Friday reading

07/22/2011 12:35 PM |

More here.

  Read More & Comment...

FDA Diabetes Advisors Wimp Out

07/20/2011 08:00 PM |

A drug that reduces blood suger by removing through the urine would be huge. 

But FDA advisors are too scared about the possible risks of the drugs to allow diabetics and doctors to see how they work in the real world.

"Several committee members said they could have voted either way.

“I changed my mind about four times in the last 10 seconds,” said Erica H. Brittain, a statistician at the National Institutes of Health who voted no. "

The fate of a new drug should be  decided by FDA's Hamlets?


 

The biggest safety concern was that in clinical trials, patients who got the drug were more likely to develop breast and bladder cancers than those in the control groups.

About 0.4 percent of women taking the drug got breast cancer, compared with 0.1 percent of the women in the control groups. About 0.3 percent of men getting the drug got bladder cancer, compared with about 0.05 percent of men in the control groups.

The numbers were very small, however, making it hard to draw definitive conclusions. Bristol-Myers and AstraZeneca argued that many of the cancers occurred too soon to have been caused by the drugs."

And get this:

"The committee members agreed that more study of the possible cancer risks and other safety questions would be needed. Those who voted no mainly believed that the studies needed to be done before approval, even though that might delay approval by years. "

How many people will die from diabetes related complications because this medicine is not approved in order to organize trials that will likely never resolve the issue? 

This is pathetic. The advisory committee members are being haunted by the ghost of Steve Nissen.

www.nytimes.com/2011/07/20/business/diabetes-drug-dapagliflozin-rejected-by-fda-panel.html  Read More & Comment...

Total Eclipse of Baltimore Sun By Anti-Vax Stupidity

07/19/2011 05:19 PM |

The Baltimore Sun has become a safe haven for anti-vax pseudo science and it's lethal stupidity.   And it does so by repeating the cardinal sin of most science or health care reporters: treating conspiracy driven theories (consisting of  an alleged link between alleged harms  and the profit-driven actions and products of BIG PHARMA.)  as scientific as, well, real science without demanding to see any scientific proof of said theory.  And by proof I mean real science: hard evidence that biological mechanisms alleged to trigger alleged harms can be shown to cause said  harms.  

Stephen Salzburg, who runs genomic research at the University of Maryland scores a direct hit on the Sun and the quacks whose crap it published in Fighting Pseudoscience

I also wrote a letter to Michael Cross-Barnet who is in charge of op-Eds at the Sun.  Here it is in the likely case they don't print my piece:

The Baltimore Sun published two articles that ignore the scientific evidence about the importance and safety of evidence-based vaccination and then make discredited claims about how to make vaccines and immunization safer.   It should be ashamed of itself for doing so.

Medical science is not a he-said, she-said process.  It is an incremental process of proving and disproving hypothesis based on biological evidence established through experimentation.   When facts don’t fit a theory or an assertion, it’s the latter that is wrong.  

By giving two pseudo-scientists, Margaret Dunkel and Mark Geier, access to it’s press, the Sun has legitimized misleading and dangerous claims about vaccine safety and about the role vaccines play in causing all sorts of childhood disorders, particularly autism.  It perpetuates assertions that contribute to the rise of vaccine preventable diseases such as measles, whooping cough and cervical cancer.  And it has legitimized the idea that wild claims about a product causing autism are “science” even if such claims have never been proven scientifically or have been disproven.   To the Sun, just raising the possibility of danger is enough to merit publication. 

I will not restate the scientific evidence about the significant benefits and incredibly small risks associated with vaccines.  One can read Stephen Salzberg’s editorial in Forbes for a concise discussion. 

http://blogs.forbes.com/stevensalzberg/2011/07/17/the-baltimore-sun-sinks-deep-into-anti-vaccination-quicksand/

The problem is not with the Geiers and Dunkels of the world who peddle their conspiracy theories and lethal prescriptions for assuring vaccine safety.   The problem is with newspapers, new shows and politicians who promote fearmongering.  

Would the Sun allow those ‘scholars’ who deny the Holocaust or claim astronauts never landed on the moon access to its editorial page?  Both types of conspiracy driven twaddle exist in spite of the facts, not because of them.  Yet the Sun, in giving Geier and Dunkel a platform, has given the scientific equivalent of Holocaust denialism legitimacy and renewed strength.  

In so doing, it has shamed itself and empowered quacks to endanger the lives of children.

 

 

  Read More & Comment...

Apres Josh, le deluge

07/19/2011 01:52 AM |

But in a good way.

 

Learn more about it via an excellent analysis in this week’s edition of BiocCentury which begins thus:

 

FDA organizational changes and personnel appointments announced last week could help depoliticize the agency’s decision making, increase its understanding of the way industry operates, and, possibly, improve coordination of drug, biologics and device oversight.

 

The reorganization, which was set in motion by the January departure of Joshua Sharfstein as principal deputy commissioner, also could deepen the bench of managerial talent at an agency that has traditionally valued technical competence over management skills. Radiological Health (CDRH), and the Center for Tobacco Products.

 

In a memo to FDA staff, Hamburg said one of her goals is to “enable the Office of the Commissioner to better support the agency’s core scientific and regulatory functions, and help tie together programs that share regulatory and scientific foundations.”

The complete article can be found here.

  Read More & Comment...

Brooks was here

07/18/2011 05:06 PM |

From Sunday’s Washington Post:

David Brooks: The scary and sloppy case for rationing

By Jennifer Rubin

 

David Brooks of the New York Times likes to fancy himself as a truth-seeker, bringing social and hard sciences to the masses. But in his Friday column on health care and death, he makes some shocking and inaccurate assertions. Given his coziness with the Obama administration one has to wonder if he is test-driving some Obama administration rationalizations for rationing.

 

Brooks is enamored of Dudley Clendinen’s “splendid” essay, as he describes, “The Good Short Life.” Brooks thrills to this definition of a life worth living:

 

Instead of choosing that long, dehumanizing, expensive course, Clendinen has decided to face death as one of life’s “most absorbing thrills and challenges.” He concludes: “When the music stops — when I can’t tie my bow tie, tell a funny story, walk my dog, talk with Whitney, kiss someone special, or tap out lines like this — I’ll know that Life is over. It’s time to be gone.”

