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To that end, it may be that the World Health Organization has come to a crossroads, because in its current guise it is not well suited to help countries facing these challenges.
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.
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.”
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.
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
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 ...
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.
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
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.
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."
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
