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

A Busy Year for FDA Legislation

With Congress on August recess, it is time to review and comment upon this year's FDA-related legislation, which seems more far-reaching than usual. Matched with an activist agenda from FDA's new leadership team, this could be a watershed year for the FDA.

A new law gives FDA jurisdiction over tobacco products, a massive new responsibility. It will be funded wholly by user fees. FDA is prohibited from using appropriated dollars for any tobacco activity. An announcement of a new center director is expected very soon. I discussed the tobacco center at: http://www.fdamatters.com/?p=303.

Before departing for recess, the Senate passed its version of the FY 10 Agriculture/FDA appropriations bill. Since it is similar to the House version and the President's request, it seems certain that FDA will be getting $295M in additional appropriated funds. For a change, FDA funding should be in place before the new fiscal year starts.

The legislation presages two issues that will need to be addressed during the next two budget cycles:

• ever harder questions about how new monies are contributing to improvements in the public health. FDA is conscious that more scrutiny is coming and expects to be ready.
  
• tension between funding new FDA responsibilities and continuing to strengthen the long-underfunded agency core. My recent column exploring the consequences of "unfunded mandates" imposed on the agency is at: http://www.fdamatters.com/?p=375.
  

Food safety reform is the most likely to pass of the remaining FDA legislation. The House approved its version just before recess. The Senate is likely to respond and final legislation should reach the President within 6 months.

The Congressional Budget Office (CBO) developed an analysis of the House-passed food safety bill. Because the bulk of new mandates are not effective immediately, FDA costs will not increase in FY 10 and FY 11. However, even after subtracting income from new user fees, the cost reaches $368M in FY 12, $749M in FY 13, and about $1B in FY 14.  In short, FDA needs to grow by $1 billion in the next 5 years…just to cover new food responsibilities. Because it illustrates the unfunded mandates problem, I recommend the CBO report to those interested in FDA's future: http://www.cbo.gov/ftpdocs/104xx/doc10478/hr2749.pdf.

Legislation creating a regulatory pathway for follow-on biologics (FOB) is the next most likely to pass, probably as part of health reform. While it produces 10-year net savings for governmental and private insurers, the benefit will not go to FDA. I have heard (but can't verify) that it will cost $300M to set up the new program and about $150M per year for ongoing staffing and other costs. As with food, this is not a reason to oppose (or support) legislation, it is just an ongoing concern. My most recent analysis of FOB politics is at: http://www.fdamatters.com/?p=412.

Congress is again looking at drug reimportation. Although included in the Senate version of the Homeland Security Appropriations bill in July, it is likely to be stripped out in conference with the House. The issue will come up again because there are more than 50 Senators from both parties who favor reimportation. Were it to become law, it would have significant impact on FDA operations and funding.

In addition to FOB, health reform bills include other provision that will impact FDA directly. I will devote a later column to these miscellaneous FDA provisions, as well as some thoughts on how health reform itself might impact FDA.

A watershed year for FDA? It could be.

Steven

Dr. Hamburg’s Speech to the Alliance for a Stronger FDA

The Alliance for a Stronger FDA is the primary advocate for strengthening FDA through increased appropriations. It is a multi-stakeholder group that represents consumers, patient groups, health professionals, research advocacy organizations, trade associations and companies.

The Alliance was privileged to have Commissioner Hamburg address its quarterly member meeting on July 22.

She thanked the Alliance for the important work it is doing. She paid tribute to the Alliance's success in building consensus among a widely diverse group of stakeholders around increased funding for FDA. She specifically mentioned information technology (IT) as one of the areas where the Alliance has given visibility to an important agency need.

Dr. Hamburg spoke at length about the key challenges facing FDA and her priorities.  

Improving the Public Health. FDA is going to measure success in terms of public health outcomes. Because of the agency's unique and critical mission and historic underfunding, the new approach will explicitly link budget requests to achieving public health goals.

Increasing and Strengthening FDA's Regulatory Science Capacity. FDA needs stronger support for regulatory science and its science base. Investment and improvement must go together in regulatory science. This requires the agency to hire more expert regulatory scientists and collaborate more broadly with the scientific community outside the agency.

Meeting the demands that globalization places on the FDA mission to ensure the safety of food, drugs and devices. Not only must FDA develop a stronger scientific base, but scientific expertise must be available on a global basis.

