Follow-on O Ship of State

04/29/2008 08:37 AM |

Excellent piece by Bryan Liang in the Los Angeles Times:

Don’t Compromise the Safety of Biotech Drugs

By Bryan A. Liang

A toy plane has a handful of parts. A Boeing 747 has several million. This makes sense. Toy planes are small, simple models, while 747s are large, high-performance aircraft that travel more than 500 mph with thousands of component systems acting together. The model costs a few dollars because it's easy to manufacture. The 747 costs about $225 million because of its highly complex nature, testing and the need to ensure safety.

The comparison is worth keeping in mind as the debate heats up over "follow-on" biologics. Biologics are today's most advanced medicines, fully tested biotechnology protein drugs that provide targeted therapy to victims of cancer and other diseases. Follow-on biologics are the second or subsequent versions, but they are not identical.

U.S. spending on them reflects the importance of these drugs in medicine's arsenal. Biologics represent the fasting-growing sector in the medicines market, with more than $30 billion spent on these drugs each year. Indeed, the top five drugs in terms of Medicare expenditures administered in physicians' offices are biologics. By 2010, worldwide spending on biologics is estimated to grow to $10 billion, and biologics will make up nearly half of all newly approved medicines. Hence, many policymakers are focused on reducing the costs associated with these drugs.

Congressional legislation is pending that would allow the sale of follow-on biologics without requiring extensive testing -- essentially following the same model used for approval of generic forms of traditional prescription drugs.

But most drugs we're familiar with, like the pills we get from the pharmacy, are "small-molecule" drugs -- simple chemical compounds. They can be easily manufactured and identically copied. The anti-convulsant drug valproic acid, for example, has a total of just 26 atoms.

Identical to the brand-name version, these generics can "piggyback" on a brand-name company's testing. That's reasonable. These small-molecule drugs -- which typically are made up of a total of 20 to 100 atoms -- can be copied perfectly. So they don't need independent safety testing, cost less to make and are cheaper -- allowing more patients to obtain the medical benefits.

But biologics are far more complex. The brand-name drug Herceptin, a biologic that's widely used to treat cancer, is made up of a total of roughly 25,000 atoms. Large biologics can have millions of atoms.

Biologics aren't made by combining chemicals in a flask. They're made by life forms such as cells, yeast and bacteria. Like humans, these life forms exhibit diversity in metabolism and composition, making the final product a unique, heterogeneous mix that cannot be copied exactly. So follow-on biologic forms of a drug can only be similar to the original, not identical.

Because of the complexity of biologics, there's more regulation. In comparison with common chemical drugs that can have generic versions -- such as penicillin -- which only require 50 to 60 manufacturing tests for safety and quality, biologics require at least four times that number.

So the policy challenge is to provide incentives for innovation while also ensuring that any follow-on forms of biologics that enter the market are safe.

The key lies in something called "data exclusivity," which is a legal mechanism for allowing a company to keep confidential the data associated with a drug's development. Data exclusivity usually lasts for several years and spurs innovation by protecting new inventions. This is the current rule for small-molecule drugs, and it should be applied to biologics as well. Strong data exclusivity is critical for biologics, which are about 50% more expensive to develop than small-molecule medicines.

However, the current state of science makes ensuring safety of follow-on biologics difficult. Currently, the technology to map out the exact chemical structure and function of one large biologic versus another is not available. That makes safety reviews inexact. And follow-on forms may induce unpredictable adverse reactions.

Several years ago, a fully tested biologic created in the U.S. was cooperatively licensed overseas to be made in Europe. But the new version caused patients to suffer "pure red cell aplasia," whereby their bodies could not make red blood cells. This may have contributed to the deaths of some patients and permanent injury to others. Yet today, after eight years of research, the cause of these reactions is still unknown.

If even cooperative company efforts can result in unpredictable adverse reactions, any follow-on product that does not undergo full testing should be of concern. Recognizing this reality, the European Union has developed a system of assessment that requires clinical testing of follow-on products in Europe before approval.

U.S. policymakers should take note. Relevant clinical data and testing should be required to ensure safety of any follow-on biologic product being considered for patient use in the U.S. And appropriate data exclusivity should be put in place to foster innovation.

If chemical drugs were toy planes, biologics would be 747s, the cutting edge of medicine. Because of their complexity, any follow-on forms must be held to a higher safety standard. As we have learned in aviation, safety is no accident.

