Howdy Partner

03/31/2009 12:50 PM |

If you work for a pharmaceutical company, ask yourself this question:  What business are you in?  To the average American, you are in the business of selling.  To survive and thrive you must be in the business of advancing the public health.  And to do that you must be seen as both teacher and expert.

And partner.

Partner with physicians, certainly.  With patients, definitely.  But also with government.  You must walk the tenuous tight rope of being both regulated entity and public health colleague with the regulatory mandarins who watch over you.

Your internal legal and regulatory departments may gasp.  But you will gain.  And it can (indeed must!) be done.

As ever greater regulatory oversight for your marketing practices comes into play across the globe, you must rethink both the type and timeframe for successful communications.  Rather than focusing strictly on short-term product sales programs, you must now create a firm foundation for trust built on the substrate of public health progams.

For example, in the United States the FDA will shortly launch an initiative called “safe use.” In addition to adverse event reporting, the FDA wants to communicate with physicians and patients about how drugs can be used safely and appropriately.  Because a product used safely is a safer product.  It’s the flip side of pharmacovigilance.  But the FDA needs allies.  It has no budget for public health outreach beyond the bully pulpit.  Who will step up to the plate to work with the agency?  What are the perceived barriers the pharmaceutical industry faces in doing so?  If you want the agency to be both regulator and colleague, so too must you be prepared to play those identical roles.  It takes two to tango.

Similarly in the EU, the rules are changing when it comes to the Brussels concept of Information to Patients (ITP).  Consider this verbiage from a recent report from the EU Parliament:

“Member States authorities may not be in a position to fully address patients’ needs in terms of the substance of information and the access via different means … The pharmaceutical industry has the potential to be an important source of information to respond to the growing demand for more and better information by patients and to help reduce the current information gap, provided that there will be adequate rules to ensure reliability, objectivity, and quality of information.”

The time is long overdue for industry to embrace public health communication programs as a powerful tool for corporate reputation, payer relations, physician education, patient empowerment, and yes – product sales.

But this strategy also requires a new appreciation of time.  No longer can industry marketers exclusively design programs for short-term unit sales purposes. That only reinforces the perception of pharmaceutical companies as hucksters.  The 21^st century demands a new paradigm.  It won’t be easy.  And it can’t be achieved through lip service.  Industry can’t talk itself out of something it acted its way into.

The roadside of healthcare sales strategy is strewn with the carcasses of failed marketing alternatives.  Advancing the public health in concert with the governments with whom the pharmaceutical industry does business is not only the right thing to do – it’s the smart thing as well.

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One A Day Is Not One Size Fits All

03/30/2009 07:08 PM |

Once-a-day heart combo pill shows promise in study
By: Marilynn Marchione, Ap Medical Writer – 2 hrs 38 mins ago

ORLANDO, Fla. – A single daily pill that combines aspirin and four blood pressure and cholesterol medicines has passed its first big test, potentially offering a cheap, simple way to prevent both heart disease and stroke.

The experimental "polypill" proved as effective as nearly all of its components taken alone, with no greater side effects, a major study found. Taking it could cut a person's risk of heart disease and stroke roughly in half, the study concludes.

This "one-size-fits-most" approach could make heart disease prevention much more common and effective, doctors say.

"Widely applied, this could have profound implications," said Dr. Robert Harrington, an American College of Cardiology spokesman and chief of Duke University's heart research institute. "President Obama is trying to offer the greatest care to the greatest number. This very much fits in with that."

The polypill also has big psychological advantages, said Dr. James Stein of the University of Wisconsin-Madison.

"If you take any medicines, you know that every pill you see in your hand makes you feel five years older. Patients really object to pill burden," and respond by skipping doses, he said.

The study was led by Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, and Dr. Prem Pais of St. John's Medical College, Bangalore, India. Results were presented Monday at the cardiology college's conference in Florida and published online by the British medical journal Lancet.

