Two's a Part D, Three's a Crowd Out

11/07/2007 09:15 AM |

Frank Lichtenberg published a study in Health Affairs demonstrating something that we already knew: a lot of the drug coverage of part D crowded out private drug coverage and increased utilization by about 12 percent. Much of the increase was in the area of generic drug spending. So much for the Big Pharma windfall. Part D was essentially what those of us who supported said it would be: a modernization of Medicare the goal of which would be to extend drug coverage to a program that did not have it and to milions of seniors who were poor and were receiving drug coverage through restrictive Medicaid formularies.

So what's the difference between supporting a Part D crowd out and not an SCHIP crowd out? Part D is a step towards privatizing Medicare -- full of choices and pasrt of an effort to get seniors to buy into private plans and everyone knows it. SCHIP is a step towards socializing healthcare and everyone knows it.

Lichtenberg points out also that Medicare Part D has the benefit of reducing Medicare spending overall. We need studies to demonstrate this happening at various income groups and disease states.

http://content.healthaffairs.org/cgi/content/abstract/26/6/1735  Read More & Comment...

Follow On Biologics Loses Momenta

11/07/2007 09:03 AM |

Those screams you heard came from "I hate Big Pharma" being hoisted on the drug safety petard of their own making as Momenta's hard to mimic version of Lovenox was being rejected by the FDA because of concerns that the company hadn't accounted for uncountrolled immune reactions to its version of the product. And of course that doesn't even begin to to address what sort of studies Momenta would have to undertake to deal with safety concerns, what risk mitigation system it would have to put in place, what post marketing surveillance it would have to conduct, what clinical trials data it would have to post, blah,blah blah.

FOBs will hit the market eventually. But it is great to see those who take drug companies to task about safety seek to rationalize rushing FOBs to market without similar consumer protections. And they care more about rushing FOBs to market than accelerating the review of new life saving medicines which Momemta is also working on. It's called I hate pharma hypocrisy.  Read More & Comment...

Oh Say Can you OTC?

11/07/2007 09:00 AM |

Had a look at the Non-Prescription Drug Modernization yet? It was just introduced by Representative Henry Waxman (R, CA), Representative Tom Allen (D, ME), and Senator Ted Kennedy (D, MA.). It’s a well-meaning, but knee-jerk reaction in response to the recent FDA advisory committee vote over banning over-the-counter cough and cold medicines for children under six.

Here’s a link to the legislation:

http://oversight.house.gov/documents/20071106143446.pdf

Among other things, this bill would allow the FDA to ban marketing of the drugs while the rulemaking process was still under way.

That’s right – “ban” advertising.

We’ve already covered how we feel about the recent AdComm vote (see two October 19th posts, “Dosing for Dummies” and “Cough, Sniffle, Sneeze – No OTC Meds for Children, Please”). Per this new legislation, we concur with our friend Adonis Hoffman over at the American Association of Advertising Agencies.

Here’s what Adonis has to say:

"We are all concerned about the cough and cold medications for children that have been in the news reports lately. Nobody benefits from false or misleading advertising of any kind, whether it is for over-the-counter or prescription medications."

He also, wisely, point out that there are already "ample and appropriate regulatory penalties in place to handle these problems. The authority of both the Federal Trade Commission and the Food and Drug Administration is intact. I'm not sure whether there is a need for new changes."

Hopefully this will be a robust debate over how good communications can improve the public health -- not another public flogging of the industry.

Just call us starry-eyed optimists.  Read More & Comment...

Affairs of the Heart

11/06/2007 04:17 PM |

Lots of info coming in about drugs in development then and now showing the (Critical) path forward is towards retargeting, retooling, repositioning drugs to specific groups and for monitoring risks and benefits post market...

1. Research from the studies showing that while Lilly's Prasugrel proved better able to prevent heart attacks than Plavix, the drug led to excess life threatening bleeding compared to Plavix at a statistically significant level in patients with acute coronary syndrome. But Lilly, consistent with a commitment to pharmacogenomics and targeted therapeutics has identified subgroups that are most likely to have that risk. The PI of the study, Dr. Elliot Antman, said that most of the bleeding was driven by two groups -- patients with a history of stroke or transient ischemic attacks and elderly, frail patients (older than 75 weighing less than 60 kg) -- who comprised 20% of the total population.

"For the remaining 80% of the patients, which I would say represented eight of 10 patients undergoing stenting, the drug works very well," Dr. Antman said in an interview.

Moreover, among one high-risk group -- diabetics -- "there was no excess bleeding and a 30% reduction in MIs compared with clopidogrel."

Wall Street sniffs that the market will be minimal. But Plavix goes off patent in 2011 while Lilly's drug could get a Pgx label with improved safety and benefit profiles. How minimal is that?

http://www.medpagetoday.com/MeetingCoverage/AHAMeeting/tb/7217

2. The CETP trilogy. Efforts to raise good cholesterol is the holy grail of the cardiovascular world Pfizer's drug sent torcetrapib chills down the spine of others developing drugs based this target. But further analysis shows that increased blood pressure and changes in electrolytes (which caused the heart attacks in Pfizer's drug study) signal the potential activation of the renin-angiotensin-aldosterone system (RAAS) by torcetrapib. The greater RAAS activation may weaken the benefit of raising HDL."