Bryan A. Liang is executive director of the Institute of Health Law Studies, California Western School of Law and co-director of the San Diego Center for Patient Safety, UC San Diego School of Medicine.

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Scientific research with an asterisk

04/29/2008 08:31 AM |

From today's edition of the Boston Globe:

Scientific research with an asterisk

By David A. Shaywitz and Dennis A. Ausiello

CONSIDER an academic scientist - we'll call him Louis - who receives funding from the beverage industry, the textile industry, and the livestock industry, and ultimately generates profound new scientific insights, beneficial both to the sponsoring companies and to the world as a whole. Are these accomplishments diminished because the work was industry funded? Should Louis - Pasteur - have an asterisk next to his name?

That's the implication of a recent New York Times profile of three academic researchers from New England who have pledged to decline industry funding and "have lost their asterisks."

The notion that academic researchers who partner with industry are intrinsically tainted reflects a misunderstanding of the importance and quality of industry research, and the role industry plays in bringing new drugs to the patients who need them.

While most of the original insights leading to new drugs and devices likely derive, at least in part, from the work of academic scientists, turning these preliminary advances into FDA-approved treatments required an exceptional investment by industry, and vital partnerships between academic investigators and company scientists.

The gaping distance between promising lab result and approved drug is apparent to anyone who has tried to reconcile the breathless news reports touting "scientific breakthrough" with the paucity of options available for patients suffering from any number of devastating medical conditions. In the last 10 years, for example, there have been more then 7,000 academic papers published on pancreatic cancer, but not a single breakthrough treatment.

The primary reason for this gap: The human body is complicated, and our understanding limited. In many cases, we are still struggling to figure out the molecular basis for important diseases. In other conditions, even when the cause is clear, designing a drug capable of selectively correcting the defect while not causing new problems, is a monumental challenge.

To overcome these hurdles, there is a need for more, not less, interaction between academic physician scientists and their counterparts in industry, engagement that should occur at every stage of the drug development process.

Our own experiences with difficult science and sick patients has convinced us that the battle is not drug companies vs. academics, but rather between dreadful diseases and the medical researchers who are trying to subdue them.

Unfortunately, industry critics often lose sight of the big picture, and routinely stigmatize pharmaceutical researchers and their academic collaborators. Young academic investigators are often counseled against "selling out" and pursuing a career in pharmaceutical research, despite the exciting drug-development opportunities such a choice might afford. Senior university researchers who might contribute considerable wisdom to drug discovery efforts are reviled in the press if they associate with industry in any way, even though these relationships are vital for the creation of new medicines.

Finally, of course, there is the money. Because pharmaceutical companies are for-profit entities, conventional wisdom holds that any data they publish should be suspect. In fact, pharmaceutical research is tightly regulated, and industry-sponsored clinical studies are typically performed in a rigorous, consistent, and transparent fashion that would be the envy of many academics. To the extent some industry studies fall short, the problem generally lies not in the results obtained, but rather in the questions never asked - a critique that applies at least as well to the pharma-bashing studies now so popular in certain medical journals.

Also puzzling is the suggestion that it is improper for drug companies to solicit the perspective of academic experts, and immoral (or at least asterisk-worthy) for experts to accept financial compensation for their time. Expert insight may accelerate the delivery of new treatments to patients, and it seems disrespectful to suggest this time should not be valued.

Still, although the relationship between universities and industry should be broadened, useful and transparent guidelines must be developed to get this relationship right. Ultimately, these interactions must be defined, protected and enhanced if the medical community is to deliver on its commitment to secure the health and well-being of patients.

Dr. David A. Shaywitz is a management consultant in New Jersey. Dr. Dennis A. Ausiello is the physician-in-chief of Massachusetts General Hospital and a director at Pfizer.

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The Moose on the Table

04/29/2008 08:12 AM |

Yesterday Senator McCain made clear the difference between his position on healthcare and that of Senators Clinton and Obama:

Senator McCain believes in free market solutions and he told the American people an important truth – the warm and fuzzy sounding policy of “universal care” is really the harsh reality of “government care.”

He then put the moose on the table – insurance deregulation.  And it’s about time.

Now that’s straight talk.  Express.

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Getting ugly early

04/29/2008 07:55 AM |

Gail Wilensky on what happens if some of the ideas presented by our candidates for the White House fail:

"The real answer is -- we don't know.  But if these ideas don't work the alternatives are largely disturbing:  price controls, stifled innovation and stemming the spread of new technology.  It gets ugly real fast."


