security guards in the committee room—both in uniform and street clothes.

 

3) Reading a statement at the start of the meeting about “good rules of behavior.”

There have been kerfuffles at advisory committees before, especially when the drug under review would be used to treat a rare or life-threatening condition. The heckling of FDA commissioner David Kessler during the 1996 advisory committee review of Abbott’s ritonavir, the first protease inhibitor for HIV, comes to mind.

And in very rare cases, FDA takes extraordinary steps to protect committee members. That same year, the review of the abortifacient RU-486 was held in an unused warehouse in the middle of a remote industrial park in Maryland. Attendees (or at least the press) were asked to park up to a half-mile away and walk into the meeting.

But this is the first time that FDA has felt the need for a comprehensive plan to ensure the security of advisory committee members. And it’s the biggest change to the advisory committee process since the agency altered its conflict of interest guidelines last year.

The trigger was a May 2007 review of IDM’s mifamurtide (Junovan) for the treatment of osteosarcoma. During the open public meeting, an apparently intoxicated individual made threatening statements to University of Michigan’s Maha Hussain, and was ultimately removed from the room. (You can read FDA’s official transcript of that exchange here.)

Later in the meeting, Hussain and other committee members pointedly suggested that FDA establish greater security measures. (Hussain, it should be noted, has had her share of controversy in committee rooms. Last year, she was also one of four votes against the approval of Dendreon’s Provenge, a decision that led to threatening e-mails, phone calls and letters.)

For drug sponsors, the new procedures aren’t likely to have significant practical implications. But they are indicative of the intense public interest in drug development, and the pressure to discover new cures and keep unsafe products off the market.

We should note that the majority of meetings aren’t controversial and hence don’t require significant security procedures. But, as Jenkins noted, “there have been some incidents where that decorum has not sustained itself, and we’ve felt the need to institute procedures to maintain the safety of our advisors.”

Hence the rope. Of course, roping off the public isn’t the only way FDA can ensure the safety of those present at advisory committee meetings. Given some of the disputes between FDA officials on drug safety issues (remember the Arcoxia meeting? The Avandia meeting?), perhaps that rope could be put to better use elsewhere.

Wouldn’t that make a good Springer show?

  Read More & Comment...

Cheap Canadian Drugs?

07/02/2008 12:31 PM |

From World Health Advocacy... www.whadvocacy.com.

Consumers in Canada spend the same percentage of their income on prescription drugs as consumers in the United States.

Government policies surrounding the pricing and reimbursement of prescription drugs in Canada do not produce lower costs for Canadians compared to Americans. Despite major differences between the Canadian and American healthcare systems, the results of a recent study show that consumers in both countries are spending the same percentage of their incomes on prescription drugs.

The price of generic drugs in Canada is more than double U.S. prices for identical drugs, while brand-name drugs are comparatively cheaper. In currency-equivalent terms, Canadian retail prices for brand-name pharmaceuticals decreased slightly between 2003 and 2007. In the same time frame, generic drug prices in Canada increased by 34% compared to U.S. prices.

The authors of the study state that Canadian government policies insulate generic drug companies and pharmacy retailers from normal market forces that would put downward pressure on prices for generic drugs. A relatively freer market in the United States produces lower prices for generic drugs to encourage consumers to substitute these generics in place of brand-name drugs.

  Read More & Comment...

The NHS New Slogan: Cancer Care As Good As Poland's

07/01/2008 07:19 PM |

I have made much about how lousy the UK five year survival rates are relative to the US.  A  researcher comes up with a statistical explanation for why the survival rates -- while bad -- may  not be as bad as Poland's: 

This is all from a Financial Times article entitled: "Why the UK's Cancer Survival Rates Look Bad"

www.ifpma.org/PressReviewEmail/PressReviewDetail.aspx

"Of the 20-plus countries in the Eurocare survey, only 10 look at the entire population. In 1998, the starting point for the latest five-year figures, Germany's figures covered just 1 per cent of the population, the Czech Republic 8 per cent, Poland 9 per cent and Spain and France 16 and 17 per cent respectively.

Prof Richards says that for instance in Italy, the figures cover only 28 per cent of the population, mainly in the affluent north "so it is almost certain their figures overestimate survival rates".

That's the good news.  And Professor Richard's makes a fair point if he can prove that the smaller slice of cancer patients surveyed are more likely to be over-represented by people who are more likely to survive.  Gee, that's just like infant mortality rates where some countries only count babies as alive if they live for 30 days while in the US we count them from the time they leave the womb. 

