FDA Leadership and Challenges: Seven Columns to Re-read for 2010

As a rule, FDA Matters does not cover the day-to-day events at FDA and in Congress. Most readers have multiple sources for news about the agency. I doubt I could do better.

Rather, the goal of this blog is to cover larger themes and provide deeper insights into the world of FDA. I place a premium on exploring FDA's future, as an observer, commentator and instigator. Here are seven columns about FDA leadership and challenges that will help you to better understand the agency in 2010.

Public Health Leadership Comes to FDA

FDA leadership–Dr. Hamburg and Dr. Sharfstein– come from an entirely different mold than their predecessors. They have begun an era of public health leadership at the agency. FDA staff and agency stakeholders will eventually come to appreciate that this difference is good for FDA. Read the rest of this entry »

Turning Data into Knowledge

Through statute and directive, FDA has been asked to collect, analyze, interpret and utilize massive amounts of data. The systems are not in place to do this, at least not at the required level of sophistication. Even if they were in place, sifting valuable information from background noise is extraordinarily hard. As a result, FDA needs to manage Congressional and public expectations as to "what is possible and when." Read the rest of this entry »

FDA and NIH: Natural Allies

Tension between CMS and FDA is a fact of life at HHS. This is not surprising because they have fundamentally different missions and world views. An analysis of the FDA-CMS relationship leads to an interesting conclusion: FDA should be doing a lot more with NIH because they have complementary missions and similar world views. They are natural allies. Read the rest of this entry »

In Praise of Predictability

FDA has always found it challenging to make its actions predictable. This problem will worsen while Dr. Hamburg redefines the agency's mission, policies, actions and working assumptions. Once this has been accomplished, the agency will become dramatically more predictable to stakeholders, including Congress. Read the rest of this entry »

To Whom Much is Given, Much is Expected

FDA has received $306 million (15%) more to spend in FY 10. This is the third good year for FDA, after years of bad ones. The agency is still severely underfunded, but progress is finally being made. Now the hard work begins: spending the new money wisely and showing that it has been used to accomplish important public health missions. Read the rest of this entry »

CARS: The Vehicle for FDA's Future

Commissioner Hamburg has spoken a number of times about the importance of regulatory science. She is right. FDA must have the scientific tools and methodologies to be a 21^st century regulatory agency. FDA needs to define regulatory science, develop programs to support it, and package them in a way that will quickly bring recognition and funding. Read the rest of this entry »

Long-term Challenges Need Short-term Attention

FDA Matters has identified seven long-term challenges for FDA. Some of these challenges may take years to accomplish; all need to be started now. Three or four years from now, Commissioner Hamburg will be judged by whether she moved the agency forward in these areas. Read the rest of this entry »

Steven

Off-Label Uses Need to Become On-Label Indications

A friend asked: what advice would you give a pharmaceutical company in the late stages of developing a new product that will be widely used off-label? The company's concern was that FDA might hold the first use to a very high, perhaps unrealistic standard to protect patients that might receive the drug off-label after approval.

In thinking about how FDA views this type of situation, I realized there were two very concrete things the company could do. Here is the FDA Matters analysis:

FDA controls the availability of prescription medicines and devices in the US. It does not control the practice of medicine. Once a drug/device is approved for marketing, any doctor can prescribe it for an indication that is not on the label of the drug or device. For example, narcolepsy drugs are often prescribed to enhance concentration and wakefulness in individuals without the disease.

The agency is remarkably positive about deferring to the professional judgment of physicians. Even still, FDA's mission is to protect the public health. It would like to see every off-label indication get the scrutiny necessary to assure it is safe and efficacious.

One of FDA's great fears is that off-label prescribing will become dominant in clinical medicine (as I am told it has in certain areas of oncology). FDA is concerned that companies will get approval for a first use, then (directly or subtly) encourage doctors to prescribe off-label. If this strategy is profitable, FDA worries that fewer and fewer companies will commit the time and money to get approval for additional indications. If a company can't promote off-label, then it is more likely to invest in clinical trials to gain approval of the additional indications.

There are two components to FDA's concerns.

First, does the company intend to do the studies to support additional indications for their product? FDA has been promised much by companies and often receives very little back.

Companies can address this FDA concern by having a clinical trial plan in place for any additional indication(s). Where FDA will permit subsequent trials to be initiated prior to first approval, doing so will further strengthen the company's case. A clear commitment to seek FDA approval for additional indications will reassure the agency that the first indication should be judged on its own merits; not elevated to a higher level by the agency's angst about subsequent off-label use.

Second, will the company try to build the market by promoting the off-label uses? By all appearances, companies often decide that off-label use will be so profitable and supplemental indications so expensive that it does not "pay" to do clinical trials for additional indications. And since companies have paid billions of dollars in fines over the last few years for off-label promotion, FDA assumes that such marketing will occur.

The path is open for a company to announce that they will be implementing the strictest possible controls on marketing and sales practices to prevent promotion of off-label uses of their product(s). In the case of a first approval of a product with multiple uses, such an announcement could assuage FDA's fears that the first use is the only indication that the company will seek.

There is a larger issue here, apart from the strategic and psychological aspects of getting a first approval for a specific product.

Getting more indications on-label should be a public health priority. FDA and industry need to discuss how to accomplish this.

Steven

Two prior columns touched on off-label use and off-label promotion:

Internet Communications: FDA Needs to Divide the Issues to Conquer the Problem
December 2nd, 2009

Creating an Internet communications policy for regulated medical product companies is so daunting that FDA has largely ignored the responsibility. November's FDA hearing on social media was an important step, but offered no sign that new policy will be announced anytime soon.

FDA needs a different approach. This is not a matter of a large, complicated problem with many facets. Rather, it is a number of smaller problems that can be addressed separately. Read the rest of this entry »

Off-Label Promotion and Whistleblowing
September 9th, 2009

Whistleblowing and off-label promotion of drugs and devices have become hot topics because of the September 2 Pfizer settlement with the federal government. While none of my views are specific to Pfizer, the company's settlement provides an opportunity to comment on off-label promotion….and to encourage bio-pharma and medical device companies to engage in deeper soul-searching. Read the rest of this entry »

Senate Debate on Drug Re-importation

FDA Matters was ahead of our time, publishing our thoughts on drug re-importation about ten weeks ago. Now the issue is being debated on the Senate floor.

At stake is whether Americans can have access to drugs being sold in overseas markets at heavily discounted prices.

Advocates point to the unfairness of Americans paying more for the same drugs, which are often manufactured in the same overseas plants and use the same suppliers as pharmaceuticals being shipped into the US. If re-importation is permitted, they envision large savings for government programs, health plans and individual patients. They also believe that safety can be assured by limiting re-importation to countries with US-level regulatory and safety controls, such as Canada.

Opponents focus on the strict controls placed on drugs being manufactured for the American market and imported by US-regulated drug companies and wholesalers. While the world is awash in billions of dollars of counterfeit drugs, comparatively little enters the US under the current system. If counterfeits become more common, there is likely to be a significant increase in costly, sometimes deadly, therapeutic failures. This would jeopardize public health and wipe out much of the predicted savings.

Ideological positions have hardened on drug re-importation. There is far more shouting, far fewer efforts to reason and educate. How do we, as patients and consumers in a complex society, decide on the best path for Americans?

