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

A Resignation and an Allegation at FDA

Several reporters called me last week to ask if I had heard about Dan Schultz's resignation as head of the Center for Device and Radiological Health (CDRH). Had I also heard about conflict-of-interest (COI) allegations against Janet Woodcock, head of the Center for Drug Evaluation and Research (CDER)? Some of the reporters wanted to connect the two events. They wanted me tell them, pundit-like, what this said about Commissioner Hamburg's approach to integrity in decisionmaking and to allegations of wrong-doing.

I disappointed them.

I see no connections between the Schultz resignation and the leak of the Woodcock allegation. One was between Dr. Hamburg and Dr. Schultz and relates to the best interests of the agency going forward. The other is between an unhappy company and Dr. Woodcock and is being handled, appropriately, by the Inspector General. The Commissioner's role, if any, would come later.

There are other important reasons to think the stories are unrelated. Over the past year, Dr. Schultz has faced a series of attacks on his stewardship of CDRH, including calls for his resignation. Whether innocent or guilty, he has been forced to operate in a beleaguered environment.

We do not know what Dr. Hamburg believes. We are told that the resignation was a joint decision. In any case, it falls within the discretionary authority of the Commissioner. They may have discussed the various charges when they met. More likely, the bulk of the conversation was about whether Dr. Schultz's ability to lead has been compromised….or whether, under the circumstances, he is the right leader for a product area slated for intense review that may become a heated public and Congressional debate.

Dr. Hamburg has said that there will be changes in the leadership team. Several have already occurred. One or two of the departures may be a result of her commitment to high ethical standards. It is more likely that people will be replaced because:

• Dr. Hamburg wants her own team, or
  
• there are policy or personality conflicts, or
  
• she has concerns about FDA being caught up in side-issues and personalities.
  

While there may have been more involved, this last reason is sufficient for Dr. Hamburg to want a change at the top of CDRH.

Dr. Woodcock's situation is totally different. There is a single public complaint made by a company that fears it is losing a high-stakes competition for market entry. They are asking only that she recuse herself in the specific matter in which the two companies are involved.

The Inspector General's investigation of Dr. Woodcock appears to be a routine response to these conflict-of-interest allegations. No one should pre-judge the situation until OIG has completed its report. I would expect Dr. Hamburg to do just that---wait for the report before deciding whether any action is needed.

The Schultz and Woodcock stories are interesting, albeit unfortunate. They are totally unrelated and tell us nothing about Dr. Hamburg's approach to leading FDA.

I am sure we will hear more from Dr. Hamburg on FDA integrity and the FDA decisionmaking process. But that wasn't this past week's story….no matter how hard anyone tried to make it so.

Steven

Transparency at FDA: A Work in Progress

A mantra of the new Administration is that government needs to be transparent. While the goal is laudable, the scope of the task is often ill-defined and everyone has their own ideas about what transparency means. FDA's efforts must be viewed as a work in progress that may stretch over years.

The agency has gotten off to a good start with a transparency task force, chaired by Principal Deputy Commissioner, Dr. Joshua Sharfstein. In an earlier post, I addressed some of the likely outcomes of the task force's work: http://www.fdamatters.com/?p=285.

What I didn't discuss at the time were some key issues the Task Force needs to address. Here are my thoughts:

Information is not transparent if it is available, but can't be found. There are hundreds of thousands of pages of information that are publicly accessible from the FDA website. This number will grow steadily as additional archival documents and newly generated materials are posted.

It can be very hard to find what you want in this mass of information. The new FDA website is an improvement. Yet, the homepages for the FDA and the Centers are too cluttered….and not organized to easily get the link you want. Until the agency home pages deliver information effectively, FDA needs to highlight the search functions on the site.

Information is not transparent if it cannot be accessed in a timely fashion. Freedom of Information Act (FOIA) requests often take months to be settled. Expanding the range and depth of materials on the website will help. Still, FOIA requests should be acknowledged within 10 days and a very high percentage fulfilled within 30 days.

Information is not transparent if it isn't readily available to the media. There is robust coverage of FDA in general circulation and trade publications and in new media (such as this blog). However, veteran FDA reporters, such as Jim Dickinson, tell me that access to agency information and FDA subject matter experts has narrowed considerably over the last 15 to 20 years. FDA needs to remove barriers to access by journalists. For most people on most topics, the media is their source of information on agency activities.

