FDA’s Growing Presence Outside of the Washington Beltway

The federal government is closed for the fourth straight day. However, it would be more accurate to say: closed in the DC area. A significant part of FDA is open and has been all week....making this a good time for FDA Matters to acknowledge and explore the growth of FDA in places far from the Washington Beltway.

Overseas Offices. FDA's commitment to creating overseas offices has been widely praised and deservedly so. The ultimate goal is to have FDA employees and offices in every area of the world where there are significant amounts of commerce in FDA-regulated products or their constituent ingredients. If food and drug problems can be identified and fixed near the beginning of the supply chain, then America becomes less dependent on successful inspections of cargoes entering the US.

FDA has created permanent offices in China (Beijing, Shanghai, and Guangzhou) and India (New Delhi and Mumbai) over the last two years. It has also upgraded and formalized its presence in Latin America (Costa Rica, Chile, and Mexico City) and Europe (Brussels and London).

Other areas, such as the Middle-East and Asia/Africa, are still overseen from FDA headquarters, but with an increasing local FDA presence in those areas. Likewise, headquarters handles various treaty arrangements (e.g. with Canada and Mexico) and relationships with international organizations.

Growth in Field Staff. Since 2006, FDA employees assigned to "field activities" has grown from 3450 to 4200. These individuals work for the Office of Regulatory Affairs (ORA) and are involved in inspections and enforcement. ORA personnel represent about 45% of the total FDA staff paid out of the agency's appropriations (non-user fee) budget.

According to FDA's website, over 85 percent of ORA's staff works in 5 Regional Offices, 20 District Offices, 13 Laboratories, and more than 150 Resident Posts and Border Stations.  This means more than 3500 FDA staffers in ORA are conducting government business away from headquarters.

National Center for Toxicological Research. NCTR is less well-know, but an important part of FDA. Its 210 employees are located in Jefferson, Arkansas, far from snowy DC. Its webpage was updated yesterday, so we know they are at work.

NCTR defines itself as conducting "FDA mission-critical, peer-reviewed, critical path (translational) research targeted to develop a scientifically sound basis for regulatory decisions and reduce risks associated with FDA-regulated products."

In plainer language, they are the applied sciences part of FDA, focused on toxicology and toxic effects of food, drugs, packaging materials and so on. As Commissioner Hamburg's campaign to promote "regulatory science" gains momentum, NCTR will be a key part of the effort.

In total, nearly 4,000 FDA staffers work outside the DC metropolitan area. This is a good thing, since the nation's food and medical products don't stop because Washington, DC had back-to-back blizzards.

Steven

For more about FDA's overseas offices, go to: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm185769.htm

For more information about the Office of Regulatory Affairs, go to: http://www.fda.gov/AboutFDA/CentersOffices/ORA/default.htm

For more information about NCTR, go to: http://www.fda.gov/AboutFDA/CentersOffices/NCTR/WhatWeDo/default.htm

The President’s Budget Request: Is 6% Enough for FDA?

The President's FY 11 budget request for FDA includes a $146 million increase in appropriated (non-user fee) funding. This is about 6% of the $2.36 billion appropriation that FDA received in FY 10. With the President's tough talk about deficit reduction, anything above a freeze should be considered good. Why was the Alliance for a Stronger FDA disappointed?

Or to be more precise, the Alliance (www.StrengthenFDA.org) appreciated that FDA got more than most agencies, but felt that an inflation level increase was insufficient for FDA. The Alliance pointed out that the increase will not cover the ever-growing demands on the agency or strengthen the agency's capacity to fulfill its mission. They added: three good appropriations cycles for FDA (FY 08 to FY 10) have not undone more than a decade of budgetary neglect.

Of the $146 million increase for the agency's appropriated budget, CFSAN would get $60 million, about an 8% increase. This is a little more than an inflationary increase and foods programs will be able to grow marginally in FY 11. This is progress…though not nearly what is needed to meet the continued challenge of keeping foods safe and the increasing complexity and international scope of the food supply chain.

Far less was provided for medical products. Drugs and biologics received a combined $28 million increase in the President's request (about 4%). Devices received an $11 million increase (less than 4%), which does not cover the cost of pay increases. Other items that will increase this year (rent, IT, training, and travel) will need to come from existing program dollars. 

There is near-universal acceptance that the federal budget needs to be trimmed. Few domestic agencies did better in the President's request than FDA.

But there are differences in the needs of federal agencies. FDA's budget is almost entirely people costs. Salaries are more than 60% of the agency's budget. When you add in benefits, rent, IT services, travel, training, etc., 80% of the budget is devoted to people and the support they need to do their jobs.

If the FDA's appropriated budget does not grow by at least inflation each year, then staff levels decrease. This is what happened in most years from 1994 to 2007.

For example, after 9/11 the agency received significant new monies to hire inspectors to decrease the risks of agro- and bio-terror. Within 5 years, this increase in the FDA field force had disappeared, due to inflation, attrition and a lack of supportive funding. There is nothing hypothetical about the consequences of underfunding FDA.