Years ago, a drug trade association ran a campaign with the seemingly-paradoxical theme: the only pill we don't test is the one you take yourself. The goal, as I recollect, was better public understanding of how testing and quality controls permeate every stage of drug development and manufacturing.

Because the actual pill can't be tested, the campaign made me realize that there is a critical leap of faith that the drug product you take is identical to the one that was originally shown to be safe and effective. This is not just a matter of chemical sameness, but also dissolution rates, absorption rates, purity, side effect profile, consistent safety and effectiveness across populations, etc.

I have the highest degree of confidence that a branded product is the same as the one that was originally tested and approved. I have nearly the same confidence in generics and regularly use them, although I have had at least one bad experience.

Beyond that, I become very concerned about drugs re-imported from overseas. Among the potential problems: ingredient substitution, inconsistent manufacturing, lack of quality controls, inadequate inspections, lack of corporate accountability, and the absence of a strict chain of custody that prevents counterfeits.

This risk is compounded because consumers, pharmacists and doctors might never know whether a therapeutic failure was a result of an individual's biology or because of an inferior copy or counterfeiting. At least with brand and generic drugs, the pharmacy puts the drug's name and manufacturer on the label of the bottle and we can reasonably assume the accuracy of the information.

I have no faith that re-imported drugs will, on a consistent basis, be identical to the original products in quality, safety and efficacy.

The promised price discounts from re-imported drugs don't justify the risk to my health from a therapeutic failure.

Steven

Long-term Challenges Need Short-term Attention

Most current readers of FDA Matters were not receiving these posts during June, when we examined seven long-term challenges for FDA. Some of these challenges may take years to accomplish; all need to be started now.

We are less than 7 months into the new Commissioner's tenure. Three or four years from now, she will be judged by whether she moved the agency forward in these areas. I think she has gotten off to a very good start, but there is immense amount of work still required.

Here are the seven challenges:

Integrating new science into traditional clinical trials. Constructing real-world clinical trials has never been more difficult. In many clinical areas, we are moving from targeting disease symptomology toward a new paradigm of altering fundamental biological processes. These issues need a broader, more systemic examination. More resources need to be applied to Critical Path and other clinical trial improvement initiatives.

Balancing safety with patient risk and need. All FDA approvals represent a balance between risk and benefit. There is a lot of variability in what the agency views as acceptable risk for patients with life-threatening conditions. There may be even more variation in their response to the needs of patients with severely disabling conditions that are not life-threatening.

In most FDA activities, medical and scientific expertise and insight is the key to decisions. Creating better risk-benefit judgments is different: patients are the experts on what they feel and believe and on what risks they would accept for what benefit. Meaningful dialogue requires that patients lead this process, not be an afterthought.

Sifting valuable information from background noise. Through statute and directive, FDA has been asked to collect, analyze, interpret and utilize massive amounts of data. This includes biological, clinical, adverse event, production and distribution data, and medical and food product tracking. FDA lacks the sophisticated systems it needs. Once these systems are developed, it is still a difficult, highly iterative process to distinguish meaningful patterns from background noise and to create actionable intelligence.

Managing globalization, rather than just responding to it. There needs to be a comprehensive, multi-year plan for managing globalization, including a budget for Congress to consider and fund. Tomorrow's problems need to be identified and addressed before they become even bigger issues. Food and drug tracking, recall authorities and overseas offices are necessary, but they are not sufficient to meet this challenge.

Resisting the bias toward negative decisions. Uncertainty is inherent in all positive decisions. Taken to the extreme, excess caution could force the whole world of food and drugs to slow down, and then stop. The correct balance is not achieved by a memo or a speech, but by day-to-day actions and enhanced communications. Systematic review of all decisionmaking processes could be an important corrective.

Staying focused on priorities. FDA's responsibilities greatly exceed its resources. Some mission creep is inevitable and some new responsibilities may be needed to benefit society and the public health. But sometimes FDA needs to say "no." Such moments are difficult. "No" will never be accepted by policymakers or the public unless FDA is clearer in defining, justifying and explaining its priorities. This must be addressed comprehensively.

Keeping the Best and the Brightest. FDA cannot succeed without a high-quality and committed workforce. Public service is an important attraction of working at FDA. It cannot be allowed to go out of style. Increased appropriations provide the opportunity to rationalize workloads, reduce burn-out, and build morale.

Do you have items you would add to this list? If so, post comments with your suggestions…or e-mail me at sgrossman@fdamatters.com.

Steven

Internet Communications: FDA Needs to Divide the Issues to Conquer the Problem

Creating an Internet communications policy for regulated medical product companies is so daunting that FDA has largely ignored the responsibility. November's FDA hearing on social media was an important step, but offered no sign that new policy will be announced anytime soon.

FDA needs a different approach. This is not a matter of a large, complicated problem with many facets. Rather, it is a number of smaller problems that can be addressed separately.

Throughout this decade, FDA has clung to the view that the same rules apply to all media: print, broadcast and web communications. The mantra, "regardless of medium," has given them a moderately safe harbor in the midst of a storm of difficult issues.

There are a number of serious problems with imposing existing FDA regulatory policies onto web-based communications between companies and patients, physicians, and consumers. Above all else, it doesn't serve the interests of patients.

Most Americans want easy access to accurate, understandable health information that will answer their questions. FTC, FDA, patients and consumers all want the same thing: information that is "truthful and not misleading." It shouldn't matter if a drug or device company is the source of the information, as long as this is disclosed. Particularly troubling is that medical products company cannot go onto the web to post comments that counter or correct misinformation.

FDA has legitimate concerns about companies' public communications about their products via advertising, marketing, news releases, unsolicited reprints, websites, etc. For example, the agency wants all such external communications to contain a fair balance of benefit/risk information and reflect the approved label indications and its supporting science. FDA also wants to prevent companies from discussing off-label uses of medical products, even in accurate and neutral terms.

The agency has already made adjustments in its policies on presenting a fair balance of benefits and risks. Print ads can have the detailed information on another page; broadcast ads can refer to a magazine ad that contains product information. Given past compromises, FDA should be able to propose a solution for fair balance in web communications without waiting for comprehensive policies.

FDA already pre-reviews many ads to ensure claims about products are accurate, consistent with product labeling and supported by scientific and medical data. This could expand to include web copy of various sorts. Comprehensive policy is not required to get started on a limited, trial basis.

The web increases access to off-label product information by allowing greater access to news, medical journals and patient sites. This is on FDA's mind when thinking about developing Internet guidelines. The agency fears that widespread availability of off-label information will lessen a company's incentives to file for FDA approval for additional indications. Getting more indications on-label is a serious and important public policy issue that FDA and industry should be discussing. It is only incidentally about web communications.

A broad dissection of the virtues and limitations of the web might lead to comprehensive FDA guidelines on product communications on the Internet. But this may be years in the making and obsolete when issued.

Instead, discussion should focus on each of FDA's concerns, of which I have mentioned three. Most can be dealt with now. Some will turn out not to be Internet policy concerns at all. There is no reason to wait for some overarching Internet policy.