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Group Urges Ban on Medical Giveaways

04/28/2008 04:27 PM |

By GARDINER HARRIS
Published: April 28, 2008

Drug and medical device companies should be banned from offering free food, gifts, travel and ghost-writing services to doctors, staff members and students in all 129 of the nation’s medical colleges, an influential college association has concluded.

The proposed ban is the result of a two-year effort by the group, the Association of American Medical Colleges, to create a model policy governing interactions between the schools and industry. While schools can ignore the association’s advice, most follow its recommendations.

Rob Restuccia, executive director of the Prescription Project, a nonprofit group dedicated to eliminating conflicts of interest in medicine, said the report would transform medical education.

Most medical schools do not have strong conflict-of-interest policies, and this report will change that, Mr. Restuccia said.

The rules would apply only to medical schools, but they could have enormous influence across medicine, said Dr. David Rothman, president of the Institute on Medicine as a Profession at Columbia University.

We’re hoping the example set by academic medical colleges will be contagious, Dr. Rothman said.

"Drug companies spend billions wooing doctors” more than they spend on research or consumer advertising. Medical schools, packed with prominent professors and impressionable trainees, are particularly attractive marketing targets."

Okay.

Here are the facts from a November 2006 GAO report:

Drug companies spent less in 2005 on DTC advertising ($4.2 billion) than on promotion to physicians ($7.2 billion) or research and development ($31.4 billion). www.gao.gov/htext/d0754.html

Now some stuff Gardiner left out:

The Prescription Project is funded by trial attorneys who sue drug companies. IMAP gets millions from George Soros.

And the report never uses the word "ban.”

Here's what is does say, courtesy of Thomas Sullivan's blog:

www.policymed.com/

For Continuing Medical Education (CME)

Academic medical centers offering CME programs should develop audit mechanisms to assure compliance with the standards of the Accreditation Council for Continuing Medical Education (ACCME), including those with respect to content validation and meals.

Academic medical centers should establish a central CME office through which all requests for industry support and receipt of funds for CME activity are coordinated and overseen.

To the extent that educational programs for physicians are supported by any commercial entity, including pharmaceutical, device, equipment, and service entities, the programs should be offered only by ACCME-accredited providers according to ACCME standards.

In respect to CME these are all very reasonable recommendations, and most universities have already undertaken significant effort to achieve these goals.

The document covers many other things not directly related to CME including:

• Gifts to individuals (Prohibiting)
• Pharmaceutical samples, (Central Distribution)
• Site access by pharmaceutical representatives, (Limited to appointment or invitation, student participation limited, more MD’s, PhD’s and PharmD’s)
• Site access by device manufacturer representatives, (credentialing, appointment or invitation, disclosure and consent of patients, student participation limited)
• Participation in (Non CME) industry sponsored programs. (Discourage faculty, transparency of payment and fair market value, prohibit attendance, paying for attendance, accepting personal gifts)
• Industry Sponsored Scholarships and other Educational Funds for Trainees (Giving Centrally, no Quid pro quo, selection sole responsibility of the university)
• Food (only for ACCME-Accredited Events)
• Travel (only for legitimate reimbursement or contractual services.
• Ghostwriting (transparency of all involved in the process)
• Purchasing (Disclosure of interest, and recuse from purchasing decisions in COI cases)
• Boards of Directors, Advisory Boards and Consulting (Valuable and Compensation to Reflect Fair Market Value)

All the news that's fit to print?

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PLoS ... or Minus

04/27/2008 05:55 PM |

Important, fascinating, discouraging, and urgent new government-sponsored study (courtesy of Harvard) shows that life expectancy actually declined in a substantial number of US counties from 1983 to 1999, particularly for women. Most of the counties with declines are in the Deep South, along the Mississippi River, and in Appalachia, as well as in the southern Plains and Texas.

The study, published in the journal PLoS Medicine, concluded that the progress made in reducing deaths from cardiovascular disease, thanks to new drugs, procedures and prevention, began to level off in those years. Those gains, as they shrank, were outpaced by rising mortality from lung cancer, chronic obstructive pulmonary disease and diabetes. Smoking, which peaked for women later than for men, is thought to be a major contributor, along with obesity and hypertension.