Some of FDA's transparency policies should be based on "lessons learned" by other government agencies. In particular, state governments have already converted to a more open, user-friendly approach. There are dozens of organizations that have comparable amounts of information stretched across hundreds of topics, yet have confronted and conquered the website clutter problem.

Other policies need to recognize FDA's uniqueness. It is a public health agency, a scientific agency and a regulator. It oversees products that represent a quarter of consumer spending. It is a repository of confidential business information with a collective value that probably exceeds $100B. Balancing these proprietary concerns with public health needs is likely to be the most difficult part of the task force's mission and may not be finalized any time soon. While this is being resolved, FDA could improve agency transparency by addressing the three issues I have raised above.

Transparency is a state of mind. It may take considerable time before "open" and "available" become the default choice of federal government agencies. It is certainly not in FDA's cultural or institutional DNA to be transparent. FDA's progress can be measured in days and months, but comprehensive policies may still take years.

Steven

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

The Best Little Chess Game in Town

One of the reigning champions of political chess, Representative Henry Waxman, has found himself in an endgame on follow-on biologics (FOB). His three decades of success have been built on extraordinary mastery of Congressional procedure, artful compromise and strategic alliances. His defeat seems unavoidable, but no one should assume that he can't yet win or draw this game.

His opponents—Representatives Eshoo and Barton, backed by former Representative Greenwood, who is head of the biotechnology trade group, BIO—have also played a masterly game. Their strategy of overwhelming numbers has made them an irresistible force, sufficient to overcome Waxman's mid-game strategy of becoming an immovable object.

The chess game is being fought over the creation of a pathway for regulatory approval of FOBs, biological "copies" that are similar to an innovator drug. While there are dozens of issues, the critical difference between the Waxman and Eshoo bills is how soon FOBs can rely on the clinical data from the innovator, rather than do expensive trials themselves. In Waxman's eyes, the innovator's data exclusivity should be 5 years, while Eshoo and Barton favor at least 12 years.

Interestingly, Waxman's position has grown weaker despite a Democratic president and larger Democratic majorities in Congress. This was not what he expected when he adjourned the game last Fall, expecting to have a stronger position in January.

Instead, Eshoo garnered a remarkable 142 bi-partisan co-sponsors this year, gained a working majority for her bill in the House Energy and Commerce Committee. In the face of this, Waxman's strategy has been to play for time---avoiding a committee vote this year, and then working for a "split the difference" compromise in conference with the Senate on health care reform.

The showdown occurred this past Friday (July 31). An Eshoo amendment was successful, 47 to 11, and FOB is now part of the health reform package in the House. With changes Representative Eshoo made in her language, the House and Senate versions are not much different, and both opt for 12 years of data exclusivity.

Chairman Waxman still has options. It is possible that FOB's will not emerge from the melding of the three different House committee versions. It is possible that the House leadership will help him keep FOBs out of the final legislation when it is considered by the House. Perhaps he and Senator Kennedy (who has wavered in his support for the 12-year exclusivity in the Senate compromise bill) will be able to appoint enough conferees who would support compromising two similar bills into one with fewer years of data exclusivity.

Given the overwhelming support in the House for Eshoo's bill, it would seem that Representative Waxman cannot prevail. However, it is not in the nature of committee chairmen to accept defeat. Henry Waxman is no exception. My advice to the biopharma industry: save any victory celebrations until the chairman has run out of options and concedes the game. It may take longer to get there than you expect.

Steven

PS. I have written twice before on follow-on biologics:

• June 23 on the nature of the FOB marketplace and the failure of the FTC's analysis to capture the market dynamics that will exist 10 years after enactment. It is at: http://www.fdamatters.com/?p=338.
  
• July 5 about the politics of FOBs and predicted a fascinating summer as legislation moved forward. It is at: http://www.fdamatters.com/?p=358.
  

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. .

Personalized Medicine in Perspective

We are told that personalized medicine will transform drug development and bring about the end of blockbuster drugs. If you believe the hype, this will all happen soon. More realistically, personalized medicine is at least a decade away from having any substantial impact. Blockbuster drugs are not going to disappear anytime soon.

