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FDA, Health Policy

Comfort from FDA with one question

Here’s a small sign that things are turning around at the U.S. Food and Drug Administration.

A few days ago, my blog entry about the presentation by Jeffrey Shuren, MD, JD, director of the FDA Center for Devices and Radiologicial Health, mentioned the concerns of many in the audience from the Medtech industry and how Shuren tried to address them. The opening quote – “We’re scared. We don’t know what to expect.” – came from Connie Hoy, vice president of regulatory affairs and compliance officer, at the firm, Cutera, a maker of laser and light based medical devices, based in Brisbane, Calif.

Hoy was kind enough to email me a couple days after the event, and her response gives a sense of the impression Shuren left. Here’s what she said:

Several take aways from the meeting:

I very much liked Dr. Shuren He seemed down to earth and clearly wants to communicate. That in itself is reassuring.

I liked that he took some responsibility for the problems in the FDA
review process. I actually think he was a little hard the reviewers,
for example, when he stated that he thought the agency lacks technical
expertise. That is not the case in the laser side of the business.

I also appreciated that he was able to point out shortcomings on
industry side with out being accusative. He is right, quality of
submissions is critical to a smooth process and it is industries
responsibility to prepare quality submissions.

I also liked the fact that he wants to build a clinical group at FDA.
BUT, that also scares me a bit. One of the things that is important is
that industry can dictate the protocols in their trials. FDA can’t be
too prescriptive or it will damage industry by possibly adding too much
cost and/ or time.

Overall, I was comforted and encouraged by what I hear.

The Stanford Biodesign Round Table, at which Shuren talked with panelists and answered questions from the audience, is now available as a video on the Web.

FDA, Health Policy

FDA walks line between innovation and safety

“We’re scared. We don’t know what to expect.”

That’s what one medical device company executive told me about the U.S. Food and Drug Administration’s plans to revamp the way it approves new technologies for market, as we were milling about before the start of a roundtable event here yesterday. Her worries were shared by many in the medtech industry who made up the audience of some 500-plus.

It was the mission of the guest of honor, Jeffrey Shuren, MD, JD, director of the FDA Center for Devices and Radiologicial Health, to assuage their fears, and explain how he and his colleagues are trying to fix what virtually everyone agrees is a troubled system: Industry officials say the approval process for devices seems to be dragging on longer than ever; they complain that the CDRH is being swayed by complaints from consumer groups that devices are being rushed onto market before they are fully checked out as safe.

Shuren didn’t candycoat the situation. He said that the medical device industry is caught in a “perfect storm,” as a result of the weakened economy, changing health-care reimbursements, new emphasis on medical cost control, declining research and development effectivenesss – “and declining predictability, consistency and transparency in FDA pre-market decision making.” That last one was the focus of his remarks, and he was optimistic. “The problems are many and the causes lie both with FDA and with industry, but I believe they are solvable,” said Shuren.

Since officially taking the helm of the CDRH in January, Shuren has helped to oversee the production of two reports: one on the 510(K) program that the CDRH uses to review applications, the other on the use of scientific evidence. Together, they offer dozens of recommendations for improving CDRH’s operations. They extend from making certain terms in the regulations less ambiguous to tapping outside scientific expertise when evaluating leading-edge innovations. Shuren said that such changes would lead to a more transparent, consistent and predictable system, making it easier for device companies to plan for the future.

And Shuren tried to dispel the notion – voiced by some at the event – that the CDRH was placing a greater emphasis on safety at the expense of innovation. “You’re right that some folks have raised safety concerns about devices coming on the market, but actually one of the bigger drivers is industry [officials] who were telling us that they were not happy with the way things were going. ” He added that he starts off his cover letter for the reports with the credo, “Foster innovation.”

“That’s one of the goals of the 510(K) program, and we take it very seriously,” he said.

The devil is, of course, in the details, and a panel of industry leaders grilled Shuren about the proposals. It’s not clear that they were satisfied with all that they heard, but Shuren’s effort to communicate (this is one in a series of meetings he has held) was appreciated. One panelist, Josh Makower, MD, a successful medtech entrepreneur and a consulting associate professor at Stanford, remarked. “You have been the most open center director we’ve seen in the history of the device industry, which is great because we are in crisis now.”