Now the bad: 

The UK has 100 per cent coverage, as do the Nordic countries. "Sweden, Norway and Finland do have appreciably better survival rates than we do, while Denmark looks remarkably like the UK across a whole range of factors," he says. "There is a real gap between us and the Nordic countries, and our task is to narrow that."

While the UK is slower than some other European countries to adopt newer cancer drugs, late diagnosis seems to be the real culprit. "Most of it is accounted for by our one-year survival rates," Professor Richards says. "If you get past that, our survival rates look much more like the European average. And one-year survival is most often correlated with advanced disease. There are relatively few cancers that will kill you in a year if they are diagnosed early". Smaller-scale studies also suggest that when patients in the UK seek help their disease is more advanced.

Does anyone have any idea why UK patients get help later when new drugs are less effective?  Anyone?

Prof. Richard suggests:

Some of that may be cultural: stoical Britons may delay seeing a doctor. The government's cancer plan aims to tackle that through better education and better screening, backed by large investments in radiotherapy.

Stoical?  Hardly.  Resigned and outraged is more like it.  But Richards also believes the Eurocare survey understates advances in survival because it is based on old data:

'Prof Richards believes that the reason Britain's figures are not better, despite the huge resources ploughed into tackling the problem, is that the numbers used for international comparisons are out of date, relating to cancers diagnosed in 1999 and 2000. "They predate the UK's big surge in spending after 1999, and any impact from the national cancer plan. We have a problem, but we are tackling it. I am pretty sure we are narrowing the gap".

In fact, many of the methodological problems with the Eurocare survey have been addressed in other articles, notably by Dr. Franco Berrino who took note of them in earlier surveys and adjusted for both over and under estimation of survival by  weighting five year survival rates of all countries studies based on limitations deriving from the quality of registry data.  Berrino, et al also use period analysis instead of the traditional cohort analysis provides long-term survival estimates that also take into consideration survival of more recently diagnosed patients.  By every measure the UK lags behind Western health systems in Europe and the US in particular which has more heterogeneity in its cancer population. 

www.thelancet.com/journals/lanonc/article/PIIS1470204507702462/fulltext  Read More & Comment...

Nissen Brings New Meaning to the Word Surrogate

07/01/2008 04:43 PM |

This afternoon Dr. Nissen has been invited to give a talk at a two day hearing of the Endocrine and Metabolic Drugs Advisory Committee designed to “discuss” the role of evaluating cardiovascular disease and/or risk in diabetes drugs.  His topic?  The need for cardiovascular assessment. 

He will make the case that the way to determine whether diabetes drugs prevent or reduce heart attacks is to conduct experiments in which certain people are prevented from taking a drug that will reduce them. 

Or will he? Depends on which way the political winds blow and the money is wired.

I as have noted on many occasions, Dr. Nissen uses surrogates – the media – and surrogate measures to get what he craves, exposure and a reputation as some sort of crusader that neither the FDA nor drug companies dare cross.  In point of fact, he is mostly best shakedown artist this side of Al Sharpton. 

We know that Dr. Nissen never lets science or statistics get in the way of a good soundbyte or payday.  Apparently two large studies of diabetics – ACCORD and ADVANCE – which measured whether drastically reducing and controlling glycemic indexes and used reduction of CV risk, as an endpoint are not enough for him.  The two large studies used different strategies and drug combinations to get people below a certain A1c level. ACCORD did so more rapidly than ADVANCE.   Both used Avandia extensively (ACCORD more so)  – and found no reduction in heart attacks.  ACCORD had a slight increase in heart attacks but at the end of the day, Avandia was use in combination with other drugs in both studies.  Some benefited, some did not.  Overall there was no reduction in heart attacks.  And there is no evidence that Avandia was associated with either. 

www.theheart.org/article/874809.do

So what will even longer and larger clinical trials show?  And should such studies, which take years to complete, be a precondition not only of drugs for diabetes but – as that Nobel Prize winning scientist Charles Grassley has noted, for every medicine for every disease?  

I am sure Dr. Nissen has a better answer.

And I bet it will be coronary intravascular ultrasonography (IVUS), which involves the insertion of a catheter into the coronary artery in order to measure the size of an atherosclerotic plaque.