"Personalized medicine" involves managing a patient's healthcare with therapies based on patient-specific characteristics. It is often defined as part of genomics, although there are and will be non-genomic therapies that fit within personalized medicine. Personalized medicine is seen as individualized treatment and "the future of drug development."

In contrast, most of our current therapeutic options are drugs and biologics intended for large cohorts of patients. This creates a focus on developing "blockbuster drugs" that will be used by hundreds of thousands and even millions of patients. It is said that the rise of personalized medicine will bring an end to "the era of blockbuster drugs."

To understand the status of personalized medicine, it is instructive to look at the history of biotechnology. As with all great transformative achievements, latecomers might imagine that success was inevitable and progress was smooth and relatively trouble-free. The reality has been quite different.

Biotechnology began in confusion, uncertainty and opposition. In 1975, the scientific community gathered at Asilomar, CA to consider the future of biotechnology. They were operating in an environment of apprehension and believed restrictive legislation might be adopted. In part because of principles, guidelines and restrictions adopted at Asilomar, biotechnology lasted just long enough to quell the worst fears that uncontrolled experiments might change the fundamental nature of man, animals and plants.

Here is my history of how biotech developed into a force:

• Rocky childhood (1970's)
  
• Became "the next big thing" (1980's)
  
• Finally had a significant impact (1990's)
  
• Some biotechs mature and big pharma swallows small biotechs for their knowledge, capacity and pipeline (2000's)
  

Notice that there is almost 20 years between childhood and impact. Fortunately for the health of the American people, biotechnology still has plenty of room to grow.

I expect something of a similar pattern for personalized medicine. The movement is, at best, in late childhood. It is not yet the "next big thing," except rhetorically. It will be at least 2020 before more than a handful of products are making an impact….and we can't know whether it will be a significant impact. The death of the blockbuster is at least 10 to 15 years away and may never occur.

One expectation is that genomic information will spur "drug development by design." This will allow the discovery of better drugs more quickly and with many fewer developmental failures. This is a much harder road than it may seem. History shows us that clinical trials can fail, sometimes quite miserably, just when everyone is most sure that the solution is logical and success guaranteed. The human body is almost always more subtle than we can discern, even with the best tools.

Deservedly, there is lots of excitement about personalized medicine. It will eventually transform drug development. However, as you read and listen, remember that:

• excitement is not the same as impact, and
  
• investment is not the same as success.
  

Steven

GAO Hits a Home Run

On July 20, the GAO released its study, "FDA Faces Challenges Meeting Its Growing Medical Product Responsibilities and Should Develop Complete Estimates of its Resource Needs."

FDA's world has changed considerably since the report was requested. Some aspects of the report describe problems that are known and already being addressed. In other important regards, the report is extremely valuable. It will be widely cited and may be instrumental in creating positive changes at FDA.

The GAO started its research using the FY 2008 funding levels as the latest available figures. Subsequently, FDA received a $150M supplemental appropriation in FY 08 and a $325M increase in FY 09. It looks like the agency will get another $295M increase for FY 10. Over this period, the FDA will also have benefitted from a significant increase in user fees.

Therefore, using FY 08 funding levels gives a distorted picture of the FDA situation today.

Further, the new Administration has joined Congress in acknowledging the critical importance of FDA. They have committed to addressing the agency's many management and programmatic needs. When Congress requested the report, it was looking for GAO to build the case for better management, stronger fiscal controls and higher productivity in the medical product area. In 2009, neither FDA nor Congress need to be persuaded.

If increased funding has changed FDA's financial and programmatic situation....and the new Administration is already undertaking management initiatives, why is the GAO report so important?

The report's primary value is that the GAO has:

• developed the issues list,
  
• compiled the data,
  
• done the analysis,
  
• drawn the conclusions and
  
• made the recommendations.
  

They have been thorough in their work. Their views represent neither an ideological Congress nor a self-serving agency. Never mind that Congress has not been ideological in its concerns about FDA management. And that FDA has not done a good job at being self-serving. To the question "who says," there is a better, highly credible answer: "GAO does."