Steven

As additional background, here is FDA Matter's interpretation of the dynamic nature of web communications:

Web 1.0 (one-way dissemination of information) is a more flexible and customizable way of delivering the same messages as print and broadcast. We are several years into the next phase, Web 2.0 (interaction and dialogue). Just emerging is Web 3.0 (intelligent software gathers and interprets information and dialogue). Print and broadcast can only duplicate Web 2.0 and 3.0 functions by transferring their content onto the web, at which point they face the same lack of clarity from FDA.

Here is a related FDA Matters column:

Patients Come First
November 11th, 2009

It is a distracting time for the biopharmaceutical and medical device industries, with health reform, mega-mergers, and a constant stream of new investigations by US Attorneys and others. All this frenzy makes it a good time to stop, draw a breath and remember why seriously-ill patients care about the success of biopharmaceutical and medical device companies. Read the rest of this entry »

Executions in China: A Thanksgiving Message

Sometimes it takes other people to give us a perspective on our own values.

Today, Associated Press reports that two men were executed in China for tainting milk powder with melamine, an industrial chemical. The adulterated milk killed at least six children and reportedly sickened more than 300,000. Those executed were the dairy farmer and milk salesman who were at the center of the scheme. The general manager of the dairy company, Sanlu Group, received a life sentence after pleading guilty.

A little over two years ago, China executed Zheng Xiaoyu, the head of China's FDA for accepting bribes to allow untested drugs to be approved for marketing. His deputy was given a death sentence that sources believed would be commuted to life imprisonment.

Should we be thankful that we live in a "civilized" society where executions are rare and limited to murders, rapists and child molesters? Even a sentence of "life imprisonment" is rarely meted out to non-violent criminals.

Or should we wonder why we aren't we more serious about intentional gross negligence that has the likely outcome that someone will die? I believe the Chinese would argue that the farmer and the salesman were as responsible as if they had held a gun to the head of six children and murdered them. In the US, the consequence of murdering children in this fashion would likely be execution or life imprisonment.

This suggests that we are not so far apart from the Chinese in our outrage at murder and toward murderers. This has been part of the rules of civilization for several millennia, but not respected in all countries of the world today. We should be thankful to live in a society that considers the most severe punishments as appropriate for murder.

What is different (and interesting) is the concept of a heinous crime. The worst possible interpretation is these were commercially-motivated executions, designed to show the world that the Chinese are tough and their products getting safer. Even still, six murders were involved in the milk tainting case and one purpose of punishment is deterrence. Whatever we may think, those considering crimes involving fake foods and drugs will think twice (and twice again?) before proceeding in China.

We haven't sent the same message to would-be malefactors in the US. Given this, we should be thankful to FDA for every day we don't encounter willfully adulterated foods and intentionally fake and dangerous drugs and devices.

Steven

PS: To anticipate and deflect some outraged feedback, this column is specifically about gross negligence where the person knew or should have known in advance that someone would die. Such events occur more often than any of us would acknowledge, although it is not an "every day" event in the United States.

November 24. 2009 news story on executions in the tainted milk scandals:

http://news.yahoo.com/s/ap/20091124/ap_on_bi_ge/as_china_tainted_milk/print

July 10, 2007 news story on the execution of the head of China's FDA:

http://www.nytimes.com/2007/07/11/business/worldbusiness/11execute.html

The Perils of Living in a Bubble

This past week, the US Preventive Services Task Force (USPSTF) issued its revised recommendations for breast cancer screening and mammography and set off a firestorm of criticism. Among the controversial items was changing initial mammography screening from 40 to 50 years of age, recommending mammography every two years instead of one, and urging an end to the teaching of breast self-examination.

There is a valuable lesson for FDA in how the announcement and aftermath unfolded.

FDA Matters is amazed at how unprepared the Task Force seemed to be for criticisms from individual patients, health professional groups and Members of Congress. It is as if they were unaware of how much comment, confusion, and dissent their views were going to generate. The Agency for Heathcare Research and Quality (AHRQ), which provides support for the Task Force, seemed no better prepared.

There may be a number of reasons why the Task Force didn't see the need to prepare better or didn't care about the responses they would receive. One possibility is that the USPSTF is made up of primary care doctors and statisticians and doesn't reflect the broader perspective of medical specialists, who provide much of the nation's care.

There is also a deep schism between those relying on statistical modeling (such as the Task Force) and those believing that common sense, patient need and clinical experience should be weighed before decisions are made. Ultimately, the Task Force conducted its business in a bubble, isolated from public discourse and perceptions and with no accountability to the women whose lives will be impacted.

In contrast, the American College of Obstetrics and Gynecology (ACOG) released its recommendations later in the week, calling for less frequent screening for cervical cancer and for screening to be initiated at a later age. Their views received appropriate attention, but generated very little controversy.

ACOG supported their position with analyses that pointed to when and how cases are identified in this slower growing cancer. They documented clinical consequences (not just cost impacts) of additional unneeded diagnostic and treatment activities. Clearly, they had engaged practitioners and other organizations in their process…and had taken their input seriously.

There is a constant tension between high-minded decisions and the realities of clinical diagnosis and care. FDA must balance these every day. Some days they do better than others.

Risk Evaluation and Mitigation Strategies (REMS), a relatively new FDA patient safety and communications initiative, represents an area that will constantly challenge the agency's ability to balance stringent purity with "real world" practicality. Under a REMS agreement with a biopharmaceutical company, FDA tries to assure that the risks of approved products are properly communicated to healthcare professionals and patients and that systems have been put into place to reduce potential adverse events and treatment failures.

To date, most REMS programs appear to reflect the complexity of drug information and distribution. Greater challenges lay ahead….and FDA may struggle to communicate its decisions and rationale well.

If FDA lives in a bubble, unprepared for people's perceptions and needs, then REMS will become a major area of controversy. As ACOG demonstrated this week, it is possible to communicate the value of new approaches to good medicine, without losing sight of what is understandable and useful for patients.

I think that Drs. Hamburg and Sharfstein have made a good start at opening up FDA's insular world. Their experiences in running big-city health departments have taught them to value real-world solutions, geared to the majority of Americans who live outside the bubble and want to understand decisions that affect them.

Steven

CARS: The Vehicle for FDA’s Future

Since Labor Day, Commissioner Hamburg has spoken a number of times about the importance of regulatory science. She is right. FDA must have the scientific tools and methodologies to be a 21st century regulatory agency. FDA needs to define regulatory science, develop programs to support it, and package them in a way that will quickly bring recognition and funding.

This is a large task for Commissioner Hamburg to take on while running FDA and overseeing products that account for one-quarter of consumer spending. Yet, the agency will never improve if she doesn't find the time. Given increasing globalization, ever more complex science, and new Congressional mandates, the agency may even lose ground without important advances in regulatory sciences.

FDA is already involved in creating scientific tools and methodologies to support good decisions. The Critical Path Initiative (CPI) has been an important first step in creating a list of worthwhile projects to advance regulatory science. Many have been funded.

The National Center for Toxicological Research, a backwater of sorts at FDA, has been quietly supporting the scientific needs of the rest of FDA by developing new scientific tools, methodologies, and knowledge. Subtract field activities from the budget of the Center for Food Safety and Nutrition (CFSAN) and a large part of the Center's remaining budget is devoted to advancing regulatory science (e.g. creating faster assays to test for bacterial contamination).