Implementing the new tobacco regulation.  FDA is currently planning a tobacco center and in the process of hiring 600 staff. No other FDA components will be forced to make cuts as a result of the added tobacco responsibilities.

Creating readiness against a global pandemic. FDA is working on the lab tests, drugs and vaccines needed to respond to H1/NI and other strains of influenza. FDA will need significant resources to be successful because the job is both complex and unpredictable.

Dr. Hamburg made a number of other observations:

• FDA is trying to recreate its capacity to react and prevent crises, but is constrained by resources.
  
• The recent GAO report documenting resource and management problem has the full attention of the agency.
  
• Food safety legislation would help to close the gaps in the current systems and create more preventive controls. This also creates resource concerns, although a safer food supply is a job that must be done.
  
• FDA has to hire a large number of people and this is a lengthy process.  Human resources at FDA is central to putting new resources to work.
  
• FDA must rethink how it is doing many of its activities, including inspections. There is a need for more specialization within a more specialized workforce.
  

Although this is a report on an Alliance meeting, FDA Matters and the Alliance for a Stronger FDA are not affiliated. This blog represents my personal views and insights as a regulatory consultant and long-term FDA watcher. It is a product of my company, HPS Group, LLC.

Steven

DISCLOSURE: I was one of the founders of the Alliance and serve as its Deputy Executive Director. It is a multi-stakeholder group that represents consumers, patient groups, health professionals, research advocacy organizations, trade associations and companies.

If you are concerned about the future of FDA, I urge you or your organization to join the Alliance for a Stronger FDA. Please contact me about membership at sgrossman@StrengthenFDA.org. .

Save the Critical Path—Part 2

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.

To meet this challenge and provide a broad vision, FDA Matters has proposed the creation of the Center for the Advancement of Regulatory Sciences (CARS). It puts FDA's science and FDA's future at the heart of the agency, where the commitment can be constant and everyone won't be running off to meet the next crisis.

"Save the Critical Path-Part 1" appeared ten days ago: http://www.fdamatters.com/?p=317. Here are some questions I have been asked since then.

What is regulatory science?

There is no standard definition for "regulatory science," although the term is widely used and generally understood. It means the tools, techniques and knowledge needed by food and medical product regulators to carry out their public responsibilities.

Fundamental to the concept is that consumers, patients and regulated industries benefit when regulators have sophisticated, state-of-the art capabilities and use them transparently, so that no stakeholder has to guess about the agency's approach. "Regulatory science" extends to every aspect of the FDA's responsibilities, including manufacturing, product tracking, laboratory procedures, post-market standards, sentinel monitoring, etc.

What are the key characteristics of CARS?

The purpose of CARS is to build the science-based decisionmaking capacity at FDA by creating and validating new scientific knowledge, tests and standards. It should produce greater consistency and predictability in the agency's regulatory activities.

CARS must be FDA-driven and funded with public monies. It must be an FDA initiative with stakeholder input, not an agency-stakeholder partnership. These characteristics are essential to obtaining and retaining Congressional support. There can be no ambiguity: this is FDA's initiative and the program's direction is coming from within FDA.

Consumers and industry benefit from an FDA that is more sophisticated in its approach, more capable in its actions, and more confident that its decisions are scientifically-derived.

Why can't Critical Path and the Reagan-Udall Foundation achieve CARS' purposes?

In Europe it has. The EU's Innovative Medicines Initiative (IMI) is multi-hundred million dollar program designed to address the main causes of delay in pharmaceutical R&D and encourage more rapid discovery and development of better medicines. In Europe, it is acceptable that this is done through a public-private partnership and it contributes to the strengthening of EMEA and national drug regulatory agencies.

If this approach were viable in the US, the Critical Path would be more deeply funded by Congress and the Reagan-Udall Foundation would be ready to accept private funding on a par with the IMI.

Neither has happened. Despite the good intentions of their advocates, there is little evidence it will. A public-private partnership of this type, heavily dependent on private support, will always make the activities and the results suspect in the US. Maybe it shouldn't be that way, but it is the reality we face as friends of the FDA.

CARS is an attempt to redefine these efforts and make them into wholly public activities that can draw broader acceptance and achieve quicker results. The goals of the Critical Path and the Reagan-Udall Foundation are a stronger, more future-oriented FDA based on improved regulatory science. If we can keep it public and FDA-centric, then this becomes possible again.