In the process, GAO has boosted some important FDA program needs and inched forward on some more difficult items. For example, FDA needs a major infusion of monies—well beyond what it's getting—to upgrade and disseminate information technology. The agency may not have enough people to review adverse events reports, but merely hiring more people cannot solve this problem. Only an IT solution can make this labor-intensive work more productive and valuable. Also, the report documents the growing demands on the agency from new legislative mandates and the difficulties in retaining staff.

At the same time, GAO "damns" user fees with faint praise about how it has given the agency flexibility and prevented it from falling further behind. In effect, GAO re-raises the difficult issue of public funding versus user fees. Nothing more is needed to start a debate…if someone wants to have one.

In sum, FDA and Congress are already working on many of the issues and recommendations contained in the new report. GAO's credibility and thorough analysis will make these efforts more productive and contribute to a stronger and better FDA.

Steven

The GAO report can be found at: http://www.gao.gov/new.items/d09581.pdf.

Upcoming at FDA Matters

Columns to expect this week and next:

• Update on Follow-on Biologics and the Dance of Legislation
  
• Status of FDA Appropriations
  
• How FDA Could Be Affected by Health Reform Legislation
  
• Exploring the Office of Regulatory Affairs
  

Unfunded Mandates Threaten FDA

FDA is finally moving toward a funding level that will strengthen the agency's core functions. In FY 08 and 09, the agency received more than $600M in new funds. FY10 is on track for another $295M. The FDA can use all this, and more. It is a vast improvement over a string of years where annual increases were closer to $50M, far less than the amount needed to break even with inflation.

With all this good news, there are still a few storm clouds that could rain on FDA's parade. The darkest of those clouds is the threat of unfunded mandates that could result from current Congressional initiatives.

Congress has already passed new tobacco legislation, which will be funded by user fees. Also under consideration are food safety reform (likely), follow-on biologics (probable), and drug reimportation (possible). Each of these three will require funds from FDA's budget.

I don't know how much it will cost to implement food safety legislation or to bring an entire new approval process into existence (follow-on biologics). Both will be expensive. Reimportation is less likely to become law, but will be very costly if we are to preserve a safe drug supply. Commenting on the overall situation, Chairman Waxman has said: FDA should not be set up to fail by being given new responsibilities without new monies for implementation.

The simple but hard question is: will Congress back new FDA responsibilities by giving the agency substantial additional funding? If not, FDA's improved budget situation will evaporate in the face of these unfunded mandates.

If new responsibilities add $250M to FDA's costs and the Agency gets a $300M increase, then that leaves only $50M for strengthening FDA's core programs and responsibilities.  The agency would be back where it was 3 years ago, when it was consistently receiving appropriations that were less than the 6% annual increase in agency costs.

The threat of unfunded mandates is real, but the time for Congress to act has not arrived. The appropriations bills are not supposed to fund legislation before it becomes law.

If any of the proposed legislation passes quickly, then there may be time for House-Senate conferees to add monies into the FY 10 agriculture appropriations bill. More likely, the vehicle would be supplemental appropriations bills for FY10. The first of these is likely to be late this year or the beginning of next year, making the absence of action at this point understandable.

Still, it would be nice to know that authorizers and appropriators appreciate the problem of unfunded mandates and are talking with each other about it. The key chairs--Representatives Waxman and DeLauro and Senators Kennedy and Kohl—need to see the emerging situation as critical to FDA's future.

Otherwise, unfunded mandates threaten and may destroy the successful effort to rebuild and strengthen FDA.

Steven

PS: Two important footnotes:

• I have taken no position on the merits of any of the legislation being considered by Congress. My sole purpose in this column is to make sure that funding keeps up with responsibilities.
  
• The opinions expressed in FDA Matters are my own. However, readers should know about the Alliance for a Stronger FDA, which has been the leading advocate for increased FDA funding. It is a 180-member, multi-stakeholder group that includes patient groups, consumer advocates, health professions organizations, trade associations and companies. It is also backed by three former HHS secretaries and six former FDA commissioners. I am one of the founders and serve as the deputy executive director. For more information about the Alliance, contact me at sgrossman@strengthenfda.org
  

Dr. Hamburg Meet Dr. Collins

FDA and NIH are natural allies, with closely-related purposes as public health agencies. They share a similar worldview that "medical and scientific knowledge derived from random clinical trials" is superior to all other sources. I explored this in an earlier column at: http://www.fdamatters.com/?p=299.