Some, like former Senator John Edwards, are using the study to further fan the class warfare flames.  And socio-economic conditions are certainly an important part of this issue but, as Sam B. Harper, an epidemiologist at McGill University who has studied the issue commented, “We know from hundreds of studies that income does have an impact on health, but it’s not a simple relationship."

Indeed.  But politicians -- and especially frustrated ones like Senator Edwards, are always looking for simplistic, talking point-friendly answers to complicated problems.

According to  one of the report's authors, Dr. Majid Ezzati, "... life expectancy disparities would have to be addressed through public health strategies directed at reducing the risk factors that cause chronic disease and injuries."

And that means a more deliberate effort at patient-based care -- focusing on earlier diagnosis (and better diagnostics) and more targeted health care (right treatment for the right patient at the right time).  What it does not mean is a knee-jerk move towards "European" style healthcare and the ensuing cost-based rationing that inevitably comes with it.

For more detail on the study, click here: www.nytimes.com/2008/04/27/weekinreview/27sack.html

We mustn't allow the next generation of Americans to be the first in our nation's history to enjoy a shorter life than their parents.  And to achieve that goal we must abandon the rhetoric of  divisiveness and work together (government, academia, and industry) towards this common purpose.
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Phase Fore!

04/25/2008 08:47 AM |

Steve Walker of the Abigail Alliance weighs in on the issue of timely commencement of promised Phase IV trials:

"I think in some cases you are probably right about the failure to conduct Phase IV studies being a "self-inflicted" wound, but there is perhaps a bigger problem in the design of a lot of the studies.  Once a drug is approved and deemed safe and effective (in many cases proven in compelling fashion despite the absence of a perfect p-value), conducting randomized studies where patients are randomized into treatment arms that do not serve their best medical interests is fraught with all kinds of ethical and practical problems, and challenges for sponsors, physicians and doctors.  Coupled with the undeniable fact that after approval the development and learning process about many drugs accelerates dramatically (a good thing that usually leaves the slow-moving FDA far behind) often causes the trials mandated by FDA to become obsolete before they start, and even more commonly before they are completed.  When that occurs, the FDA's and other's mandates that the trials be conducted anyway degenerates into nothing but a form over substance pursuit of compliance for no other purpose than compliance.  That should not be the purpose of the regulation of medical products because it is harmful to the public health, not to mention a waste of money and patients.   Read More & Comment...

Bayh-Bayh To Another Barrier to Euro-Innovation

04/24/2008 06:13 PM |

From our friends at www.Fastercures.org...It looks as though Europe is tearing down another anti-capitalist wall: the one between academia and industry that slowed translation of biotechnology into products.  How?  By using the same approach that President Reagan took by expanding the Bayh-Dole through executive order with Federal Technology Transfer Act.  That put government agencies on notice to share all patentable technologies with the private sector to promote investment al presto. 

This will make the pharmaceutical purists and conflict of interest capos sick am I sure.  There is now nowhere in the world where their views have been turned into policy or law...except North Korea or Cuba.   Here's the post from Fastercures Smartbrief...

EC wants more research headed to product development
The European Commission is asking for more interaction between universities and pharmaceutical companies to ensure that research knowledge is more quickly translated into products and services. The EC adopted a recommendation on how member states can revise their policies to allow public research organizations to leverage intellectual property more effectively. In-PharmaTechnologist.com  Read More & Comment...

Wood That Everyone Had Same Sane Views on the FDA

04/24/2008 05:33 PM |

Alastair Wood's excellent editorial in the NEJM, rising above the hysterics with wit and intellect:

content.nejm.org/cgi/content/full/358/17/1774  Read More & Comment...

Study Buddies

04/24/2008 09:27 AM |

According to Bloomberg (the news service not the mayor):

“Drugmakers haven't made progress in starting studies that they promised to conduct after their products were approved by U.S. regulators. The Food and Drug Administration determined that 1,044, or 62 percent, of incomplete studies for conventional drugs and biotechnology medications had yet to be started as of Sept. 30. At the same time in 2006, 1,026, or 63 percent, of the unfinished studies hadn't begun, according to the FDA.”

Here's a link to the complete story:

www.bloomberg.com/apps/news

Yes, I know, it’s not that simple – but that being said, it’s true.  And that has to change.  While this issue does play into the hands of the usual suspect safety jihadists (note quote in article by Peter Lurie) – promised studies should be commenced promptly.