The study tested the Polycap, an experimental combo formulated by Cadila Pharmaceuticals of Ahmedabad, India. It contains low doses of three blood pressure medicines (atenolol, ramipril and the "water pill" thiazide), plus the generic version of the cholesterol-lowering statin drug Zocor, and a baby aspirin (100 milligrams).

Participants were about 2,000 people at 50 centers across India, average age 54, with at least one risk factor for heart disease — high blood pressure, high cholesterol, obesity, diabetes or smoking.

Four hundred were given the polypill. The rest were placed in eight groups of 200 and given individual components of the pill or various combinations. Treatment lasted 12 weeks.

Compared to groups given no blood pressure medicines, the polypill lowered systolic blood pressure (the top number) by more than 7 units and diastolic (bottom number) by about 6 — comparable to levels for people given the three drugs without aspirin and the cholesterol drug.

LDL, or bad cholesterol, dropped 23 percent on the polypill versus 28 percent in those taking the statin drug separately. Triglycerides dropped 10 percent on the combo pill versus 20 percent with individual statin use. Neither pill affected levels of HDL, or good cholesterol.

Anti-clotting effects seemed the same with the polypill as with aspirin alone.

Side effect rates also were the same for the polypill as for the five separate medicines.

"That was a big surprise. I would have expected five times the number of people to have side effects," said Dr. Christopher Cannon, a cardiologist at Harvard-affiliated Brigham and Women's Hospital in Boston who had no role in the study.

Collectively, the results show the polypill could cut the risk of heart disease by 62 percent and the risk of stroke by 48 percent, based on what previous studies show from lowering risk factors by these amounts, the study concludes.

Polycap's maker sponsored the study, and Yusuf has been a paid speaker for several makers of heart drugs. No price for the polypill is available, but its generic components cost only $17 a month, Cannon said.

A bigger study is now needed to see whether the polypill actually does cut heart attacks and strokes, he wrote in a commentary in the medical journal.

"It won't be for everybody," he said. Some people would be overtreated by getting medicines for conditions they don't yet have, such as high cholesterol. Others may be undertreated by too-low doses in the combo pill. Several polypills of different strengths may be needed, Cannon said.

"We have to be cautious about assuming that one size fits all," Stein said. "Treating risk factors is a lot like cooking — the ingredients count."

A polypill also would need federal Food and Drug Administration approval, even though all of its components have long been sold separately. The dosing issue could become a regulatory nightmare, Cannon warned.

"A final challenge: would the availability of a single magic bullet for the prevention of heart disease lead people to abandon exercise and appropriate diet?" he wrote in the medical journal.

That could make the risk of heart disease worse, and undo the good of the drug, Cannon said.
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The Comparative Effectiveness "I Hate to Cookbook"

03/30/2009 12:43 PM |

My mother was not a terrific cook.  One of my most lucid memories of my mother in the kitchen was the always open "I Hate to Cookbook" by Peg Bracken.  Who knew this would be an omen of healthcare reform to come?

My mother didn't like to cook -- but she wanted her family to have "balanced" meals.  (Remember "balanced" meals?) The results were predictable and adequate.  (Sorry Mom.) 

Similarly today, our comparative effectiveness nabobs want to field "comparative effectiveness" studies that don't make them think too hard.  These studies (outlined here) will result in predictable findings based on "adequate" 20th century science that don't challenge any conventional wisdom.  If we want real healthcare form -- is adequate acceptable?

No!  No!  No!

Literature reviews do not replace robust 21st century science. 


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Cookbook Medicine From NIH

03/30/2009 02:40 AM |

I don’t think I could make this up if I wanted....these are actual RFPs from NIH.  Talk about creating cookbook or one size fits all medicine.... Just do a literature review and....presto! Out pops an “optimum” treatment for an entire group of people.   Meanwhile it funds studies on personalized response to drugs and biomarkers for aging but fail to incorporate them into the RFPs!!!   Do they miss the irony?  
 