Undoubtedly, FDA will find ways to be more efficient in FY 11, which will relieve a little of the pressure of doing more without new money. However, the amount to be gained in this manner is not large.

In contrast, there are plenty of areas for additional investment. FDA is operating a 1990's IT system, requiring it to work with databases that are incomplete and do not provide sophisticated support for decision making. Training the FDA workforce is another priority for additional funding.

FDA is still very much in the catch-up mode from past underfunding. Six percent is not enough!

Steven

For purposes of disclosure, I am one of the founders of the Alliance for a Stronger FDA and serve as deputy executive director. FDA Matters is not affiliated in any way with the Alliance.

Chart provided by the Alliance for a Stronger FDA:

President Obama's FY 11 Request for the FDA

Compared to the Alliance for a Stronger FDA's FY 11 Request

Budget Authority Appropriations (does not include user fees)

Function Note: budget authority only, by center	FY 08 Actual (December 2007)	FY 09 Final (March 2009)	FY 10 Final (October 2009)		FY 11 Alliance Request	FY 11 President's Request
Food	$   510 million	$   649 million	$   784 million		$ 955 million	$ 848 million
Human Drugs	$   353 million	$   413 million	$    465 million		$ 580 million	$ 484 million
Biologics	$   155 million	$   183 million	$    206 million		$ 255 million	$ 215 million
Animal Drugs/Feed	$     97 million	$   116 million	$    135 million		$ 165 million	$ 141 million
Devices & Radiological Health	$   238 million	$   280 million	$    315 million		$ 385 million	$ 326 million
Natl. Ctr. For Toxicological Research	$    44 million	$    52 million	$    59 million		$ 72 million	$ 61 million
HQ, Office of Commissioner and Other	$    97 million	$   121 million	$    144 million		$ 183 million	$ 162 million
Rent & Facilities Cost	$  220 million	$   223 million	$    237 million		$ 250 million	$ 259 million
SUBTOTAL, Salaries and Expenses	$ 1.714 billion (+$145M over FY 07)	$ 2.039 billion (+$325M over FY 08)	$ 2.346 billion (+$307M over FY 09)		$ 2.845 billion	$2.496 billion
Building and Facilities Repair	$ 8 million	$ 16 million	$ 16 million		$ 12 million	$ 12 million
TOTAL, ALL Budget Authority Appropriations (no user fees)	$1.722 billion	$2.055 billion	$ 2.362 billion		$ 2.857 billion (Proposes + $495M over FY10)	$2.508 billion (Proposes $146 million over FY 10)

Because OMB includes new and proposed user fees in their totals, these numbers vary considerably from those being discussed by the Administration and reported by many sources. Notably, the President's request includes user fees being collected for the new tobacco center at FDA, monies that exactly match the cost of new responsibilities added this year.

FDA, SOTU, and the President’s Budget Request

The President's State of the Union (SOTU) address gave no clues as to the fate of the FDA budget for FY 11 (begins October 1, 2010). Both the general and specific details for the agency await the February 1 release of the President's budget request.

While the House and Senate have control over the final amount that FDA receives, the President's request is the baseline against which the Congress works. FDA Matters is pleased to offer a guide to interpreting this first stage of the FY 11 appropriations process.

What the State of the Union didn't tell us. There was hope that the President would make reference to FDA or touch upon food safety. This didn't occur and there was almost nothing on public health in the address. Even a reference to cancer research did not lead to a mention of support for NIH.

The President announced a three-year freeze on discretionary domestic spending, followed by inflationary increases for the rest of the decade. Within this, some agencies and programs will continue to grow, while others will need to be cut substantially or eliminated. Other than to exclude defense and veteran's affairs, the President did not give any indication of who would be favored with budget increases.

What to expect when the President's budget request is released. It will be confusing. Increased revenue from existing and new user fees is likely to be included in totals showing that FDA is growing. This will mask whether the non-user fee budget authority (BA) appropriations (public funds) will increase under the President's request.

Media often report straight from the OMB summary sheets, so don't believe any reported numbers unless they recognize the distinction between user fees and BA appropriations. Another potential point of confusion is whether the user fees that fund the new Tobacco Center will be represented as providing more resources to FDA.

The distribution of any new funds among the FDA functions is also important. It is possible, for example, for food safety to receive increases while the rest of FDA is flat-funded.

Looking strictly at BA appropriations, FDA received $2.35 billion for FY 10. Based on year-over-year inflation in FDA costs, the agency needs an increase of $120 to $140 million just to maintain current staffing and program levels. Any less will mean cutbacks within the agency.

It is possible the President's request will include new responsibilities for FDA. Unless separate additional funding is provided, this will also hinder efforts to strengthen the agency.

For comparison purposes, FDA received a $306 million increase in FY 10. The Alliance for a Stronger FDA is recommending a $500 million increase for FY 11.