Translation: if your drug (Merck and BMS) doesn't activate the RAAS pathway or you can develop a blood test that predict who won't or will have that effect you might be able to bring other HDL drugs to market.

http://www.drugresearcher.com/news/ng.asp?n=81155-pfizer-merck-bristol-myers-squib-bms-torcetrapib-cetp
It's biomarker based research at it's best. Good news for patients. Bad news for Merrill Goozner and others who want to claim biomarkers are just a tool for making drugs unsafe.  Read More & Comment...

Lies, Damn Lies, & Press Releases from Jamie Love

11/06/2007 06:56 AM |

Maybe they should call it Médecins Avec Menteurs.

In an e-mail today from the folks over at Médecins Sans Frontières discuss this week's meeting in Geneva of the WHO's Intergovernmental Working Group for Public Health, Innovation, and Intellectual Property (IGWG).

Here's what MSF has to say about the current fight against "neglected" diseases:

"“The R&D system is broken. It is not delivering,” said Dr. Tido von Schoen-Angerer, Director of MSF’s Access to Essential Medicines Campaign."

And here's what the infamous Jamie Love said in an ensuing paragraph:

"We need new mechanisms and institutional responses to move toward a paradigm of innovation plus access, rather than a set of poorly functioning trade-offs. The big ideas in the negotiation are patent pools, prizes and a treaty on medical R&D. They are also the most
controversial."

What a terrific example of the "Big Lie."

Consider what Solomon Nwaka (leader of drug discovery activities at the Special Programme for Research and Training in Tropical Diseases at the WHO) wrote (along with other co-authors from Pfizer) on the subject of finding ways to battle tropical diseases:

"Scaling up drug-discovery capacity for neglected diseases means designing a mechanism that is attractive to all stakeholders — such as industry, academia, governments and international agencies — involved in drug discovery. Despite a lack of market incentive, about half of the research projects currently focusing on neglected diseases are conducted by pharmaceutical companies. Several large companies, most notably GlaxoSmithKline, Novartis, AstraZeneca and Eli Lilly, have founded research institutes dedicated to research into tropical diseases. Industry also makes a substantial contribution in kind to public–private product-development partnerships. Also, in recent years, funding from governments and philanthropic foundations has helped to establish new drug-discovery units for tropical diseases in developed and developing countries."

Here is a link to the complete article in Nature:

http://www.nature.com/nature/journal/v449/n7159/full/449166a.html

And let's not forget what Dr. Margaret Chan, WHO's Director-General had to say about why communicable diseases remain such a large problem in poor countries and are often neglected by research and development. One reason, she said, is that the pharmaceutical industry "has little incentive to develop drugs and vaccines for markets that cannot pay."

Indeedn if a company stands no chance of recouping even a portion of that investment, where is its incentive to tackle the many diseases that ravage the developing world?

And yet, according to MSF, "intellectual property is not a significant factor in contributing to innovation for diseases that disproportionately affect developing countries."

Thomas Carlyle said, "Our main business is not to see what lies dimly at a distance but to do what lies clearly at hand." Mr. Love and his friends at Médecins Sans Frontières are trying to sell a "vision" that, conveniently, blames the West for the problems of the developing world while what "lies clearly at hand" is almost exactly the opposite -- that the rule of law that has allowed for the development of the modern pharmaceutical industry via protection of interllectual property is what lights the road to victory over the scourge of neglected diseases.  Read More & Comment...

Defenseless Against New Bugs: Thanks to the Politics of Fear

11/05/2007 10:12 AM |

Another dividend from the politics of fear: an empty antibiotic pipeline and an FDA that has pushed the safety bar for new drugs against bugs to unachievably high standards.

More people will die because of the absence of new drugs. The policies that have brough this about were built on false premises and false fears. mistrust has become an important source for scientific investigations themselves. Scientists nowadays build a career on technophobia within society. They are the first group who form the
scientific core of the precautionary coalition. They feed this information to consumer groups and politicians who, through the media and policies and hearings institutionalize mistrust, fear and suspicion.

The politics of fear breads both inaction and regulatory paternalism. Nothing is safe so everything must be regulated and tested. More is studied but nothing new is introduced because novelty has unknown risks which are judged more dangerous than the problem it was designed to solve.

So we are left with hardly any new drugs against emerging pathogens. That is the way the Luddites would have it. Better dead people than thriving, profitable drug companies.

http://www.nj.com/business/times/index.ssf?/base/business-3/11941492275600.xml&coll=5  Read More & Comment...

Debunking Some Health Care "Urban Myths"

11/05/2007 09:03 AM |

Like they say, everything you read in the newspaper is true except for those things you know about personally. This isn't always how urban myths begin -- but is certainly one of the most potent ways they are perpetuated.

Three of the most common "urban myths" of American health care (courtesy of folks like Michael Moore, Paul Krugman, et. al.) are that (1) the infant mortality rate in the US "proves" the total inadequacy of our system, (2) there are 47 million uninsured Americans -- proving the inequity of our system, and (3) We spend "too much" on health care -- proving the wastefulness of our system.

As the Ol Perfessor used to say, "Let's look at the numbers."