The Center for Drug Evaluation and Research (CDER) also plays a role. Developing biomarkers is part of advancing regulatory science, as are new tools for surveillance and bioinformatics. The value is realized when these become part of tomorrow's regulatory decisions.

CPI was once considered the way to pull all of these activities together to advance regulatory science at FDA. It has not developed the vision or support necessary to accomplish this. Efforts to develop public-private funding for CPI activities have also been a distraction. We now know that Congress needs to fund these activities so the regulators lead regulatory science, not the regulated.

Several months ago, FDA Matters proposed the creation of the Center for the Advancement of Regulatory Sciences (CARS) at FDA. The Center was to be a defining enterprise—consolidating existing activities within FDA, providing a separate basis for advocacy and funding, and making clear that advances in regulatory science serve the future needs of the FDA Centers. I believe the CARS concept can be a starting point for discussing how advancement of regulatory science can become integrated into FDA's mission.

By talking about advancing regulatory science, Commissioner Hamburg is onto something important. We need to support her and help her develop broad acceptance of regulatory science among the policymakers who authorize programs and appropriate monies for FDA.

Steven

A definition of "regulatory science" and additional discussion are contained in my earlier columns:

Save the Critical Path—Part 1, June 17th, 2009

The American public and the global marketplace wish to have access to innovation—whether in medical products or foods. Simultaneously, there are strong countervailing concerns about product safety. Both occur within an environment in which FDA's knowledge and tools are inadequate and failing.

The Critical Path program and related initiatives in CFSAN and other centers are designed to meet this challenge. Unfortunately, there has never been a sustained agency-wide commitment to these efforts. Further, most of Congress has not embraced the Critical Path, either conceptually or with substantial funding. Read the rest of this entry »

Save the Critical Path—Part 2, June 28th, 2009

Transforming FDA into a first-class, 21st-century regulatory agency will not be easy. It requires planning, commitment and a broad vision. Science-based decisionmaking is a central part of the transformation, but it doesn't just happen by itself. Regulatory science needs to provide the tools, standards and knowledge for FDA to handle an ever-more complex world of science and commerce. Read the rest of this entry »

The Science Board’s IT Report: Too Technical to Read, Too Important to Ignore

Some of FDA's most difficult tasks are: defining the agency's role in nanotechnology, creating a pathway for follow-on biologics, implementing a risk-based food safety system, and establishing the right policy for "new media" communications.

All rolled together, they are not as complicated or important as transforming information technology (IT) at FDA.

The anecdotes are legion:

• adverse events reports come in electronically, are printed and re-keyed into a database;
  
• hardware and software vendors bring people out of retirement to service FDA's out-dated systems (so-called legacy systems);
  
• a report e-mailed to Capitol Hill for the next day arrives after the meeting.
  

I can only vouch for the last one, but the others are believable.

In August, the external FDA Science Board reviewed a report on information technology submitted by its subcommittee. FDA has put substantial resources and made valuable commitments to creating new systems. The biggest gains have been in infrastructure. Progress is being made in hardware, software, integration, capacity, security, infrastructure, and planning.

Clearly, the subcommittee liked what it saw. Their review also highlighted continued challenges in creating a 21^st century IT system capable of supporting all of FDA's mission-critical activities.

The report made some news in trade publications for a few days, then was quickly gone from public view. The issues are too technical to interest most people. Even with a glossary, I confess to not understanding at least half of the report.

Maybe the lack of visibility is alright if FDA and its contractors can absorb the many suggestions and recommendations in the report. FDA Matters recommends that an external review be undertaken every 3 or 4 months to be sure the effort remains on track.

While one can quibble about specific Congressional directives that depend on information technology systems, the main direction has been appropriate. FDA needs to fix the machines, create the databases, and integrate functions

This initiative is so important that non-IT people need to keep informed. Simply put, the agency's ability to conduct its work, increase effectiveness, and become more sophisticated is more contingent on the IT overhaul then the personnel that are being hired into the various centers to conduct the actual work of the agency.

In 5 years, nobody at FDA will be able to do their job if the IT overhaul isn't a success.

Steven

The FDA Science Board subcommittee report was completed in August and can be found on the FDA website at:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ScienceBoardtotheFoodandDrugAdministration/UCM176824.pdf

In an earlier column, I addressed another facet of the agency's IT challenge:

Turning Data into Knowledge   June 2nd, 2009

Through statute and directive, FDA has been asked to collect, analyze, interpret and utilize massive amounts of data. This includes biological, clinical, adverse event, production and distribution data, medical and food product tracking, and the Sentinel system for early discovery of potential drug safety problems. The systems are not in place to do any of this, at least not at the required level of sophistication. Even if they were, sifting valuable information from background noise is extraordinarily hard. As a result, FDA needs to manage Congressional and public expectations as to "what is possible and when." Read the rest of this entry »

Why Do Some People Dislike FDA?

Yesterday, I received separate posts from three organizations that are anti-industry, one of which dislikes FDA and one of which hates FDA. They are not alone in these feelings. There are many groups and individuals who believe that industry and physician professional societies run FDA. I don't accept their premise or the "facts" from which they launch attacks.

On the same day, I got an update from Americans for Medical Progress (AMP), an organization that educates media and the public about the importance of animal testing in advancing human health. FDA could not do its job without animal studies, both their own and those submitted by sponsors. AMP is among the "good guys" and can always use more support for their work, www.amprogress.org.

I would like to say that all the advocates, such as AMP, are realists and advance the common good by advocating for NIH and FDA….and that all the extreme critics and haters are irrational and inflammatory. It isn't that simple.

The FDA I know is a regulatory agency staffed by smart people trying to do their best. Given its mission, FDA is inherently imperfect and always vulnerable to criticism. The agency has been chronically understaffed and hasn't been able to give every decision the attention it might deserve.

I am on my tenth FDA commissioner. Bad decisions were made during each of their tenures and they all experienced bad days when nothing seemed to work the way it should. Meantime, hundreds of drugs and devices have been approved without subsequent mishap. Our food supply is vulnerable because of globalization, yet it is the safest in the world.

Those who dislike or hate FDA focus almost exclusively on those bad decisions and on the agency's most difficult days. In their minds, that is the FDA. They don't see the rest of the days where things went well: public health improved, patients received new FDA-approved therapies and more than 300 million Americans ate food without an outbreak of foodborne disease.

Because they ignore the good days and focus only on the bad, the haters feel justified in concluding that the agency is corrupt and deserving of vilification. I disagree vehemently with this premise.

I see some of the same problems they do, but recognize the problems are only a small part of FDA's mission and accomplishments. Given this wider perspective, it is misguided to impugn FDA and its staff. Bad days occur, but not because of impure motives or because agency officials blindly listened to the industry's views.

Those who dislike and even hate FDA serve a purpose. Scrutiny makes everyone think and work a little harder to make good decisions. Companies with safe manufacturing plants can still get in trouble with FDA if they haven't documented their safety-related activities. So, too, FDA needs to be able to show it has listened carefully and decided wisely. It can't just assert its decisions are good ones. Better documented and more predictable decisions are needed.