IVUS is the "imaging technique that is the hottest and most important right now in anti-atherosclerotic drug development.”

www.pharmaasia.com/article-6017-imagingsharpensdiseaseresearch-Asia.html

Who said that?  Dr. Nissen.  And who conducts most of the IVUS studies in the US. 

Dr. Nissen.

Indeed, Dr. Nissen says that a number of drugs currently in clinical trials are aiming to use imaging as a primary endpoint for registration.

I am sure they are and I wonder who is conducting those trials?

Not that there is anything wrong with tooting your own horn so to speak as long as you don’t seek to infer from ”surrogate measures” studied in Phase I anything conclusive about how the drug will work…..


Nissen regarded the surrogate measures in ENHANCE as unreliable.  So why in 2003 did he propose to Merck and Schering-Plough a IVUS study of Vytorin called QUEST: "short for Quantitative Ultrasound Ezetimibe and Simvastatin Trial. Ezetimibe and simvastatin are the generic names for Zetia and Zocor, respectively."

That study, according to Nissen’s Boswell, Matt Herper of Forbes.com, would have been an 800-patient study to see if adding their new cholesterol drug, Zetia, to Merck's cholesterol-lowering blockbuster Zocor can prevent plaque from collecting on the artery wall better than Zocor alone. The patients would be followed for 18 months.

www.forbes.com/2003/11/10/cx_mh_1110merck.html

Merck nixed the study and went with another group and IVUS approach to run what became ENHANCE.  Same method, different bank account.

Nissen pounced, saying there was no reason to use Vytorin at all. 

But if Nissen, as he most recently claimed, believes in an individual approach to reducing LDL and glycemic levels why ban a drug because it doesn’t work IN GENERAL or because it make aggravate risk because of meta-analysis.  Why not promote the Critical Path and more patient specific approaches to life cycle management of drugs including adaptive trials designs and biomarkers.  Could that be competition for IVUS perhaps?

Will Nissen promote larger trials that keep important drugs away from people to promote IVUS in favor of a path that target safer more effective therapies using tools other than those he is paid to operate?

It is hard to stay on message when you are trying to stay in the headlines.

Or line your pockets. 

  Read More & Comment...

A Troy Ounce of Preemption

07/01/2008 12:36 PM |

Who has the final word on "safe and effective?"

Different people have different opinions.  We side with former FDA Chief Counsel Dan Troy.

Here's a new video podcast that features Dan telling it like it is:

Dan Troy on FDA Preemption

And you know what they say, an ounce of preemption ...  Read More & Comment...

FDA: Not Yes or No But Who and When?

06/30/2008 05:59 PM |

There are a lot of problems with newspaper articles that are based, not on the fact, but on the perception of a problem that Tabloid medicine has created:

"…the Vioxx debacle, which sparked harsh criticism of both drug companies and their chief regulator, appears to have led to a climate shift. The drug industry largely has itself to blame for allegedly manipulating clinical data, concealing dangerous side effects and aggressively promoting risky products, which created widespread mistrust…."

online.wsj.com/article/SB121476772560213981.html

First, can one be blamed for alleged behavior. Second, where is the evidence of all these actions?

Well, it was largely generated by the same cast of characters:

“Outspoken scientists, watchdog groups, medical-journal editors and politicians have fanned worries about safety. The wave of post-Vioxx drug scares included concerns that GlaxoSmithKline PLC's widely used diabetes drug, Avandia, could raise heart-attack risk, and that Pfizer Inc.'s smoking-cessation drug, Chantix, may be connected to suicides. More than 80 U.S. deaths linked to contaminated heparin from China have further ratcheted up public anxiety. The FDA has been battered by criticism that it wasn't vigilant enough, including from Cleveland Clinic cardiologist Steven Nissen, Sen. Chuck Grassley of Iowa and Rep. John Dingell of Michigan.”

And when you want to keep fanning fears it helps not to be has vociferous in alerting the public when subsequent studies show Avandia has no heart attack risk or that multiple factors might associated Chantix to suicides (such as an increase in the number of addicts with mental illness taking the drug.) Ditto when drug safety vigilantes like Nissen and Grassley (I would not put Congressman Dingell in that camp) engage in fearmongering about Ritalin, SSRIs and Ketek because they know an unquestioning media fails to put the risks and reasons in context….

All of which begs the question, does any of this have any impact on drug approval rates and times?

The short answer: Sometimes it does but increasingly -- I hope – science-based regulation will not just shape drug development times but also who gets what drug, i.e. personalized medicine.