Well that “dehumanizing, expensive course” allows millions of Americans who would have died in past years to “kiss someone special.” But is someone confined to a wheelchair (no dog walking) or who needs help dressing not living a life of value? Clendinen, and in turn Brooks, begin down a slippery slope as they decide that, really, is it worth it to keep grandpa around for years if he can’t tie his tie?

 

Brooks then embarks on a flight of misinformation to suggest we’re wasting much of that money. He finds other useful sources:

 

As Daniel Callahan and Sherwin B. Nuland point out in an essay in The New Republic called “The Quagmire,” our health care spending and innovation are not leading us toward a limitless extension of a good life. Callahan, a co-founder of the Hastings Center, the bioethics research institution, and Nuland, a retired clinical professor of surgery at Yale, point out that more than a generation after Richard Nixon declared the “War on Cancer” in 1971, we remain far from a cure. Despite recent gains, there is no cure on the horizon for heart disease or stroke. A panel at the National Institutes of Health recently concluded that little progress had been made toward finding ways to delay Alzheimer’s disease.

Much of this is flat-out wrong or misleading. We may not have “cured” all cancers (Brooks is misinformed if he thinks “cancer” is one disease). But survival rates for many types of cancer have soared, especially for breast, prostate and lung cancer. Five-year survival rates for the range of cancers went from 50.1 percent to 65.9 percent in 2000. Peter Pitts of the Center in the Public Interest told me in a phone interview that for many cancers ”early detection and aggressive treatment” can now extend life or result in effective “cures,” that is long-term remission.

 

A recent report from the Center for Disease and Prevention control explained:

As a result of advances in early detection and treatment, cancer has become a curable disease for some and a chronic illness for others; persons living with a history of cancer are now described as cancer survivors rather than cancer victims . From 1971 to 2001, the number of cancer survivors in the United States increased from 3.0 million to 9.8 million … The number of cancer survivors increased from 9.8 million in 2001 to 11.7 million in 2007. Breast, prostate, and colorectal cancers were the most common types of cancer among survivors, accounting for 51% of diagnoses. As of January 1, 2007, an estimated 64.8% of cancer survivors had lived 5 years after their diagnosis of cancer, and 59.5% of survivors were aged 65 years. Because many cancer survivors live long after diagnosis and the U.S. population is aging, the number of persons living with a history of cancer is expected to continue to increase.

In other words, in just six years the number of cancer survivors increased nearly 20 percent. Interestingly, women and seniors have benefited the most. “Women are more likely to be survivors because cancers among women (e.g., breast or cervical cancer) usually occur at a younger age and can be detected early and treated successfully; in addition, women have a longer life expectancy than men. Among men, a substantial number of cancer survivors had prostate cancer, which is diagnosed more commonly among older men. The large proportion of cancer survivors aged 65 years reflects the increase in cancer risk with age and the fact that more persons with diagnoses of cancer are surviving 5 years.” Put differently, millions more Americans are alive because of progress in cancer research and treatment. I don’t know how one would put a price on the value of lives saved, the contributions those survivors continued to make to society and the children they gave birth to and raised.

 

Brooks likewise bizarrely claims that there is no “cure” for a heart attack. He surely picked the worse example possible. A heart attack used to be a death sentence or a recipe for permanent convalescence. Now with the advent of beta-blockers, new medical technology and surgical innovations survival rates have risen dramatically. (Researchers, for example, found “rates [of in-hospital mortality] decreased among all patients from 1994 to 2006, falling more markedly in women than men. The steepest drop, 52.9%, occurred among women younger than 55. The mortality rate for men in the same age group decreased by 33.3%.)

Alzheimer’s hasn’t been cured, but drugs to slow the rate of deterioration provide building blocks needed for continued progress. For diabetes the results are stunning. (“People diagnosed with diabetes between 1965 and 1980 lived approximately 15 years longer than those diagnosed between 1950 and 1964 (53.4 years vs. 68.8 years).

 

Brooks, Pitts says, makes a fundamental error by setting up “cures” as the metric for assessing medical progress. “It is well-established that innovation in health care comes in incremental steps,” he explains. With increasingly personalized treatment made possible by genetic research the type and timing of drugs can be designed for optimal results. If we don’t spend money to make progress that might, for example, slow the rate of Alzheimer’s we’re not going to invest millions in one fell swoop to locate the “cure.” Pitts says, “If you don’t reward innovation,” by funding the painstaking process of step-by-step research we will cease making progress toward long-term survival rates and cures, a result that is not morally or politically acceptable in this country. He observes, “The average American male’s life expectancy has increased by a decade over the last 50 years, largely to due pharmaceuticals. We innovated our way to that.”

 

Moreover, Brooks ignores diseases such as AIDS, once a death sentence, that is now, albeit by use of expensive drugs, a manageable, chronic disease. Should we not have spent the money? Pitts, noting the dramatic improvements in drugs to treat mental illness, explains that millions of people in the past were never treated at all. “Now people with depression are functioning beautifully.”

 

Brooks says, “Most of us will still suffer from chronic diseases for years near the end of life, and then die slowly.” True, but the alternative is more dead people.

Brooks in the end doesn’t have the nerve to reach the logical conclusion of his arguments. He declares, “Obviously, we are never going to cut off Alzheimer’s patients and leave them out on a hillside. We are never coercively going to give up on the old and ailing. ” Well, then what is the point of his column? If he can’t stomach these outcomes why shouldn’t we continue to spend substantial sums to improve and elongate life?

 

Perhaps the point is to rationalize reductions in health-care dollars spent on the elderly, which by gosh is precisely what the Obama administration is trying to pull off with its Independent Advisory Patient Board. Limiting care, conscience free! After all, do all these old people really enjoy living to 90?

 

By all means we should have the debate over public and private resources. Let’s come up with market solutions that increase competition and reduce cost. Let’s minimize out unnecessary, external costs (e.g. malpractice insurance). And for the record, I am in favor of living wills and allowing those with terminal illnesses to refuse care. But let’s not kid ourselves.

 

Anyone, for example, who has had an elderly parent, a friend with cancer, or an experience with mental illness knows the difference our health-care system, warts and all, has made in the lives of millions and millions of Americans. Who of us would choose to receive only the medical care available 20 years ago? And, from where I sit, I’m not ready to throw in the towel on my loved ones (or anyone else’s) because they can’t walk the dog.

  Read More & Comment...

New thinking on NCDs - CMPI’s first international event

07/15/2011 11:46 AM |

  Read More & Comment...