1. Infant Mortality

According to N. Gergory Mankiw, Professor of Economics at Harvard University, "The United States has lower life expectancy and higher infant mortality than Canada, which has national health insurance." This fact, according to Mankiw, is often taken as evidence for the inadequacy of the U.S. health system. But a recent study by June and Dave O'Neill, economists at Baruch College, from whom these numbers come, shows that the difference in health outcomes has more to do with broader social forces.

According to Manikow, "Americans are more likely than Canadians to die by accident or by homicide. For men in their 20s, mortality rates are more than 50 percent higher in the United States than in Canada, but the O'Neills show that accidents and homicides account for most of that gap. Maybe these differences have lessons for traffic laws and gun control, but they teach nothing about the U.S. system of health care.

Americans are also more likely to be obese, leading to heart disease and other medical problems. Among Americans, 31 percent of men and 33 percent of women have a body mass index of at least 30, the dividing line between overweight and obese, versus 17 percent of men and 19 percent of women in Canada. Research by the Harvard economists David Cutler, Ed Glaeser and Jesse Shapiro concludes that the growing obesity problem in the United States is largely attributable to its ability to supply high-calorie foods inexpensively.

Infant mortality rates also reflect broader social trends, including the prevalence of infants with low birth weight, which is correlated with teenage motherhood. Whatever its merits, a Canadian-style system of national health insurance is unlikely to change the sexual mores of American youths"

2- 47 Million Uninsured

This number from the Census Bureau is often cited as evidence that the health system is failing for many families. Yet, as Mankiw observes, "by masking tremendous heterogeneity in personal circumstances, the figure exaggerates the magnitude of the problem."

The 47 million includes about 10 million residents who are not U.S. citizens. Many are illegal immigrants. Even with national health insurance, they would probably not be covered.

The "Big Number" also includes millions of the poor who are eligible for Medicaid but have not yet applied. Per Mankiw, "they are uninsured in name only."

And about a quarter of the uninsured have been offered employer-provided insurance but declined coverage.

3- We spend "too much" on health care

In 1950, Americans spent about 5 percent of their income on health care. Today the share is about 16 percent. Mankiw believes that "many pundits take the increasing cost as evidence that the system is too expensive.But increasing expenditures could just as well be a symptom of success."

And he hits a homerun with a clear. concise, and uncomplicated explanation. "The reason Americans spend more than their grandparents did is not waste, fraud and abuse, but advances in medical technology and growth in incomes. Medical science has consistently found new ways to extend and improve lives. Wonderful as they are, they do not come cheap."

Consider the question posed by economists Charles Jones of the University of California and Robert Hall of Stanford: "As we grow older and richer, which is more valuable: a third car, yet another television, more clothing - or an extra year of life?"

Perhaps this should be added as a question to the next spate of Presidential debates?  Read More & Comment...

rahm emanuel's unsafe medicines act

11/04/2007 09:26 AM |

Rahm Emanuel wants a stand alone vote on drug importation. So do many erstwhile Republicans like Grassley who have made a mini-career terrorizing the public about the risks of unsafe drugs. How do they square their claim the FDA is unable to protect public against unsafe medicines with a GAO report that the FDA can event inspect the overseas facilities that would import the medicines that Grassley et al assert the FDA is in a position to certify as safe?

Audit: FDA hampered in review of imported drugs

"By Douglas Stanglin, USA TODAY
The Food and Drug Administration can't adequately inspect foreign drug manufacturers because its database is so outmoded it doesn't even know how many foreign firms are shipping drugs to the United States, a government watchdog group and former FDA officials told Congress on Thursday. "

Grassley and Emanuel couldn't be playing politics with drug safety? Neither could AARP or Consumers Union who lead the charge against Kennedy Enzi because it claimed it was too lax and who supports drug importation. Of course not!! The common theme of course: screw drug companies no matter what the impact on patients or the public health because it scores political points.

http://www.usatoday.com/news/health/2007-11-01-fda-imports_N.htm  Read More & Comment...

New Drug Approvals Down

11/02/2007 02:35 PM |

Spending on medicines is down and the number of new drugs reaching the market is declining as well. No one wants to acknowledge the while a cautious FDA is part of the problem the overarching challenge facing industry -- and us -- is just how new all the targets current drug development targets are and how difficult it will be to personalize or tailor treatments to specific groups of patients. And the tools for doing so and improving the preventive capacity of next generation drugs will be snatched from companies if the industry's enemies get their way and blow up the Critical Path before it even gets started. The campaign of disinformation regarding the goals of the Critical Path and the science behind still shocks me. The ideological hatred borders on a psychological disturbance.  Read More & Comment...

Congresswoman DeLauro: Mislead By Goozner and Gang on Reagan Udall

11/01/2007 02:23 PM |

Where did Cong. Rosa DeLauro get her ban the Reagan Udall idea from?...And where did she get the idea that biomarkers are somehow a source of inferior science? this from Kaisernet...

" FDA seems to be moving "with unusual speed" to organize a private-public foundation to help support the agency, and some critics are saying the initiative might be "little more than a front for the industries it regulates," CQ Today reports. The group, known as the Reagan-Udall Foundation, was established in the FDA reauthorization legislation, which President Bush signed into law Sept. 27.

The 14-member board of the foundation must include three academics, two consumer advocates, one health care provider, four industry representatives and four "at-large" members with "experience relevant to the purpose of the foundation." While five of the nominees will be chosen by FDA, some critics are concerned the at-large seats will be filled by industry representatives (Adams, CQ Today, 10/2). FDA began taking nominations on Wednesday (Edney, CongressDaily, 10/3).