All of this can be taken too far….so that over-cautious decisions become a source of delay or failure in meeting the needs of patient and consumers. The haters would certainly like it that way. The extreme critics serve some useful purposes in a narrow sense, but they are wrong about the big picture of FDA's mission, intent and accomplishments. It is critical that we act civilly in the face of this hatred. That said, we must act to counter their arguments and make sure that the extreme version of FDA-bashing has no reputable standing in Congressional, media and public discourse.

Steven

More predictable decisionmaking at FDA was discussed in an earlier column.

In Praise of Predictability September 3rd, 2009

FDA has always found it challenging to make its actions predictable. This problem will worsen for a number of months while Dr. Hamburg redefines the agency's mission, policies, actions and working assumptions. Once this has been accomplished, the agency will become dramatically more predictable to stakeholders, including Congress. Read the rest of this entry »

To Whom Much is Given, Much is Expected

There is good news to report now that House-Senate conferees have finalized work on FDA's FY 10 budget. FDA received $306 million (15%) more to spend this fiscal year. Every center will have more resources to work with (see table at the bottom of this article).

This is the third good year for FDA, after years of bad ones. The agency is still severely underfunded, but progress is finally being made. Now the hard work begins: spending the new money wisely and showing that it has been used to accomplish important public health missions.

Because FDA has been shortchanged for so long, it is almost unfair to expect results in anything less than 3 to 5 years. However, Congress will only be patient for so long. FDA and Dr. Hamburg don't have much time to produce serious improvements.

Even acknowledging that a vastly larger appropriation is still needed, it is understandable why Congress won't wait very long before expecting results:

• In the past two fiscal years (since FY 08), the budget for food programs has increased by more than 50%. Much of the extra money is allocated for field activities (inspections and enforcement).
  
• Budgets for CDER, CBER and CDRH have all grown by more than 30% in the last two fiscal years.
  
• The overall agency appropriation has increased by $776 million over the last three fiscal years (since FY 07). The represents a 50% increase in funding.
  

Dr. Hamburg and Dr. Sharfstein are responsible for moving the agency forward. Congress and the American people will hold them accountable.

They can't do it alone. FDA staff is smart, committed and largely effective. Yet, territorial behavior is fairly common and creates multiple problems. The Commissioner must create a vision of the agency that gives FDA employees a reason to work for the entire agency, not just for their own division or unit.

"To whom much is given, much is expected" applies to all of FDA. It will take a team effort to meet the lofty, but legitimate, expectations that have been created.

------------------

In prior columns, I have focused on other aspects of the appropriation process. Here is an update:

• FDA's Office of Regulatory Affairs (ORA) receives more appropriated funding (about 1/3 of the total) than any other part of FDA. For FY 10, appropriated funding directed to ORA increased by 20% to $847 million. This situation led me to dub the head of ORA as The Uncrowned Prince of FDA, at http://www.fdamatters.com/?p=499.
  

• Unfunded mandates are a continuing concern for FDA, threatening the funding progress that has been made over the few years. Pending legislation (e.g. food safety reform) has not advanced since I last wrote on this topic. On a smaller scale, the FY 10 conference report adds $7 million to cover some new program requirements, in effect acknowledging that these would otherwise be unfunded mandates. My column, Unfunded Mandates Threaten FDA, is at: http://www.fdamatters.com/?p=375.
  

Steven

The House-Senate conference report can be found on pages 210 to 216 at: http://appropriations.house.gov/pdf/Ag_Conf_Rpt_FY2010.pdf.

FY 10 Appropriations for the Food and Drug Administration

Compared to Earlier Years (based on Conference Agreement)

Budget Authority Appropriations (does not include user fees)

(Prepared by the Alliance for a Stronger FDA)

Function Note: budget authority only, by center	FY 08 Actual (December 2007)	FY 09 Final (March 2009)	FY 10 President's Budget Request	FY 10 House-Senate Conf. Final
Food	$   510 million	$   649 million	$   783 million	$ 783 million
Human Drugs	$   353 million	$   413 million	$    458 million	$ 465 million*
Biologics	$   155 million	$   183 million	$    206 million	$ 206 million
Animal Drugs/Feed	$     97 million	$   116 million	$    135 million	$ 135 million
Devices & Radiological Health	$   238 million	$   280 million	$    315 million	$ 315 million
Natl. Ctr. For Toxicological Research	$    44 million	$    52 million	$     59 million	$ 59 million
HQ, Office of Commissioner and Other	$    97 million	$   121 million	$    144 million	$ 144 million
Rent & Facilities Cost	$  220 million	$   223 million	$    237 million	$ 237 million
SUBTOTAL, Salaries and Expenses	$1.714 billion	$2.039 billion	$ 2.338 billion	$ 2.345 billion
Building and Facilities Repair	$ 8 million	$ 16 million	$ 12 million	$ 12 million
TOTAL, ALL Budget Authority Appropriations (no user fees)	$1.722 billion	$2.055 billion	$ 2.350 billion	$ 2.357 billion

* The $7 million increase is intended to pay for some of the additional costs that CDER will bear as a result of Conference report language that contains increased financial commitments to the Critical Path program, generic drug reviews and other CDER programs.

“No Surprise” That Medical Devices Are Under Scrutiny

Five weeks ago, I wrote a column entitled, "Re-Evaluating the Medical Device Approval Process." It was not widely-read. I assumed it was because everyone already knew that a review was underway at FDA with more activity coming. Apparently, I was wrong.

A lot of people, including Wall Street, seemed surprised when FDA kicked its medical device re-evaluation effort into high gear over the last 10 days. I am not sure why they were surprised. The FDA re-evaluation was a certainty and has significant consequences for businesses and investors.

The medical device process and 510(k) approvals have been in question for a number of years. It has been a long time since there has been a thorough re-evaluation.  GAO is perpetually raising concerns about medical devices and a number of key Congressional leaders are interested. Also, the 510(k) approval process is necessary and defensible, but not easy to understand. It will continue to be a target for media, investigators, and crusaders until the process is re-evaluated and any needed changes made.

In April, Principle Deputy Commissioner Sharfstein acted affirmatively in response to the GAO's early 2009 report on medical devices. Last week, FDA set out its plans for a credible, effective re-evaluation of medical devices. This latest phase of the re-evaluation process featured three major items from FDA:

• Commissioning an IOM study of the medical device classification process, focused on the 510(k) process (which allows new devices to be approved by showing "substantial equivalence" to previously approved products);
  
• Release of FDA's analysis and recommendations based on review of the decision to grant 510(k) approval to a device manufactured by ReGen Biologics; and
  
• Creation of internal working groups to recommend and implement changes without waiting for the IOM report.
  

As FDA made clear during its press conference, the ReGen case is not the reason for FDA's review of the medical device approval process. Rather, approval of the ReGen device has proved to be instructive because so much went wrong. Among other things, there were violations of internal FDA protocols, inconsistent interpretations of the law, widespread confusion within FDA, poor communications with the sponsor company, and questionable involvement of Members of Congress

FDA has turned this experience into an inventory of ways to improve its performance in reviewing medical devices. FDA's analysis of the ReGen approval is well-done and worth reading.

My earlier column had two purposes: to alert readers that medical device re-evaluation is a large, pending activity within FDA; and to argue for FDA to take strong steps so that the re-evaluation process would not be driven by Congressional hearings and legislation.