WSJ's TM Trance

07/14/2011 11:42 AM |

Back in college, I went to a Transcendental Meditation Center, partly out of genuine interest but mainly because a girl I was interested in was going.

 

TM was touted as a technique for achieving inner peace back in the day.   I remember having to bring some flowers and fruit as an “offering” to a photograph of the Maharishi Yogi, the founder of the TM movement.  My mantra instructor (I guess that’s the term) -- a guy in a linen outfit and wire-rimmed glasses – had me kneel in front of the Yogi’s photo while he chanted and threw grains of rice at the picture.   Though I was a relatively non-observant Jew then I found the ceremony silly.  But not as silly as the claim that if I shared my mantra (ha-yam, not to be confused with Chaim or ham) with anyone it would stop working.   And of course my instructor encouraged me to sign up for some lifetime plan of mantra and TM coaching.   All that notwithstanding I did find TM helped distract and relax me.  But so did taking a nap.

 

Which leads me to a recent Wall Street Journal op-ed by director David Lynch and TM executive Norman Rosenthal: A Transcendental Cure for Post-Traumatic Stress - Wall Street Journal

 

Now claiming that TM cures soldiers with PTSD is rather audacious, especially since there is no science to back it up.   A five patient study without a control arm is not science, it is a TM retreat.   What’s more the authors claim that TM “has been found to reduce blood pressure and decrease the risk of heart attacks and strokes—other conditions in which an overactive fight-or-flight response may play a role. In a similar manner, TM may modulate nervous system responses, thereby allowing affected veterans to relax and leave behind the traumas of war.”

 

Let’s set aside the fact that the Maharishi University School of Management or TM adherents have mostly conducted the studies supporting TM’s benefits.   The research about TM as a medical treatment or “cure” is limited and conflicting.  As one review of TM’s cure claims found “ “15 trials comparing relaxation with sham therapy found a non-significant reducing in blood pressure. “   There are only small studies looking at TM’s benefit.  Even those that monitor brain function, never establish whether it’s aspects of the TM regimen or TM itself that may help people cope to PTSD, substance abuse and depression. TM is never compared to sleep for instance.  Indeed, there are other mindfulness meditation or therapy approaches that have been better studied and have shown to be beneficial.    

I believe that TM and other mindfulness modalities do help some people to the extent that they engage in it on a regular basis.  But Dr. Rosenthal is plugging a book extolling the value of TM as a cure.  He also claims TM is superior to all other forms of mindfulness-based therapies.   There is no science to back these claims up.  Rosenthal also happens to promote the kind of long term personalized sessions the TM rice thrower wanted me to sign up for when I was in college.  

 

I don’t get how the WSJ not only allowed the publication of what is essentially free advertising to Dr. Rosenthal but also promoted TM as a cure for PTSD.   Maybe the editors of the editorial page should meditate on that. 

Om.

 

  Read More & Comment...

Asked and Answered

07/14/2011 11:08 AM |

A Drugwonks reader writes (relative to the recent Pew report on FDA's need for more authority for overseas inspections and related matters):

There is another answer here.  Section 801 of the FDCA, which has been revised recently to reflect the global reality, establishes an algorithm for FDA review of imports that priorities scarce resources according to product type, existence (or not) of registration, and other factors.  The provision even addresses importation in cases of medical emergency and personal-use importation.  It reflects careful attention from Congress – and makes clear that products originating ex-US get heightened scrutiny precisely because they’re not coming from inspected facilities.  Asked and answered, people.  Or should I say “by the people.”
  Read More & Comment...

Drug Importation? Pew!

07/14/2011 10:34 AM |

Did somebody say “drug importation?”

Didn’t think so.

According to the Pew Health Group, the FDA needs much more power to protect the U.S. supply of drugs as more and more are made in other countries.

 

The new study found that increased outsourcing of manufacturing, a complex and globalized supply chain, and criminals all help to create the potential for counterfeit or substandard drugs to reach patients.

 

Well, duh – but important to regularly reinforce.

 

 “It is clear the FDA was set up to deal with a domestic industry,” Allan Coukell, the director of medical programs at Pew Health Group, told National Journal. “But drugs are increasingly manufactured globally and are outside of the oversight of the FDA. There is a real need to update legislation to reflect the realities of the industry.”

 

The FDA is bound by a 1938 law that only gives the agency the authority to inspect products manufactured in the United States. “There’s only so much the FDA can do under the current law,” FDA Office of Compliance Director Deborah Autor said in a statement.  

 

As Peggy Hamburg said at a recent meeting of the Council on Foreign Relations:

* The new reality of food and drug regulation is that it’s global. In fact, it should be a topic for conversation at the next meeting of the G20.

* The recent crises in both food and drug safety will only repeat themselves unless regulatory agencies from around the world work in closer and more regular partnership.

* There is a responsibility on the part of the FDA and other more developed regulatory agencies around the world to help build “regulatory capacity” for those nation’s that want and need assistance.

* Part of a closer working relationship means a more regular and robust sharing of global intelligence on issues of counterfeiting.

* And lastly, “We can’t inspect our way out of this problem."

All good things – progressive things -- but, short of a regulatory Marshall Plan, things that will have to rely (at least initially) on personal relationships between senior officials at various regulatory agencies and a focus on what’s best for global public health writ large is convergent with what’s best for any given nation.

It’s not as easy as it sounds.

  Read More & Comment...

Deck Chairs or Decisiveness?

07/13/2011 05:43 PM |

And now a message from Peggy Hamburg:

Dear Colleagues,

I am writing today to let you know about some changes that I will be making to the agency’s management structure. As you probably recall, back in January, I told you that I was initiating a review of the Office of the Commissioner.  As I explained at that time, this review was driven by the expanding and rapidly changing nature of the Agency’s responsibilities, and the need for a management structure that reflects these changes and best supports your efforts. 

I consulted with former Commissioners, as well as with HHS Secretary Sebelius, and considered many options before arriving at the structure that I am announcing today.

The most important thing driving my consideration of this is the changing nature of both the Agency and the job of Commissioner.

Today, the Agency faces several key challenges: 

First, we are a very large agency, with an incredibly broad span of responsibility.  We regulate products that account for between 20 and 25 percent of every consumer dollar spent in the U.S. and that total more than a trillion dollars annually.  For the most part, these are products that people rely on in fundamental ways every day.

Second, as technology and science continue to evolve, we are faced with the challenge of making sure that new ideas translate into the products and opportunities that people need and count on to protect their health.   Innovative products that are truly transformative create unique scientific and regulatory challenges, and FDA must be a consistently powerful catalyst for innovation.

