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

House Votes on Health Reform: What’s Next?

By the incredibly close margin of 220 to 215, the US House of Representatives adopted health reform legislation on Saturday evening, November 7, 2009. In the end, abortion restrictions were added…and liberals were forced to accept these and provide the margin of victory.

The content of the House bill is of little significance. However, its passage is an historic event, creating a near-certainty that President Obama will be signing final legislation in the next 3 months.

Everyone's attention will now return to the other side of Capitol Hill. Senate Majority Leader Harry Reid has only one task: find the combination of health reform provisions that can command 60 votes in the Senate. He knows the answer is not in the House bill.

To get to 60 votes, Reid will need to agree to giving states the option of joining a government-run insurance plan or accept a mechanism where a government-run insurance program is triggered only if insurance reform doesn't reduce premiums. Not unlike the House, President Obama will be needed to persuade Senate liberals that this is a better outcome than no legislation at all.

Holding 60 votes may be as challenging as getting 60 votes. News stories have mentioned the possibility that Senators might offer 2000 amendments, regardless of what package Senator Reid offers. Leaving aside the weeks of Senate floor time this would require, every vote would hold the potential to break apart the 60 vote majority that Senator Reid would have labored to put together.

Sharp limits on amendments will be required. Perhaps, the 60-vote majority will have to agree to a text beforehand and then oppose all amendments. The same problem would recur in House-Senate conference...so there will probably be no conference. Instead, four to 10 weeks from now, President Obama will be back on the House side, persuading liberal members that the Senate bill is the best possible. He will be urging them to vote to accept that bill when it comes back to the House for consideration.

So, the House bill means nothing, but its passage will push forward a political process that Democratic leadership cannot allow to fail. They will have no choice but to twist arms until the votes and the process makes success possible.

Where is FDA legislation in all of this? Some version of follow-on biologics will be in the final legislation. The House bill won't matter. The specifics will be those agreed to in the Senate over the next few weeks.

Where is FDA in all of this? Advocates need to strongly and continually reinforce the relevance of the agency in a political world that will be dominated by implementation of health reform. The arguments may seem obvious: safe and effective drugs, biologics and devices are an essential part of preserving and improving human life. This will be true in a reformed system as much as it is today. The difficulty is knowing whether any Members of Congress will be listening.

Steven

Animal Research: One of FDA’s Core Values

Earlier this year, ABC's Nightline did a story about alleged abuses at the nation's largest primate research center. Fueled by this, the Great Ape Protection Act (HR 1326) now has 95 co-sponsors, compared to 29 sponsors on a similar bill in the last Congress.

The bill would virtually eliminate research using chimpanzees, even where there is no other animal model that could serve to predict safety in humans. This is a threat to animal research and, ultimately, to ourselves. The loss of chimpanzees would be a serious blow to research and would encourage animal rights activists to push for even more restrictions.

The value of animal research in the life sciences is considered an NIH issue. The research advocacy groups opposing the legislation are all part of the network that supports NIH

FDA Matters believes that the FDA and its stakeholders should be equally concerned.

Animal research is the vital first step in the development of new medical products. Before any safety or efficacy testing is permitted in humans, FDA must be satisfied with animal testing data submitted by the product sponsor. Pick any medical breakthrough and you will find animals were tested prior to humans.

For understandable reasons, we tend to focus on the human part of new products. What patients will be helped and by how much? By the time a company files a New Drug Application (NDA) or the equivalent in biologics and devices, the headline is the human data. While the animal data is always relevant, it has largely served its purpose as the gateway for human trials.

We talk about the people part without recognizing that the pipeline of innovative drugs and devices would narrow without chimpanzee research. It would collapse completely if a broader range of research on animals (e.g. monkeys, pigs, sheep, dogs, rats) was heavily restricted.

Everybody should be for protecting the welfare of animals. Any means to lessen our dependence on research animals should be welcome. Animals should always be treated ethically and pain reduced or eliminated. The fewest number of animals should be used to reach a conclusion that can be relied upon. Laboratories should be accredited and subject to inspection. Problems should be addressed within a facility under the watchful eye of government, accrediting and licensing agencies.

While purportedly about the welfare of animals, the House bill is really designed to grant rights to animals, starting with chimpanzees. There are elaborate arguments about whether animals should have rights or just have their welfare protected. For me, the choice is easy. I want a product or procedure tested in animals before it is given to me or my loved ones. I believe in protecting animals, but human rights come first.