What Congress does next. Just as the President has weighed FDA against competing priorities, so must Congress. Action will accelerate through the Spring, with hearings, mark-ups and negotiations. Congress will be trying to get appropriations done by September 15, well before the elections.

Why advocacy is essential to funding the FDA. The Alliance for a Stronger FDA has 180 members and represents all FDA stakeholder groups: consumer and patient groups, health professional societies, associations, companies and individuals. Former FDA commissioners and Secretaries of HHS have chosen to be honorary members and support efforts to provide better funding for FDA.

The Alliance has been a potent force over the last 3 years by successfully reversing a decade of budgetary neglect of FDA. The Alliance needs your support to continue its work in what appears to be a very rough year. For information about becoming a member, please write to me at sgrossman@StrengthenFDA.org.

Steven

For purposes of disclosure, I am one of the founders of the Alliance for a Stronger FDA and serve as deputy executive director. The Alliance is not affiliated in any way with FDA Matters or with my consulting practice, HPS Group, LLC.

An earlier column with additional background:

Can FDA Withstand the FY 11 Budget-Cutters?

December 6th, 2009

The President's FY 11 budget request is likely to be deeply constrained. Having advocated successfully for a number of costly initiatives, President Obama will need to show that he can also reduce the deficit. He asked Cabinet secretaries to submit their budget requests at a no-growth level and an alternative budget on the assumption that their Department might be reduced by 5% overall. Read the rest of this entry »

Mr. Brown Goes to Washington

The election of Massachusetts' new Senator, Scott Brown, has set off a media frenzy about the fate of health care reform legislation. However, the ramifications of his election reach far beyond health reform.

FDA turns out to be a good example. FDA Matters sees at least three consequences of his election that may affect the agency in 2010.

Congressional Focus. Health reform is still alive, but it will require considerable effort to re-start the process and advance new legislation. This could mean yet another year in which the nation's dialogue on health issues will be largely limited to one topic, health reform.

If health reform is re-started, Congress may enact food safety reform and hold scattered hearings on medical devices, drug safety, and medical innovation. However, Congress will lack the time and focus to attend to other important FDA issues.

Regulatory Pathway for Follow-on Biologics. A regulatory pathway for approval of follow-on biologics (FOB) is a probable casualty of the Brown election and the demise of current health reform legislation. Chairman Waxman has never wanted FOB in health reform. In the days before Senator Brown's election, he was reportedly working with the White House and the Democratic leadership to reduce the 12-year data exclusivity that had been in both the House and Senate-passed legislation.

If FOB is to be adopted in 2010, it will probably have to be as stand-alone legislation. This is a mixed blessing for the biopharmaceutical industry. While it gives Chairman Waxman a new opportunity to shape the House version, the strength of the industry has been in the ranks, rather than with leadership. The key to the industry's earlier victory in the House was that the legislation sponsored by Representative Anna Eshoo had 140 bi-partisan co-sponsors from every part of the country.

The time for legislation may also have passed. I believe more companies are going to file full Biological License Applications (BLA), rather than waiting for a generic-oriented pathway. BLA's are more expensive, but there are offsetting proprietary advantages. Some companies may also be able to build their US BLA on clinical data that had been compiled to support abbreviated applications in Europe.

Deficit Reduction. Senator Brown's election may also be a harbinger of another trend that could impact FDA. President Obama had already announced that the Administration's appropriations requests for 2011 (considered in 2010) would focus on deficit reduction.

Congressional enthusiasm for deficit reduction is always strong on rhetoric, but weak on follow-through. Many members of Congress see the Massachusetts special election as reflecting a growing and ugly mood in America about the economy and jobs. Because the federal deficit is an important contributor to this mood, Members of Congress may take deficit reduction more seriously this year.

If the deficit reduction fervor increases further, FDA is at-risk of receiving a very small increase at a time when the agency's needs are growing and it still working to overcome a decade of budgetary neglect.

It is rare for a Congressional special election to affect DC. This one is different and we are likely to see considerable change as Mr. Brown comes to Washington. FDA Matters will continue to watch closely how the election may impact: Congressional attention to FDA, the follow-on-biologics debate and the fate of FDA's appropriation.

Steven

For more background on the battle over FOB's in the House last year:

The Best Little Chess Game in Town

August 3rd, 2009

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. Read the rest of this entry »

A New Food Agency Has Become Unnecessary (For Now)

FDA Matters applauds the appointment of Mr. Michael Taylor to be the first Deputy Commissioner for Foods at FDA. With more authority, experience and stature than any previous food leader, he has the opportunity to shape and re-shape food regulation and the safety of the food supply.

Because Mr. Taylor will be outstanding in this new post, the campaign for a separate food agency will go away, at least for a couple of years.

People solve problems, reorganizations don't. Whatever problems exist within FDA would still exist within a separate food agency. Sometimes matters get even worse, as they did with the creation of the Department of Homeland Security.