FDA has now taken those strong steps. I hope that Congress will respect this effort and not intervene.

If the medical device approval process is under re-evaluation….then scientific and medical review staff at FDA (and their supervisors) are going to be careful in their actions. Protocols will be followed, every step will be fully documented, all interested staff will be involved, and near-final decisions will be reviewed more carefully.

This will slow the FDA approval of medical devices until needed changes have been made and confidence in the process restored. Does this actually surprise anyone?

Steven

My original column is at: http://www.fdamatters.com/?p=448. This includes my explanation of the issues and why re-evaluation of the medical device approval process was certain to occur. I conclude that the end-result will be "more than a few tweaks and less than an overhaul" of the medical device approval process.

The FDA press release announcing the IOM study of the 510(k) process: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm183497.htm

The ReGen report and the FDA news conference transcript: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm183745.htm

FDA Should Stay Out of Health Care Reform

When the new NIH director, Dr. Frances Collins, was interviewed by the New England Journal of Medicine, he stated that one of his priorities is to: "put science to work for health care reform." I hope that Dr. Hamburg isn't having similar thoughts about involving FDA in health care reform.

Health care reform is our nation's #1 health priority. It does not lack for attention, participation and debate. Hundreds of billions of dollars will be driven by the outcome. However, our country will not be better off if every health-related agency diverts its attention and finite budgets to the cause.

I have been watching NIH for more than 30 years. All NIH directors have had the same goal: keep NIH and its biomedical research mission out of politics. Some directors have done this by pretending politics doesn't exist. Others have protected the agency by being consummate politicians. Both strategies have been successful at different times and in the hands of different directors.

I do not remember any NIH director openly welcoming politics into the agency.

The NEJM interviewer asked Dr. Collins' whether NIH will become politicized if it takes an active role in health care reform. He responded:

That is always a risk. I am exploring this. I don't know the answer precisely. I do think the idea that NIH's responsibility for trying to influence public health ends at the point of running a clinical trial and publishing the results may be a little narrow for the climate that we are in. While we are a research organization, and that's always going to be our focus, maybe there is more opportunity now….."

"Putting science to work for health care reform" will politicize NIH. This will not be good for biomedical research...or for America's patients who are waiting for treatments and cures. I hope Dr. Collins' comes to this realization quickly and does not let NIH get distracted.

This same point applies equally to FDA. The agency's plate is full with mission-appropriate responsibilities, including implementation of its new authority over tobacco. More work is coming through food safety reform, follow-on biologics and other administrative and legislative initiatives.

The new FDA leadership has made a strong point that science, not politics, should be the basis of FDA decisionmaking. To this, we can all say: bravo! Involving the agency in health care reform guarantees that politics will creep into the agency's activities and conclusions.

Getting involved in health care reform may be trendy….but it will be destructive, if not disastrous, for FDA. The agency needs to stay on mission and out of health care reform.

Steven

Dr. Collins' NEJM interview can be found at: http://healthcarereform.nejm.org/?p=1808&query=TOC.

Dr. Collins Meet Dr. Hamburg

FDA and NIH should be working together more closely and productively. For this to occur, Dr. Hamburg and Dr. Collins need to bless a higher level of cross-agency commitment. The critical next step is a publicly announced meeting of the two to develop and advance a common agenda.

In an earlier column, I concluded that FDA and NIH are natural allies, with closely-related purposes as public health agencies. They share a similar worldview that medical and scientific knowledge should be derived from random clinical trials.

Subsequently, I wrote a column about the cultural and organizational barriers to a closer working relationship between NIH and FDA. I urged Commissioner Hamburg to meet with Dr. Collins to start breaking down those barriers.

Dr. Collins was interviewed in last week's New England Journal of Medicine and stated his five priorities:

• integrating new technologies to make basic research more productive;
  
• translating basic research into clinical applications;
  
• science in support of health care reform, notably comparative effectiveness;
  
• global health; and
  
• reinvigorating the NIH-oriented research community through support for more young researchers, more innovation-oriented grant review panels, and a stable and predictable funding trajectory for biomedical research.
  

These are appropriate priorities for NIH, but not reassuring to me as an FDA advocate.

Dr. Collins knows that most NIH-driven medical advances can't go "from bench to bedside" except through FDA. Yet, he only mentions FDA once in the interview—to observe that the FDA has put the only clinical trial involving stem cells on hold. Although cooperation on this trial is a good thing, NIH and FDA need a broader, deeper and longer-lasting set of activities and goals.

Undoubtedly, NIH and FDA representatives are discussing how their new bosses can work together within the new Administration. This is necessary and useful, but not sufficient to dramatically improve the relationship between the agencies.

I am clamoring for something that is more public than emissaries feeling each other out.

The two agencies working together are powerfully synergistic….and boundless in the benefits they could bring to the American people by joining forces. The involvement of NIH Institute Directors and FDA Center Directors is essential to building a better, more productive relationship. But it will never happen if it requires them to overcome cultural and tribal impediments that keep resource-maximizing organizations from fully sharing responsibilities, decisions and monies.

Unless Drs. Collins and Hamburg personally create the expectation of cooperation at the highest levels, there will be little movement at the center/institute level. Only Dr. Hamburg and Dr. Collins can set the proper tone, provide guidance and break down the barriers. I previously asked Dr. Hamburg to meet with Dr. Collins.

Now, I urge Dr. Collins to meet with Dr. Hamburg. Please.

Steven

Dr. Collins' NEJM interview can be found at: http://healthcarereform.nejm.org/?p=1808&query=TOC

My two earlier columns on this topic:

FDA and NIH: Natural Allies
June 12th, 2009 http://www.fdamatters.com/?p=299.

Dr. Hamburg Meet Dr. Collins
July 12th, 2009 http://www.fdamatters.com/?p=366.

The Uncrowned Prince of FDA

Which FDA line manager has the most appropriated resources to work with in FY 09? Is it Janet Woodcock, head of the drug center or Stephen Sundlof, head of the food center? The correct answer: neither.

The person with the most resources is Michael Chappell, Acting Associate Commissioner for Regulatory Affairs. In FY 09, he had primary responsibility for about $700 million, 1/3 of the agency's appropriation. He also had management responsibility for 3700 individuals, more than 40% of the agency's appropriated workforce. He is the uncrowned prince of FDA.

Few people know his name or much about the operational entity known as the Office of Regulatory Affairs (ORA). The Office's funding is tucked into each center's appropriation under the unremarkable line item: field. ORA does not even rate a link on the FDA home page. A description of ORA is two levels down:

The FDA's Office of Regulatory Affairs is the lead office for all FDA Field activities as well as providing FDA leadership on imports, inspections, and enforcement policy.  ORA supports the five FDA Product Centers by inspecting regulated products and manufacturers, conducting sample analysis on regulated products, and reviewing imported products offered for entry into the United States.  ORA also develops FDA-wide policy on compliance and enforcement and executes FDA's Import Strategy and Food Protection Plans.  http://www.fda.gov/AboutFDA/CentersOffices/ORA/default.htm

The relative invisibility of ORA appears to be intentional. For example, when the agency issues a press release about an enforcement action, the relevant center director gets the first quote; ORA is always quoted much further down.

Is ORA's continued low profile a good thing? I don't think so.