Chimpanzees are crucial to animal research. If the House bill were to become law, important animal research might be halted in vaccines, hepatitis A, B and C, HIV/AIDS, malaria and some types of cancer. I am told that in these diseases areas, research on chimpanzees often provides essential information that cannot be obtained in any other way.

The importance of animal research needs to be a core value for FDA. The stakeholder community needs to "seize the day" and make clear where its stands. Those who benefit from animal research (including patients) need to provide the manpower and financial resources to counter the animal rights movement in America and its threat to medical progress for humans.

Steven

The ABC Nightline story is at: http://i.abcnews.com/Nightline/story?id=6997869&page=1.

A good review of appropriate animal research activities and processes is at: http://www.arvo.org/EWEB/dynamicpage.aspx?site=arvo2&webcode=AnimalsResearch

There are many good organizations that work to counter the People for the Ethical Treatment of Animals (PETA) and other animal rights organizations. One of the most effective is Americans for Medical Progress (AMP), an organization that educates media and the public about the importance of animal testing in advancing human health. Among other projects, they are organizing scientists to be more pro-active and articulate about the importance of testing on animals. AMP can always use more support for their work, www.amprogress.org.

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.

While I am sure there are some "innocent" companies that are the targets of allegations, there are far too many expensive settlements and verdicts for industry to claim that they are victims of overzealous prosecutors and "get rich" whistleblowers. Earlier, FDA Matters called on the biopharmaceutical and medical device industries to recognize that "sales are not more important than laws." ("Off-Label Promotion and Whistleblowing" at www.fdamatters.com/?p=479)

I worry that companies figure they are ahead financially as long as profits exceed penalties. Not for long! The civil and criminal complaints are going to increase and settlements and verdicts are going to get larger. Legislation will get even more restrictive….and a wave of bad publicity will haunt the medical products industries and may forever destroy the public appreciation of the human benefits these companies provide.

US attorneys, state attorneys general, and inspectors general will keep probing until there is nothing left to investigate in the biopharmaceutical and medical device area. This won't happen anytime soon.

Over 180 pharmaceutical fraud cases involving more than 500 drug products are being investigated by the Department of Justice under the False Claims Act. Reportedly, most involve allegations of false and misleading statements made with intent to defraud or mislead. An additional back-log of 1000 whistleblower cases is waiting for DOJ to decide whether to participate. (From comments made by Jennifer Bragg, a partner in the law firm, Skadden, Arps, as reported in Dickenson's FDA Webview).

CEO's need to see corporate accountability as their personal responsibility. The handwriting is on the wall, based on the recent successful criminal prosecution of a small biotech CEO. Sometime soon, a US attorney is going to decide that monetary settlements should not be allowed to wipe out criminal charges. As a result, some senior executives in multi-billion dollar pharma companies may go to jail.

CEO's can no longer afford to trust themselves or their corporate management in judging whether they have followed the law. They need to verify. This requires tougher questions, independent audits of sales and marketing efforts, and alerting physicians to report to the company any meeting where a company representative made false or misleading claims. These companies should be hiring and empowering former prosecutors and investigators to review both policy and performance.

I believe in the transformative power of the biopharmaceutical and medical device industries to lengthen lives, deliver cures, control symptoms, and relieve pain. My advice to CEO's is clichéd but true. When the subpoenas arrive: "Do not ask for whom the bell tolls, it tolls for thee." Is anyone listening in the corporate suites?

Steven

The article cited in Dickenson's FDA Webview is available at:

'Whistleblower' Cases Dominate FD&C Act Prosecutions [639 Words] [ Price : $14.95]

With more than 180 pharmaceutical fraud cases now under investigation by the Department of Justice, FD&C Act prosecutions are now largely driven by "whistleblower" lawsuits, according to Eugene Thirolf, director of DoJ's Office of Consumer Litigation. 10/14/2009

CARS: The Vehicle for FDA’s Future

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

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

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

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

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

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

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

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

Steven

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

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

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

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

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

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

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

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

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

The anecdotes are legion:

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

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

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

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

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

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

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

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

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

Steven

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

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

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

Turning Data into Knowledge   June 2nd, 2009

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

Why Do Some People Dislike FDA?

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

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

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

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

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

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

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

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

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

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

Steven

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

In Praise of Predictability September 3rd, 2009

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

Health Reform and FOB’s: From Debate to Done in Thirty Days

On Tuesday morning, October 13, the Senate Finance Committee is scheduled to vote on its version of health reform legislation. This is ground zero in a contest of political will and national priorities that began over 65 years ago. This is big…a tidal wave of change coming to the US health care system.