Seven Challenges for FDA--revisited

Most current readers of FDA Matters were not receiving these posts during the first week when we examined seven long-term challenges for FDA. Today's column updates this topic. It underscores the need to plan for FDA's future and not let the day-to-day demands consume all the available time.

Each of these challenges requires substantial effort. Two or three years from now, these are the items that everyone will say: "glad we started early."

Here is an updated version of 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, as well as more resources 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. FDA often undervalues the needs of patients with 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.

Note: Each of these challenges will be explored individually in separate posts.

The first of these: "Turning Data into Knowledge" was posted on June 2 and can be found at: http://www.fdamatters.com/?p=275.

The second: "Save the Critical Path-Part 1" was posted on June 17 and can be found at: http://www.fdamatters.com/?p=317.

Steven

Save the Critical Path—Part 1

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.

Only a strong, well-resourced FDA will have the time and manpower to address the future and give sponsors and other stakeholders the guidance they need. This can only be accomplished with monies that are specifically set aside for advancing regulatory science. It must be a major function of FDA, organized and funded separately from the divisions with every-day product responsibilities. In short, FDA needs to have an organizational home to promote knowledge and create standards in the regulatory sciences.

FDA Matters proposes the creation of a new entity at FDA: the Center for the Advancement of Regulatory Sciences (CARS). It will work with all centers (food, vet med, biologics, devices, drugs) to meet their existing, ongoing and future needs for knowledge, tools and standards.

Functionally, CARS should operate with the center directors as the primary clients and with the goal of helping each Center achieve its mission. CARS must be FDA-driven with stakeholder input, not an agency-stakeholder partnership. This is essential to obtaining and retaining Congressional support

The new Center should be closely aligned (through grants, contracts and strategic partnerships) with knowledge and expertise in academic medicine and other government agencies. The benefit to FDA of creating such relationships was an important part of the FDA Science Board report (December 2007). The Science Board found that external collaborations were underdeveloped and were particularly crucial for FDA in dealing with emerging sciences and technologies.

An initial funding level of $200 million per year would emphasize the importance of advancing regulatory science. It is vitally important that these funds be appropriated; none of the funds should come from user fees. There should be no ambiguity: this is FDA's initiative and the program's direction is coming from within FDA. This amount is about 10% of FDA's current appropriated budget and far more than the current investment in Critical Path and related initiatives.

There are a number of barriers---not least the bias toward current results, rather than future development. Yet, there are good reasons why Congress, FDA and all FDA stakeholders should support advancement in the regulatory sciences. Food and medical academia should also be supportive: CARS makes them into an FDA partner and stakeholder.

CARS is about the future of FDA. Let's embrace that future and show why it is worth such a large investment.

Notes:

Part 2 will appear next week and provide additional supporting arguments for CARS.

If you have questions about CARS that you would like answered in next week's column, please send them to me or post them below as a comment.

Readers are encouraged to register on the site to receive regular updates. Registering also provides the opportunity to post comments.

Steven

sgrosssman@fdamatters.com

“The Principal Makes the School” and Other Thoughts for the New Tobacco Center

My experience has been that "the principal," not the teachers, is the key to having a great school. Outstanding principals attract the best teachers and get maximum performance from everyone. The point for Dr. Hamburg: picking the right director for the new tobacco center is your only mission-critical job. All the other details can be handled by your staff and the new center director.

Here are some of the keys to successfully implementing the new tobacco legislation:

Minimize transfers from other parts of FDA. This probably violates some important management principle about letting people bring their talents to the job that interests them most. Still, FDA's budget is growing quickly and its responsibilities even quicker. There are dangers to FDA's overall mission if existing teams are diluted by a large number of transfers to the new center.

Manage the new tobacco center as if it were a separate agency. There will be crises and hearings, complaints and campaigns aimed at the tobacco center. FDA needs to create a self-sufficient center that minimizes the distractions for the rest of FDA. There is one reality that cannot be avoided: the Commissioner has only 24 hours per day.