Congressional and media attention are increasingly focused on FDA's capacity to perform effective inspections and rigorously enforce the law. The agency's good name and public credibility are tied to success in these areas.

Since the Commissioner has so many roles, she needs someone to be the highly-visible, public face of tough enforcement at FDA. Two decades ago, when I worked at HHS, the Inspector General was a former professor who had become the supervisor of the organized crime units in the FBI's Chicago Office. He was a good, smart man and a friend…but you knew immediately that you didn't want to be a target of one of his investigations. FDA needs someone like him.

Well run, conscientious companies have little to fear. If you run a solid plant operation, import ingredients with care, use lots of system controls, and renew your commitment to pedigree and chain of custody, you are unlikely to be affected by a stronger ORA. If you have an inspections or enforcement problem: cooperate with FDA and correct it quickly.

On the other hand, if you are cutting corners, heedless to consumer and patient risk, or stonewalling the agency, you deserve what you get from ORA, strengthened and visible or not.

Commissioner Hamburg intends to make the agency more scientifically knowledgeable, more innovation-oriented and a more reliable partner in its interactions with industry and other stakeholders. A year from now, she will have little leeway to accomplish these goals if she hasn't taken the necessary steps to increase inspections and strengthen enforcement.

In doing so, it makes sense to take ORA out of the FDA shadows and make it a more visible force.

Steven

Post-script: While controlling a surprisingly large amount of the resources, ORA does not operate alone. Each center works with ORA to jointly develop work plans that direct inspection and enforcement priorities for the next fiscal year. My understanding is that this process is a serious endeavor that consumes an appropriately large amount of staff time and effort.

In Praise of Predictability

FDA has always found it challenging to make its actions predictable. This problem will worsen for a number of months while Dr. Hamburg redefines the agency's mission, policies, actions and working assumptions. Once this has been accomplished, the agency will become dramatically more predictable to stakeholders, including Congress.

I have written how Drs. Hamburg and Sharfstein's public health backgrounds make them different from their predecessor over the last 35 years--who were mostly researchers, teachers and clinicians from academic health centers. "Public health" as practiced in a big city health department has a gritty immediacy that shapes every activity. In contrast, academic health centers are devoted to providing clinical services to patients and educating students and house staff. Public health is a valuable by-product, but rarely a primary mission.

"Predictability" also means something different in city government than it does at a university. Public health departments are on the frontlines for all public health decisions--from the availability of flu vaccine to monitoring restaurants for sanitary conditions. Leadership must persevere in the chaotic environment of a big city. Every day brings unpredictable events generated by external forces. Success is achieved by having a tight organizational structure and "standard operating procedures" (SOPs) that cover nearly every potential challenge. In most situations, employees, stakeholders, mayors, and councilmen know what to expect. .

Unpredictable external events play a much smaller role in the life of an academic medical center. The combination of a medical school, a teaching hospital, and biomedical research labs is considered one of the most complex systems in our society. Leadership is more inwardly focused, trying to make the different components work together….and work well. Organizational predictability almost always take a backseat to people management, work flow and revenue generation.

My point is that Drs. Hamburg and Sharfstein have been schooled in the value of creating predictability. Generally speaking, their predecessors were not.

Predictability is in short supply at FDA currently--because the new leadership team is identifying the agency's internal and external problems and constructing appropriate solutions. The "new normal" that eventually emerges will be: more focused in the face of a broadening mission; more committed to serious enforcement; and more dedicated to innovation that is consistent with public health and science.

In the process, agency policies and actions will be increasingly based on SOPs, public and industry guidances, and clear articulation of scientific and legal positions. These will be implemented by a larger, tighter organization that will be more consistent in its decisions.

Although some of this evolution will be painful for FDA-regulated industries….they will eventually benefit from greater predictability and less ad hoc decisionmaking at FDA. And all stakeholders benefit from the increased public credibility that FDA will earn when its decisions are easier to understand, better grounded in science and public health and more predictable.

Steven

Re-evaluating the Medical Device Approval Process

Earlier this year, a GAO report concluded that many high risk medical devices have not been adequately reviewed. In June, the House Health Subcommittee held the first of what may be a series of hearings on medical devices. The media appears increasingly interested in medical devices and is raising more questions.

All these events are a prelude to FDA and Congress undertaking a major re-evaluation of the product approval process for medical devices. It would be a relief if FDA could diagnose and treat its own medical device problems, leaving the Congress and the media to watch.

Whether FDA acts or Congress makes changes in law, I believe that the overall device approval process will change. Yet, it will still be recognizable to those who have worked with the 1976 Medical Devices Amendments, as further amended in 1990. During the re-evaluation process, every aspect of medical device regulation is going to be scrutinized as never before.

The stakeholders are likely to divide into two camps:

• those who think the system is fine with a few tweaks, and
  

• those who think a substantial set of changes are needed.
  

The final result is likely to be somewhere in between: more than a few tweaks, less than an overhaul.

There are multiple issues to address, such as device classification, post-market studies and surveillance, safety of devices, inspections, etc.

Setting the appropriate level of premarket review for a medical device is likely to be the most contentious issue. Under the Federal Food, Drug and Cosmetics Act (FDC Act), as amended, a device can be considered a class III device if it presents a high risk to patients and society or if it is based on a new technology. Class III devices are required to submit data on safety and efficacy to FDA. The sponsor can only market the product if FDA grants a Premarket Approval (PMA).

The vast majority of devices—including some class III devices--do not have a PMA. Some devices placed in class III under the FDC Act are based on a new technology and may not represent a high risk. In these cases, FDA may down-classify the device to class II, which are devices that represent a moderate risk.

Class II devices generally require a 510(k) Premarket Notification. Under the 510(k) process, a sponsor must show that a device is "substantially equivalent" to a device already marketed. The 510(k) is significantly less rigorous than a PMA and "substantial equivalence" has been broadly interpreted.

In April, the FDA responded to the GAO report by announcing that 25 types of class III medical devices will undergo safety and effectiveness review. After receiving information from sponsors, the agency will evaluate the risk level for each device type. Some of these devices are likely to become class II. Those devices found by the FDA to be of high risk to consumers will be required to submit PMA applications.

This makes me wonder: does FDA currently have the statutory authority to resolve most of the issues that surround the medical device approval process?

If so, FDA should evaluate issues, then act to solve any problems themselves. This would provide better assurances about the safety and effectiveness of medical devices, while avoiding the delays and drama that are inherent in the Congressional process.

This column is dedicated to the memory of Senator Ted Kennedy,

who was a champion of an effective FDA over many decades.

Steven

Public Health Leadership at FDA

Dr. Hamburg and Dr. Sharfstein have a style and approach that is already distinct from their predecessors. One of my earliest columns, two weeks before Dr. Hamburg's swearing in, explored why.

I predicted it would take 6 months for the patterns to be clear. We are halfway there, still evolving, and right on track. Do you agree?

Steven

From May 15, 2009.

The world will soon realize that the new FDA leadership–Dr. Hamburg and Dr. Sharfstein– are cut from an entirely different mold than their predecessors. When Dr. Hamburg is sworn in, she will formally begin an era of public health leadership at the agency. FDA staff and agency stakeholders will eventually come to appreciate that this difference is good for FDA.