Enter Mike Taylor, the person who can solve the problems. He has been an advisor on foods to the Commissioner for months and has been promoted to line manager and decisionmaker for every food activity within FDA. Most of us think only of the Center for Food Safety and Applied Nutrition (CFSAN), but there are food programs in the Center for Veterinary Medicine, Office of Regulatory Affairs and elsewhere at FDA. He will be responsible for all of them.

Mr. Taylor has all the elements for providing transformational leadership: experience, knowledge, respect, determination and foresight. By bringing leadership to foods, he will eliminate the urgency-- and probably the need-- for a separate food agency.

Intriguingly, Mike Taylor has been an advocate for a single food agency and there is some question about how that might affect his leadership. It won't. Some might think his appointment accelerates the move to a separate food agency. It doesn't.

Circumstances have changed. To continue to advocate for a separate food agency, Mr. Taylor would need to point to activities and policies that would be different and better if done outside FDA. It is hard to imagine what those would be--with him in charge and a supportive Commissioner. Or said another way: neglect, not the organizational structure, has always been the problem.

Things may look different in a couple of years. A new food safety law seems certain to be adopted in 2010. Implementing that law might create new reasons to support a separate food agency.

If so, an additional benefit of Mike Taylor's appointment would be continuity. His leadership and his structure would be carried over into a new organization. And he would have no trouble being confirmed by the Senate if that were required.

Which leaves one remaining question: will increased attention to food come at the expense of attention needed by the medical products function at FDA? I see no reason to think so. The broad, grassroots push of patient groups for safe and effective treatments has no counterpart on the food side.

Steven

Has FDA Slipped Back into Anti-industry Mode?

An industry CEO wrote me to observe: FDA is returning to the anti-industry paradigm of the past.  His concern is understandable. Yet, I respectfully disagreed with him. It is natural to fear change. It is easy to confuse activism with ideology.

FDA Matters believes there are two perspectives from which to judge the situation of FDA versus industry.

The first perspective is relative. The nation elected a liberal Democratic president committed to change. He had the opportunity to appoint an ideological FDA commissioner…someone who would have seen FDA's mission as re-regulating the entire FDA world after 8 years of perceived neglect.  

Instead, the President appointed Dr. Margaret Hamburg, an experienced administrator whose strength is pragmatic approaches to public health problems. As I have written before, being a big city health commissioner predisposes and reinforces pragmatic rather than ideological thinking.

Compared to what might have been in a Democratic administration with Democratic congressional majorities…FDA and Dr. Hamburg are a lot more open to industry concerns than could be expected.

The second perspective is thematic.  Commissioner Hamburg has been explicit about embracing innovation and recognizing that a safety-only perspective is counter to the public health. New medical products are more than just hope; they relieve suffering, restore functioning, strengthen families and sometimes they provide cures. These are all public health values, too.

The ongoing revolution in biological sciences is very much on Dr. Hamburg's mind. The commissioner speaks often about how FDA needs to strengthen and expand regulatory science at FDA to develop the tools necessary to evaluate increasingly complex medical products.

This is definitely pro-industry. An FDA that is ill-equipped and uncertain is one that won't be able to evaluate new science or recognize subtleties. FDA's default response then becomes "no." Dr. Hamburg does not want this to happen any more than industry does.

Some of the alleged anti-industry initiatives need to be seen in context.

Almost all FDA-regulated companies intend to abide by the law. Yet, there are lots of missteps that go unrecognized and lots of evidence of people cutting corners or being outright frauds. In the face of this, FDA enforcement had become lax. For the most part, companies are being pushed into greater vigilance of their own actions…..where good and bad practices may mean life or death for some patients and consumers. While painful to some, I don't see this as anti-industry.

Context is also important in assessing whether the current review of the medical device approval process is anti-industry, which some believe. I see the review as long overdue, given the importance of medical devices and the arcane way in which they are approved. A comprehensive re-examination has not occurred in more than 15 years. In the end, I think FDA and the Institute of Medicine (IOM) are going to reach conclusions that are "uncomfortable but acceptable" to industry. The industry will be able to flourish once the controversy is behind them.

It hurts FDA, as well as industry, if there are fewer new drug and device approvals or if systems cannot be put in place to make our food safer. The success of FDA-regulated industries is important to FDA.

Dr. Hamburg understands this and is acting accordingly.

Steven

Some related columns from FDA Matters:

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

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

Executions in China: A Thanksgiving Message. Sometimes it takes other people to give us a perspective on our own values. Today, Associated Press reports that two men were executed in China for tainting milk powder with melamine, an industrial chemical. The adulterated milk killed at least six children and reportedly sickened more than 300,000. Read the rest of this entry »

"No Surprise" That Medical Devices Are Under Scrutiny. My column entitled, "Re-Evaluating the Medical Device Approval Process" was not widely-read. I assumed it was because everyone already knew that a review was underway at FDA, with more activity coming. Apparently, I was wrong. Read the rest of this entry »

Stigmatizing the Obese and Criminalizing Food

Well-meaning policymakers are constantly advocating for specific solutions to societal problems. They intend to create a better world and often they do.