It is true that time is money, especially in drug discovery and development (same for devices and diagnostics). But the truth is the reaction to Vioxx could have been avoided with a post market system in place that could identify who was at greatest risk. Many of the product delays discussed – while in part due to the fact that the Office of New Drugs is overwhelmed and kicking everything back to the detriment of the public health -- would be overcome by the routine use of regulatory tools to speed up and improve the accuracy of toxicity screens, by wider use of combinations of drugs and diagnostics that measure and predict patient response to medicines and disease progression, etc.

To be sure, much of the information FDA reviewers are requesting could be obtained in the “real world.” But I believe that the questions they are asking are legitimate ones. Indeed, they are often the questions that companies themselves face but do not know the answer to or afraid to find out. To conduct an in-depth study of a safety issue absent large clinical trials and reliable assays would kill and drug and likely deny large number of patients who would benefit from a medicine access even as researchers were trying to establish the mechanism causing toxicity for a small percentage of people.

If we wait for drugs to be perfect and confer no risks, there will be no new drugs. No one wants that. Which is why we are developing predictive tools and should insist upon patient-centered real time updates of how well drugs and devices are performing.

I think rather than whining about how slow the FDA has become, pharma CEOs should demonstrate that they are putting their shoulder to the wheel to make better, safer medicines more quickly available. There are many such initiatives and partnerships focusing on these efforts. The recent efforts of the Predictive Safety Testing Consortium (PSTC) in developing safety biomarkers are great example. The PSTC, whose members consist of scientists from 16 institutions, including 13 major pharmaceutical companies, was organized and led by the Critical Path Institute (C-Path).

Talking about these programs and increasing support for them might not change the story line of reporters who want to write about “fast” and “slow”, “safe” and “dangerous”, drug safety “advocates” and Big Pharma, but it will change medicine for the better. Fast or slow will be replaced by what drug for which person.  Read More & Comment...

Did the Earth Move for You?

06/30/2008 03:50 PM |

A draft constitution that "enshrines" the principles and values of Britain's National Health Service (NHS) was published today for consultation by Alan Johnson, the UK's Secretary of State.

According to the NHS release:

“The first of its kind in the world, the Constitution follows extensive discussions with staff, patients and the public over the last year. It reaffirms the rights to NHS services, free of charge without discrimination of any kind. For the first time, it will bring together in one place and clarify for staff and patients their rights and responsibilities to ensure the NHS operates fairly and effectively.”

The draft Constitution can be found at www.dh.gov.uk/consultations

The Association of the British Pharmaceutical Industry describes the document as,

"measures that offer the opportunity to effect a seismic change in patients' right to access the best and most modern medicines based on clinical need."

Others disagree.

Antoine Clark, international editor of Pharma Marketletter, commented,

"Seismic? I don't feel the Earth move!"

Here’s his read on what “free of charge without discrimination of any kind” means in NHS parlance:

Health care except in the case of:

1) week-ends and Mondays;

2) smokers;

3) drinkers;

4) fat people;

5) grumpy old people;

6) people living in the wrong post code;

7) people living in England;

8) people who don't know how to make a noise and kick up a fuss;

9) people who require the latest medical care;

10) people who want to have dental care;

11) foreigners (except when it is politically inconvenient to deny them or they vote Labour; and

12) people who have the nerve to pay extra for private care, as in "Please Sir, can I have some more?

  Read More & Comment...

The Pharmaceutical Past is Prologue

06/30/2008 01:15 PM |

The Wall Street Journal reports that, “Last year, the FDA approved just 19 new medicines, the fewest in 24 years, and announced about 75 new or revised "black-box" warnings about potential side effects -- the agency's strongest -- twice the number in 2004.”

True. But numbers are just numbers. The story is somewhat different when you put those numbers in perspective.

According to the Journal story, “Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research, denies that the agency has become "more conservative" about drug safety. Rather, she says, the industry's faltering research efforts are mostly to blame for the fewer product approvals. She says the agency continues to base its decisions on science, not outside pressures. New methods, she adds, have helped it become more vigilant about side effects. She attributed the increase in black-box warnings primarily to a few large groups of medicines that were relabeled."

Reality bites.

Bringing new drugs to market has always been a scientifically challenging and expensive proposition – and it remains so. But the big difference today isn’t (gasp!) politics – it’s that, while discovery and development embrace 21^st century science, regulatory science lags behind. At present, the FDA is using 20^th century tools to review 21^st century medicines.