Third, we have seen the dramatic transformation of globalization – more products, more countries, more access by consumers and companies to global supplies – and this presents an enormous challenge to FDA in ensuring the safety and quality of the products we regulate.

Finally, we continue to be faced with administrative challenges.  In these difficult economic times, our agency’s budget requires constant attention.  And, simply providing the support and services for our 12,000 plus employees – everything from phones to IT to office space on our beautiful, growing White Oak campus – is a daunting job.

I take very seriously my responsibility to lead FDA along a path that will meet these challenges.  One crucial part of this responsibility is to create a structure in the Commissioner’s Office that best supports your efforts and reflects the changing nature of the Agency. 

The structure of the Office of the Commissioner that I inherited was created in 1970, when the FDA consisted of three Centers and a field office.  By 2011, we had grown to seven Centers, and a Commissioner’s Office with more than 1,600 staff.  Over the years, as Congress created new programs that cut across Center responsibilities, those programs were placed by default in the Office of the Commissioner. 

The new organizational alignments more accurately reflect the agency’s responsibilities, subject matter expertise and mandates in an ever more complex world, where products and services do not fit into a single category.

Let me begin by saying that, for most of the FDA, this organizational alignment will likely not have a significant impact on you or your day-to-day work. 

The most obvious change you will see is that the Agency’s programs, in terms of a reporting chain to me, will be divided into “directorates” that reflect the core functions and responsibilities of the Agency. This new management structure will enable the Office of the Commissioner to better support the agency’s core scientific and regulatory functions, and help tie together programs that share regulatory and scientific foundations.  I will rely on the leadership of these directorates to help provide the necessary direction and coordination needed by an Agency of this scope.

I am establishing a new Deputy Commissioner for Medical Products and Tobacco, who will provide high-level coordination and leadership across the Centers for drug, biologics, medical devices, and tobacco products.  The Centers will, of course, remain as discrete management entities under their current expert leadership.  In addition to this strategic role with the Centers, this position will oversee our Special Medical programs. 

I am pleased to announce that Dr. Steven Spielberg, former Dean of Dartmouth Medical School and currently Director of the Center for Personalized Medicine and Therapeutic Innovation at Children’s Mercy Hospital in Kansas City, has accepted this position. In this role, Dr. Spielberg will serve as both advocate and a support for Center Directors in their important work for FDA.  

 I will also be creating a directorate focused on grappling with the truly global nature of today’s world -- food and drug production and supply, as well as the science that undergirds the products we regulate -- so that the FDA can move from being a regulator of domestic products to one overseeing a worldwide enterprise.  

To oversee this transformation, I have asked Deborah Autor, now Director of CDER’s Office of Compliance, to take on the role of Deputy Commissioner for Global Regulatory Operations and Policy.  In this position, Deb will provide broad direction and support to the Office of Regulatory Affairs and to the Office of International Programs, with a mandate from me to make response to the challenges of globalization and import safety a top priority in the years to come. Dr. Murray Lumpkin, who has served with dedication and accomplishment as Deputy Commissioner for International Programs and Director of the Office of International Programs, will take on a new role as Senior Advisor and Representative for Global Issues.  In this role, he will be charged primarily with special projects that draw on his expertise working with counterpart regulatory agencies on issues of global regulatory harmonization, governance and capacity-building.

The third directorate is the previously established Office of Foods, which we created to make our oversight of FDA’s food and feed program a more seamless enterprise. That task is even more important today as Mike Taylor leads the implementation of the Food Safety Modernization Act.

The fourth directorate will be a new Office of Operations, headed by a Chief Operating Officer.  The COO will oversee the agency’s administrative functions, such as human resources, facilities, information technology, finance, and other activities that provide support to your organizations.  Within this Office, I am bringing the budget formulation and budget execution functions together under a CFO position.  We have initiated a search to fill the Chief Operating Officer position.

The Office of the Chief Scientist, charged with our important efforts to improve FDA’s science and address issues of cross-cutting scientific concern, will continue to do so. The National Center for Toxicological Research will report to the Chief Scientist, Dr. Jesse Goodman, and, like the other Centers, will remain a discrete management entity within this new directorate model.

Within the new, smaller, immediate office of the Commissioner, John Taylor will remain as Counselor and will have the additional responsibility to oversee the policy and planning functions, the Office of Legislation, and the Office of External Affairs. I want to thank John for serving as acting Principal Deputy these past months, in addition to his duties as Counselor.  He has tirelessly supported me and the Agency with enthusiasm, energy, expertise, and good humor.

You can find revised organizational charts, reflecting this realignment here. In addition, I will share a video message of this announcement shortly.  Your managers will be available to answer any questions you might have in the coming days.

In closing, I want to take a moment to thank you so much for all that you do.  FDA is an extraordinary place, with so many highly-dedicated professionals and support staff who are committed to promoting and protecting public health. You accomplish a tremendous amount every day and I am grateful for all of your work. These organizational changes are intended to help further your important work and the mission of this remarkable Agency.

Sincerely,

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs

  Read More & Comment...

Avastingate Redux

07/13/2011 01:00 PM |

A first test of whether the drive to require larger numbers of patients enrolled in clinical trials to measure overall survival as an endpoint (rather than progression free survival) in the wake of FDA's Avastingate is due this week:

"Seattle Genetics Inc. (SGEN) and Takeda Pharmaceutical Co.’s drug brentuximab for Hodgkin’s lymphoma and a less common type of the disease may require more data on benefits compared with treatments already on the market, U.S. regulators said.

The Food and Drug Administration is trying to determine whether the experimental treatment given the trade name Adcetris should receive accelerated approval in an agency staff report released today. An FDA panel of outside advisers on July 14 will weigh applications for the medicine to treat anaplastic large cell lymphoma and Hodgkin’s lymphoma.

The agency is seeking more patient data to be able to weigh more clearly the drug’s benefits. The FDA may decide whether to approve by Aug. 30. The experimental treatment could generate peak sales of $850 million in 2020, according to a note last month from Rachel McMinn, a research analyst with Bank of America Merrill Lynch.

“Small size limits the benefit-risk analysis,” the FDA said in questions to outside advisers released with its report. “For this application, consideration for accelerated approval would be consistent with regulatory actions taken in the past decade for similar hematology applications based on single arm clinical trials.”