In the process, their good purpose is sometimes hijacked by unintended consequences. FDA Matters believes this is the inevitable fate of policies that tell Americans what foods they are allowed to eat.

I applaud the enthusiasm of public health advocates for their anti-obesity initiatives and hope a large number of Americans will cut their food intake and make wise food choices. Unfortunately, unintended consequences are likely to neutralize these public health efforts, resulting in little or no net progress against obesity. It is a wasted opportunity.

Stigmatizing the obese. I suspect that most obese people (1/4 of the American population) already experience substantial negative feedback about their weight. It comes from family and friends, strangers in the mall, and the persistent cultural message that "thin is in." Obese people surely feel they are under assault from the world around them.

In the current environment, the self-worth of obese people is under attack by society…and ill-will toward the obese is increasingly acceptable. These are not effective ways to encourage behavioral changes.

Public health may not have caused the cultural shift toward stigmatizing obesity…but the public health community has a responsibility—by its utterances and its campaigns—not to make the situation worse.

These are foreseeable, albeit unintended, consequences of campaigns to reduce obesity. Public health should not be complicit. There is still time to send a more nuanced message that discourages ridicule of individuals who are obese and provides more encouragement and assistance to those who struggle to lose weight.

Criminalizing Food. Efforts to restrict access to foods that are sugary, fatty, salty, high-calorie, etc. are also doomed to failure. People want these foods. And by now Americans should understand that prohibition is not an effective public health strategy.

Where access to foods is restricted, black markets will form. A recent BBC news story describes an enterprising English lad who was caught selling "crisps" (British equivalent of our potato chips) at his school. He was suspended for violating the school's "healthy snacks policy." With true entrepreneurial spirit, he had also marked up the price.

Things are just starting to heat up on this side of the Atlantic. Last year, New York City decided to severely limit school bake sales and regulate what foods are allowed in school vending machines. Ironically, sports programs are likely to be the hardest hit by loss of income from these sources.

We are not to the point of criminalizing foods. But I worry that moralism about food is on the ascendancy. It is absurd to be worrying about "food pushers" lurking on the edge of the school grounds trying to corrupt our youth. It is sad to see time, energy and money diverted from what really counts: improving nutritional education and increasing support for obese people who want help losing weight.

Our relationship to food is both complex and highly emotional. By all means, let's spread the public health message that obesity has serious personal health consequences. But we need to do it in a way that helps people, not hurts them. To do this, we must be careful that the unintended consequences don't ruin the good that could be achieved.

Steven

The BBC story on the student suspended for selling unhealthy snacks on school grounds:

http://news.bbc.co.uk/2/hi/uk_news/england/merseyside/8412310.stm

A description of the situation in New York City:

http://www.nytimes.com/2009/10/03/nyregion/03bakesale.html?_r=2&scp=1&sq=bloomberg%20and%20bake%20sales&st=cse

Messages to the FDA-Regulated: Seven Columns to Re-read for 2010

This past year has been a tumultuous one for FDA-regulated industries as they struggled to provide new and safer medical products and safer foods, while weathering much criticism.

FDA Matters has explored a number of industry issues in 2009. As they evolve in the new year, I will continue to provide readers with my analysis and commentary. Meantime, here are seven columns that provide insight about FDA-regulated companies. They provide useful background for 2010:

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. There has been a lot of fuzzy thinking about what type of companies will be players and how they will position themselves. Read the rest of this entry »

"No Surprise" That Medical Devices Are Under Scrutiny

My column entitled, "Re-Evaluating the Medical Device Approval Process" was not widely-read. I assumed it was because everyone already knew that a review was underway at FDA with more activity coming. Apparently, I was wrong. Read the rest of this entry »

The Beatings Will Continue…

….until the biopharmaceutical and medical device industries clean up their act.

It has been an expensive year for pharmaceutical companies. Billions of dollars have been paid to federal and state governments and whistleblowers in settlement of allegations and lawsuits. The complaints include off-label marketing and overcharging Medicaid, but there are many others. Read the rest of this entry »

Patients Come First

It is a distracting time for the biopharmaceutical and medical device industries. All this frenzy makes it a good time to stop, draw a breath and remember why seriously-ill patients care about the success of biopharmaceutical and medical device companies. Read the rest of this entry »

Black, White, Shades of Gray

Civil and criminal investigations are becoming more prominent in the world of FDA-regulated industries. Being FDA-regulated means "always worrying that you will have to say you're sorry." But it matters whether you are apologizing to FDA or trying to apologize to investigators. Read the rest of this entry »

FDA: Invisible Arbiter of What Constitutes Disease

The nature of disease and constantly changing definitions are pertinent to FDA, which often makes decisions on behalf of society that reshape our understanding of disease. Read the rest of this entry »

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

Creating an Internet communications policy for regulated medical product companies is so daunting that FDA has largely ignored the responsibility. FDA needs a different approach. This is not a matter of a large, complicated problem with many facets. Rather, it is a number of smaller problems that can be addressed separately. Read the rest of this entry »

Steven

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

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

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

Public Health Leadership Comes to FDA

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

Turning Data into Knowledge

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

FDA and NIH: Natural Allies

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

In Praise of Predictability

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

To Whom Much is Given, Much is Expected

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

CARS: The Vehicle for FDA's Future

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

Long-term Challenges Need Short-term Attention

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

Steven

Scientific Reductionism and the End of Medicine

"For the last 400 years, science has advanced by reductionism ... The idea is that you could understand the world, all of nature, by examining smaller and smaller pieces of it. When assembled, the small pieces would explain the whole." (John Holland).

