By Ed Silverman. The Wall Street Journal. Published Feb. 5, 2015.

Link to original article here. 

Has the other shoe dropped?

Following mounting speculation, FDA commissioner Margaret Hamburg has told staffers that she will step down at the end of March, after a nearly six-year run heading the agency. The news comes just 10 days after the FDA hired Robert Califf, a widely regarded Duke University cardiologist, as deputy commissioner for medical products and tobacco.

That move quickly set off speculation that Califf would, in fact, soon succeed Hamburg, since he starts his new job later this month. And his new job involves overseeing a large swath of the agency – the FDA’s Center for Drug Evaluation and Research; the Center for Biologics Evaluation and Research; the Center for Devices and Radiological Health, and the Center for Tobacco Products.

An FDA spokeswoman declined to say whether a search was under way or, if so, how long the process may take. For now, FDA chief scientist Stephen Ostroff will temporarily assume command until a new commissioner receives congressional approval.

Hamburg, who has been one of the longest-serving FDA commissioners, presided over a string of accomplishments and controversies. A key mission from the start of her tenure was to bolster drug safety. There had been scandals over undisclosed side effect data for such medicines as the Vioxx painkiller and contaminated heparin that was imported from China and blamed for 81 deaths.

“It’s fair to say that Dr. Hamburg came to [the agency] at a time when the FDA was under a cloud,” says Peter Pitts, who was an FDA associate commissioner for external affairs before Hamburg’s arrived and is now a policy consultant to drug makers. “Whether or not the criticism the agency was receiving was fair (most of it was not) isn’t the point. Morale was low. Moral authority amongst constituents was fading.”

Despite efforts to bolster safety, Hamburg was widely criticized following an outbreak of fungal meningitis in 2012 that was traced to a compounding pharmacy and blamed for 64 deaths. Acknowledged as the worst U.S. public health crisis in decades, the FDA was accused of failing to properly oversee compounders, and Hamburg received some harsh grilling from members of Congress.

She was also chastised for her efforts to loosen rules governing conflicts of interest between industry and the outside experts who sit on FDA advisory panels. Hamburg complained that the rules – which set limits on financial ties, for instance – made it more difficult to attract qualified panelists, although she later backed away from this position. But some consumer advocates say her oversight remained lax.

“Too often, the FDA has succumbed to industry and political pressures, implementing policies and taking actions that tilt too far toward the bottom-line interests” of industry, says Michael Carome of Public Citizen, which regularly spars with the FDA over safety issues. He argues the FDA needs a commissioner who will be an “aggressive, proactive crusader.”

There was also controversy over an FDA decision to approve an opioid painkiller, even though it did not have tamper-resistant features and an agency advisory panel recommended against approval. The FDA argued that the drug, Zohydro, offered a needed option to pain patients, but Hamburg was chastised for allegedly overstating the number of people who may have benefited.

“Under Hamburg, the FDA approved a steady stream of new opioids despite an epidemic of opioid addiction caused by overprescribing,” says Andrew Kolodny, who heads Physicians for Responsible Opioid Prescribing and argues the agency has been too friendly to industry. “I’m pleased to hear that Hamburg is leaving.”

At the same time, Hamburg won plaudits for emphasizing programs, such as breakthrough therapy designations and accelerated approvals, which have sped drugs to market faster. This remains a hot-button issue, especially among patients who clamor for treatments for hard-to-treat and rare diseases. In recent years, the number of novel new medicines that FDA has approved has steadily increased.

The issue also resonates, of course, with the pharmaceutical industry, which benefits whenever drugs are launched more quickly. “These programs have proven invaluable in bringing groundbreaking new therapies to patients more efficiently, while maintaining the FDA’s high standards for safety and efficacy,” says Jim Greenwood, who heads the BIO trade group, in a statement.

Hamburg also was caught up in a highly charged political battle. In 2011, former Health & Human Services Secretary Kathleen Sebelius overruled an FDA decision to allow the Plan B emergency contraceptive to be sold over-the-counter to younger teenagers. The FDA maintained the treatment was safe. Two years later, the FDA was able to proceed and approved its use.