The foundation largely will be financed through private donations, including those from food, pharmaceutical and medical device companies, according to CQ Today (CQ Today, 10/2). It is meant to help fund research to modernize the agency, according to CongressDaily.

Critics are concerned that if drug makers gain too much influence on the foundation, the resulting criteria established for evaluating products could be excessively industry-friendly. Merrill Goozner, head of the Center for Science in the Public Interest's Integrity in Science Project, said, "The last thing you want is an industry-run board in which they create a science-sounding rationale before they put the FDA rubber stamp of approval on something that hasn't been proven." Diana Zuckerman, president of the National Research Center for Women & Families, said, "You have a situation where most of the money will be from (industry groups) -- they're going to control the board and therefore they're going to control the executive director, staff and the research."

http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=47990

Shame on Goozner and the rest for deliberately misleading Del Lauro and the media on what biomarkers do and can offer people in terms of safer drugs. I was there at Critical Path conference he blogged on when Janet Woodwock patiently explained the difference between a surrogate endpoint (cholesterol levels) and genetic markers that are predictive of disease progression or drug response. He is either dumb or manipulative. Or both. Here's what the FDA recently said in a guidance on drug-induced liver toxicity regarding biomarkers:

"As part of the Critical Path Initiative, 3 the FDA is working with industry, academia, and other experts to broaden our understanding of the biochemical and genetic bases of DILI. In June 2006, the FDA co-sponsored a scientific workshop to determine the feasibility of developing a mathematical (in-silico) model for DILI from which other predictive experimental models can be derived to characterize potential hepatotoxicity. The long-term goal is to develop a model, or models, that can help researchers identify criteria for determining when early clinical intervention (i.e., stopping the drug) is appropriate. It is also hoped that predictive bioassays and biomarkers can be identified that will help determine which patients most likely will suffer liver toxicity from specific compounds.

This urgently needed research is not a regulatory requirement, but is an important opportunity. At present, we are able only to search among patients with drug-induced injury to predict what might happen to others. Ideally, we should seek to identify individuals at increased risk before administering a drug that they cannot tolerate. The goal is to be able to identify persons who should never be exposed to a given drug because they are idiosyncratically hypersusceptible to, or unable to recover from, DILI caused by it. If tests that screen for people susceptible to severe DILI can be developed, a hepatotoxic drug could remain available to people who are not susceptible to severe DILI, instead of having to withdraw the drug from the market, allowing no one to benefit from it.

* In addition, identification of common genotypic characteristics among patients experiencing DILI in response to one or more class-related hepatotoxic agents might permit the development of in vitro or ex vivo tests or genetically altered animal strains that can be used to better predict serious hepatotoxic potential, or the lack thereof, of new drugs belonging to the same or closely related classes. "



Yeah, I guess a foundation that will develop tools designed to screen drugs for safety and effectiveness based on genetic markers and standardize that approach for evaluation is a bad thing. Even worse to have the companies themselves foot the bill.

I give DeLauro a pass for not knowing enough in this instance. (Note to the FDA: Hie thee to Rosa's office for a briefing on what's what. ) Not so Goozner and Zuckerman. Anyone can be wrong. Only idiots persist in their errors. Or miscreants.  Read More & Comment...

What if we called it the "Reagan/Udall/DeLauro Foundation?"

11/01/2007 02:11 PM |

Rosa L. DeLauro. The "L" stands fro "Luddite." Consider this press release that just crossed our desk:

Washington, DC – Congresswoman Rosa L. DeLauro (Conn. – 3), as part of an on-going effort to ensure that science – and not industry interests – informs decisions within the Food and Drug Administration, sent a letter to Dr. Andrew von Eschenbach, FDA Commissioner, expressing concern about the Reagan-Udall Foundation and seeking information about its creation.

“While the intended goals of the Reagan-Udall Foundation are worthy, given that it will be funded primarily by pharmaceutical companies, the FDA would be responsible for ensuring that the Foundation does not further increase the industry’s influence within the FDA,” DeLauro wrote. “Although the mission of the foundation is intended to support research that encourages an expedited FDA approval process, I believe the Reagan-Udall Foundation has the potential of endorsing the approval of drugs and devices based on lower standards for safety and efficacy, and without appropriately designed clinical trials.”

We have previously commented on such absurdity on October 15th ("Concerned Scientists") and again on October 17th ("Critical Wrath").

And, yes, this is same Rosa DeLauro who spoke so passionately in favor of H.R. 2693, The Popcorn Workers Lung Disease Prevention Act.

What else can be said?  Read More & Comment...

Hey, I Thought Big Pharma Was Unstoppable....

11/01/2007 01:42 PM |

If you took the industy's more strident, conflicted and ideologically motivated critics at face value (Avorn, Wolfe, Nissen, Angell, Kassirer,Relman, Goozner, Consumers Union, Families USA/Soros, etc. )...the FDA is a rubber stamp, user fees are payoffs that turned the agency into a lapdog for instant approvals of every unsafe and ineffective medicine, marketing is just a series of bribes to doctors to prescribe useless drugs when generics are available...and companies could price every new drug at higher and higher prices.