Yes, there are many relevant and extenuating circumstances (note quote from PhRMA), but, as far as industry is concerned, this is a self-inflicted wound that spin cannot fix.


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EU Considers Merging onto the Healthcare Information Superhighway

04/24/2008 07:54 AM |

Maybe it has something to do with the strength of the Euro -- or maybe it has something to do with a patient's right to know.  And just maybe things are beginning to change.

Have a look at this new article (from the Journal of Life Sciences) on how the EU is pondering changing what's allowable vis-a-vis what they call "Information to Patients" and we in the US call "Direct to Consumer Communications:

www.tjols.com/article-640.html

Bottom line -- knowledge is power.

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Gene -- but not heard

04/23/2008 08:05 PM |

Finally we are going to settle the issue of genetic testing and personal privacy.  And it's about time. 

According to Andy Pollack's story in today's New York Times:

"Proponents say the new law, more than a dozen years in the making, would help usher in an age of genetic medicine, in which DNA tests might help predict if a person is at risk of a disease, allowing action to be taken to prevent it.

Some of the tests already exist, like one for breast cancer risk, and new ones are being introduced almost every month. But backers of the legislation say many people are afraid of taking such tests because they fear the results would be used to deny them employment or health insurance.

“This bill removes a significant obstacle to the advancement of personalized medicine,” said Edward Abrahams, the executive director of the Personalized Medicine Coalition. His group is an organization of drug and diagnostic companies, academic institutions and patient groups that advocate using genetic information to choose the most appropriate treatment for each patient."

Here's the rest of the story:

www.nytimes.com/2008/04/23/business/23gene.html

All sounds good, right?  Hopefully. 

We'll wait and see, when the payer is the government , if Uncle Sam retains the same "keep your hands outta my genes" philosophy.

But, in the meantime, well done.
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Heparin Hypocrisy - Hyped Up Safety Fears on ADHD Drugs -Does Medicaid Kill Poor People

04/23/2008 07:17 PM |

Yet another show trial held by another congressional committee on the FDA...There have been four or five over the last two months on heparin alone. Andy von Eschenbach, who is gaining momentum, along with the FDA, in shifting the agency towards a science and systems based approach to regulation -- using real time technology to promote full time compliance -- has to sit and take the following from the likes of Bart Stupak (D-Michigan):

"Last year, this nation's regulatory failures resulted in dead dogs and cats. This year, it has tragically led to the deaths of people," said Rep. Bart Stupak, D-Mich. "If we don't make some rapid progress on fixing the foreign drug inspection program, the next melamine or heparin tragedy will soon be upon us."

That's rich coming from a guy who helped push up the suicide rates by scaring parents away from antidepressants. and who is pushing for drug importation at a time when Al Qaeda and Hezbollah are involved in drug counterfeiting....Andy must have to shower after sitting through such a show trial...

www.fraudaid.com/scamspeak/conprods.htm

Meanwhile the Steve Nissen fear factory spews out another piece of tabloid medicine: EKG monitoring of all kids getting stimulants for ADHD.. Now there's a way to achieve Nissen (who has never studied ADHD) goal of making a physician's hand quiver before writing a scrip for the drug....But will it improve prescribing? Ron Winslow of the WSJ nails it:

"Since 1999, fewer than 30 sudden deaths among children have been linked to the drugs, which are currently taken by more than 2.5 million youngsters in the U.S. Issues of cost, available expertise in reading children's ECGs and concern about false-positive tests are prompting some experts to question the rationale for urging an ECG in particular.

"This is a $250 million recommendation," says Mike Ackerman, a pediatric cardiologist at the Mayo Clinic in Rochester, Minn., who estimates the total cost of an ECG at about $100. "We're really trying to find a needle in a haystack, and we have no data yet to know that the screening program they're recommending would capture" those few at-risk individuals. Dr. Ackerman was a member of another American Heart Association panel that last year stopped short of recommending routine ECG screening for heart abnormalities in young competitive athletes."

Read the Wall Street Journal article

FInally a pattern appears to emerging that has escaped even the great John Wennberg: the life expectancy of poor people is declining even as that of others is increasing. Women in particular are dying earlier than men in rural areas. Can we say Medicaid and SCHIP anyone? And I should note that Frank Lichtenberg spotted a decline in life expectancy among the elderly in the VA, the same VA that Shannon Brownlee -- Wennberg's Boswell -- is pushing as the example of what we all should be forced into in the Dartmouth comparative effectiveness utopia. Eeech...