The event lasted more than two hours and a webcast is to be made available later this week on the home page of the Stanford Biodesign progam, which hosted the event with Stanford Health Policy and the Program in Health-Care Innovation at the School of Business.

Infectious Disease, Public Health, Science Policy

Improving vaccine response to flu pandemics

The H1N1 influenza did not cause the devastating pandemic that many feared, but it did draw attention to how our nation lacks the ability to quickly produce sufficient quantities of a vaccine against the flu. A report issued this morning from the President’s Council of Advisors on Science and Technology outlines steps that the federal government can take both in the short term and over the long run to speed up the making and delivery of vaccines, potentially saving thousands of lives in the process.

Ann Arvin, MD, Stanford’s vice provost and dean of research and a founder of the Stanford-LPCH Vaccine Program, is one of the eight committee members responsible for the report.

Among the suggestions: accelerate identification of newly emerging pandemic viruses (so vaccine production can start sooner), develop a collection of stock viral “backbones” to allow faster production of specific vaccine strains, and develop faster and more reliable tests to document vaccine potency. The report also recommends steps to dramatically alter the way vaccines are produced, most notably by “moving away from the current practice of growing influenza viruses in fertilized chicken eggs, which is an inefficient method, and using modern cell-culture systems instead.”

None of this comes without some spending, and the report calls for investing $1 billion or more annually for the next several years to accomplish these objectives. It notes that the funds can be justified on a cost-benefit basis, as the advances in these areas would improve our nation’s defenses against a variety of other deadly pathogens, in addition to the savings they would provide in preventing deaths from influenza.

Indeed, some work relevant to these initiatives is already under way by researchers at Stanford, as outlined in a medical school release last year. In addition, grants from the stimulus fund are supporting a Stanford research effort to explore why vaccines against influenza prompt different responses in different people and why some people are more vulnerable to flu than others to begin with.

Education, Health Policy, Medicine and Society, NIH, Science Policy

Payback time for NIH grant recipients?

What if scientists who benefit from grants from the National Institutes of Health had to devote some small portion of their time explaining to the public what their work is about? That’s the idea being floated by Suzanne Pfeffer, PhD, Stanford biochemistry professor and the new president of the American Society for Biochemistry and Molecular Biology.

In her column in the August issue of the society’s magazine, Pfeffer estimates that if every NIH investigator donated 60 minutes of their time, that could amount to 10,000 hours of educational activities such as talks to elementary school students, public forums and tours of scientists’ laboratories.

The idea is well within the realm of the possible, and indeed a similar measure is already in place for recipients of grants from the National Science Foundation. Pfeffer offers detail on how such an effort could work, and she offers, in a nutshell, why it makes sense:

Explaining science to the public is very important. First, we owe it to them. Taxpayers support a large proportion of biomedical research in the U.S. and in other countries around the world. At a time when public understanding of science could use a major boost, who better to explain the excitement and importance of scientific discoveries than highly trained biomedical researchers?

Health Policy, Stanford News

Beyond Berwick brouhaha: Medicare chief another step to health-care reform

The White House announcement that President Barack Obama was doing an end run around the U.S. Senate and doing a recess appointment of a new head of the Center for Medicare and Medicaid Services, or CMS, has, not surprisingly, caused something of a kerfuffle.

Donald Berwick, MD, a Harvard medical school professor and president and CEO of the nonprofit Institute for Healthcare Improvement, just become the agency’s first permanent chief since 2006. He was nominated for the job months ago, but his appointment was being held up by Republicans, who said that he would impose government rationing – and that he favors socialized medicine. By officially making the appointment while the Senate is in recess, Obama moves past the effort to pillory Berwick and lets him get started on the job.

Still, it’s worth noting that despite the efforts to pigeonhole Berwick as some sort of leftwing radical, he doesn’t fit that caricature. As noted in an editorial in the Washington Post, he was endorsed by the two previous heads of the agency under President George W. Bush, as well as their counterpart under President George H.W. Bush. The Kaiser Health News Service has created a resource guide page about Berwick that offers a balanced view: It shows that while Berwick has ambitions to overhaul our health-care system, his ambitions are guided by initiatives that are as noncontroversial as apple pie – such as changing medical practices so as to eliminate unnecessary infections in hospitals and prescription errors that cause thousands of deaths each year.