Oh wait, drug approvals are at an all time low and generic drug use is at an all time high.

If this group was right these would be the best of times because they are uncontrolled monopolies with endless power. Of course if this group was right, kids would not be dying from underuse of SSRIs and VA patients would not be dying sooner than seniors in Part D.

But everything has limits and goes through cycles. Science, competitive strength, even the intelligence of the critics. Check that. Some things never change. To paraphrase Fred Allen, every time they open their mouths they subtract from the sum of human understanding.  Read More & Comment...

Illegal, Unsafe, and More Expensive

11/01/2007 09:41 AM |

FDA Says Consumers Continue to Buy Risky Drugs Online
Self-medication a concern; FDA-approved generics may be cheaper alternative

A yearlong U.S. Food and Drug Administration (FDA) investigation into drugs mailed to the United States from foreign countries suggests that consumers may be buying drugs online to avoid the need for a prescription from their physician. The FDA sampling of imported drugs also indicates that consumers continue to spend money unnecessarily on potentially risky drug products bought over the Internet.

The investigation found 88 percent of the 2,069 drug packages examined appeared to be prescription medicines available in the United States. Of the remaining products, some were dietary supplements, some were foreign products with labeling that was illegible or incomprehensible, and some were medications not available in the United States. More than half (53 percent) of the products sampled have FDA-approved generic versions, likely sold at lower costs, according to earlier studies that have shown generics in the United States to be generally cheaper than a comparable drug in Canada or Western Europe. In fact, approved generic versions of approximately half (47 percent) of the sampled products can be bought for $4 at several national chain pharmacies, a price often lower than the shipping costs for the same drugs purchased online.

"The data lead us to believe that many people are buying drugs online not to save money but to bypass the need for a prescription from their doctor since these Web sites typically do not require the purchaser to have a prescription," said Randall Lutter, Ph.D., FDA's deputy commissioner for policy. "In essence, they seem to be getting and using prescription drugs without a prescription, an intrinsically risky practice."

These data are based on surveys conducted from September 2006 to August 2007 in international mail facilities and courier facilities across the country. At each city, all parcels suspected by customs and border patrol of containing pharmaceuticals were stopped for a period of 24 hours. FDA then recorded data on the contents of these parcels, before handling them in accordance with its usual procedures.

In general, a Web site can appear legitimate, but in fact be a front for an illegal operation. FDA urges consumers to beware of unregulated Internet drug sellers, because many of their products might not contain the correct ingredients and could contain toxic substances. Several drugs found in this survey require special monitoring by physicians or other health care professionals for potential adverse events and to ensure their effectiveness. These include antibiotics, antidepressants, the blood thinner warfarin, and levothyroxine (a thyroid replacement hormone).  Read More & Comment...

Important Distinctions

11/01/2007 08:10 AM |

Headline in today’s edition of the Wall Street Journal reports on a new IMS report that, “Prescription-Drug Sales Growth Is Expected to Slow.”

Here’s a link to the complete WSJ story:

http://online.wsj.com/article/SB119387833538878513.html?mod=dist_smartbrief

What the headline means is that the sales volume of on-patent drugs will slow, not that the use of pharmaceutical products will decrease. Important distinction.

As the WSJ reports, “IMS forecasts that about two-thirds of prescriptions dispensed in the U.S. next year will be generics, up from 50% in 2003.”

The article also comments on the pipeline and regulatory environment, “Drug companies, meanwhile, aren't churning out enough new medicines to keep dollar sales growing at the same pace. And regulators such as the Food and Drug Administration, burned by several drug-safety scandals, are casting a tougher eye on new products before allowing them on the market.”

First, as to the FDA “casting a tougher eye,” the agency always casts a tough, educated, professional eye on its actions. And new legislation gives the FDA even more authority and funding to do its job better. “Better” not “Tougher” – it’s an important distinction.

As to the fact that drug companies aren’t “churning out” enough new medicines, one thought – new drugs are never “churned out.” That’s a pretty glib statement considering that, despite the increase in R&D spending, the number of new innovative products being submitted to the FDA for approval is decreasing. In fact, output of new products has been dropping since 1997. FDA is now receiving fewer applications for new drugs than in mid-1990’s. The number of new device applications is also decreasing.

And the rate of failure is increasing. Almost 50% of applications are failing in late-stage Phase 3 trials. This costs companies millions of extra dollars and is driving up the cost of successfully bringing a new drug to market. In 2003, researchers at Tufts Center for the Study of Drug Development estimated these costs to be $802 million, and some sources suggest that the total cost is closer to $1.7 billion.

As the late US Senator Everitt Dirksen once said, “A billion here and a billion there, and pretty soon you’re talking about real money.”

The high cost of R&D is forcing many companies to make the short-term business decision to focus product-development on those molecules that have a much higher potential to recoup expenditures. Unfortunately, this trumps attempts to develop potentially risky but breakthrough products for diseases affecting smaller populations, the orphan drugs.

Consider the implications if FDA could help companies to fail faster. Using the lower end of the Tufts drug development number …

* A 10% improvement in predicting failure before clinical trials could save $100 million in development costs.

* Shifting 5% of clinical failures from Phase 3 to Phase 1 reduces out of pocket costs by $15-$20 million

* Shifting ¼ of failures from Phase 2 to Phase 1 would reduce out of pocket costs by $12-$21 million.