It is a perfect time to put the agency in the hands of experienced public health leaders with real world experience. The shift will be both interesting and salutary. Notably, there will be a consistent standard in decisionmaking. The answer to every question and pressing issue will be: we will explore what is right from a public health perspective, and then act accordingly.

FDA staff and agency stakeholders argue for their position by saying they are advancing the public health, while secretly believing that other factors will drive the final decision. It is disarming, then, for the Commissioner to actually treat "public health benefit" as the agency's North Star.  Of course there will be many disputes, but everyone will have to build their rationale on public health grounds, knowing that it is the real basis of decisionmaking.

Several misunderstandings drive concerns about public health leadership at FDA. Public health is about helping people and communities to get healthy and stay healthy. Prevention is preferred because it preserves health, while therapies "only" restore health. Preferring prevention is not the same as being against therapy. Public health is not anti-therapeutic nor could any FDA commissioner be anti-therapeutic.

Public health does not require safety to be an absolute value that cannot be offset by other considerations. Innovation to restore health is just as much a public health value as safety. Dr. Hamburg has affirmed this.

What it means to run a big city health department has also been misunderstood. The imperative to act is immediate and real, but you learn that "what appears to be real" has to be examined before any decisions are made. Nothing you're told can be relied upon until it had been rechecked and sometimes double and triple re-checked. An over-simple example: reports about unsanitary conditions in a restaurant might just be from the eatery across the street that has lost business.

Dr. Hamburg and Dr. Sharfstein have limited track records on FDA issues. This uncertainty breeds anxiety. Six months from now, everyone will see that the agency is being run by steady, pragmatic leaders. Indeed, it is quite difficult to run the public health department of a large city without these virtues.

Hot Town, Summer in the City

Thirty years ago, Washington closed down every August. The heat and humidity were beastly and Congress was gone. Over the intervening years, DC has become a 12-month town, with August one of the busier times.

For FDA, there has been so much August-action that this column had to fit my analysis of two developments: the appointment of the new tobacco center director; and the reorganization of the Commissioner's office.

Appointment of the first Director of the Center for Tobacco Products. In an earlier column (http://www.fdamatters.com/?p=303), I identified the ideal credentials for the new director of the tobacco center:

• broad government experience,
  
• close-up familiarity with FDA,
  
• public health and regulatory perspective, and
  
• the gravitas and presence to handle the heat from Congress and stakeholders.
  

Commissioner Hamburg's choice, Dr. Lawrence Deyton, is a near-perfect match. He is scientifically-grounded, policy savvy, has strong managerial experience and has worked at VA, NIH, HHS and as a staffer in Congress. He is currently the chief public health and environmental hazards officer at the Veterans' Administration.

Based on news accounts, Dr. Deyton has experience with tobacco policy and cessation programs, but it is a very small part of his resume. He had no role in the long effort to create the new Center. None of the stakeholders appear to know him or to have worked with him. All of these are to FDA's advantage and underscore the political shrewdness of the choice.

Passage of the new tobacco law was anti-climactic. The appointment of the new director begins the part that is fresh and exciting. Government regulation of tobacco is finally a reality, with the mandate to turn rhetoric into action.

To Dr. Hamburg, I say "well done." To Dr. Deyton, I say: "never forget the enormity of cigarette-related disease and the need for the strongest possible public health regulations to combat it."

Re-organization of the Commissioner's Office. It is very seductive to imagine that moving boxes around on an organization chart solves problems. It doesn't.

Nonetheless, there is much to ponder in the newly-announced reorganization of the Commissioner's Office. It offers substantive changes that make sense. Here are the three most important:

• Creation of a new Office of Foods, headed by a deputy commissioner for foods. The food center and the veterinary medicine center will report directly to this new office, adding management responsibilities to what was previously a staff function. Creation of the new office ends confusion about who is in charge of food. These changes will take pressure off the commissioner. It creates the optimum structure for making foods more effective within FDA. Ultimately, this may decrease the perceived benefit of creating a separate food agency.
  

• Combining policy and planning with budget. These functions are closely related and need to provide similar visions of FDA's future. Reporting to different people has been an impediment.
  

• Elevating the Office of the Chief Scientist to deputy commissioner status, with more programmatic responsibilities. This provides renewed credibility to the oft-repeated message that FDA needs to elevate its scientific mission. It also increases the responsibilities of Dr. Jesse Goodman, one of the agency's most respected leaders.
  

Although this is still moving boxes around on an organization chart…these changes should make it easier for talented leadership to deliver optimum results. I like it.

Steven

One Disease + Two Concerns = FDA’s Need To Communicate Better and Modernize Standards

Diabetes is like other chronic diseases: matters worsen over time, the ultimate downstream consequences are severe, and patients can affect the course of their disease by careful attention to their health. One difference: diabetics have a valuable, universally available tool: blood glucose monitors and test strips. Larger lessons can be learned by asking: how reliable is that tool?

For more than 11 million Americans, monitors and strips are a central part of everyday life. Frequent readings let diabetics monitor their own situation and adjust diet, behavior and medications. They have all been taught to "live by the numbers."

A few months back, Gardiner Harris of the New York Times broke the story that blood glucose meters are allowed to have a +/- 20% margin of error. He also reported that different meters can produce dramatically different results from the same blood sample.

FDA has recognized the problem and is pushing for changes in international standards for the accuracy of diabetic meters. Failing that, they will probably go through the more lengthy process required by the Administrative Procedures Act. All this is good….and credit goes to Gardiner Harris and FDA leadership.

Meantime, diabetic patients are left to wonder whether their home meters are providing accurate and reliable information.

This concern was compounded by last week's announcement that certain types of strips cannot distinguish between glucose and other sugars. When combined with certain medicines and therapies, these strips may give inaccurately high readings.

FDA's public health advisory covered all the basics nicely: which meters/strips are involved, how FDA reached its conclusion, what patients should do next, etc. It was explicit in its direction to high risk diabetics taking any of the named medications: alert your doctors and decide on a different type of meter and strips.

It was much less helpful for the millions of diabetics who are committed to slowing their disease progression, but are not insulin-dependent or at risk for hypoglycemia (low blood sugar). They are just as dependent on accurate meter readings; except the immediate consequences are less drastic. They would want to know: given that sugars are in lots of products, why is the problem limited to a small number of medications? And: why doesn't dietary intake of non-glucose sugars result in inaccurate meter readings?

Public health advisories need to reflect a broad understanding of the patient audience and their likely questions. I suspect that this advisory missed the concerns of lower risk diabetics because the real public health target was hospitals using home monitors on seriously-ill patients. But the entire public gets the announcement…and diabetics who follow the news are already unsure whether meters and strips are tools or distractions. I assume there were good answers for them, but I couldn't find it in the public health advisory.

There is another point to make. Diabetic meters/strips are constantly being improved, but the standards for accuracy are old and don't reflect progress in computerization, miniaturization, fluid dynamics and bio-chemistry. With this example, FDA should start systematically identifying other drug, device, diagnostic and food standards that are based on old science and need to be modernized.

Neither FDA nor industry will be able to act quickly on updated standards. An FDA list, however, would put industry on notice to get started.

Steven

Gardiner Harris' most recent New York Times story on this issue:

Standards Might Rise On Monitors For Diabetics
July 19, 2009