Have you ever heard someone accused of "reductionist thinking?" You probably will in 2010 because scientific reductionism is a critical, but rarely articulated, foundation of personalized medicine.

Reductionism is an attempt or tendency to explain a complex set of facts, entities, phenomena or structures by another, simpler set of constituent parts. Historically, scientific reductionism has held that all biology can be explained in terms of chemical reactions. In turn, these chemical reactions can be explained at the atomic level by physics.

An example of scientific reductionism is the belief that a blueprint for understanding and curing all disease will result from mapping genomes (human, bacteria, etc.). In effect, the complexity of biology ultimately yields to a much simpler paradigm based on de-coding the meaning of each component in the human genome and then delivering medical therapy personalized to the individual's genetic make-up. To oversimplify a little, biology then becomes a predictable "machine," subject only to additional reductions that yield smaller pieces and even more insight.

In contrast, many scientists believe that the complexity found in biology is more than just the inability of scientists to simplify the tangle of life and disease. No matter how much we know about genomic causation and associations, we will never have a full picture of life nor unlock the secrets to all diseases. These scientists believe that life is more than the sum of its parts. To them, reductionism is not wrong; it just produces an incomplete vision of biology because it cannot account for systems effects. A new field, systems biology, is trying to develop ways to understand the complex, irreducible biological qualities of life.

FDA Matters views scientific reductionism as a source of actionable knowledge. But just as the book, "The End of History," was more provocative than predictive, there is no "end of medicine" where human biology is reduced to the point of near-total knowledge and flawless cures.

Thus, personalized medicine will not defeat biological complexity. Further, the reductive process will incorporate knowledge from the human genome, but then take us past it into even more difficult and unpredictable challenges to understanding biology and curing disease.

Meantime, public policy is being shaped by the belief that biology and medicine will eventually yield answers that are concrete and totally reliable. But even when personalized medicine provides better targeted therapies, there will still be phase II and phase III clinical trials that inexplicably fail to show patient benefit. After approval, even the most well-documented and logical therapies may prove harmful and require modification or recall. FDA will need to constantly manage the expectations of Congress, the media and the general public to be sure that they understand that no amount of knowledge or evidence renders a medical therapy certain or riskless.

One prominent futurist has said: if we can just live long enough, progress in medicine will allow us to live forever. I say: not so.

The nature of medicine will be quite different 20 years from now, but unpredictability will still be common. As we develop vast amounts of new biological and medical information, old uncertainties about diseases and drug development will be resolved. New uncertainties will emerge.

Steven

Off-Label Uses Need to Become On-Label Indications

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

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

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

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

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

There are two components to FDA's concerns.

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

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

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

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

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

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

Steven

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

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

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

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

Off-Label Promotion and Whistleblowing
September 9th, 2009

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

Senate Debate on Drug Re-importation

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

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

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

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

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

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

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

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

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

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

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

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

Steven

Long-term Challenges Need Short-term Attention

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

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

Here are the seven challenges:

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

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

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

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

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

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

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

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

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

Steven

Can FDA Withstand the FY 11 Budget-Cutters?

Tradition says nothing happens between Thanksgiving and New Year's Day.  People check out mentally and, as often as possible, physically. Not this December, not in Washington, DC.

Most attention is on the US Senate, which is working this weekend and remains under threat of "no days off" until healthcare reform legislation passes. Just as intensely, but much less visibly, the Executive Branch is working full-tilt to complete the President's Budget Request for FY 11 prior to the State of the Union speech in late January.

Of the two December activities, the President's budget is far more important to FDA.

The President's FY 11 budget request is likely to be deeply constrained. Having advocated successfully for a number of costly initiatives, President Obama will need to show that he can also reduce the deficit. He asked Cabinet secretaries to submit their budget requests at a no-growth level and an alternative budget on the assumption that their Department might be reduced by 5% overall.

With Congressional elections less than a year away, Congress will also feel pressure to dramatically reduce government spending. This will be particularly acute for Democrats, because the President's party usually loses a substantial number of seats in the mid-term elections.

Much of the government is likely to be flat-funded in the President's budget request. Even agencies and programs that advance Democratic policy priorities may not get increases.