The Finance Committee bill, once passed, will be melded with the version passed in the Senate Health, Education, Labor and Pension (HELP) Committee. Although it's a small detail in the massive health reform bill, the future of follow-on biologics (FOB's) depends on what comes next.

Since early July, FDA Matters has expressed its political admiration for Representative Anna Eshoo's bi-partisan success in garnering more than 140 cosponsors for her bill. I have never seen a committee chairman face the overwhelming odds this presented to Representative Henry Waxman.

Yet, I reminded my readers that Chairman Waxman has a long-history of "not having the votes" and winning anyway. I repeated this observation in August and again in September. This was confirmed, indirectly, by Waxman in a speech he gave about two weeks ago when he told his audience that he hadn't given up on his version of FOB legislation. He asked them to keep working to get his bill passed.

There are at least four opportunities for the very similar House and Senate FOB provisions to be altered to favor Chairman Waxman's position:

• when the two Senate committees merge their health reform bills,
  
• when the three House committees merge their bills,
  
• when the bill goes to the Senate floor and can be amended, and
  
• during the House-Senate conference to reconcile differences between versions passed by each body.
  

Three of these opportunities will take place behind closed doors where anything can happen. You don't need to "have the votes" to prevail….only to be in the room when the decisions are made. Chairman Waxman will be in Speaker Nancy Pelosi's office when the deal is cut on the House side. His ally, Senator Charles Schumer, will be in Majority Leader Reid's office when the Senate bill is agreed upon. Both Waxman and Schumer will be on the House-Senate conference committee.

I no longer think it will happen this way. This multi-step process is a recipe for legislation to be bogged down until next year when health reform and FOB's will die an agonizing election-year death.

To avoid those delays, the Senate bill will be the Finance Committee bill with:

• some provisions from the HELP committee version,
  
• some provisions necessary for Reid to get to 60 votes in the Senate to avoid a filibuster, and
  
• a few provisions that are high priorities for the House (other than a public plan).

The President will then endorse the Senate bill. Assuming Reid has negotiated carefully and counted correctly, the agreed-upon bill will be moved quickly to the Senate floor. The 60 Senators will have agreed not to offer amendments on the Senate floor (allowing one amendment will allow hundreds).

As soon as the Senate-passed bill reaches the House, the Speaker will schedule an "up or down" vote. The President will help her keep the Democratic majority together. There will be no House-Senate conference.

The pending "behind closed doors" Senate negotiations may be the only time further changes will be made. Afterward, Members of Congress will be able to blame Reid and Pelosi that they weren't allowed to offer amendments favored by whatever constituents and health care stakeholders they were trying to help.

The bio-pharma and generic industries probably have no more than two to three weeks to persuade the Senate negotiators to take their side on data exclusivity and other FOB issues. There may be no second chance.

We are going to go from "debate to done" in thirty days.

Steven

My prior columns on follow-on biologics are at:

Fall Scorecard for Follow-on Biologics,
September 11, 2009

Health Reform and Follow-on Biologics September 6th, 2009

The Best Little Chess Game in Town August 3rd, 2009

Follow-on Biologics and the Dance of Legislation July 5th, 2009

The Follow-on Biologics Market June 23rd, 2009

To Whom Much is Given, Much is Expected

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

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

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

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

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

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

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

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

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

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

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

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

Steven

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

FY 10 Appropriations for the Food and Drug Administration

Compared to Earlier Years (based on Conference Agreement)

Budget Authority Appropriations (does not include user fees)

(Prepared by the Alliance for a Stronger FDA)

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

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

“No Surprise” That Medical Devices Are Under Scrutiny

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

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

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

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

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

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

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

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

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

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

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

Steven

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

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

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

FDA Should Stay Out of Health Care Reform

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

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

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

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

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

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

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

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

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

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

Steven

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

Drug Reimportation: A Matter of Faith

Legislation to permit drug reimportation has resurfaced and the Senate may vote on it within the next 4 to 6 weeks. It may be considered as an amendment to the health reform legislation or come up as a free-standing bill. 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 reimportation is permitted, they envision large savings for government programs, health plans and individual patients. They also believe that safety can be assured by limiting reimportation 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 reimportation. 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 reimported 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 reimported drugs will, on a consistent basis, be identical to the original products in quality, safety and efficacy.

In most circumstances, potentially inferior goods sell at a steep discount to cover the consumer's risk of product failure. In health care, this is not considered acceptable. The promised price discounts from reimported drugs don't justify the risk to my health from a therapeutic failure.

Steven

Dr. Collins Meet Dr. Hamburg

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

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

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

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

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

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

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

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

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

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

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

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

Steven

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

My two earlier columns on this topic:

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

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