Such backbone will be missed by some, especially now and Hamburg’s departure comes at an unfortunate time, according to Diana Zuckerman, who heads the National Center for Health Research, a non-profit think tank. She worries that a sweeping law Congress is drafting called 21^St Century Cures will have a detrimental effect on how medical products are regulated.

“Hamburg has been a strong voice for public health and this is a major loss at a dangerous time for the FDA,” she tells us. “The proposed legislation represents a frightening assault on the agency and the safety of medical products, and the FDA will need a strong leader to protect its public health mission.”

And in a statement, Ellen Sigal, who heads Friends of Cancer Research, a non profit, says Hamburg “changed the direction of the FDA, creating an environment of science-based collaboration that has fostered a new era of regulatory science focused on expediting the best treatments to patients.” We should note that various drug makers are among its supporters.

AND HERE IS THE MEMO THAT HAMBURG SENT TO FDA STAFF….

Dear FDA Colleagues:

It has been a privilege to serve as your FDA Commissioner for almost six years.  So it is with very mixed emotions that I write today to inform you that I plan to step down as FDA Commissioner at the end of March 2015.  As you can imagine, this decision was not easy.  My tenure leading this Agency has been the most rewarding of my career, and that is due in no small part to all of you – the dedicated and hard-working people that make up the heart of this Agency.  While there is still work ahead (and there always will be), I know that I am leaving the agency well-positioned to fulfill its responsibilities to the American public with great success.

I feel so fortunate to have worked at an organization as remarkable and productive as the FDA.  The expertise, dedication and integrity of our people and the unique nature and scope of FDA’s role make this Agency truly special.  Every day, FDA employees around the world recommit themselves to the Agency’s work, to quality science, to facilitating innovation, and to the protection of public health.  And because of your dedication and your service, we have been able to achieve so many significant milestones over the past years.

From creating a modernized food safety system that will reduce foodborne illness; advancing biomedical innovation by approving novel medical products in cutting-edge areas; and responding aggressively to the need to secure the safety of a globalized food and medical product supply chain, to taking critical steps to reduce the death and disease caused by tobacco, we have accomplished a tremendous amount in the last six years.  We can honestly say that our collective efforts have improved the health, safety and quality of life of the American people.

At the heart of all of these accomplishments is a strong commitment to science as the foundation of our regulatory decision-making and of our integrity as an Agency.  And while there are far too many significant actions, events, and initiatives to count, there are some highlights of the past years that I particularly want to mention.

In the foods area, we have taken critical actions that will improve the safety of the food Americans consume for years to come.  These include science-based standards developed to create a food safety system focused on preventing foodborne illness before it occurs, rather than responding after the fact.  We have taken several significant steps to help Americans make more informed and healthful food choices.  These include working to reduce trans fats in processed foods; more clearly defining when baked goods, pastas and other foods can be labeled “gluten free;” updating the iconic Nutrition Facts label; and, most recently, finalizing the rules to make calorie information available on chain restaurant menus and vending machines.

We have also made great strides in advancing the safety and effectiveness of medical products. Some of these important steps include new oversight of human drug compounding and provisions to help secure the drug supply chain so that we can better help protect consumers from the dangers of counterfeit, stolen, contaminated, or otherwise harmful drugs.  We are continuing to increase the speed and efficiency of medical product reviews.  We just had another strong year for novel drug approvals, with most of these drugs being approved on or before their PDUFA goal dates and most being made available to patients in the United States before they were available to patients in Europe and other parts of the world.  We launched a powerful new tool to accelerate the development and review of “breakthrough therapies,” allowing FDA to expedite development of a drug or biologic to help patients with serious or life-threatening diseases.  In fact, almost half of the novel new drugs approved in 2014 received expedited review with a combination of breakthrough designation, priority review and/or fast track status.  These included drugs for rare types of cancer, hepatitis C, type-2 diabetes and idiopathic pulmonary fibrosis, as well as a number of groundbreaking vaccines.  We have also established a regulatory pathway for biosimilar biological products that will create more options for patients.