There are three other reasons why FY 11 may be a rough year for FDA funding:

• a number of unfunded mandates (FOB, food safety) in upcoming legislation may consume FDA's budget increases ($300M is not an increase if the agency gets $400M in new responsibilities),
  
• FDA could get lost in the funding and implementation of health care reform, and
  
• increases over the last three years may be seen as sufficient to tide the agency over during a difficult budget year.
  

FDA's fate on FY 11 appropriations is not sealed. It will require many good arguments and hard work for the agency to get a meaningful increase in the year ahead.

The Alliance for a Stronger FDA will continue to lead the fight to get the agency more funds. Since the Alliance's founding three years ago, FDA's budget has increased by nearly $800M, a 50% increase. (FY 10 compared with FY 07).

The Alliance has 180 members, representing all FDA stakeholders: consumers, patients, associations, companies and individuals. They all agree that the agency needs to be better funded. Three former Secretaries of Health and Human Services and 6 former FDA commissioners support the Alliance's efforts and are honorary members.

If your organization, company, association, law firm or consulting firm are not members of the Alliance, please contact me at sgrossman@StrengthenFDA.org for details about joining. The Alliance also has individual memberships for those not associated with an organization.

The broader and deeper the Alliance membership, the more successful they can be. If FDA matters to you, please act now to help strengthen the agency through increased appropriations.

Steven

In the interests of disclosure, I am one of the founders of the Alliance and serve as its Deputy Executive Director. FDA Matters represents only my own views and is a product of my health policy and regulatory consulting firm, HPS Group, LLC. The Alliance and HPS Group are not affiliated in any way.

My last column on appropriations addressed FY 10's successful efforts…and examined one of the key long-term concerns: FDA's need to show that new monies have been well-spent in ways that support and promote the public heath:

To Whom Much is Given, Much is Expected
October 6th, 2009

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Steven

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

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

Here is a related FDA Matters column:

Patients Come First
November 11th, 2009

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

Executions in China: A Thanksgiving Message

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

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

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

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

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

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

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

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

Steven

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

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

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

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

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

The Perils of Living in a Bubble

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

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

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

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

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

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

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

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

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

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

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

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

Steven

FDA: Invisible Arbiter of What Constitutes Disease

According to Wikipedia, "disease" refers to any condition that causes pain, dysfunction, distress and social problems. (http://en.wikipedia.org/wiki/Disease). What constitutes disease is more varied and changeable than this definition might suggest.

The nature of disease and its constant changes are pertinent to FDA, which often makes decisions on behalf of society that reshape our understanding of disease.

Some diseases are culturally-defined. Homosexuality has long been treated as a disease or medical disorder. Scientific knowledge and societal attitudes have shifted over the last 25 years. Homosexuality is increasingly viewed as a variation on human behavior, rather than a disease or condition. FDA would never consider an "anti-homosexuality pill."

In the opposite direction, obesity has long been a symbol of wealth and well-being. Today, it is being redefined as a disease, complete with claims that it is an epidemic. FDA decided obesity was a "disease" years ago and has considered a number of "anti-obesity pills."

Other diseases reflect new thinking about what constitutes illness. Examples would include post-traumatic stress disorder, attention-deficit hyperactivity disorder and restless leg syndrome. FDA has approved drugs that treat each of these.

The Food Drug and Cosmetics Act provide the agency some leeway in how it looks at disease. The term "drug" means, among other things:

• "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and
  
• articles (other than food) intended to affect the structure or any function of the body of man or other animals." (FD&C Act, Section 201(g)(1)).
  

This dual definition has allowed the agency to finesse the issue of pregnancy. I assume that birth control and fertility drugs are viewed as affecting the structure or function of the body. The agency would not want to claim that pregnancy is a disease or that preventing (or causing) it constitutes disease treatment.

FDA seems to make these judgments without any fanfare. My own benchmark is the formalization of erectile dysfunction (ED) as a disease. I expected FDA to go through some extra, visible steps, to show that it had considered whether ED was a disease for which therapies were appropriate. I did not see this occur during the FDA review or at the time of approval.

The question "is this a disease" doesn't come up every day at the agency. When FDA does make judgments, it appears embedded in the work rather than a notable event.

One of the great future challenges will be for FDA to decide if "anti-aging" drugs are possible. The answer may be "yes," pointing to the function and structural changes that are clearly made by aging and the opportunity to stabilize and reverse them. This would allow anti-aging to be a drug's formal indication for prescribing and would be allowed as a label claim.

If "no," then sponsors of anti-aging drugs will need to show a direct link between their drug and an aging-related disease, such as diabetes or dementia. My understanding is that most anti-aging pipeline drugs are being developed on the assumption that FDA is not ready to decide and that "anit-aging" may never be an approved indication.

When the aging issue becomes timely, FDA will be there to decide. It will bring more experience to the process than most FDA watchers realize.

Steven

Black, White, Shades of Gray

Civil and criminal investigations are becoming a more prominent feature in the world of FDA-regulated industries. People who never gave any thought to this….suddenly find themselves needing to understand how investigations work.