This is why the agency’s Critical Path Program and the Congressionally-mandated Reagan/Udall Foundation are so crucial to our 21^st century healthcare future -- as well as to the future of the pharmaceutical industry.

The comments of Schering-Plough CEO Fred Hassan (courtesy of the Journal article) are instructive:

“Mr. Hassan believes an intensifying focus on safety and a diminished tolerance for side effects at the Food and Drug Administration have dramatically lowered the odds that the drugs would make it to market -- at least not without a lot of extra time and money.”

Not so fast. It is today as it has been in the past and must be in the future – the quest for appropriate risk/benefit balance. Side effects are “tolerated” insofar as the benefits are appropriate. As to the “extra time and money” comment – there’s no benefit from wishing for the “good old days.” Time marches on and so does science. Perhaps a better focus would be on more innovative clinical trial designs – and on the FDA’s promised guidance on adaptive clinical trial designs.

The past is prologue.

"What will it take to get new drugs approved?" Mr. Hassan asks. "The point is, we don't know."

Yes we do. Better development science and better regulatory tools for the FDA.

Here's the full Journal story:

Journal Story Here

  Read More & Comment...

Pharmaceutical Imperialism

06/30/2008 12:41 PM |

According to an opinion piece in The Guardian newspaper, “If you suffer from epilepsy and you live in Athens you are less likely to receive the vital drugs you need for treatment than if you live in London, Berlin or Amsterdam. And, says Konstantinos Lourantos, president of the Association of Pharmacies of Attica, the fact that they are freely available in other parts of Europe contributes to their shortage in his country. The reason? Lourantos, whose organisation represents some 3,500 pharmacists in and around Athens, blames companies that buy up medicines in Greece and export them to other EU countries, exploiting the price differences for drugs across the EU.”

Lourantos says: 'For example, there is a medicine called Lamictal for epilepsy which is imported to Greece but it is re-exported in such a huge quantity that there is very little left.' He says the problem affects supplies of a number of drugs, including Astra Zeneca's Seroqual for treating bipolar disorder and Risperdal, an anti-psychotic treatment.

Here’s a link to the complete story:

Guardian Story

My eldest son has epilepsy. I don’t want his access to the medicines he needs to lead an active life to be on the backs of those in other countries who have their drugs pirated away by parallel trade arbitragers.

Whether you call it parallel trade in the EU or "drug importation," on the Presidential campaign trail -- it's still pharmaceutical imperialism.

  Read More & Comment...

JAMA's Version of the Matrix

06/27/2008 02:08 PM |

If you don't know if you are being manipulated than how can you tell if it's you that are being controlled by outside forces or someone else? If everyone is unconsciously being biased without knowing it how can we really judge what is right or wrong apart from the shadowy influences. And who or what is controlling those influences we think are controlling those influences we think are subversive?

This from the mind of Catherine D' Angelis, Editor D' Jefe of JAM, courtesy of Tom Sullivan's Policy and Medicine blog:

“Medical schools and professional medical associations have developed policies and guidelines in response to increasing concerns over potential conflicts of interest.

While many physicians agree with these concerns, some view conflict-of-interest policies as affronts to their integrity and an indictment of the ethical conduct of the profession as a whole. These individuals believe that their training as scientists and their devotion to professionalism protects them from external influences that might bias their opinions.

However, this view may be based on an incorrect understanding of human psychology. Conflicts of interest are problematic, not only because they are widespread but also because most people incorrectly think that succumbing to them is due to intentional corruption, a problem for only a few bad apples.

In this Commentary, we argue that succumbing to a conflict of interest is more likely to result from unintentional bias, something common in everyone. We review studies in neuropsychology, behavioral economics, cognitive psychology, and clinical epidemiology to illustrate this point."

All of which means there is no escape from conflict and therefore no end to regulation or thought control. Which begs the question: if that's the case, what qualifies the equally corrupted D' Angelis and her ilk for ruling over the everyone else?

www.policymed.com/2008/06/jama-everyones.html  Read More & Comment...

Marsha! Marsha! Marsha!

06/27/2008 02:03 PM |

We recently interviewed Representative Marsha Blackburn (R, TN) on her views about healthcare reform.

Have a look:

View video podcast here
  Read More & Comment...