Here's the article by the ever wonderful Maggie Fox of Reuters with a link to the study which is pretty methodologically sound:

www.reuters.com/article/scienceNews/idUSN2146521720080422  Read More & Comment...

Foul Shots

04/21/2008 03:22 PM |

My latest article on the vaccine-autism mythology....

www.nypost.com/seven/04202008/postopinion/postopbooks/foul_shots_107320.htm
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OMB & Healthcare Reform: Not so easy (and not so fast)

04/21/2008 12:36 PM |

Important article in today's Wall Street Journal on OMB's Peter Orszag.

Here's how it begins ...

As the presidential candidates and Congress rev up the debate over the future of health care, Peter Orszag is already playing one of the toughest positions: referee.

Mr. Orszag, a 39-year-old economist, is the director of the Congressional Budget Office, the influential agency charged with toting up congressional bills' impact on the federal budget. Such scoring can sink bills that can't offset their costs with savings -- a serious risk for proposals that aim to expand federal health programs to cover more citizens.

Mr. Orszag increasingly is focusing on health issues, taking an unusually high profile for his nonpartisan office. He has become a prominent speaker at health conferences and co-wrote two pieces in the New England Journal of Medicine. He has launched a blog, cboblog.cbo.gov/, boosted the number of staffers who work on health to 47 from 31 and is seeking to add more. The agency has 235 employees.

"This actually is our fiscal future, and policymakers do not have as much analysis and options as they would need to make sound long-term decisions," says Mr. Orszag.

Here’s a link to the complete article:

http://online.wsj.com/article/SB120874132955630171.html?mod=hps_us_inside_today

The CBO's health-care work "will be very instructive to members when we attempt to take steps to right the ship," says Sen. Kent Conrad, the North Dakota Democrat who chairs the Senate Budget Committee.

Indeed – but let’s also add to the equation short-term versus long-term issues.  And as obvious as that sounds, long-term often gets glossed over – particularly during a national election cycle – when "tough problems" (like safety and cost and rationing of care) don’t necessarily support more populist sound-bites like “importation” and “universal coverage.”

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Gray Lady Gives Up the Ghost

04/21/2008 10:37 AM |

Over a year ago the Wall Street Journal published a piece “exposing” that some medical journal articles are – gasp – drafted by professional medical writers and then edited (often heavily so) by the bylined authors before they are published!

 

The New York Times must have missed it, because on Saturday the New York Times ran a very similar article.  All the news that’s fit to print? 

 

Here’s how Stephanie Saul began her article, “The pharmaceutical industry glimpsed its own ghost this week, and the apparition could not have arrived at a worse time for drug makers.”

 

Cute.  Here’s a link to the complete article:

 

www.nytimes.com/2008/04/19/business/19ghost.html

Ms. Saul’s represents only the latest example of the media positioning ANYTHING paid for, promoted, supported, encouraged, approved, or assisted by Big Pharma has BAD. And not just BAD but REALLY BAD. SO BAD, in fact, that it deserves the full evil empire treatment. The “issue” the article is pegged to is the FDA’s brave stance on the free and fair dissemination of scientific data (aka:  journal articles) by pharmaceutical companies to physicians and other audiences. According to Ms. Saul, this controversy (made new again by a report that Merck used ghost writers for journal articles relating to Vioxx) “raised new questions about the validity of many published research studies, even in peer-reviewed publications.”   I thought passive voice was a no-no in journalism?

 

The real question on the table is whether it’s right and appropriate for pharmaceutical companies to be involved in the drafting of medical journal articles that are based on their own studies of their own products.  Hullo?  Okay, let’s try this – how about, is it right and appropriate for pharmaceutical companies to blur the line between marketing and science?  That’s a better question, but it presupposes that all marketing is bad and all science is good. 

 

Let’s pursue that proposition.  Who would think marketing and science make poor bedfellows?  Well, cui bono? Surprise! The people at the front of the anti-marketing, pro-science queue are the editors of our medical journals.  After all, if these self-appointed Sultans of Science cease to be the singular gatekeepers of new scientific information then, quite logically, the world will come to an end.  The canard that ghostwritten articles in any way denigrate the nature of the material is such a transparent and disingenuous attempt on the part of medical journal editors to discredit the pharmaceutical industry that it is (or should be) embarrassing.  It brings into real question the better (Marcia) angels of their nature.