 “Comparing Drug Treatment Effectiveness in Ethnic Minority Populations. Research suggests that treatment response can vary among different minority populations due to genetic, environmental and cultural factors. Still, it is unknown which treatments work best for which ethnicities. Comparative effectiveness studies in ethnic minorities would test pharmacotherapies and behavioral treatments for substance abuse that have already shown efficacy in some populations. Results could reveal optimal treatment types for various populations, many of which are currently under-studied or under-served in terms of treatment need, including African Americans, Native Americans, and Hispanics. “
 
Comparative Effectiveness Research on Cancer Screening. The effectiveness of cancer screening has been established through randomized trials and other evidence for breast, colorectal and cervical cancer. However since screening for these cancers were initially introduced, there has been rapid and substantial innovation in new early detection technologies. Many of these technologies have disseminated into the practice of screening but without sufficient evidence as to their comparative effectiveness relative to earlier established technologies. In addition newer technologies may influence how the earlier technologies are most effectively used. Comparative effectiveness research in this area would augment evidence from controlled screening trials with: data from observational studies in defined populations of screening, intermediate and final outcomes; head-to-head studies of the technical performance characteristics, physician and patient acceptability and cost of alternative screening technologies, and decision models designed to project the costs and benefits of different screening technologies and strategies over the long-term at the individual, program and policy level
 
Comparative Effectiveness Studies of Non-Pharmacological Treatments for Chronic Low Back Pain. Observational studies or secondary data analyses to compare the effectiveness of: non-pharmacological treatments or integrative health care approaches for chronic low back pain when used in addition to and/or as an alternative to standard conventional care.
 
Comparative Effectiveness Research in Cancer Primary Prevention. A number of chemoprevention agents have been shown to be potentially effectiveness for the prevention of common cancers. But dissemination of chemoprevention remains low and controversy remains about the side effects associated with these agents. Comparative effectiveness research in this area would have the following aims: to document the level of dissemination of chemoprevention agents and the examine the physician, patient and health system factors that either facilitate or retard this dissemination; to conduct head to head studies of alternative chemoprevention agents and or approaches (e.g. risk stratification) to determine the relative clinical risk and benefits and economic cost of these alternatives. These studies could be conducted as adjuncts to existing controlled trials, as retrospective analysis of health system data or as prospective studies of cohorts of patients and physicians within the context of various healthcare delivery systems.
 
Selecting the Optimal Initial Treatment Regimen for Patients With Newly Discovered Type 2 Diabetes. The natural history of type 2 diabetes, treated by widely used current regimens, is marked by gradual increases in glucose levels, loss of insulin secretion, progressive increases in drug therapy, and frequent development of chronic complications. Clinical trial data suggests that aggressive early therapy attempting to keep glucose levels near normal is associated with a more benign long-term course. The optimal treatment regimen (effectiveness and avoidance of hypoglycemia) is not known, but current drugs provide options for multiple treatment approaches. In view of the numerous options, pilot studies are needed to assess the short-term effectiveness of common treatment strategies.
 
Personalized drug response and toxicity. Application of pharmacogenetics and pharmacogenomics, quantitative and systems pharmacology (this could be part of a larger grouping to include systems biology and systems genetics), ADMET pharmacology, preclinical models, and new technologies and approaches to complement pharmacogenomic studies to enhance signal-to-noise ratios and aid mechanistic studies, and consensus standards for normal and altered phenotypes in drug response and toxicity.
 
Imaging and Fluid Biomarkers for Early Diagnosis and Progression of Aging-related Diseases and Conditions including Neurodegenerative Diseases. Diseases and conditions of aging have a huge public health burden, and the ability to diagnose these early and follow their course would greatly help in treating and managing them.
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The French (dis)connection

03/27/2009 03:20 PM |

The keyword: don’t ever go to hospital. Much as the French will prance about the superior quality of their health system, the facts are increasingly unfavourable in terms of public provision.