We know what that might mean for cancer patients in Pazdur-land. 

Meanwhile as I blogged a couple of weeks ago, the Kevorkian Center for FDA Reform run by Harvard's resident anti-innovation scold Jerry "Use My Academic Detailing Without Evidence of Improved Outcomes" Avorn is pushing for longer and larger studies that would run small firms like Seattle Genetics into bankruptcy...

You can read Avorn and his colleague Aaron Kesselheim's blueprint to ration innovations by expanding clinical trials here:

Characteristics of Clinical Trials to Support Approval of Orphan ...

  Read More & Comment...

Liz and other biz

07/13/2011 09:26 AM |

As reporter in BioCentury, HHS will appoint Elizabeth Dickinson as acting FDA chief counsel, effective Aug. 8, according to an internal memo from acting HHS General Counsel William Schultz. Dickinson, who has been at FDA's Office of Chief Counsel since 1994, will replace Ralph Tyler, who is departing. The memo noted that HHS plans to convert the chief counsel position into a career job; currently, it is filled via political appointment.

And on a more therapeutically personalized note, FDA released draft guidance on the development of in vitro companion diagnostics. The document clarifies FDA's definition of a companion diagnostic, reiterates the agency's intention to conduct simultaneous reviews of a product with its companion diagnostic, and identifies situations where the agency may approve a targeted product in the absence of an approved companion diagnostic. However, the guidance does not address the design or conduct of clinical trials of products in combination with companion diagnostics.

FDA defines a companion diagnostic as a device that provides information essential for the safe and effective use of a corresponding therapeutic. The agency added that the definition does not include clinical laboratory tests intended to provide "useful" information where that information is not a determining factor in the safe and effective use of a therapeutic.

The guidance notes that product labeling should only identify a type of approved companion diagnostic device, rather than a specific manufacturer's device. FDA said this will facilitate the development and use of more than one approved diagnostic of the type described in the companion product's label. Comments are due 60 days after publication in the Federal Register, which is expected Thursday.

  Read More & Comment...

Innovation Reborn

07/12/2011 03:34 PM |

Janet Woodcock gave an excellent overview of the resurgence in novel treatments getting the FDA approval.   The years of effort to validate drug targets based on disease mechanisms is now yielding important, first in class products are paying off.  There is still a lot of room for increased productivity, particularly in the area of orphan drug development and molecular diagnostics.  But it is clear that the model of development Dr. Woodcock envisioned when she lead the Critical Path Initiative is paying off.

Imagine what industry and the FDA could do if it expanded on that model by creating more Critical Path Institutes, for example. 

And imagine how these breakthrough products will languish if CER holds up or delays access. 

You can read Dr. Woodcock's testimony here:

Testimony of Dr. Janet Woodcock, July 7, 2011
  Read More & Comment...

Taking a shot at misinformation

07/12/2011 08:07 AM |

From the op-ed pages of the Baltimore Sun:

Vaccine safety: Misinformation about vaccine risks is making us less safe

By Sandeep Rao

Last month, the Maryland Department of Health and Mental Hygiene reported the first case of measles in the state since 2009.

This development demonstrates that even Maryland, which has one of the highest vaccination rates in the U.S., is not immune to a larger trend facing the nation. This past year, the U.S. has seen the largest increase in measles cases in almost two decades, according to the U.S. Centers for Disease Control and Prevention. The rise in measles cases over the first half of this year is double the rate typically seen compared with previous years.

Most of those diagnosed with the disease did not receive the measles, mumps, and rubella (MMR) vaccine.

In the U.S., most children receive the MMR vaccine series by age 2. Of those patients diagnosed with measles, most survive; however, fatal brain and lung complications can occur.

A survey released earlier this month by the CDC showed almost 80 percent of parents are uncomfortable with the concept of childhood vaccination. Among the reasons provided, roughly 30 percent cited the potential for learning disabilities, such as autism, for their hesitation to vaccinate.

Some of the fear of vaccination is driven by disease-driven litigation tied to junk science.

The landmark research linking the MMR vaccine to autism was initially published in 1998 by Dr. Andrew Wakefield in the Lancet, a respected British medical journal. Other researchers' inability to replicate his findings spawned further investigation. Subsequent inquiry into Dr. Wakefield's research demonstrated that his subjects were recruited by a plaintiff's lawyer preparing a lawsuit against vaccine manufacturers.

Additionally, not only had Dr. Wakefield received payment from these attorneys two years prior to initiating his research study, but he also had a patent application for a rival measles vaccine. In addition to the numerous conflicts of interest, Dr. Wakefield's research was also found laden with altered data. Finally, the Lancet took the unprecedented step of retracting the original published peer-reviewed article.

The best medical research suggests no link between vaccination and autism. Nonetheless, the absence of data has not stopped families from pursuing their claims of disability through available legal channels.

Lawyers intent on creating a mini-industry out of lawsuits against vaccine makers have threatened the supply of vaccines to the American public. Many drug companies in the U.S. were pushed out of the vaccine business in the 1980s from large settlements related to whooping cough-tetanus-diphtheria (DTP) vaccine reaction lawsuits. In response, Congress in 1986 created an alternate legal system of "vaccine courts," compensating patients financially based on known vaccine-related side effects. Payments on the judgments of these tribunals are funded by a tax levied on each vaccine.

Despite the lack of solid research confirming a causal link between vaccines and autism, there are petitions from more than 5,000 families pending before the courts, arguing otherwise. However, as per the common scientific axiom, the plural of "anecdote" is not "data."

In February, the Supreme Court heard a challenge to the legality of the federal law that created this no fault, nonjuried tribunal system, which shields drug companies from product liability lawsuits. In a 6-2 decision, the court reaffirmed the success of these vaccine courts, whose judgments are based on known science rather than fickle juries, which are often swayed by personal stories of hardship.

Writing in the majority opinion, Justice Antonin Scalia found the law "reflects a sensible choice to leave complex epidemiological judgments about vaccine design to the [Food and Drug Administration] and the National Vaccine Program rather than juries."

While scientifically baseless claims of disability have no weight in these courts, they have had a monumental effect on the lay public.

The response following Dr. Wakefield's initial study in the United Kingdom was palpable. MMR vaccination rates in Britain dropped from 92 percent in 1996 to 84 percent by 2002. Measles and mumps cases subsequently grew at rates tenfold to thirtyfold compared with periods prior to the study. A decade of suboptimal levels of vaccination in the U.K. has now compromised herd immunity to measles, (that is, the immunity gained by an individual susceptible to a disease through the critical mass of the surrounding immunized community).