 

Other folks with an agenda here (and who are portrayed in the New York Times story as “advocates”) are those who have a vested interest in not having more expensive drugs available for patient care – aka payers.  And, of course, there’s the mandatory quote from Sid Wolfe.

 

Next time you read an op-ed in your favorite newspaper by a well-known personage consider if a ghostwriter was employed.  Answer:  Probably.  Next time you hear your favorite politician give an address ask yourself if the speaker wrote the speech.  Answer:  Probably not.  And then ask yourself this – does it make a difference?  If the article or the address truly represents the beliefs of the “byline,” then it’s like that TV commercial, “We don’t make a lot of the things you use.  We make a lot of the things you use better.”

 

Me, personally, I’d rather read articles that are well written. I also believe that if the incursion of professional writing assistance makes the articles better, then that’s a good thing because it tends to make dense data more easily understandable.

 

Isn’t that the point? Or is it just me?

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Patents Passion and the Public Health

04/20/2008 03:19 PM |

When it comes to healthcare everyone, it seems, wants to talk about patents.

Congress wants to reform them.

The WHO wants to circumvent them.

Some, such as Bernie Sanders (the Senator from Ben & Jerry's) want to eliminate them.

All concerned address the issue with passion and an interest in improving global public health.

But, even with the best intentions, they're missing the point. We need to focus beyond reforming patent law. We need to rethink the existing system to encourage pharmaceutical innovation (both incremental and discontinuous) in order to realize the potential of the Biomedical Century.

And not just in the US -- but globally.

The solution isn't exclsively patent reform -- that's too narrow. We need to consider new strategies that enhance and protect intellectual property rights. What we need to seriously study -- and transnationally -- is the issue of data exclusivity.

There are some numbers that are too important to ignore. Today it takes about 10,000 new molocules to produce 1 FDA-approved medicine. And if that's not frightening enough, only 3 out of 10 new medicines earn back their research and development costs. And here's the kicker -- unlike other R&D-intensive industries, pharmaceutical investments generally must be sustained for over two decades before the few that make it can generate any profit.

Current patent life just doesn't cut it. Not in the US. Not in the EU. And certainly not via TRIPS.

If we don't think seriously about moving away from patent reform and towards more robust protection of data exclusivity we are going to seriously jeopardize the potential for new medicines -- at a time when science makes potential breakthroughs tantalizingly close.

Do we really want promising compounds abandoned because of awkwardly crafted and inconsistent (read "unpredictable") patent terms?

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The Critical Path to Safer Drugs

04/18/2008 09:47 AM |

Robert Goldberg

Ray Woosley's pioneering collaboration with the FDA to move drug safety in to the 21st century are paying off...Let's see who objects...

From the San Francisco Chronicle....

The Food and Drug Administration is poised to throw its support behind a powerful new method of predicting the safety of experimental drugs, a step that could help pharmaceutical companies bring treatments to market more quickly - and reduce patients' risk.

The process being considered uses seven indicators - known as biomarkers - that signal kidney injury when found in the urine of test subjects.

"Today, the FDA gives approval for a new drug or device, but there has previously been no way to obtain approval for a new and better way to test a drug for its safety," said Raymond Woosley, president and CEO of the nonprofit Critical Path Institute, which is working with the FDA to safely speed drug development.

Currently, experimental drugs are tested in animals before being taken to human clinical trails. But animals' reactions aren't always the best predictor of whether substances will be safe for humans. Drugs harmless to animals can hurt humans, and vice versa. If a drug toxic to the kidneys passes animal tests today, the damage might not show up until it is too late.

"Using current tests, you have lost about 70 percent of the kidney function before you pick it up," says William Mattes, director of toxicology at the Critical Path Institute in Tucson.

The new biomarker process has the potential to save a patient's kidneys.

The ultimate goal of the pharmaceutical industry is to have a range of such marker tests that would signal dangerous side effects like heart failure, liver damage or cancer. Samples of blood, urine or saliva, for example, would be taken from participants in a clinical trial. If certain biomarkers indicated the patient was at risk, the trial could be stopped before any major damage occurs.
Seventeen companies have joined the research into biomarkers at the Critical Path Institute. These include giants like Bristol- Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck and Co. and Pfizer. The companies contribute their expertise but, according to Woosley, the institute does not accept commercial funding.