On the medical device side, the average number of days it takes for pre-market review of a new medical device has been reduced by about one-third since 2010.  The percentage of pre-market approval (PMA) device applications that we approve annually has increased since then, after steadily decreasing each year since 2004.  We also published the Unique Device Identification (UDI) final rule that is intended to improve the tracking and safety of medical devices.  And we proposed a risk-based framework for laboratory developed tests (LDTs) to help ensure patients and providers have access to safe, accurate and reliable tests, while continuing to promote innovation of diagnostic tests to help guide treatment decisions.

We have ushered in the era of personalized medicine across all of our medical product centers. For example, many cancer drugs are increasingly used with companion diagnostic tests that can help determine whether a patient will respond to the drug based on the genetic characteristics of the patient’s tumor.  A growing percentage of our recent approvals have involved targeted therapies, offering many patients more effective response profiles and/or reduced likelihood of side effects.

We made significant progress in implementing both the letter and spirit of the Family Smoking Prevention and Tobacco Control Act.  Our tobacco compliance and enforcement program has entered into agreements with numerous state and local authorities to enforce the ban on the sale of tobacco products to children and teens; conducted close to 240,000 inspections; written more than 12,100 warning letters to retailers; proposed the extremely important foundational “deeming” rule; and broken new ground for FDA with the launch of the Agency’s first public education campaigns to prevent and reduce tobacco use among our nation’s youth.

As Commissioner, my goal has been to shape and support an FDA that is well-equipped to meet the challenges posed by scientific innovation, globalization, the increasing breadth and complexity of the products that we regulate, and our new expanding legal authorities.  I have worked hard to advocate for FDA and our unique and essential mission, including building new partnerships to support our work.  The Agency has received numerous votes of confidence with the bi-partisan enactment of a series of landmark bills extending our authority in the areas of tobacco, food safety and medical products.  In addition, we have achieved a dramatic increase in our budget, from some $2.7 billion in FY2009 to almost $4.5 billion in FY2015.

As hard as it is to leave this Agency, I am confident that the leadership team that we have in place will enable FDA to capitalize on, and improve upon, the significant advances we’ve made over the last few years.  Many of these leaders have been with the FDA throughout my tenure, and I am proud to say that we’ve recently made some wonderful new additions.

And with respect to the agency’s senior leadership team, I am pleased that Dr. Stephen Ostroff has agreed to serve as Acting Commissioner when I step down.  Since joining the Agency in 2013, and most recently serving as FDA’s Chief Scientist, Dr. Ostroff has successfully overseen numerous significant initiatives, while helping to ensure that scientific rigor, excellence and innovation are infused across the Agency.  I have every confidence that he will take on this new role with the same energy, dedication and care.

I want to extend my deepest gratitude to each and every one of you for your service and for making FDA an agency that is not only an exciting and rewarding place to work, but also a place of remarkably meaningful achievement and impact on the health and well-being of Americans.

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs

By John Fritze, The Baltimore Sun. January 27, 2015.

House Republicans are considering significant changes to the way billions of dollars in National Institutes of Health grants are awarded to research institutions under a proposal intended to speed medical breakthroughs.

The proposal, which Republican lawmakers unveiled Tuesday, would require the Bethesda-based NIH to set aside more money for high-risk research and young, emerging scientists while also giving the director more power to shape the agency’s direction.

Nearly a year in the making, the proposal from the House Energy and Commerce Committee represents a political shift from the Republican Party’s persistent effort to undercut the Affordable Care Act toward a focus on medical research that might ultimately draw bipartisan support.

The 393-page document has implications for major research institutions such as the Johns Hopkins University and the University of Maryland, Baltimore, which are among the largest recipients of NIH money in the nation.

“If we want to achieve great things at the NIH, one of the things we have to do is empower younger investigators,” said Rep. Andy Harris, a Maryland Republican and Hopkins-trained anesthesiologist whom the panel gave credit for several provisions. “I don’t think these are Democrat or Republican ideas.”

The proposal also calls for changes at the Food and Drug Administration, such as the speeding of clinical trials and extending patents for drugmakers who develop therapies for complex diseases such as Alzheimer’s. Debate over those proposals is sure to set off a flurry of lobbying by universities, drug companies and medical device manufacturers.

Yet the draft drew a tepid response from some Democrats, including one of the lawmakers who has been most closely associated with its development. Colorado Rep. Diana DeGette said in a statement Tuesday that while she appreciated the public airing of ideas, she does not endorse the proposal.