Audit-proof the accounting for the tobacco user fees. It is 100% certain that there will be challenges as to whether the user fees are accurately paying for all the costs. FDA should bring in someone from outside (maybe from GAO or a big accounting firm) to create a cost accounting system that is parallel to, but separate from, the rest of FDA

Let's return briefly to the question of picking the best "principal" to head the new tobacco center. Ideally, the person would have broad governmental experience, close-up familiarity with FDA, a public health and regulatory perspective and the presence and stature not to dissolve during a critical press conference or a heated Congressional hearing.

The inclination may be to hire a public health leader who has led the fight against smoking. Unfortunately, most of these leaders lack experience as regulators.

Kate Rawson of the RPM Report floated a name in March that should be given serious consideration: Dr. Steven Galson, the acting surgeon general. She cites his experiences at CDC, EPA and as head of CDER at FDA.

I don't know whether he is interested and this is not an endorsement. Dr. Galson does have the ideal credentials I have suggested: broad government experience, close-up familiarity with FDA, public health and regulatory perspective and the gravitas and presence to handle the heat. He has the added advantage of not depriving FDA of existing leadership in order to staff the tobacco center. Another name being discussed: Mitchell Zeller, a former associate commissioner and director of the FDA's Office of Tobacco Programs. While not a physician, he also has many of the characteristics that Dr. Hamburg should be looking for.

Kate's RPM column can be found here:

http://therpmreport.com/Free/cdb495e7-06f4-4dbe-b265-41b0227d9381.aspx?u

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.

FDA's mission is the approval of safe and effective therapeutic agents. It believes that actionable knowledge comes from prospective, randomized, double-blind controlled clinical trials. Its view of individualized patient treatment: it should be based on the results of rigorous clinical trial information. Yet, they do not impose this on physicians, who may practice medicine as they see fit. FDA will consider information from observational trials, natural history controls and medical literature, but these generally supplement information derived from clinical trials.

In contrast, CMS' mission is to pay for the health care of individuals eligible for coverage through statute. They try to assure health care access that maximizes quality and minimizes public cost. To them, actionable knowledge is retrospectively derived: therapies approved by FDA and treatments reviewed favorably in compendia and having support in a broad cross-section of medical literature. Increasingly, CMS is interested in supplementing these sources with more retrospective data: population studies and analysis of claims data and electronic medical records. Ultimately, CMS' target population is beneficiaries, not patients. Knowledge about the needs of classes of beneficiaries is usually thought sufficient without reference to individualized needs.

While my FDA vs. CMS comparison involves some sweeping generalizations, it also explains a lot of behavior. For example, CMS kept offering its Medicare claims data to FDA and, for a long time, FDA wasn't interested. FDA has now accepted the Medicare data from CMS. However, the dialogue will always be limited by CMS' perception that they are giving FDA an extremely valuable tool and FDA's perception that it is potentially useful, but of limited value. As noted in an earlier post: FDA believes that retrospective "real world" data sets = uncontrolled variables + inconsistent data collection + questionable data accuracy. In short, nothing that FDA would base a safety or efficacy decision on…unless it had no choice.

If you look at what type of knowledge counts to FDA, its natural ally is NIH. They both believe in the virtue of prospective clinical trials as the basis of actionable knowledge. NIH generates more clinical trials—directly or through grants—then any other entity in the world.

FDA and the National Eye Institute provide a model of cooperation that should be fostered FDA-wide and NIH-wide.  NEI had started to work with endpoints based on medical imaging and biological evidence of disease progression. FDA's standard endpoint was still: how many lines on an eye chart had the patient improved or regressed. From working together, both NIH and FDA have advanced knowledge in the field and moved closer to standards appropriate for an increasingly sophisticated therapeutic area.

NIH-funded trials often have to be re-done because FDA won't accept the endpoints or some other aspect of the clinical trial design. In many of those instances, NIH should be running trials with different endpoints to advance clinical knowledge or validate those endpoints. Many times though, early coordination would reduce the chances that expensive trials will need to be repeated….and patients might get beneficial therapies quicker.  A high level of coordination should be possible because NIH and FDA share similar values about the importance of knowledge derived prospectively. There are differences between them, but they are ones of degree, not kind.

FDA Faces Critical Juncture with FY 2010 Appropriations

On Thursday afternoon, June 11, the House Appropriations Subcommittee on Agriculture will have a mark-up that includes FDA appropriations for FY 2010 (starts October 1, 2009). This mark-up, and the one that will follow in the Senate, will be critical events in the capabilities and effectiveness of FDA for the next 5 to 10 years.