Wylie Coyote: Federal Marshal

06/27/2008 01:46 PM |

According to the Wall Street Journal, “European Union investigators are widening a probe of the pharmaceutical industry as they look into whether drug companies have used unfair tactics to block competition and prop up prices.”

The EU sent questionnaires to drug wholesalers and trading firms, asking them about pharmaceutical companies' distribution methods and other practices.

That’s kind of like asking the Association of Hungry Foxes about chicken coop security regulations.

Specifically, the EU is asking about the distribution methods drug companies’ use in Europe, and whether they are blocking competitors from distributing medicines.

Heinz Kobelt, secretary-general of the European Association of Euro-Pharmaceutical Companies, the trade group representing parallel traders, says EU investigators sent him a questionnaire in mid-May asking whether drug companies were using litigation or other tactics to thwart parallel trade.

So, Mr. Wylie E. Coyote, what do you think of the business practices of Mr. Roadrunner?

According to the Journal report, “Mr. Kobelt said the questionnaire asked for his group's views on so-called direct-to-pharmacy distribution channels, which Pfizer Inc. and AstraZeneca PLC have recently established in Britain. Direct-to-pharmacy channels differ from traditional distribution in that the drug company pays wholesalers a set fee to deliver goods to pharmacies, rather than selling to the wholesaler. The drug companies say the approach helps them keep better control over their goods and prevents counterfeit medicines from getting into pharmacies. Wholesalers say big pharmaceutical companies are trying to prevent parallel trade, a charge the companies deny.”

Is this the debate then? Big Pharma trying to reduce fraud and counterfeiting versus parallel traders who want to protect their profits? What’s best for the consumer?

Relative to the value of parallel trade, consider the insights of. W. Neil Palmer of RTI Health Solutions. (By way of bona fides, Neil has served as a senior official with the Canadian Patented Medicine Prices Review Board -- the dreaded PMPRB -- as well as with the Health Division of Health Canada, and the Kellogg Centre for Advanced Studies in Primary Care in Montreal.)

His take on the European experience with parallel trade:

* It is not the policy of EU governments to use parallel trade to deliver savings to their individual health care systems.

* Because savings are not passed on to consumers and payers.

* Patient care may be jeopardized because of quality, supply chain integrity and regulatory compliance issues -- as well as potential shortages occurring in exporting nations.

* Increased parallel trade results in decreased competitiveness of the pharmaceutical industry in local markets. And, since the profits of the parallel traders aren't reinvested into R&D, opportunities are lost for the patient, the local health care system, and the economy.

As far as safety goes, its been proven time and time again that parallel trade is the weak link in the European pharmaceutical chain of custody. Counterfeiters know it and so do national authorities across the EU.

For more on this issue, see here: www.drugwonks.com/blog_post/show/5362

Perhaps the EU is investigating the wrong people?

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From the Folks Who Gave Us Comparative Effectiveness: Copays That Compromise Health

06/27/2008 02:49 AM |

The folks from the Drug Effectiveness Research Program, on retainer to Agency for Health Care Research and Quality and who set the de facto reimbursement guidelines for Medicaid preferred drug lists also recommend co-pays as a way to steer people into other drugs. Guess what?

Prescription use dropped about 17% after introduction of policy, Oregon study finds

THURSDAY, June 26 (HealthDay News) -- Adding small co-payments to Medicaid prescription drug plans reduces the use of medications by patients with chronic diseases, says a U.S. study.

Daniel M. Hartung, of Oregon Health & Science University, and his colleagues analyzed the effect of small co-payments -- $2 for generic and $3 for brand-name -- for prescription drugs introduced for Oregon Medicaid enrollees in 2003. The co-pay fees weren't required for patients who were unable to pay.

The researchers examined pharmacy claims data on about 117,000 Medicare enrollees with depression, schizophrenia, respiratory disease, cardiovascular disease and diabetes.

The patients' overall use of prescription drugs decreased by about 17 percent after introduction of the co-pay policy.

"Subjects with chronic diseases were less likely to reduce the use of drugs used for that disease compared with drugs not for that disease," the study authors wrote.

Most state Medicaid programs now use co-payments to help control prescription drug costs, but few studies have examined how these co-payments affect medication use, the researchers noted.

"This study suggests that in response to cost-sharing, patients discriminate what therapies they reduce based on the diseases they have," they wrote.

The study was published in the June issue of Medical Care.

In Oregon, co-payments for some outpatient services were introduced at the same time as the drug co-payments. But there were no significant changes in the use of those outpatient services, the study found.