Others said they were wary of significant new requirements for the National Institutes of Health, particularly since there islittle discussion of additional funding for the agency. Research groups have complained that federal money for research has been inconsistent and has not kept pace with medical inflation.

“The problem has been Congress,” said Diana Zuckerman, president of the National Center for Health Research. “When Congress tells the NIH to do something — when it tells any federal agency to do something, there are a lot of unforeseen consequences.”

Sen. Barbara A. Mikulski, a Maryland Democrat long considered a champion of the National Institutes of Health, said she is reviewing the proposal.

“Maintaining America’s innovation edge is a subject worthy of national discussion and debate,” she said.

Dr. Francis Collins, whom President Barack Obama named as NIH director in 2009, has frequently lamented the difficulty young scientists have in securing grants. The average age of first-time recipients of the agency’s most sought-after funding is 42, even as studies suggest that scientists are likely to come up with their best ideas in their mid- to late 30s.

The House proposal includes an idea pushed by Harris to dedicate an NIH fund specifically for young researchers.

Republicans also want the leaders of individual centers and institutes, such as the National Cancer Institute, to report to the NIH director instead of the secretary of health and human services. And they would give NIH leadership more power to transfer money from one institute to another and would require the head of each institute to personally sign off on research grants.

The proposal also includes a program to dedicate an unspecified amount to high-risk research, in which unexpected breakthroughs are often developed.

An NIH spokeswoman said that officials are reviewing the draft and that the agency urges Congress “to work in a bipartisan way to more rapidly translate scientific discoveries into therapies that will improve patient outcomes.”

Neither Hopkins nor the University of Maryland responded to requests for comment Tuesday. Hopkins President Ronald Daniels used an article in a scientific journal this month to call for reforms to increase opportunities for young researchers.

Several medical research groups applauded the announcement.

“The initiative could be a game-changer for the medical innovation ecosystem,” Research!America President and CEO Mary Woolley said in a statement.

The proposal also represents something of a political victory for Harris, Maryland’s only Republican in Congress, who has been expanding his reach on medical issues in recent years. Harris, who conducted NIH-funded research on cerebral blood flow during childbirth, influenced several provisions of the bill despite not serving on the Energy and Commerce Committee.

There is little discussion in the draft about overall funding for the National Institutes of Health, which has hovered around $30 billion for the past several years. Harris, a member of the House Appropriations subcommittee that approves health agency spending, said he believes the changes could make it easier for the new Republican majorities in both chambers to consider allocating more money for NIH.

“I’m not averse to increasing NIH funding,” Harris said. “If they’re willing to listen to some of these reforms … then I think Congress is going to be willing to consider an increase in funding.”

By Sabriya Rice. Modern Healthcare. October 7, 2014

Medical technology companies are warning that burgeoning pay-for-performance and risk-based reimbursement models will motivate providers to block access to clinically important innovations.

Healthcare economists and quality experts, though, counter that the new models appropriately put the onus on manufacturers to prove their products are worth the cost.

The tension was the centerpiece of a news conference held by the leaders of AdvaMed, the industry’s trade group, at the start of its annual conference in Chicago Monday.

“We have to ensure these new payment models include safeguards to protect patients from unintended consequences,”AdvaMed CEO Stephen Ubl said. Ubl, flanked by AdvaMed Chairman and Covidien CEO Joe Almeida, said too many of the contracts put too much emphasis on cost targets over quality benchmarks.

New payment models have proliferated quickly in recently years, nurtured by provisions of the Patient Protection and Affordable Care Act. More than 360 accountable care organizations have signed contracts with Medicare, agreeing to strive for cost and quality targets to earn some of the savings achieved (or in some cases return money to the government if they fail). Many providers are striking similar agreements with private payers—Blue Cross and Blue Shield Association recently said that it’s now paying one in five dollars under incentive-based contracts—or assuming financial risk with their own insurance products.