Being FDA-regulated means "always worrying that you will have to say you're sorry." But it matters whether you are apologizing to FDA or trying to apologize to investigators.

If you did something that the agency considers "wrong," then the best response is to admit it forthrightly and act quickly to undo your mistake. FDA program staff or inspection/enforcement staffs are more likely to work with you to resolve the situation if they feel you have been cooperative, honest and contrite.

While a good approach for most situations, it may not suffice if you are under investigation by FDA's Office of Criminal Investigations, the HHS Inspector General, the Department of Justice, US Attorneys, State Attorneys General or any of several committees of Congress.

Investigators have a different way of thinking, something I learned while a Senate staffer in the early 1980's.

In general, investigative staff saw the world in black and white. There were good guys and bad guys.

The investigators' objective was to expose wrong-doers and make sure they never had the opportunity to do wrong again. It rarely occurred to the investigators that intent, extraneous events or misunderstandings might provide reasons to temper their judgments. Dealing with such nuances was not part of their job nor did they try to understand the wrong-doer or why the problem occurred.

As a legislative staffer, my world was painted in shades of gray. No good guys, no bad guys….just other legislative staffers with whom I needed to work in order to achieve my chairman's legislative objectives. I could not have done my job if I held absolute views about people or policy. I was in the business of nuances.

I suspect that most individuals in FDA-regulated industries are like me. The constant search for bad guys is not part of their jobs or temperament. They have no special insight or experience in dealing with investigators who view the world in such sharp contrasts of good and bad.

It is never a positive experience to be sitting across the table from an investigator. All options are likely to be bad ones, including public humiliation, civil liability and criminal prosecution. Exoneration is a remote possibility, even if you fervently believe you have done nothing wrong.

An FDA-regulated company can limit their exposure to such situations. This requires systems that review and monitor company actions at a very granular level. It requires a level of transparency that makes most companies nervous. It requires prompt action to dismiss any employees who violate company rules and any supervisors who looked the other way. No exceptions can be made, even if it includes someone from the executive suites.

Companies that follow this path are less likely to become the target of an investigation. A company under investigation that can document strict programs--prospectively initiated and rigorously enforced—will usually do much better than one promising "never to do it again." A pre-existing company commitment to tough enforcement may be the only way to get an investigator to consider your alleged wrongdoing in shades of gray, rather than black and white.

Steven

My earlier columns related to this topic are:

The Beatings Will Continue… November 1st, 2009

….until the biopharmaceutical and medical device industries clean up their act.Read the rest of this entry »

Off-Label Promotion and Whistleblowing September 9th, 2009

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

Patients Come First

It is a distracting time for the biopharmaceutical and medical device industries. Everyone is scrambling to gain advantage in the Senate health reform negotiations. Two major pharmaceutical companies disappeared in mega-mergers last week. Reportedly, more medical product companies are working on settlements with the Department of Justice.

All this frenzy makes it a good time to stop, draw a breath and remember why seriously-ill patients care about the success of biopharmaceutical and medical device companies.

Medical products—drugs, biologics, devices—are the hope of millions of Americans who are in ill health, disabled, or face the prospect of chronic disease. Patients want relief from symptoms, reduction in pain, the slowing of chronic disease and fewer restrictions on their ability to think, communicate and manage their own lives.

Who can deliver this? NIH research is essential to the advancement of biomedical science. But it is industry that creates the products for FDA to review for safety and efficacy. Take the companies out of the equation and you have nothing.

For this reason, seriously-ill patients need the biopharmaceutical and medical device industries just as much as industry needs patients. They share a common mission and a pressing need to improve public and individual health. It should be basis for a stronger alliance than exists today.

To unlock this additional potential, industry needs to rise above the many distractions that are unrelated to the needs of patients. Patients don't care which company bought another company, what US Attorney is announcing a lawsuit today, or whether there is a regulatory pathway for follow-on-biologics. Seriously-ill patients want innovations that provide relief and cures and they want to be able to manage their own care.

FDA's two hearings this week--one on risk communications and the other on the use of social media in medical product promotion--provide a timely example. Patients want reliable information in a context they can understand. They would like to be informed without being scared by long lists of unlikely side-effects. Patients want their doctors to be knowledgeable and don't really care how their doctors received truthful, medically-useful information.

In short, patients are not interested in communications that elevate structure over content, coherence or accessibility.

Arguably, this is an area where industry let itself become distracted by its battle with FDA on marketing issues. An earlier resolution might have been possible if a patient-centric approach had been advanced, rather than a commercial one.

Most seriously-ill patients wake each morning wondering how they will surmount the day's challenges. They are concerned about the health of all Americans, but can't help being focused upon their own medical situation. Most of the people I know in the medical products industry wake each morning with the hope that their day's efforts can contribute to improving the health of all Americans, as well as provide specific benefits to seriously-ill patients.

The world-views of patients and industry are not dissimilar. They can share a dream (and an action plan)…if it is built on an unwavering commitment to patients coming first.

Steven