This comes on the heels of other studies showing that decreased drug use is associated with a spike in illness...

Where are those geniuses in Health Affairs who said Medicaid was the most efficient way to provide coverage for more people now? Along with the rest of the Left they are willing to sacrifice the quality of life of the people they "care" about to implement their program...

The same goes for those who see comparative effectiveness as a cost containment tool...

Read Article here  Read More & Comment...

No Clinical Trials Please, We're British

06/26/2008 01:23 PM |

According to a report in the FT, “Leading pharmaceutical groups are cutting back on clinical research in the UK, claiming insufficient commitment by the government and the National Health Service to support new drug development.”

Pfizer of the US, Roche of Switzerland and Merck-Serono of Germany are among the companies which have told the Financial Times they have, or will, reduce the number of British patients enrolled in trials to test experimental medicines for life-threatening diseases such as cancer.

The result, the companies claim, is that few patients in Britain are receiving “gold standard” treatment -- so there is too small a group against which to compare their experimental drugs.

Add this to the list of the negative unintended consequences of HTA/Comparative Effectiveness.

The drug companies are increasingly frustrated by the National Institute for Health and Clinical Excellence, the government’s medicines advisory body, which on Wednesday handed them fresh setbacks by advising against NHS use of Pfizer’s Avastin and Merck-Serono’s Erbitux.

The warnings are a fresh embarrassment for the government, which has stressed its commitment to pharmaceutical research in the UK while imposing a fresh 5 per cost cut after unilaterally scrapping the existing price contract with industry only halfway through its five-year term.

Pfizer has already recently canceled UK participation in four clinical trials, including one for cancer, because it could not recruit sufficient patients who were taking the existing international “gold standard” approved drugs against which to compare with its experimental treatment.

NICE argues it approves most medicines and those that it has rejected have offered very limited value.

Really? Perhaps NICE should speak with Brian Turner, (Oaks Green Mount, Rastrick, United Kingdom) 74, who suffers from wet age-related macular degeneration in his left eye. He went blind in one eye after the NHS denied his request for Avastin. The NHS told Mr. Turner that treatment would only be approved if his other eye became affected and complete blindness was a risk.

Here's Brian telling his own story:

www.biggovhealth.org/testimonials/brian-turner/

And what about Dorothy "Dot" Griffiths (Stoke-on-Trent, United Kingdom), a breast cancer patient who, in July 2005, organized the advocay group "Fighting for Herceptin" and successfully lobbied the British Parliament after the NHS refused her request for the life-prolonging drug Herceptin because of ... cost of treatment.

Here's a link to Dot's story:

http://www.biggovhealth.org/testimonials/dorothy-griffiths/

Here’s a link to the complete story in today’s Financial Times:

http://www.ft.com/cms/s/0/f0e08f2a-42ee-11dd-81d0-0000779fd2ac.html

For more such healthcare “horror stories,” click here:

http://www.biggovhealth.org/stories/

And here’s a link to a new op-ed in the Journal of Life Sciences on the topic of what government-run healthcare provides – or doesn’t:

http://www.tjols.com/article-694.html

It’s time to tell the truth about Big Government Healthcare.

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BigGovHealth Is Efficient

06/25/2008 02:17 PM |

On the heels of our www.bigGovHealth.org  launch comes this from Health Affairs:

Covering low-income people through public programs such as Medicaid and the State Children’s Health Insurance Program (SCHIP), rather than through private health insurance, results in lower per person medical spending and considerably lower out-of-pocket expenses for consumers. That’s the conclusion of a new study published today on the Health Affairs Web site, which looks at different ways of providing health insurance to Americans with family incomes below 200 percent of the federal poverty level. (For a family of four, 200 percent of the 2008 FPL is $42,400.) http://content.healthaffairs.org/cgi/content/abstract/hlthaff.27.4.w318
           

Has anyone been paying attention to what's been happening to access to care in public health programs here, Europe and Canada?  Not on the left where ideology trumps concern for patients:

Many states have used the same approaches to cover the uninsured and to make existing premiums less expensive. Instead of doing so, such proposals have driven many doctors out of government-run programs and have rationed access to new medicines. Private insurers are leaving markets. And patients who are forced to wait months for needed care often wind up not getting the medicines they need.

For example, Nicole Garrett's three teen-age children lost their private coverage, so she lost her private coverage and enrolled them in Michigan's managed-care Medicaid program.