To witness, check  “The black book on hospitals” (Livre noir des hôpitaux, Calmann-Lévy 2009) which enumerates an awful range of black spots, mishaps and tragic deaths of patients who nevertheless had full faith in the French model and universal care.

That figures; what about statistics? Try this one for size: on average 40 deaths every day, in terms of “undesirable events”. Obviously this figure covers more than people dying from medical errors, negligence and other mistakes in the hospital environment. The ballpark ranges from 350,000 to 460,000 deaths annually for hospital stays, of which some 120,000 to 190,000 might have been avoided, according to the authors.

Anecdotal evidence attests that astonishing number of physicians in the (public) hospital environment are either alcoholics, drug addicts or afflicted by some mental disorder. For obvious reasons, no statistics on this scandal are readily available; but how come these people, albeit hopefully a minority, are still allowed to practice? (Just imagine having surgery by a psychotic doctor!)

The primary reason is simple: hospital doctors (or nurses) are government employees and thus enjoy life-time employment. Any private company would try (with difficulty but still) to fire such people, especially in view of their life-or-death responsibilities.

France retains the advantage of a relatively dynamic private sector; but although private clinics are a lot more efficient and benefit from a much lower budget, they are under constant political assault. The budget divide is roughly 80/20 in favour of state-run hospitals. Nevertheless, France is world champion of hospitals/clinics per head: one institution per 20,000 people compared to one for 40,000 people on average in Europe.

The private sector has an obligation to perform; this is where most of restructuring has taken place for economic reasons. The public sector has an obligation to ask for greater budgets despite decreasing results.

Cherchez l’erreur.



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Imitation of Accuracy: Follow on Biologics Are NOT Copycats

03/27/2009 01:55 PM |

Well sort of.  In the grade school play ground kind of way where you imitate someome or copy someone else without much experience.  Or just for fun. 

Or profit.

Because follow on biologics are no more copycats than my two children are copycats because they came from the same combinnation of DNA.  You can't even say that about twins.  

Needless to say, just by ignoring all the science and safety concerns and searing them into law doesn't make follow on biologics similar in structure, treatment or safety.  It's just saying they do.  Hell, in the Waxman bill you can even take the innovator's name.  Why not just take over the company?

The propnents of a short cut to follow on products want to do testing...it's just that they want the testing to be unsuspecting doctors and patients who will not be told they are being put on an imitation until after the fact.  Post market safety commitments?  Why, that's just for start up biotech companies with no cash flow and only five years of market or data exclusivity...   And by they way, forget about tracking safety if the killer takes on YOUR name. 
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QALYwood Confidential

03/27/2009 12:27 PM |

Okay – so just what exactly is a Quality Adjusted Life Year (QALY)?

Here’s a nice primer courtesy of a new Time Magazine interview with NICE Chairman Sir Michael Rawlins:

“A QALY scores your health on a scale from zero to one: zero if you're dead and one if you're in perfect health. You find out as a result of a treatment where a patient would move up the scale. If you do a hip replacement, the patient might start at .5 and go up to .7, improving by .2. You can assume patients live for an average of 15 years following hip replacements. And .2 times 15 equals three quality-adjusted life years. If the hip replacement costs 10,000 GBP to do [about $15,000], it's 10,000 divided by three, which equals 3,333 GBP [about $5,000]. That figure is the cost per QALY."

So, how much is a year of life worth?

"The most controversial area is where you place the dividing line between what is cost effective and what is cost ineffective. That is the "how much is life worth?" question. And there is no real empirical research to guide you. We have looked at what other government departments do. Our Department of Transport, for instance, has a cost-per-life-saved threshold for new road schemes of about about 1.5 million-pounds-per-life, or around 30,000 GBP per life year gained. The judgment of our health economists is that somewhere in the region of 20,000-30,000 GBP per Quality-Adjusted Life Year (QALY) is the [threshold], but it's not a strict limit."