According to the UK Health Protection Agency, their equivalent to the CDC, the U.K. now faces endemic levels of measles within its population, allowing for the continuous spread of the disease.

In a viral age, the persistence and prevalence of vaccine misinformation among the public may take some time to correct. However, regaining the health protection afforded by effective vaccination programs will take longer.

Dr. Sandeep Rao is a fellow at Johns Hopkins Hospital. His email is srao28@jhmi.edu.

  Read More & Comment...

Drop and give me 20

07/11/2011 10:01 AM |

FDA currently is approving two-thirds of critical drugs in the first review cycle, CDER Director Janet Woodcock told the House Energy and Commerce Health Subcommittee July 7, disputing complaints that the agency's approval process is stifling innovation and capital investment in the pharmaceutical industry.

FDA approved 20 new medications during the first half of 2011, one shy of the 21 approved in all of 2010, she added.

(True, but FDA approves about 60% of priority reviews within a single review cycle -- by pulling staff away from standard reviews.)

The rate of first-cycle drug approvals is at the highest level seen in 20 years, she pointed out during a hearing that opened debate on reauthorization of the Prescription Drug User Fee Act with a look at how FDA's oversight of drug development impacts investment in new therapies.

Subcommittee Chairman Joe Pitts, R-Pa., said at the hearing that he wants to avoid a last minute rush to pass PDUFA V, and plans to have the reauthorization completed and signed by the president by June 30, 2012, well ahead of the Sept. 30, 2012, expiration date of the current law.

Details of the agreement are to be published on Sept. 1, with final recommendations sent to Congress by Jan. 15, 2012.

Despite the quick timetable for reauthorization and implication that the legislation would be relatively "clean," both subcommittee Chairman Joe Pitts, R-Pa., and full committee Chairman Fred Upton, R-Mich., used the hearing to voice concerns that uncertainty in the FDA approval process are stifling medical innovation and delaying access to new therapies.

Upton said the committee will examine the lack of predictability and certainty at FDA, two issues that "appear to be stifling American innovation, costing American jobs and hurting American patients."

"What we have heard," Pitts said, is that the approval process often fails in terms of certainty, predictability and transparency, and this is "frustrating both the drug sponsors and the public, who are waiting for treatments and cures to everyday maladies, chronic illnesses and terminal diseases."

  Read More & Comment...

Sometimes Sanity

07/08/2011 09:15 AM |

During my tenure at the FDA I was the senior official in charge of advisory committee oversight and the final decision-maker on who got a COI waiver and who did not. Many did not — but those who did received their waivers because FDA professional career staff made a strong case that these people weren’t just important to the advisory committee — but critical.

And we should all pay attention to the nomenclature.  It’s not about “conflict of interest” – it’s about (as Secretary Sebelius correctly says) “interest.”  And having an “interest” is not necessarily a bad thing – as long as you’re transparent about it.

If we allow FDA adcomms to become the realm of the second best and the almost brightest –what have we done to the advancement of America’s health? The answer is a significant disservice.

In the February 7, 2010 edition of The Lancet, Richard Horton points out that the battle lines being drawn and between clinician, medical research and the pharmaceutical industry are artificial at best -- and dangerous at worst.  Dangerous, because all three constituencies are working towards the same goal -- improved patient outcomes.

Horton’s main point is that we must dismantle the battlements and embrace of philosophy of "symbiosis not schism."  It's what's in the best interest of the patient.

And so it is with this in mind that I share some promising news (as reported today in The Hill.)

GOP wants FDA bill to boost drug industry's role

Republicans want to roll back new conflict-of-interest rules they say are depriving the Food and Drug Administration of needed expertise from the drug industry.

Democrats, meanwhile, will focus largely on the safety of imported drugs as Congress begins work on a five-year FDA reauthorization bill.

Congress tightened the FDA's conflict-of-interest rules in 2007, as part of the last FDA reauthorization. But Republicans on the House Energy and Commerce Committee said they may try to loosen the standards in the next reauthorization, which needs to pass next year.

Committee Chairman Fred Upton (R-Mich.) said the upcoming bill should reverse "rigid, unrealistic conflict-of-interest provisions" that have delayed drug approvals. The rules govern who can participate in FDA advisory panels, which study safety and effectiveness issues.

"No longer can we afford to sideline experts simply because of their ties to the pharmaceutical industry," Rep. Phil Gingrey (R-Ga.) said Thursday at an Energy and Commerce health subcommittee hearing.

Janet Woodcock, the director of FDA's drug center, said the limits have slowed down the advisory committee process. The agency sometimes goes through the long haul of finding experts in a given field only to discover ties to the pharmaceutical industry toward the end of the process, she said.

The FDA has already begun negotiating with drugmakers and consumer advocates over the reauthorization bill. Thursday's hearing marked the first formal involvement from Congress.

Technically, the purpose of the FDA bill is to reauthorize the programs through which drug and medical device companies pay the FDA to review their products for approval. But because it's a must-pass measure — the people and offices that approve new products are paid for almost entirely by industry fees — it consistently becomes a magnet for broader policy changes.

Upton said Thursday that he also wants to reexamine a piece of the last reauthorization that gave the FDA more power to regulate drugs after they've been approved. The FDA can now require drugmakers to study certain safety issues and add new warnings to drug labels.

Upton and other committee Republicans say FDA overregulation is stifling innovation and preventing drug and device companies from creating new jobs. Rep. Henry Waxman (D-Calif.) argued that while getting new products to market is important, the FDA's mission should be protecting public health rather than fostering job creation.

Energy and Commerce Democrats indicated that the safety of imported drugs will be their biggest policy focus. Rep. John Dingell (D-Mich.) began working on an import safety bill in 2007, the food-safety portion of which passed on its own in 2009.

The FDA inspects foreign factories far less often than domestic ones, and it can't make a surprise visit outside of the United States. Those limitations received extra scrutiny following the 2007 heparin contamination, which Dingell cited repeatedly at Thursday's hearing.

  Read More & Comment...

Keeping the Spark Alive

07/08/2011 08:57 AM |

From today's Wall Street Journal:

An ObamaCare Drug Preview in Germany

Do you want penny pinchers nixing safe medicines before they've had a chance in the marketplace?

 

By John C. Lechleiter

 

Germany was in many ways the birthplace of the pharmaceutical industry. But today, German policies place the industry's future progress at risk.