AdvaMed is promoting an industry-funded white paper based on the responses of nine unnamed health insurance companies interviewed about their movement toward pay-for-performance and risk-based contracts. Five said they had become more selective about approving coverage for new technologies in the past three years. Four said they plan to demand more evidence before covering products. All said costs were driving their organizations to explore new reimbursement models. The findings are published in the Journal of Medical Economics.

“They run the risk of really tipping too far, so physicians have incentive not to adopt things that really benefit patients,” AdvaMed Senior Vice Presdient David Nexon said in a phone interview.

Representatives for insurers Cigna and Aetna, which responded to requests for comments on AdvaMed’s conclusions, said new technology is embraced if it adds value. “Providers, members and payers deserve and increasingly want to have proof,” an Aetna spokeswoman said. Cigna said in a statement that “technology that simply adds cost without improving quality, health, satisfaction and productivity is counter to our goals.”

Mark Pauly, professor of Health Care Management at the University of Pennsylvania called it an overstatement to suggest that new payment models will inspire widespread failure to adopt products that promise significant benefits to patients. The models add an appropriate hurdle, he said. Manufacturers that can’t provide evidence “won’t go over the hurdle.”

Diana Zuckerman, a researcher who has been critical of the Food and Drug Administration’s procedures for approving and monitoring medical devices, said the industry isn’t accustomed to having to prove that a product is cost-effective. “Something can be clinically appropriate and not be necessary,” said Zuckerman, who is president of the National Center for Health Research.

Manufacturers, though, are in a difficult situation, acknowledged Tom Skorup, VP of applied solutions for the ECRI Institute, a not-for-profit organization that studies the quality and costs of medical technologies, procedures and drugs. Many manufacturers are finding ways to partner with providers to generate evidence. “The greater the collaboration in the creation of the evidence, the fewer the barriers to the potential for uptake,” he said.​

By Thomas M. Burton, The Wall Street Journal

September 29, 2014

Researchers Say Public Data Unavailable on Majority of Newly Approved Devices

The majority of moderate- to high-risk medical devices approved by the U.S. Food and Drug Administration lack publicly available scientific evidence to verify their safety and effectiveness despite requirements in the law, according to a study released Monday.

Researchers reported in JAMA Internal Medicine that 42 of 50 selected medical devices cleared by the FDA over five years lacked such data, despite a 1990 law calling for sufficient detail to justify their FDA clearance. The law calls for public data about studies, which may include clinical studies, involving human patients.

“If wonderful studies are being done, there is no evidence of this, and there’s no way for the public to see it,” said Dr. Diana Zuckerman, a study author and president of the National Center for Health Research, a public health think tank in Washington. “It’s shocking how little information is available despite an FDA leadership that talks about transparency.”

The study’s authors, who were from the health-research center, called for better enforcement of that law.

In response to the findings, the FDA said that it “reviews a significant amount of data—far more than what is publicly available.” The agency said its approach “has served the American public well by balancing the need for robust evidence to assure safety, while expeditiously bringing new technologies” to the market.

At issue is a type of medical-device approval under which about 400 implanted devices annually—the majority of moderate- to high-risk ones—are cleared by the FDA for marketing.

Under that system, called a 510(K) review, the company doesn’t have to conduct studies in human patients, as is generally the case with drug approvals, although it may. Most devices can get FDA clearance simply by showing that they are roughly equivalent to another product, called a predicate device, that is already on the market. The theory is that if the older device has proved safe and effective, the new one should be also.

The 510(K) process has led to cases like metal-on-metal hips, which can leave metal filings in the body.

But the Safe Medical Devices Act of 1990 required companies to make publicly available evidence of why the new product truly is comparable to the old one; the evidence can include studies of patients, known as clinical trials, but it isn’t necessary.

The Institute of Medicine, the research branch of the National Academy of Sciences, in 2011 called for an overhaul of this type of FDA clearance, saying in a report that “reliance on substantial equivalence cannot assure that devices reaching the market are safe and effective.”

“A lot of these are high-risk devices that get on the market with no studies at all,” said Dr. Rita Redberg, medical professor at the University of California, San Francisco, and the chief editor of JAMA Internal Medicine. “When there are studies, they’re not available” for the public to see.

She said that she sees no evidence that the leadership of the FDA under the Obama administration has heightened the level of safety assurance required.

Read original article here.