That's a tough decision to make for bureaucrats, is it not?

"For many difficult questions, we capture public preferences by our citizens council, a representative sample drawn from the general public. For example we asked if should we give greater priority to children than the elderly. The group decided that a year of life was worth just as much when you are a grandparent as when you are a child. That is very culturally specific and might not apply to other countries in the world."

Thanks Sir Michael.

But, according to Dr. Frank Lichtenberg of Columbia University, for a healthcare technology assessment (HTA) scheme (such as the NICE model) 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.

Lichtenberg 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.

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.

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

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Mitt Happens

03/27/2009 12:08 PM |

From today's Wall Street Journal:

Praise Mitt Romney. Three years ago, the former Massachusetts Governor had the inadvertent good sense to create the "universal" health-care program that the White House and Congress now want to inflict on the entire country. It is proving to be instructive, as Mr. Romney's foresight previews what President Obama, Max Baucus, Ted Kennedy and Pete Stark are cooking up for everyone else.

In Massachusetts's latest crisis, Governor Deval Patrick and his Democratic colleagues are starting to move down the path that government health plans always follow when spending collides with reality -- i.e., price controls. As costs continue to rise, the inevitable results are coverage restrictions and waiting periods. It was only a matter of time.

They're trying to manage the huge costs of the subsidized middle-class insurance program that is gradually swallowing the state budget. The program provides low- or no-cost coverage to about 165,000 residents, or three-fifths of the newly insured, and is budgeted at $880 million for 2010, a 7.3% single-year increase that is likely to be optimistic. The state's overall costs on health programs have increased by 42% (!) since 2006.

Like gamblers doubling down on their losses, Democrats have already hiked the fines for people who don't obtain insurance under the "individual mandate," already increased business penalties, taxed insurers and hospitals, raised premiums, and pumped up the state tobacco levy. That's still not enough money.

So earlier this year, Mr. Patrick appointed a state commission to figure out how to control costs and preserve "this grand experiment." One objective is to change the incentives for preventative care and treatments for chronic disease, but everyone says that. It sometimes results in better health but always more spending. So-called "pay for performance" financing models, on the other hand, would do away with fee for service -- but they also tend to reward process, not the better results implied.

What are the alternatives? If health planners won't accept the prices set by the marketplace -- thus putting themselves out of work -- the only other choice is limiting care via politics, much as Canada and most of Europe do today. The Patrick panel is considering one option to "exclude coverage of services of low priority/low value." Another would "limit coverage to services that produce the highest value when considering both clinical effectiveness and cost." (Guess who would determine what is high or low value? Not patients or doctors.) Yet another is "a limitation on the total amount of money available for health care services," i.e., an overall spending cap.

The Institute for America's Future -- which is providing the intellectual horsepower (we use the term loosely) for reforms like those in Massachusetts -- argues that the cost overruns prove the state must cap how much insurers are allowed to charge consumers and regulate their profits. If Mr. Patrick doesn't get there first, that is. He reportedly told insurers and hospitals at a closed meeting this month that if they didn't take steps to hold down the rate of medical inflation, he would.

Even the single-payer cheerleaders at the New York Times have caught on to this rolling catastrophe. In a page-one story this month, the paper reported on the "expedient choice" that Mr. Romney and Democrats made to defer "until another day any serious effort to control the state's runaway health costs. . . . Those who led the 2006 effort said it would not have been feasible to enact universal coverage if the legislation had required heavy cost controls. The very stakeholders who were coaxed into the tent -- doctors, hospitals, insurers and consumer groups -- would probably have been driven into opposition by efforts to reduce their revenues and constrain their medical practices, they said."