More than a century after Eli Lilly's founding, many of us still trace our company's greatest "spark" to Germany, and to a scientist born in 1877 named George Henry Alexander Clowes. An Englishman, Clowes was determined to become a great chemist and was dedicated to improving human health. In the late 19th century, such a goal meant one thing: Go to Germany. Clowes left Germany not only with a Ph.D. in chemistry but also with a conviction that breakthroughs against disease depended on the collaboration of industry, academia and medicine.

Twenty-six years later in 1922, Clowes had crossed the Atlantic and become the head of research at a small company in Indianapolis. He helped to spearhead the commercial manufacture of insulin for the treatment of diabetes—turning what was once a death sentence into a manageable condition.

Today in Germany, it's doubtful that George Clowes would find much inspiration. The ethos of hard work certainly still exists, but intrusions of bureaucracy, misunderstandings of science, and an exaggerated emphasis on short-term cost savings are jeopardizing the country's legacy as a pharmaceutical powerhouse.

Of particular concern is a new law passed last year that imposes a complex new assessment mechanism to determine the added benefit of new pharmaceutical products, which in turn is used to set prices. The situation in Germany bears close scrutiny in the U.S., as health-technology assessment processes grow in significance under the recent health-care overhaul.

Our concerns begin with the timing of Germany's assessment: at the point of launch. Pharmaceutical companies invest hundreds of millions of dollars into clinical trials to prove the efficacy and safety of new medicines—but efficacy and safety are not the same things as added benefit. We introduce products into the market with well-founded hypotheses about their unique benefits, but rarely with definitive evidence. By insisting that we provide such evidence before a single patient has used a medicine in regular medical practice, German authorities are devaluing the final and arguably most important stage of pharmaceutical development.

Contrary to popular mythology, so-called blockbuster medicines are not the result of slick marketing campaigns but of demonstrated success in the actual practice of medicine. At Lilly, we wonder how many of our earlier blockbusters—which might have appeared very similar to existing medicines at their launch but proved more effective in practice—would have survived the requirements of Germany's new early assessment requirement. Similarly, we wonder if incremental innovations in the treatment of cancer, for example, or new medicines that limit side effects and improve patient compliance with doctors' orders in diabetes care, will be considered beneficial under Germany's new system.

Even that bleak conclusion assumes that the early assessments will be carried out in a fair and transparent manner, which is far from assured based on what the industry has seen so far. Companies such as Lilly are looking at the all-important "comparators" being assigned to our new molecules in the assessment process. In many cases, German authorities appear to be comparing cutting-edge products with decades-old generic products and still pricing the new products just pennies above the generics. Our conclusion is that we are being set up for negative decisions on added benefit and ruinous price controls as a result.

The wisest decision that a company can make in such circumstances may be to delay the launch of a new medicine in Germany until evidence can be generated elsewhere. The other alternative may be to keep new drugs off the German market entirely to prevent the global reputational damage of a slap from the German authorities.

Meanwhile, the broader uncertainties created by the new German law—literally any product can be drawn into the new evaluation process without advance notice—wreak havoc on our industry's business planning.

Now is the time to step back and consider the unintended consequences of Germany's new law, and make sure we don't repeat the same mistakes in the U.S. We share Berlin's goals of generating value and limiting unnecessary costs in health care. We see ways of harnessing and improving health-outcomes research.

Most of all, we believe that dialogue between government and industry is the only way to ensure that the cradle of the pharmaceutical industry remains a nurturing environment for new medicines in the 21st century.

Mr. Lechleiter is chairman and CEO of Eli Lilly & Co.

  Read More & Comment...

Junk Science on Autism

07/07/2011 07:50 PM |

A new study purports to show that environmental factors are more likley to cause autism than genetic mutations.  I won't get into the weeds on the methodological problems of the research since genetic association studies are, absent analysis or sequencing of genes, full of statistical assumptions that vary from paper to paper.  Moreover, when discussing the contributions of genes and 'environmental' factors to a behavior or disease, the term environment really means "anything we can explain by genetics that is not explained by demographics." 

http://archpsyc.ama-assn.org/cgi/content/full/archgenpsychiatry.2011.76#YOA15046T2

Which begs this question:  Since so many of the likely 'environmental' factors alleged to be linked to autism (, inflammatory diseases, mitochondrial disorders, vaccines, water supply, chemicals) have been discredited, how reliable is a study -- one that is at odds with every other genetic association study regarding autism -- that claims environmental factors are twice as likely to trigger autism than genes?  How good is a model that predicts things at odds with what experience demonstrates?

Of course the media never examines this question, never puts this study into context and never looks at the toxicological studies showing that certain toxins some swear cause autism, impotence, cancer, etc. are not even present in concentration levels necessary to cause of biological reaction (benign or not).      Not suprisingly, BPA is now being held up as the next new culprit causing autism.  Thus the recent EPA review of BPA levels in humans will go unmentioned:

EPA Study Findings:

·         Consistent with previous human and animal studies, this new study confirms that human exposure to BPA is extremely low, and BPA is efficiently metabolized and rapidly excreted in urine. Of particular importance, these results confirm the validity of the controlled human volunteer pharmacokinetic studies that have been used by regulators in BPA risk assessments. 

 

o   Based on how much total BPA (after hydrolysis of metabolites) was found in urine (average exposure was 21% greater than the 95^th percentile exposure determined by CDC’s population-scale urine biomonitoring data), the authors concluded that “BPA exposures in this study can therefore be viewed as representative of, or exceeding, the high end of the U.S. BPA exposure distribution.”

 

o   Total BPA was detected in only 14% of the 320 blood samples, only one of which was above 1 ppb. Total BPA was below the sensitive limit of detection (0.3 ppb) for 86% of the samples.

 

o   Estimates of peak BPA levels in the blood were 1 to 3 orders of magnitude below levels associated with potentially adverse health effects in the most sensitive experimental rat models. 

 

o   Free BPA was below the limit of detection in all 320 blood samples analyzed by the CDC lab, even for samples with detectable total BPA. Based on their results the authors note that reported high levels of BPA in blood are unlikely to be valid. (“Furthermore, the current results obtained using analytical methodology 10-45 times more sensitive than the previous human study by Voelkel et al. suggest that reported BPA concentrations in human blood of 1.4-19.2 nM [~0.3-4.4 ppb] (Vandenberg, Chahoud et al. 2010) are highly unlikely in the general population exposed orally to amounts as much as ~4 times greater than the 95^th upper percentile of aggregate exposure in the general U.S. population.”)