Hence the urgency of the FDA’s Critical Path program.  Read More & Comment...

A Critical Path for Comparative Effectiveness Research and CMS

10/31/2007 04:49 PM |

Without fanfare or media coverage the European Medicines Agency reaffirmed that use of epo shoudl be handled by doctors -- not by bureaucrats -- and that there should be no hard and fast hemoglobin level imposed from above, rather a flexible level achieved as befits the needs and quality of life of individual patients.

That puts Europe light years ahead of our CMS that has deemed it cost effective and safe to toss tons of seniors into the dark ages of blood transfusions. I wonder what Pharmalot and others who had predicted a tightening of EMEA guidelines will say? Ditto the fact that the EMEA also took a mature approach to Avandia. But that is a post for another day.

For now, it is clear that CMS over-reached using the wrong data to achieve an over-restrictive decision inconsistent with the emergence of patient-centric medicine. EMEA is moving in that direction. So is FDA. Both have Critical Path programs designed to integrate the tools and knowledge to promote patient variation into the development and use of new drugs. Why not a Critical Path for CMS to achieve the same goal in developing insights into the value of new treatments?

So here's my proposal for a Critical Path for Comparative Effectiveness for CMS. Comments and thoughts welcome.

CMS should initiate a Critical Path for comparative effectiveness much as the FDA developed a Critical Path for drug approval and development. “The Critical Path Initiative is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured.” CMS needs to initiate in a manner that is as transparent and as collaborative as that undertaken by the FDA to promote a national effort to modernize the science information the evaluation of the value of treatments. Just as the key scientific insights guiding the FDA critical path are genetic variations and biomedical informatics that predict and inform individual responses to treatment, CMS needs to establish a process to incorporate knowledge and tools that personalize evidence of response in its decisions.

It should to the extent possible use coverage to evidence development, research grants and partnerships with industry, the FDA, NIH, the new Reagan-Udall Critical path institute to “ harness the potential of bioinformation used to evaluate and predict safety, effectiveness, and value of treatments for each patients.


Rather than focusing on coverage decisions, CMS should focus on identifying opportunities and developing tools to improve clinical decision-making based on new science. The FDA has developed a Critical Path opportunities list in cooperation with many interested parties that provides 76 concrete examples of how new scientific discoveries—in fields such as genomics and proteomics, imaging, and bioinformatics—could be applied during medical product development to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products. CMS should begin the process of developing a similar list of ways new discoveries and tools such as electronic patient records could be used to improve the predictive and prospective nature of medicine.

As a first step, CMS could use the reopening of the ESA coverage decision as example for how to achieve a more targeted and patient-centered use of ESAs in chemotherapy. An opportunities list could be generated around this particular issue with continued coverage conditioned upon participation in Critical Path activities.  Read More & Comment...

Just in Time For Halloween: The Super-Bug Scare

10/31/2007 03:51 PM |

It is getting hard to figure out what to panic about first: Lead in lipstick? Cough medicines for kids? The statin surge among adolescents? How about MRSA in the boysroom? Can anyone guess which is associated with more deaths: MRSA or influenza? The answer is (b) influenza with 36000 deaths a year with another 11000 deaths linked to respiratory infections linked to flu as well. MRSA, 85-90 percent which are hospital related and found among the elderly who are immunocompromised is linked to about 17000 deaths. Handwashing anyone?

Get your Halloween chills the old fashion way. In the meantime read CMPI Sr. Fellow Mark Siegel's calming piece on MRSA in today's NY Post. It's before the article on Joe Girardi.

http://www.nypost.com/seven/10312007/postopinion/opedcolumnists/rx_for_the_superbug.htm  Read More & Comment...

Rudy's Right Regarding Cancer Care

10/31/2007 01:20 PM |

There is a lot of consternation about the fact that Rudy's ad comparing prostate cancer care in the UK and the US had some musty numbers on survival rates. They were wrong numbers that five minutes on the Web could have solved. Hence the error detracts from but doesnt' change the fact that you are more likely to die and less likely to survive five years after being diagnosed in the UK than any other Western country. To suggest, as some have, that five year survival rates, are not predictive or not a marker of quality of care, is absurd. The fact is, as a recent article in the Lancet points out survival rates reflect increased screening but only to the extent that it leads to treatment. Screening without treatment would not translate into fewer cancer deaths, which it has at a faster rate in the US than anywhere else. Indeed, controlling for screening, the key variable for increased survival and declining death rates is access to new medicines.

Which is the point of Rudy's ad. And the point of this recent article in UK's Daily Telegraph:

I won't let Daddy die: Girl of six raises £4,000 for life-saving drugs the NHS won't provide
By LUCY LAING
" Faced with the prospect of losing her father to cancer, Chantelle Hill reacted a little differently to the average six-year-old.

Instead of letting the grown-ups deal with it, she decided to save him herself.

Now, she has raised more than £4,000 to buy the life-saving drugs David Hill needs after he was told they were not available to him on the Health Service. "

Apparently NICE and the NHS decided that Tarceva, the drug Chantelle will pay for, but NHS won't, was not "an effective use of NHS resources".