Now they tell us. What really whipped along RomneyCare were claims that health care would be less expensive if everyone were covered. But reducing costs while increasing access are irreconcilable issues. Mr. Romney should have known better before signing on to this not-so-grand experiment, especially since the state's "free market" reforms that he boasts about have proven to be irrelevant when not fictional. Only 21,000 people have used the "connector" that was supposed to link individuals to private insurers.

Which brings us to Washington, where Mr. Obama and Congressional Democrats are about to try their own Bay State bait and switch: First create vast new entitlements that can never be repealed, then later take the less popular step of rationing care when it's their last hope to save the federal fisc.

The consequences of that deception will be far worse than those in Massachusetts, however, given that prior to 2006 the state already had a far smaller percentage of its population uninsured than the national average. The real lesson of Massachusetts is that reform proponents won't tell Americans the truth about what "universal" coverage really means: Runaway costs followed by price controls and bureaucratic rationing.

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Physician Empowerment: No Good Deed Goes Unpunished

03/27/2009 02:37 AM |

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Fighting Wolverines Fight Prostate Cancer

03/26/2009 02:01 PM |

With all the brouhaha over the relative efficacy of prostate cancer screenings, you'd think the media would be watching for some really important news -- like a biomarker that could change the whole paradigm.  Alas, the MSM seems to have missed the story entirely.  Not shocking, but nevertheless disappointing considering the play they gave to the cost-effectiveness angle just last week.

But drugwonks won't let that happen

According to researchers from the University of Michigan, a newly identified marker for prostate cancer progression may also offer a new target for treatment. Previous research has found that decreased levels of the marker galectin-3 are linked with neoplastic progression in prostate cancer. However, increased levels of galectin-3 are believed to be associated with tumorigenicity in a number of other tumor types.

The University of Michigan team believed this difference was due to the fact that galectin-3 was cleaved during prostate cancer progression. Their study found that cleaved galectin-3 is present in a late-stage prostate cancer and that reducing levels of galectin-3 inhibited development of metastatic prostate cancer.The findings suggest that cleaved galectin-3 may serve as a diagnostic marker and treatment target for prostate cancer progression.

The study shows "that galectin-3 is cleaved during the progression of prostate cancer and might be associated with metastasis, cell growth and tumorigenicity. Expression of intact versus cleaved galectin-3 thus might be used as a marker for prognosis of prostate cancer and a therapeutic target for the treatment of prostate cancer," wrote study author Avraham Raz and colleagues.

Go Wolverines!

The study appears in the April issue of The American Journal of Pathology.

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BIGT Changes for Nice?

03/25/2009 07:45 PM |

Our Congress is confiscating bonuses and the administration is set to limit executive pay. It is launching a Medicare Part D benefit that limits access to new medicines based on price and one size fits all comparative effectiveness...

Meanwhile in the UK, the government seems to be finding a way to keep it's biotech industry and the patients who depend on it alive before it's too late:

Click Here to Read More
 
Grim Outlook For UK Biotech Industry
Mar 11, 2009
By: Sarah Houlton

One-third of publicly owned UK biotechs have less than six months’ money left in the bank, and just 0.2 percent of the London Stock Exchange is now made up of biotech companies. “A new approach to funding is needed to fill the gaps left by investors,” claims Aisling Burnand, chief executive of the BioIndustry Association.

“We are faced with a very different world than we were a few years ago,” says Bioscience Innovation and Growth Team chairman Sir David Cooksey. The BIGT just released Bioscience 2015, an industry report designed to map out the market for the next six years.

First released in 2003, the report had been written to look forward 12 years and forecast where industry would be. In this revised and refined report BIGT has have lowered its sights.

The main problem, Cooksey claimed, is that investors simply do not see enough reward to justify the risk in putting their money into the sector. “There are hurdles in the way such as NICE and the EU clinical trials directive, which has been more stringently applied in the UK than in other countries,” he says. “We have to change the balance.”