Last week's announcement of Dr. Francis Collins to be NIH director provides a unique opportunity for FDA. Dr. Hamburg needs to meet Dr. Collins….and create a shared vision.

Government agencies are no different than corporate divisions: they crave positive attention, fight to accumulate bigger budgets and more personnel, and resist any attempts to lessen their autonomy. Tribal rules apply. Outsiders---no matter how well-meaning—cannot be assumed to have your organization's best interests at heart.

One could ask: why should FDA and NIH be different than this grim picture of organizational behavior? The answer is: they aren't. Except in rare cases, having a noble organizational purpose does not suspend the accumulative and suspicious culture that is inherent in any group.

There are countless joint initiatives and working groups that link FDA and NIH. Common purposes and a similar world view often push them together…but I am told that many of these meetings are productive only in a very narrow sense. Although the work gets done, the spirit of common purpose is often weak. Enthusiasm for power-sharing is low. Extending projects to related areas is sometimes never discussed. But opportunity is everywhere.

FDA and CMS relate in a different way. As described in my earlier article, the agencies do not have common purpose and do not have a shared view of what knowledge is important. Because of these fundamental differences, opportunities for shared initiative are limited and relations will always be strained. For FDA and CMS, good will and occasional joint successes can never overcome the distance between them.

Not so FDA and NIH. The two agencies working together are powerfully synergistic….and boundless in the benefits it could bring to Americans. The interest of NIH Institute and FDA Center directors is essential to building a better, more productive relationship. But it will never happen if it rests on their ability to overcome the cultural and tribal impediments.

Only Dr. Hamburg and Dr. Collins can set the proper tone, provide guidance and break down the barriers. Dr. Hamburg, meet Dr. Collins. Please.

Steven

Follow-on Biologics and the Dance of Legislation

Political scientists love to watch the dance of legislation. FDA watchers are eager to see how thorny agency issues will be decided by Congress. Both will be fascinated by the latest moves and turns in Congressional consideration of legislation on follow-on biologics (FOB).

I can't recollect an instance in which a House chairman faced such massive bipartisan opposition. But never count House Energy and Commerce (E&C) Committee Chairman Henry Waxman out. He has made a career of not having enough votes… and winning, anyway.

Mr. Waxman is proposing generics-friendly legislation (HR 1427). As the committee chair, he is well-positioned. Plus, he has 12 co-sponsors, including the chairman (Pallone) and ranking minority member (Deal) of the health subcommittee. Usually, this is enough to win outright or with only modest compromises.

But Waxman is in a stand-off with committee member and fellow Democrat, Representative Anna Eshoo. Her bill (HR 1548) is considered friendly to the biotechnology industry. She is joined by the ranking minority member of the full committee (Barton). Together they have amassed an extraordinary 108 bi-partisan cosponsors. This is one-fourth of the House's total membership!

Representative Eshoo has the momentum, having added 50 co-sponsors since April 15, compared to 2 for Representative Waxman. Further, Waxman is under pressure to include follow-on biologics in the health reform bill mark-up, duplicating the legislative situation in the Senate.

Chairman Waxman is reportedly resisting any effort to move legislation on follow-on biologics. He lacks the votes to prevail and must stall for enough time and leverage to work his political magic.

On the Senate side, Chairman Kennedy is sticking with a two-year old bipartisan compromise, which is much closer to the Eshoo position than to Waxman. He has put the FOB bill into the health reform legislation being considered by the Senate HELP Committee this month.

Enter the generic drug industry, Senator Schumer, and the AARP...and the Senate plot thickens.

The generic drug industry chose not to make a deal in 2008—in the reasonable belief they would do better with a Democratic Congress and President. They are hoping to retrieve the situation with Senator Schumer, who has introduced the Waxman bill in the Senate (S 726). His bill (and seven bi-partisan co-sponsors) assures that the Kennedy bill will not move forward without visible dissent. Meantime, the AARP reportedly told Senator Kennedy's staff that they will not support the HELP committee's health reform bill unless the FOB portion is modified to be more like the Waxman-Schumer bill.