According to a 2007 article in the Wall Street Journal by Vanessa Furhmans, when Nicole's 16-year-old daughter, Jada, needed to see a rheumatologist, the one listed in her managed-care Medicaid plan's network would not see her. Nicole notes, "When we had real insurance, we could call and come in at the drop of a hat."

Mr. Kennedy was rushed into surgery less than two weeks after his diagnosis. Jada's wait just for an appointment was a bit longer: The wait to get into a public clinic was more than three months. By the time she found a Medicaid-approved rheumatologist in a nearby county to take her in months later, Jada's debilitating pain had caused her to miss several weeks of school.

Edith Andrews of Zanesville, Ohio, faced the same problem when her twin girls, Sara and Samantha, were born prematurely nearly four years ago. Each weighed less than 3 pounds and needed a ventilator to breathe.

According to an article in the Cinncinnati Enquirer: "To get care she had to take her infants to a Zanesville clinic or an emergency room, where they saw a different doctor every time, if they saw a doctor at all."

When Sara's lung collapsed, Edith couldn't find a Medicaid pediatrician to care for her. "Sarah's complications got worse and worse, and there was never a doctor around when I needed to talk to somebody." She finally found a doctor to take her daughters on as patients after a year of searching.

Mr. Obama (and those providing support his approach in Health Affairs) would also create a new health board to create lists of "cost effective" new drugs and medical devices, and set prices for their payment. Similar review boards in Canada and Europe delay access to new medicines by months or years and are biased by cost-containment considerations.

In the Medicaid and SCHIP programs, such "preferred lists" have made it harder for people like Melissa Brown of Cincinnati to get the right drugs for her 6-year-old son, Max, who suffers from bipolar disorder and other psychiatric illnesses. Under private insurance, her doctor was able to choose a drug that controlled unpredictable and violent behavior. The drug treatment she got for Max "changed his life."

But now Melissa and Max are in Medicaid and bureaucrats, not doctors, will decide which drugs he will get, based on the cost-effectiveness standards Mr. Obama wants to impose on us all. Max will have to change his prescriptions and get authorizations for new medications...."

www.washtimes.com/news/2008/jun/17/obamacare/

And of course the public health system has worked so well north of the border for our new found friend Shona Holmes:

Shona began losing her vision in 2005 and got an MRI in Ontario that showed a brain tumour.  That was only after she had to wait three montns for an appointment for a neurologist and another for the MRI which was preceded with a misdiagnosis of the tumor as a stroke in the ER.   Forced onto a wait list (up to six months to see an endocrinologist) as her eyesight deteriorated, she went to the Mayo Clinic in Arizona where she eventually got surgery to remove the tumor.   The Canadian health system refused to pay for the care at Mayo which, if she had not received, would have meant death.   Now she and her husband have exhausted their savings to pay for the care they should have obtained without a fight and only paid 30 percent of their income in taxes for over the last 30 years.

Effficient?  If you mean by efficient reducing per patient costs by letting people die sooner by denying access to care. 

 

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In Verbatim Veritas

06/25/2008 01:28 PM |

When Michael Moore came out with “SiCKO,” we realized that we had to counter his effort with our own.

We understood the need to fight anecdote with anecdote and make sure that we avoided Moore-ian hyperbole.

What we needed were patients from Europe and Canada who would be willing to share their personal stories about how Big Government healthcare let them down in their times of trial.

As it turned out, finding these patients, these people and their stories proved easy. In a word – Google.

It also made us wonder -- why haven't members of the American MSM done the same in order to balance their regular use of anecdotes portraying the glitz and glamor of EU/Canadian-style “universal” healthcare?

NOTE: That is a rhetorical question.

We also spoke with healthcare policy experts from the UK and Canada. Something else rarely seen in the MSM.

Then we had to decide whether or not to take on the same snarky tone as the Man from Flint. It was tempting.

But we didn’t -- because the patients we interviewed responded with such honesty and majesty that when they shared their stories of frustration, perseverance, and courage – we knew additional interpretation wasn’t necessary.

After all, if the patient is to be at the center of the healthcare conversation, so too must the patient be at the center of the story, or in this case BigGovHealth.org – the movie.

Here’s a link to our seven minute masterpiece:

www.biggovhealth.org/testimonials/highlights/

For additional footage on each of these patients and thought-leaders click on the appropriate video testimonial.

Everything else, as the Talmud says, is commentary.  Read More & Comment...