This drying up of finance for biotechs is a real problem. “Biotech companies have not given good enough returns to investors to make them want to come back. Private sector angels, venture capitalists, and public markets have all turned away. We need to make it more attractive, and then I have no doubt that as the extra funding is rolled out we will get the situation where there is more participation in terms of the public sector.”

However, Cooksey does not believe that a large investment by government is the right way ahead, in contrast to the demands made by Sir Chris Evans and a group of his fellow venture capitalists at the end of last year. “We’ve not said, ‘Let’s have $1 billion in [government] funding,’” he claims. “If you look at history, governments putting a lot of money into technology development with civil servants picking the winners has not had much success.” Rather, they are looking for regulatory help and enhancements to the existing R&D tax credit scheme to encourage pharma companies to invest in biotech.

He believes that if Big Pharma were given more confidence in the biotech sector and had a more collaborative involvement at an earlier stage, it should give investors more confidence, too. “We are looking for real support from government to put a regulatory environment in place that will be effective in the longer term,” he adds. “We need to look at how to change the drug development pathway, use modern techniques to make it cheaper, faster and safer—it’s currently unnecessarily expensive. We are in danger of it no longer being worth a company’s while [to get into drug discovery] as they will never get to be able to sell a product at the price they need and which is also acceptable [to the payers].”

However, he says, this cannot be done by the UK on its own—it will have to involve the EU and the FDA, too. “Changes in the global regulatory system will take time and effort,” says serial entrepreneur and former BIA chairman Simon Best. “In the past four or five years, the sector has fallen out of favour. If we can do more work using modern tools such as genetics and genomics, and run smaller, better focused trials, it will be a reduced ask for investors.”

There is also the suggestion of allowing patients to receive drugs for life-threatening diseases after Phase II trials on a conditional licensing basis. “Hopefully safety issues would be flagged up more quickly, and the poor uptake of innovative drugs could be addressed,” Best said. “We want to see more pivotal trials carried out in the EU, maybe allowing conditional licenses while still doing Phase III trials in the US. This would allow us to address safety issues much earlier, and identify which patient populations could most benefit—or would most likely to have problems. I’m not convinced that post-marketing surveillance is the way ahead.   Read More & Comment...

The Other Sweet 16

03/25/2009 12:20 PM |

We’re all used to state AGs suing drug companies for inappropriate promotion of off-label indications (Neurontin comes to mind – among others).  Now there’s an interesting new wrinkle.

16 state Attorneys General (Oklahoma, Alaska, Utah, Iowa, Colorado, Kansas, Maine, Missouri, Nebraska, New Mexico, North Carolina, Rhode Island, South Dakota, Texas, West Virginia, and Wyoming) have written to Abby Black (Director, Center for Drug and Health Plan Choice at CMS) to complain that Part D participating insurance companies are requiring that their customers fail on a variety of off-label therapies before they will be reimbursed for medicines that have the more appropriate, on-label indication relevant to their particular conditions.

The AGs write, “Just as it is inappropriate for pharmaceutical companies to market drugs for off-label uses, it is equally inappropriate for health insurance companies to refuse to reimburse for physician-prescribed medications unless a patient first undergoes treatment with drugs that are off-label. … This practice of requiring treatment with an off-label drug before reimbursing a patient for using a drug approved by the FDA for that specific condition subverts the legislatively mandated approval process for drug indications by substituting the judgment of health insurance companies for that of the FDA. It undermines the doctor-patient relationship by empowering health insurance companies to make broadly applicable medical decisions best left to a physician considering the needs of a specific patient. This “one-size-fits-all” insurance-company mandate is inappropriate and dangerous.”

 

Many issues here – particularly the validity of the FDA label for anything post Wyeth v. Levine – but an equally important question is when is off-label not off-label? At present, the answer seems to be; when it's on-formulary and off-patent.

 

Case in point, pregabalin (Lyrica) and Iowa (coincidentally, the state represented in the United States Senate by Charles Grassley).