My article in the latest issue of Stanford Medicine magazine may help put what Berwick wants to do in some context. What he and other health reformers are essentially saying is this: Let’s get more health care for less money. At first blush, it sounds like a real estate agent offering some beachfront propery in Nevada, but the premise actually embodies what has made our nation so vibrant. Through innovation, we can achieve – and we have done so in the past – greater productivity. The nation’s leading hospitals and health-care organizations are all now trying to implement quality improvement campaigns that will deliver better care while reducing costs.

Of course, for every Model T, there’s also an Edsel, and so it’s certainly not a given that whoever is in charge of the CMS is going to be able to realize such savings. As the agency overseeing Medicare and Medicaid spending, it has the ability to reward certain practices and penalize others, but figuring out how best to do that is no small feat.

Global Health, Infectious Disease

African measles deaths from vaccination gap

Amid all the debate in the United States about whether vaccines are safe, people sometimes lose sight of what happens when children miss their measles shots. A failure to provide widespread immunizations for this disease in eastern and southern Africa over the past year is a painful reminder of the results of such lapses. According to a brief item posted today by the International Society for Infectious Diseases,

A steep increase in cases of measles in eastern and southern Africa
has put recent gains in reducing mortality due to this highly
contagious disease at risk of being reversed. As of mid-June 2010,
the outbreak has affected more than 47,907 children in 14 countries,
resulting in 731 deaths. The most recent confirmed measles outbreaks
were reported from Malawi, Mozambique and Zambia.

The outbreak is attributed to failure to achieve sufficient vaccination coverage due to lack of funding for immunization from governments and other partners to the anti-measles initiative conducted by the World Health Organization and UNICEF. The outbreak is also the result of certain groups refusing to be vaccinated. UNICEF Regional Director for Eastern and Southern Africa, Elhadj As Sy, said:

Measles IS easily preventable. In order to sustain our efforts and
successes in combating the disease, we urgently need to fill the
funding gaps. Otherwise, we will again see more measles deaths in the
near future.

Health Policy, In the News

91 days of health-care reform

The landmark health-care reform package took effect 91 days ago – on March 23 – and the Obama administration now is trying to turn the 2,700-page bill into a working program. What that means is that we all need to watch closely how the law is being enacted. In that light, there are two pieces of news today that are worth noting.

First, the Department of Health and Human Services today announced it was establishing a Patient’s Bill of Rights that begins to turn some of the law’s promises into reality. According to HHS, these rules, which take effect Sept. 23, will prohibit insurance companies from past practices that they used to limit the care they cover, as well as eliminating any requirement that you need to get prior approval before going to an emergency room or that women need to get a referral to see an Ob/Gyn. While it isn’t at all surprising, it is still important to see that it’s happening.

Second, is a New York Times story about how Obama’s nominee to head up the Medicare program, Donald M. Berwick, MD, faces a bruising confirmation battle due to Republican opposition. How this plays out is critical for the success of the legislation. A huge component of making this bill work is the ability to enforce protocols for care that could lead to big cost savings. The Republicans who oppose Berwick’s appointment are trying to cast him as a proponent of rationing. Berwick’s supporters say that he is an advocate for uniform standards that will ensure that all of us are getting better care – and that there is more care available for all of us because of the improved efficiencies that accompany adoption of such standards. How this nomination battle plays out could augur how successful will be the future efforts to rein in costs.

FDA, Science Policy, Technology

Brainstorming on how FDA can promote device innovation

The United States is the world leader in creating lifesaving medical devices, but can we get even better at it? The U.S. Food and Drug Administration is seeking ideas on how it might be able to enhance the process of identifying serious unmet public health needs and then developing devices to help resolve them. The agency sent out a release today about a daylong workshop it’s holding on June 24 to explore this subject at the Hilton Hotel in Gaithersburg, Md. Although the event is open to the public, seating is limited. It isn’t being webcast or videotaped.

Among the speakers are several with connections to Silicon Valley, including Bonnie Norman of Intel Corp.; David Klonoff, the medical director of the Dorothy L. and James E. Frank Diabetes Research Institute of Mills-Peninsula Health Services in San Mateo, Calif.; and Jack W. Lasersohn, a member of the board of directors of the National Venture Capital Association and a founding general partner of the Vertical Group, a firm with offices in Palo Alto and Summit, N.J.