 

o   While subjects of this study did not include pregnant women, the authors also add that “recently reported mean urine concentrations in pregnant women are low enough that blood and serum levels are likely to be below current detection limits.”

 

o   Samples with detectable total BPA were further analyzed in the FDA lab to confirm the findings. Very low but detectable levels of free BPA were found in 3 of these samples, but further analysis revealed that contamination was most likely the source of the free BPA. The authors note, “the evidence presented here and elsewhere for low-level contamination (Markham et al., 2010; Twaddle et al., 2010), even in the face of extraordinary attention to this problem, suggests that these infrequent positive determinations near the detection limit should be suspect” and “Thus, some attributions of high blood BPA concentrations from oral exposure seem implausible.”

 

24-Hour Human Urine and Serum Profiles of Bisphenol A During High Dietary Exposure  tinyurl.com/3efsdw8

Will we -- and the media -- unlearn the lessons of Wakefieldism?

  Read More & Comment...

Blame Innovation!

07/07/2011 09:08 AM |

Blame innovation!

According to an editorial in today’s New York Times, “A prime driver of our escalating health care costs is the advance of medical technology …”

Indeed. 

The driver of the Gray Lady’s oration is the decision by Medicare to pay for both Provenge (advanced prostate cancer) and Avastin (for breast cancer – even if the FDA removes this as an on-label indication).

The Times objects to both treatments “staggering high cost” and “modest help to the typical patient.”

Are these treatments “too expensive?” Well, as they say inside the Beltway, where you stand depends on where you sit.”  Too expensive for whom?  And there lies the rub.

When our nation’s biggest health insurance provider – Uncle Sam – is footing the bill, the real payer is the American tax payer.  You and me.

That being the case, how do we feel about spending our tax dollars on end-of-life care for our fellow citizens?  After all, these treatments aren’t cures.  They extend patient life. Some gain months, others years. 

This is a tough and timely question for both public and private debate – and not just amongst policy wonks and editorialists. Do we want a health care system that is cost-based or patient-centric? Should end-of-life care be rationed?  If so, by whom and by what measure?

And if we decide not to pay for new medicines, the clear signal to the pharmaceutical industry is “cease research and development for new treatments for killer diseases."

Blame innovation? Consider:

Innovation is slow.  As any medical scientist will tell you, there are few "Eureka!" moments in health research. Progress comes step-by-step, one incremental innovation at a time.

Innovation is hard.  Today it takes about 10,000 new molecules 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.

Innovation is expensive.  In 2003, researchers at Tufts Center for the Study of Drug Development estimated the costs to bring a new medicine to market to be $802 million, and others suggest that the total cost is closer to $1.7 billion

Innovation is under attack.  From accusations of the “me-too” variety, to crackpot schemes to replace pharmaceutical patents with a “prize” system, life for innovator pharmaceutical companies is rough and tough. 

But innovation is important – and not just for pharmaceutical industry profits. Increases in life expectancy resulting from better treatment of cardiovascular disease from 1970 to 1990 have been conservatively estimated as bringing benefits worth more than $500 billion a year. In 1974, cardiovascular disease was the cause of 39 percent of all deaths. Today it is about 25 percent. Cerebrovascular diseases were responsible for 11 percent of deaths back then. In 2004 they caused 6.3 percent of deaths. Kidney diseases were linked to 10.4 percent of deaths and now they are associated with 1.8 percent. And that’s just for the United States.

As Harvard University health economist (and Obama healthcare advisor) David Cutler has noted: "The average person aged 45 will live three years longer than he used to solely because medical care for cardiovascular disease has improved. Virtually every study of medical innovation suggests that changes in the nature of medical care over time are clearly worth the cost."

Blame innovation – because now we are living long enough to suffer in larger numbers from cancer and Alzheimer’s disease. Diseases that cannot be cured (at least not yet) and are expensive to treat.

And what of the “typical” patient?  The current gold standard of drug testing, the randomized controlled clinical trial, isn’t specifically designed to identify patient subpopulations who might benefit from a treatment that does not aid the general population. According to the folks at our nation’s newspaper of record, Avastin “provides almost no benefit for the typical woman with advanced breast cancer.” Well – true, except for the subpopulation of women for whom it does.  The problem isn’t that Avastin “doesn’t work,” it’s that we have no way of identifying which women it will work for.

The solution isn’t to carp on cost – it’s to develop better diagnostics to help physicians identify the “four rights” – the right drug in the right dose for the right patient at the right time.  We need to focus not on cost effectiveness but on clinical effectiveness.

But nowhere in the Times’ editorial is there a call for increased FDA funding for the development and regulation of molecular diagnostics – something that is urgently needed and, alas, rarely discussed.

Rather the Times’ editorial ends as follows, “Whether the drug is worth its high price is a question our health care system is currently unprepared to answer.”

Really?  It seems that Medicare is not only prepared to answer the question – but that, via their decision to reimburse for both Provenge and  Avastin, they have.

At least for now.  After all, we're entering into a Presidential election cycle.

  Read More & Comment...

More Science, Less Salt

07/06/2011 09:10 PM |

A "systematic reviews" about the clinical effectiveness of reducing salt intake on high blood pressure showed no effect. 

Of course many experts weighed in on the study:

"Critics say this new review is based on just seven studies that were not designed to test the effects of sodium reduction interventions on CV events and mortality and is therefore unreliable. "

One physician, Lawrence Appel, was particularly harsh: "The authors truncated the best set of trials, TOHP1 and TOHP2, which has extended follow-up of >10 years, to just the trial period, 1.5 years for TOHP1 and three years for TOHP2. This set of trials, with extended follow-up, documented a significant reduction in CVD events."

This is the same Lawrence Appel who continues to push ALLHAT and a diuretic alone as the gold standard for treating hypertension to the exclusion of several new, large studies demonstrating that a combination of blood pressure meds reduce the risk of death from stroke and other ailments more effectively. 

A little more consistency in how medical studies are evaluated and applied would be helpful.  The totality of evidence matters.  But what matters more is moving away from population based conclusions towards individualized and mechanism specific approaches to care. 

Epidemiology, the foundation of comparative effectiveness research, is so 19th century.

See: Advising people to eat less salt is not best approach to reduce CVD at theheart.org  Read More & Comment...