Iowa Medicaid requires preauthorization for pregabalin -- which is FDA-approved for (among other indications) fibromyalgia.  In Iowa a patient with a diagnosis of fibromyalgia must first fail on at least two of the State's "preferred" agents -- trycyclic anti-depressants, topical lidocaine, or gabapentin.  None of these three agents are approved by the FDA for the treatment of fibromyalgia.

But they are less expensive than the on-patent, on-indication product.  So what we've got here is step-therapy based on off-label usage.  Not unheard of, certainly, but it does start sending some interesting policy messages about the appropriateness of off-label use in various circumstances.  (And it's more than a little bizarre when you consider that Pfizer, the manufacturer of pregabalin, had to pay a $430 million fine for off-label promotion of gabapentin.)

The actions of the Hawkeye State Department of Human Services are even more peculiar considering that Senator Grassley (R, IA) asked the U.S. Government Accounting Office (GAO) to investigate off-label prescribing -- and not because he thought it was a valuable tool for patient care.

So here's where we stand:  Off-label use of on-patent medications is bad, but off-label use for generics is good.  Translation:  off-label use is good when it saves the payer money.

Here’s how the Sweet 16 end their letter to CMS:

“Insurance company requirements that patients utilize off-label treatments before being reimbursed for FDA-approved treatments are dangerous and should not be permitted.  The same policy considerations that support a ban on off-label marketing by pharmaceutical companies support the prohibition of this insurance company practice.”

 

Here is the complete letter to CMS.

 

Are you paying attention Mr. Waxman?

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Drug Spending Slows and Cost Sharing Climbs. Is There A Connection?

03/25/2009 02:15 AM |

Patient Cost-Sharing on the Rise: Results from the
Benefit Design Index
By Melinda C. Haren, RN; Kirk McConnell

The cost of employee health coverage continues to grow faster than inflation,1 putting additional economic pressure on employers ...

American Health and Drug Benefits

Cost sharing of Rx is climbing faster than premiums AND inflation....drug spending is falling.  We know that compliance falls and disease burdern increases as a result.  

Meanwhile insurers diddle about reimbursing for personalized medicine which is very cost effective and product ...

The Economic Impact of Personalized Medicine: Genetic Testing in Metastatic Colon Cancer May Save $604 Million Annually
By Caroline Helwick

So much for controlling health care costs.
  Read More & Comment...

To Sir, with Love

03/23/2009 03:35 PM |

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

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

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

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

Watch this space for more details.

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

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

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

But I digress.

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

Here are the concluding paragraphs to whet your wonkish appetite:

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

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

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

  Read More & Comment...

Blumenthal's Soros Connection

03/20/2009 06:07 PM |

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

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

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

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

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

03/20/2009 12:48 PM |

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

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

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

Congratulations Jesse. 

  Read More & Comment...

The Sharfstein Shudder

03/19/2009 12:26 PM |

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

Here's what CongressDaily has to say:

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

By Anna Edney, CongressDaily

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

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

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

"Companies are clearly going to get more scrutiny."

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  Read More & Comment...

Comparative Ignorance on Prostate Cancer Screening

03/19/2009 03:29 AM |

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

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

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

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

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

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

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

Continued Here

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

Where to begin?

Unnecessary and harmed by screening?

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

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

Read More

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

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

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

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

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

Read More

Here is info on the PSA Test

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

Then again both the NY TImes and the American Cancer Society are desperately seeking to show the flag on comparative effectiveness. They have done the job well on prostate cancer screening. At the expense of cancer patients and medical progress.
  Read More & Comment...

My Daughter's Battle With AHRQ

03/18/2009 06:55 PM |

The folly of comparative effectiveness reviews
By Robert M. Goldberg

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

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

Healthcare Reform Quote of the Week

03/18/2009 12:25 PM |

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

 

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

 

Further:

 

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

 

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

 

We’ll see soon enough.

 

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

 

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

 

Thank you Senator Wyden.

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