The most contentious issue in both Houses is the length of time during which innovator companies can prevent a FOB from being approved based on the innovator's research. This so-called "data exclusivity" should not be confused with the far-more-desirable "market exclusivity," which is not part of any bill.

In round numbers, Waxman is proposing 5 years of data exclusivity, Eshoo 14 years and Kennedy 12 years. There is no objectively correct number—just differing beliefs in how much time is needed to make sure that the growth of an FOB market doesn't reduce incentives for innovation. An average of the three numbers suggests a compromise of about 10 years.

Enter the Federal Trade Commission and the White House…and the whole plot thickens further.

The FTC analysis—featured at a House hearing and widely covered in the media—contends that no data exclusivity is needed to preserve incentives for innovation. Now there are four numbers and the average is 7.5 years. Last week, the White House jumped in to officially advocate for 7 years.

The endgame on data exclusivity is becoming clear. It will be between those who will accept seven years and those who will insist on at least 10 years. Even knowing this, it is hard to tell whether and when the logjams will be broken in the House and Senate.

The unfolding politics of FOBs are going to make for a fun summer and may creep into football season! Someone is likely to score a touchdown (or learn to dance the tango)!

Steven

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.

The Follow-on Biologics Market

Since the debate began several years ago, the policy and politics of follow-on biologics (FOB) have been driven by assumptions and projections of the anticipated market. In my opinion, there has been a lot of fuzzy thinking about what type of companies will be players and how they will position themselves. The Federal Trade Commission report, released last week, is just the latest illustration.

My own analysis suggests there will be multiple market entrants vying for market share and creating price competition. It will take some patience until we get there, but it will happen. In this environment, it will be important to stimulate investment in new, innovative biological products. Without reasonable time to recoup costs, new product development will slow.

I started to think about the nature of the FOB market last year when predictions about FOB's started to jar my sensibilities. The FTC's report is just a larger platform for advancing questionable analysis. There are two economic principles that are central to understanding the issues.

First concept: shadow pricing. The first generic drug is usually priced about 20% to 30% below the innovator product. The innovator doesn't compete on price because they know that the generic will be continuously re-priced to stay the same increment below the innovator's price. This is called "shadow pricing." As each new entrant joins this market, competition erodes this structure until prices fall significantly. FTC believes that there will only be one or two competitors in each segment and shadow pricing will limit price competition.

Second concept: barriers to entry. Generally speaking, the more it costs to be a part of a market, the fewer players will enter it. At this moment, generic drugs have a low barrier for entry. In contrast, the FTC believes that there will be significant barriers to entry in the generic biologics market. Only the largest biologic products will draw any competition. And only a handful of companies will develop FOB's because of the expense of putting together a safe and effective product, combined with the $250M to $1B estimate for a new facility to make these products.

There are two significant errors in the FTC analysis. First, FTC fails to recognize the generic drug market evolved into what it is today because of the way it was structured in 1984. The key Hatch-Waxman trade-off--additional patent protection for market access for generics—has worked extraordinarily well. If FTC had made the same comments in 1984, there would be neither an innovative pharmaceutical industry nor a booming generic drug industry today.

Second, FTC fails to account for the likely impact of innovation in the FOB marketplace. For example, more refined methodologies will evolve for characterizing biologics. Ways will be found to build facilities less expensively and to streamline production.

FTC states that lack of interchangeability and direct substitution will limit market penetration for FOB's. The problem with this viewpoint is that the market is already saying otherwise. Teva and Sandoz (Novartis' generic subsidiary) will be in the FOB market from the beginning. Merck, J&J, Pfizer, Amgen and others are positioning themselves to join within a few years. All are well-financed and have experience competing in crowded markets. Why would they commit billions to a market that can't be penetrated?

Over time, innovation will bring costs down. Competition will bring prices down. It seems unlikely that shadow pricing and high barriers to entry will characterize the FOB market in ten years.

My vision of a multi-player FOB market with price competition does not answer the question: how much intellectual property protection is needed for innovators? It does say the FTC is wrong to argue for none.

Steven

FTC's testimony to the House Energy and Commerce Committee is at:

http://energycommerce.house.gov/Press_111/20090611/testimony_harbour.pdf.

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.