Cancer, FDA

FDA on Mylotarg: Too fast or too slow?

The U.S. Food and Drug Administration issued a release today about a cancer drug being withdrawn from the market that underscores the agency’s troubles with its accelerated approval process for certain drugs: The FDA can speed up the steps to get them onto the market, but can it speed up the steps to pull them off?

Here’s the background on the latest situation: In 2000, the agency approved the use of the drug Mylotarg for certain cases of acute myeloid leukemia under the accelerated approval process. That essentially means that it based its decision on findings that were promising, but not definitive. As part of the deal, it required the company (then Wyeth, which was since acquired by Pfizer) to conduct a follow-up study.

Now, some 10 years later, it appears that in at least one study the drug caused an increase in the numbers of deaths of people who used it, which, according to a story by Bloomberg, is the result of deadly liver complication. Because of this, the FDA requested that Pfizer, the drug’s maker, take it off the market, and the company voluntarily did so. This is the first case of a drug that’s gone through the accelerated approval process being withdrawn because of FDA action.

The results sheds light on some glitches in the system. The fatalities came to light because of the follow-up study that was launched in 2004 – four years after the FDA approved the drug. An item on the Huffington Post reports that company then halted the study some five years later, in August 2009, because of the negative results. What’s more, evidence that the drug wasn’t as promising as had been thought were aired in 2007 when European regulators refused to approve the drug, saying that studies had not shown it saved lives.

So why did it take 10 years for such a decision to be made? Some might say that the accelerated approval process is a bad idea, but an FDA official quoted in the Bloomberg story suggests that the problem is in the lack of adequate follow-up studies and that four years should not pass between accelerated approval and the launch of these studies:

The delay underscores the need for more oversight of follow-up studies with drugs that win accelerated approval, said Robert Kane, acting deputy director for safety in the FDA’s Division of Hematology Products.

“Accelerated approval still has a place in the approval process but it’s also more important that we learn over the years that the whole development plan be set up well in advance,” Kane said today in a phone interview. “The trials should be planned and if possible underway when the sponsor submits the application.”

Autism, In the News, Media

It's over: No MMR vaccine-autism connection

The Web is buzzing with the news that the British medical journal, The Lancet, has completely retracted the 1998 paper that sparked widespread fears that the MMR vaccine was causing an autism epidemic. (It’s summed up neatly in this New York Times piece .)

Perhaps the most interesting question being raised in the wake of the Feb. 2 decision is this: What took so long?

Members of the medical research community have been paraphrased and quoted at the end of a post on Booster Shots, a blog from the Los Angeles Times , saying that this action should have been taken years ago. “Finally” was the reaction in an item on the New Yorker’s blog by Michael Specter, who recently was featured in a podcast from the medical school, discussing his book, Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives. I was one of a number of writers who had written over the last five years about how there was no link between the MMR vaccine and the spike in autism diagnoses. (My article “The Demonization of Immunization” ran last spring.)

To be fair, the Lancet already did a partial retraction a few years ago, when 10 of the 13 authors asked to have their names removed from the paper. Its editor was pushed to take this final step when the UK General Medical Council, which oversees the licensing of doctors in England, completed what was said to be its longest-ever medical misconduct inquiry, starting in July 2007: It ruled that the lead author of the Lancet article, Andrew Wakefield, MD, had violated at least 30 ethical rules and concluded, among other things, that he had provided false information relating to the study and acted with “callous disregard” for the children in the study. Of course, Wakefield is insisting he has been framed, and there is still a core group of people who remain adamant about a connection between MMR and autism, though they are becoming increasingly irrelevant.

Still, it is troubling how long it took for this theory to be debunked. What’s so striking about the ruling and the retraction is that it essentially mirrors the special three-part investigation that ran in The Sunday Times of London in 2004 by Brian Deer (who, by the way, wrote what I think is by far and away the strongest story about the medical council’s decision). Deer’s story eventually had its effect, and now journalists everywhere are echoing his points. While some in the U.S. media exercised similar skepticism, it is remarkable how long it took for so many outlets in this country to accept the scandal that Deer’s brilliant reporting uncovered.

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