After years of drought for FDA, Congress has invested substantial new monies in the agency in FY 08 and FY 09. There are a number of reasons: strong Congressional champions, widespread media coverage of FDA problems, and the education and lobbying efforts of the Alliance for a Stronger FDA.

President Obama has started the FY 10 cycle with a request for a $295M increase for FDA. Given the long, bipartisan history of miniscule presidential requests for FDA, this was an important break with the past. While supporting the President's request, the Alliance is advocating for about $100M more.

Thursday's mark-up is the first time we will see how Congress intends to respond to the President's request. In addition, the mark-up may provide insight into the appropriations committee's view of new legislation that may give FDA significant new responsibilities in 2009.

Tobacco legislation—likely to pass the Senate this week—will be funded by user fees. After that, Congress is likely to pass a major expansion of food safety inspection capacity. Commissioner Hamburg has already stated that the agency does not have the resources to implement the House bill unless it receives new monies. Reimportation of drugs and follow-on biologics are less likely to be adopted than food safety, but are genuine possibilities this year. Each will be expensive.

The risk is that the gains of the last two years and another $300M for FY 10 will wind up paying for new responsibilities, rather than strengthening the agency. Hopefully, Chair Rosa DeLauro (D-CT) will reference these additional needs in her opening remarks. Or there might be committee language acknowledging the need for additional funds if Congress passes new laws that give FDA more responsibility.

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

For those not familiar with the Alliance for a Stronger FDA, its 180 members represent the full range of agency stakeholders. They are strong advocates for increased appropriations for FDA and united in the belief that "a stronger FDA benefits everyone."

In the interest of full disclosure, I was one of the founders of a predecessor organization and now serve as deputy executive director of the Alliance. FDA Matters is not affiliated in any way with the Alliance.

The more members the Alliance has, the stronger its voice on Capitol Hill and in the media. If you want more information about the Alliance, write me at: sgrossman@strengthenFDA.org.

Turning Data into Knowledge

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."

Above and beyond its day-to-day information technology needs, FDA will require substantial monies to develop these new databases. Further, the agency lacks the data-mining experts needed to make sense of the data that is received. Such individuals are few and in high demand. Even were the agency given the funds to hire 100 of them this year, it would probably not come close to reaching this goal. Even when the required expertise is on-board, it is a difficult, iterative process to turn data into usable knowledge.

FDA must take account of the littered field of others' past failures and limited successes. Even programs that work well may have limited applicability to FDA's daunting task. The VA system operates with electronic medical records, a finite number of known participants and a partially closed system of care. The Drug Abuse Warning Network (DAWN) tracks only drug-related hospital emergency department visits and drug-related deaths reported by coroners and medical examiners. Each has key characteristics that are not present in tracking food and product use--and consequences--in a real world setting.

FDA has been told that the Medicare claims data set (provided by CMS) gives them a fast start along this difficult path. Perhaps not. I often use the following equation to explain:

Real world data sets = uncontrolled variables + inconsistent data collection + questionable data accuracy.

FDA is used to the type of knowledge derived from controlled clinical trials. In contrast, claims data is notoriously unreliable with few tools to identify and correct for systemic bias.

With very limited staff, FDA has done yeoman work on the initial phases of developing its Sentinel initiative. The goal is a nation-wide electronic safety monitoring system for post-market surveillance. It will use existing data from health systems, hospitals and insurers. An operational system will be a challenge. Creating one that minimizes false positives is more than just a challenge.

There are also some larger issues that will need to be addressed. Even with new hires throughout the agency, medical knowledge and food surveillance needs are growing faster than FDA expertise. Not every "cluster" leads to a medically or scientifically valuable insight. The consequences of premature responses and over-reactions are substantial and often severe. Nonetheless, the tendency in our society, even sometimes at FDA, is to forget that the association of data points often tells us nothing about causality. Finally, it is hard to know the implications of studies that show that more information often does not produce better decisions. This runs counter to FDA culture and is counter-intuitive to the way most of us think.

In sum, FDA has a large job in the area of information technology, data collection and data interpretation. In addition to the need for monies and expertise, there are inherent, as well as institutional barriers to success. Managing expectations will be a test for the new FDA leadership and the senior staff.