I know there will be some who read this post and bleat about how some people can't afford drugs because they don't have insurance. Good point. But what's the point of insurance of any kind if your six year daughter has to ask your neighbors for money to pay for a drug that extends your life and improves it's quality? Could it be that our health system, which needs work, is better and more compassionate in this regard?

http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=490001&in_page_id=1770  Read More & Comment...

Heaven have MRSA

10/30/2007 12:40 PM |

Scott Gottlieb tells it like it is via this column in today's edition of The Wall Street Journal ...

Attack of the Superbugs
By SCOTT GOTTLIEB

One of the early morning television news shows recently staged a live feed from a suburban Maryland high-school. It was the latest to close after a student contracted a virulent and drug-resistant bacterium called methicillin-resistant staphylococcus aureus, or MRSA. Pronounced "mersa," it's become this season's equivalent of shark attacks, every day bringing new, terrifying reports, although the dangers of such bacteria are hardly new.

Researchers working at the Centers for Disease Control and Prevention reported this month that nearly 19,000 Americans died in 2005 from MRSA, and about 95,000 were infected. Doctors have been reporting for years that MRSA was cropping up with alarming frequency. The same is true for other bacteria. In Rochester, N.Y., doctors recently reported nine children stricken with a strain of the bacteria that causes ear infections -- streptococcus pneumonia -- that was resistant to all 18 antibiotics commonly used to treat the condition.

The real news isn't that these bugs exist, but how woefully unprepared we are to deal with them. As we make progress in fields like cancer, we are taking a U-turn on bacteria. Despite advances in drug development, the bugs have increased their IQ nearly as fast as research, outwitting our medicines. Efforts have turned to preventing bacterial spread and clamping down on antibiotic prescribing.

There's no question that poor hospital hygiene, overuse -- and sometimes misuse -- of antibiotics contribute to educating bugs at our expense. But preventative efforts alone won't solve our bacterial challenges. What we need most are better diagnostic tests and new medicines.

This is high-stakes science, but the pipeline isn't promising. Since 1998, just 10 new antibiotics have been approved by the the Food and Drug Administration, only two of which work in fundamentally new ways. Only 13 new antibiotics are in development inside big drug companies, compared to an average of 60 more than a decade ago. Since leaving the FDA this year as its deputy commissioner, I've advised a few biopharma firms making antibiotics and the venture investors supporting them. Regrettably, however, many big drug makers have followed the lead of Eli Lilly, a pharmaceutical company that once pioneered antibiotics, only to exit the business entirely.

The problem? There's not a lot of payoff for developing drugs aimed at infections. First, they last only days, or at most weeks, limiting sales. And the better the drug, the more likely doctors and hospitals are to keep it on the shelf as a last resort. Most hospitals require that doctors get special approval to prescribe the best new antibiotics. In that regard, what's good for public health isn't necessarily good for antibiotic development.

Capricious regulation is another problem, adding to uncertainty and, in turn, the cost of development. For drugs targeted to many common bacterial ailments, the FDA historically required so-called non-inferiority trials. This meant a new antibiotic needed to prove it was generally no worse than existing treatments in order to win regulatory approval. Otherwise, conducting trials to prove a new antibiotic was better than a sugar-pill placebo -- or superior to existing drugs -- would require huge trials and, in some cases, was simply unethical if it meant asking patients with potentially serious infections to risk treatment by placebo.

That changed just last year when a handful of FDA reviewers became miffed that companies would get drugs approved through these non-inferiority trials without proving the new drugs were better than older medicines, and then market the new drugs for broad upper respiratory indications. The reviewers brought their complaints to Congress, which has since leaned on the FDA, at one point asking the Government Accountability Office -- staffed with lawyers and policy analysts -- to opine on the nuanced scientific question of non-inferiority trial design. The political intrigue has pushed the FDA to raise its approval bar in some areas, jettisoning the non-inferiority approach for some ailments while leaving a mess of uncertainty for many others.

So how do we surmount these obstacles to get the drugs and diagnostic tests we need to stay ahead of aggressive bacteria like MRSA?

First, we need to recognize that developing drugs aimed at super bugs is not an ordinary pharmaceutical business, and requires unique incentives. If public-health policies compel doctors to hold the best new antibiotics in reserve, we need to compensate with incentives for developing those niche drugs.

One way would be to clarify the rules under the 1983 Orphan Drug Act to include drugs that target resistant bugs. That law provides special incentives for drugs that treat rare diseases, including patent protections and streamlined regulatory review. The FDA needs to create better opportunities for companies to target not only conditions -- such as pneumonia or skin infection -- but also specific bacteria, like multi-drug resistant staph.

The FDA's guidance on other aspects of antibiotic drug development is similarly murky due, in part, to fluid standards. Congress recently had to write into law a demand that the FDA produce guidance on antibiotics for acute exacerbations of chronic bronchitis and acute bacterial sinusitis (finally released yesterday). Merely issuing documents doesn't guarantee clarity, and one of the FDA's recent documents on an aspect of antibiotic development ran several pages, saying little.

The FDA should collaborate with the Infectious Disease Society of America (IDSA) to develop meaningful guidelines that provide clear pathways to new drug development. The IDSA's credible voice could also buttress the FDA against the maneuvering of a handful of staff who take their views to politicians when they lose internal scientific debates.