Initially, the seven biomarker testing processes will be qualified by the FDA for use in preclinical animal studies, and only as a complement to current tests.

"This qualification process allows the industry to have an accurate view of the application of these biomarkers in drug development. They are not replacing anything that is done today. But the goal, as we gather more and more information, is to eventually be able to include them in clinical trials," said Federico Goodsaid, senior staff scientist at the genomics group at the FDA Office of Clinical Pharmacology.

Goodsaid is responsible for the development of the FDA's biomarker qualification pilot process, which began about a year ago when 23 potential biomarkers for kidney damage were submitted to the federal agency. The evaluation process at the Critical Path Institute has since selected the seven most efficient ones.

Named for the risky period when a drug is taken from the preclinical stage into clinical trials, the Critical Path Institute was founded two years ago by the FDA in collaboration with University of Arizona and Menlo Park's SRI International to break a worrying trend within the pharmaceutical industry: In the past decade the number of innovative therapies submitted for FDA approval dropped by 50 percent, but the cost of drug development increased dramatically.

Meanwhile, scares like the one associated with the painkiller Vioxx, which turned out to cause heart attacks and strokes, have further fueled this trend.

Unique for the Critical Path Institute is that FDA is a cofounder. Today, the European Medicines Agency - an agency similar to the FDA - also participates as an adviser. The agency is expected to qualify the seven biomarker testing method simultaneously with FDA.

"This is the first time they have coordinated their decisions," Mattes said.

Sidney Wolfe, director of the health research group at Public Citizen, a nonprofit public interest organization, supports the use of biomarkers as long as they are properly validated. But he is critical of the FDA's attitude toward present drug safety tests.
"Findings of toxicity in the currently required animal tests are not taken seriously enough by companies or by the FDA," Wolfe said.
He cites two recent examples of drugs in trouble, both of which showed toxicity in laboratory animals: the diabetes drug Avandia from GlaxoSmithKline and Vytorin from Schering-Plough and Merck, a cholesterol-lowering medication.

"Avandia showed evidence of heart damage in animal studies and, for Vytorin, tests showed serious toxicity in laboratory animals, regardless of how low a dose of this combination drug was used," says Wolfe.

The official announcement of the qualification of the seven biomarkers for kidney injury is expected from the FDA any day.
"It is in a very advanced stage of that process," Goodsaid said. "We should have some news soon."

Posted by Robert Goldberg on April 17, 2008 4:40 PM   Read More & Comment...

McCain Straight Talk On Health Care

04/18/2008 09:45 AM |

Robert Goldberg

From his speech in Pittsburgh...

Americans also worry about stagnant wages, which are caused in part by the rising cost of health care. Each year employers pay more and more for insurance, leaving less and less to pay their employees. As president, I will propose and relentlessly advocate changes that will bring down health care costs, make health care more affordable and accessible, help individuals and families buy their health insurance with generous tax credits, and enable you to keep your insurance when you change jobs.

Many retired Americans face the terrible reality of deciding whether to buy food, pay rent or buy their prescriptions. And their government should help them. But when we added the prescription drug benefit to Medicare, a new and costly entitlement, we included many people who are more than capable of purchasing their own medicine without assistance from taxpayers who struggle to purchase their own. People like Bill Gates and Warren Buffet don't need their prescriptions underwritten by taxpayers. Those who can afford to buy their own prescription drugs should be expected to do so. This reform alone will save billions of dollars that could be returned to taxpayers or put to better use.

Posted by Robert Goldberg on April 17, 2008 4:21 PM  Read More & Comment...

Slamma JAMA

04/18/2008 09:43 AM |

Peter Pitts

What ever happened to dialogue and ... ethics?

In it's reporting/editorializing on the recent "what-did-Merck-know-and-when-did-it-know-it" saga, JAMA accuses some pretty high-powered healthcare professionals of shilling for shillings.

Now it comes to light that the folks JAMA denounced weren't even given the chance by the Sultans of Science to defend themselves.
Here's what the Washington Post says,

"Although the two studies question the integrity of dozens of physicians and scientists, the JAMA authors did not seek responses from them. Several of those people yesterday called the conclusions incorrect, incomplete or unfair."

Don't "real" journalists" seek out both sides of the story? Don't real scientists?

Posted by Peter Pitts on April 17, 2008 7:15 AM  Read More & Comment...