Drs. Hamburg and Sharfstein: “The FDA as a Public Health Agency”

Wasting no time, Drs. Hamburg and Sharfstein have written an essay, entitled "The FDA as a Public Health Agency." (Available on-line at: http://content.nejm.org/cgi/content/full/NEJMp0903764). Noteworthy in the new essay is the "big tent" approach they plan to use. They repeatedly refer to consultation with regulated industries, consumers, patients, and the public. They describe specific areas for working more with CDC, NIH, CMS, and the Department of Agriculture.

Drs. Hamburg and Sharfstein touch upon a potpourri of agency issues:

• FDA should be judged by its success in assuring a safe and nutritious food supply and innovative, safe and effective medical products. This must go "beyond such intermediate measures as the number of facilities inspected or drugs approved."
  

• The potential good of a medical product or policy should be balanced against its potential harm. They add: "Some benefits are not worth the risk; some risks are worth taking."
  

• The focus of increased work with NIH should be on accelerating the development of cures. The focus of increased work with CMS should be the exploration of ways to shorten the time from approval to reimbursement.
  

• The focus of increased work with CDC should be on infectious-disease emergencies, outbreaks of foodborne illness, enhanced safety systems, and nutrition.
  

• A new approach to external affairs is foreshadowed by discussion of risk communication, more focus on the scientific basis of agency decisions, and greater transparency.
  

Both by words and tone, the overriding message of the Hamburg/Sharfstein article is that the FDA is a public health agency and will be run by the principles of public health as applied to the issues and opportunities facing the FDA. My May 15 commentary, "Public Health Leadership Comes to FDA," (http://www.fdamatters.com/?p=211) puts some additional texture on this:

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

This NEJM essay demonstrates that having "limited track records on FDA issues" has not stopped Drs. Hamburg and Sharfstein from having a good sense of the issues and well-developed ideas about how to improve FDA. Ultimately, we, as readers, learn from the essay that Drs. Hamburg and Sharfstein have the knowledge and commitment to address the challenges faced by FDA.

Long-Term Challenges for New FDA Leadership

When Dr. Hamburg arrives, she will face a number of competing priorities, along with a large backlog of policy and enforcement decisions that have waited for permanent leadership. There is a risk that important long-term challenges will go unaddressed…merely because they are not part of an immediate crisis or subject to pressure by the Secretary, the President, or Congress. Two or three years from now, these are the items that everyone will look back upon and say: we should have gotten started sooner.

Here is my list of seven such 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 impacting fundamental biological processes. Preventive treatments raise different issues than curative treatments. Two or three generations of products (in trials now and over the next few years) are "at-risk" unless the Critical Path is accelerated and expanded and other "clinical trial improvement" initiatives are developed.

Balancing safety with patient risk and need. Severely-ill patients deserve more balanced and more patient-centric policies with regard to dangerous treatments that have proven to provide great benefit to some patients (NB: "proven" does not mean phase 1 or early phase 2 trials). The Risk Evaluation and Mitigation Strategy (REMS) program helps, but these issues need a broader, more systemic examination.

Sifting valuable information from background noise. FDA is building a Sentinel system for early monitoring of problems, has access to the Medicare database and will be collecting incredibly large amounts of information about safety, food and drug imports, global product supply lines, clinical trials, patient registries, etc. It is a difficult, highly iterative process to distinguish meaningful patterns from background noise…in order to create actionable intelligence.

Managing globalization, rather than just responding to it. This is closely related, but distinct, from food import safety, heparin contamination and related crises. 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. Offices in China and India are necessary, but by no means sufficient.

Resisting the bias toward negative decisions. Up to a point, caution is the appropriate response to uncertainty. Yet uncertainty is inherent in all positive decisions. Taken to the extreme, the whole world of food and drugs could 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. Systemic review of all decisionmaking processes is the ultimate corrective.

Staying focused on priorities. FDA's responsibilities greatly exceed its resources. Some mission creep is inevitable; some new responsibilities may be needed to benefit society and the public health. But sometimes FDA will need 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. Again, 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.

Please focus on issues and projects that have long-term consequences and take time to develop…but for which there is no immediate crisis or pressure.

We will take the suggestions, compile a list and send it to Drs. Hamburg and Sharfstein.

Steven

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