Finally, we badly need better tools for rapidly detecting resistant infections in blood, even screens for bacterial genes. Today it can sometimes take days to discover that a patient is infected with a resistant bug. If there were better diagnostics -- similar to the "rapid" strep test -- bacterial infections could be distinguished early and doctors could treat patients with confidence. Drug companies could also more easily develop drugs targeted to specific bugs, conducting clinical studies aimed at specific pathogens, and making sure the right patients got the right drug early in the course of their illness, when drugs can make the most difference.

But the diagnostics business has been a lower-margin affair for many years, steering product developers into other fields. There are complicated reasons for this, but Medicare has systematically tried to drive down prices for diagnostic tests, often refusing to pay for new tests altogether. In turn, the big companies that make the tests committed a fundamental mistake early on, by adopting a strategy of charging lower prices for the throw-away test kits and premium prices for the platforms they run on -- a reverse of the old razor-blade model.

The big diagnostic companies figured they would make most of their money off the platforms. They're regretting that now. The strategy may have worked if they had continued to innovate, but now many of the best ideas for new tests are coming out of small firms that have little ability to sell their own big platforms, and a hard time premium pricing diagnostic tests in a market conditioned by the big firms to expect cheap razor blades.

Most existing antibiotics are as old as the earth, screened out of nature where they resided, doing battle with bugs for centuries. We need to accelerate this evolution in our laboratories. Public policy mistakes are partly to blame for creating this inhospitable environment for new development, and it will take a concerted effort to improve it. The only sure way to stay ahead of bacterial evolution is by escalating this arms race.

Dr. Gottlieb, a practicing physician and resident fellow at the American Enterprise Institute, was previously a Deputy Commissioner of the Food and Drug Administration.  Read More & Comment...

When is a medical device not a medical device?

10/30/2007 07:58 AM |

The first thing that needs to be said about medical devices is that we should stop calling them medical devices. They are, in every sense, medical technology.

And technology, as we all know, is what makes the world go ‘round.

That being said, we must take medical technology as seriously as we do pharmaceuticals.

And, as the use of medical technology (from stents to scans) becomes ever more important and more pervasive, so too must we focus on safety.

But we must not fall into the false security of the Precautionary Principle which warns us to do nothing until we know everything. Why is this a bad idea? Because we can never “know everything.” And when it comes to FDA regulated products, be they drugs or devices or combination products – there will always be risk that comes along with benefit.

Can we do a better job regarding medical technology safety? Yes. Must we? Absolutely. Are we?

Here’s what Dan Schultz, director of CDRH had to say in today’s Wall Street Journal on that point:

"Are there ways to identify problems more quickly? I think the answer is yes. But if you require a clinical trial for every design change, what does that do to the ability of bringing new technologies to market?"

What, you mean there's no easy answer? Sorry Senator Grassley.

Here’s a link to the article:

http://online.wsj.com/article/SB119370397918375690.html?mod=hps_us_pageone

Vigilance must not supplant progress. They must advance together and learn from each other.  Read More & Comment...

Thoughts from the John

10/29/2007 08:38 AM |

Seems as though John Edwards must have been absent during the law school lecture on the US Constitution – specifically the part that relates to Freedom of Speech. In a speech the other day he called for, among other things, mandatory FDA approval before drug companies launch major ad campaigns.

Must have tested well in focus groups.

Similar bloviation during debate over FDA reform was quickly dismissed because of some more educated members of Congress familiarity with the First Amendment.

But, as we all know, facts and reality have very little to do with Presidential campaigns.

Further proof of this was Senator Edwards’ remark that drug advertising misleads patients and drives up health care costs.

Neither of these statements is true. As to “misleads patients,” what DTC does do is send patients (aka – consumers) into the offices of their physicians were they have important dialogue about their health. In many of these DTC-initiated visits a previously undiagnosed condition is diagnosed. And earlier diagnosis and treatment decreases health care costs.

As to whether or not DTC increases the cost of medicines, consider this – when you compare the prices of medicines within a given therapeutic category along with their spending on DTC, there is no correlation. Also, when you compare the amount of money spent on DTC versus research and development – they don’t even have the same number of zeroes.

According to Edwards, "The excessive costs of prescription drugs are straining family budgets and contributing to runaway health care costs.”

Another nice sound bite that belies the truth. Only 11.5% of the US health care spend is on pharmaceuticals – the same pharmaceuticals that keep people out of the hospital (over 30% of our health care expense). Proper medication keeps people healthy, at work, and paying taxes.

But that’s not as popular a sound bite in Iowa and New Hampshire (where Senator Edwards shared his comments with primary voters).

"With such aggressive and often misleading drug company marketing, it's too easy for advertising -- instead of doctors or proven results -- to influence families' health decisions," Edwards' campaign quoted him as saying.

Often misleading? Really? Does he even know about “fair balance” and “adequate provision?” Does he even know about the research that shows how few people actually even try to read various brief summaries?

Probably not. And that would explain why the “Edwards Plan” also calls for drug advertising to disclose more information about side effects and comparisons of drugs against placebos and alternatives.

Someone should ask him about this during the next candidate debate. (And speaking of “comparisons,” someone should also ask him about his understanding of comparative effectiveness.)

Further, the Edwards plan would institute a two-year delay on consumer advertising of all new drugs.

So, not only do we not really need Freedom of Speech – we also don’t need new and timely information about new and timely medicines.

Gevalt.  Read More & Comment...