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Scott Gottlieb, MD - Washington, DC

This text contains Dr. Gottlieb's prepared remarks. It should be used with the understanding that some material may have been added or deleted during actual delivery.

Speech before
Windhover's FDA/CMS Summit
Washington, D.C.

Remarks by
Scott Gottlieb, MD
Deputy Commissioner for Medical and Scientific Affairs
Food and Drug Administration

December 5 , 2006

I was asked today to talk about what I think is going to happen to health policy here in Washington over the next twelve months, but I want to focus my remarks instead on something more fundamental when it comes to healthcare, and that is what is going to happen in millions of encounters that patients are going to have with their doctors over the next year, millions of individual decisions that are going to be made, and how the kinds of policies we are making here in Washington could end up affecting those choices.

There is no question that the policies that we make here in Washington are having a bigger impact than ever before on the kinds of decisions that innovators make about whether to develop a certain medical product, or how to develop it and how it will be marketed. This is true not only for new medicines, but also for new medical devices, and it is driven by the obvious fact that more of the medical products that we rely on to improve our health are being paid for by the public sector. This comes about not just with the creation of Part D, which puts almost half of all drug expenditures in this country under the government's direction when you add up all the things paid for by Medicare, Medicaid and the Defense Department, but also the demographic shift that is underway that is putting more of the users of these new technologies also under government reimbursement.

But simultaneous to this, there is another trend underway that could place not only more of the decisions about how medical products are made and marketed under the influence of the Federal agencies, but also more of the medical decisions about how they are used -- the kinds of decisions that ordinary people make every day in the private consultation with their doctors. Just as we need to be mindful of how the policies we make here in Washington impact the incentives that exist for private innovators to develop needed medical products, we need to be equally mindful of how our decisions here in Washington impact the ability of patients and doctors to make personal choices about their health and their treatment plans -- choices free from federally-imposed rules that could inadvertently intrude upon those relationships, and the choices people make.

In particular, there are two areas of new policy development here in Washington that I believe, if we are not careful, could impact on how private medical decisions get made by taking away from patients and providers some of the latitude they have to make individual decisions that are tailored to individual needs. These three areas of policy development are: First, plans to manage risk by managing how new drugs are prescribed by physicians; and second, an impetus to curtail provider discretion to prescribe medicines for uses that aren't part of a product's approved labeling.

In each of these areas, we need to make sure that we not intrude our policies in unwanted ways into the personal decisions that people make about their health. Instead, we need to pursue opportunities for creating health policies that leave discretion to patients and providers while providing people with the tools to make more informed and intelligent decisions by dismantling information asymmetries that exist today that prevent people from knowing all they can about the safety and effectiveness of medical products when faced with a tough medical choice.

I have said before that we need to work carefully as we move toward a more lifecycle approach to the regulation of new drugs and the management of their risks. There is no question that as new drugs become more complex, and their potential applications more diverse, we need to be doing more than ever to evaluate new medicines after they are approved, so that we can develop good information when new safety problems emerge, as well as develop new evidence that a drug may have additional benefits not anticipated in the original approval.

But as we develop a more comprehensive approach to evaluating risk and benefit and managing risk over the life of a medical product, we need to be mindful that our approaches do not get in the way of medical decisions but serve to inform and support those choices. In particular, I think there is an essential tension that emerges when it comes to discussion in some health policy circles about the intersection between FDA's work and with the practice of medicine.

On the one hand, there is a desire to see government agencies, including mine, take a more active role in minimizing risk from medical products by more actively setting forth conditions on how they should be used. I am speaking specifically about the growing attraction to legislative actions that would expand on the concept of risk management plans that place restrictions on how a medicine can be prescribed and delivered.

These risk management plans have historically addressed real concerns about the potential for unsafe use of certain medical products that have risks associated with them that in many cases can be readily avoided with the proper interventions and supervision. But historically, these risk management plans have been adopted in the setting of very specific kinds of risks. In fact, let me be clear on one thing: I believe the places where FDA has employed risk management plans have been, for the most part, well thought out and judicious. In the face of broader health system challenges, including challenges in funding our healthcare system, many of the risk management plans we have helped sponsors design are the reflection of very solid public health people trying to help the population as a whole. While these efforts may have sometimes conflicted with individual decision flexibility, we have worried much about the impact that these plans could have on decision-making and FDA has taken great care to try and preserve patient and physician choice and discretion.

I do not see this same careful thinking embodied in some of the policy ideas that are being put forth into the public discussion right now.

There is an implicit distinction between the medical challenges where FDA has encouraged the adoption of risk management approaches and the scenarios where these measures would be adopted under some current proposals. For example, FDA might encourage a risk management plan for a drug that carries with it an uncommon but serious risk of an allergic reaction, called anaphylaxis, might require doctors to pre-medicate certain patients who might be at higher risk of these reactions or to watch patients for a certain time after receiving the medicine to make sure they don't develop one of these problems. To take another example, drugs that might carry a serious risk of causing birth defects might require doctors to perform a pregnancy test on woman of childbearing age. In fact, there are examples of just such drugs that we have approved, where just such risk management plans have been a voluntary condition of their approval.

These kinds of risk management plans mostly have one thing in common. They are aimed at mitigating very severe risks that we know can be actively avoided with certain interventions or with appropriate medical supervision. That is quite apart from what some people seem to have in mind in broader policy circles when they talk about risk minimization plans that are aimed instead at limiting prescribing or pushing certain prescribing decisions into the hands of specialists.

Indeed, the risk management plans are being advocated with the hope that with more restrictions, doctors will think longer and harder about prescribing certain drugs where the decision about balancing the subtle risks that all medications carry against the known benefits can sometimes be a hard and personal decision. The point is that advocates of these plans are starting with a sound idea, which is that FDA can sometimes do something to facilitate some of the toughest decisions doctors' and patients must make. But promulgating a risk management plan for each drug is the wrong way to achieve that.

The best way to influence these kinds of decisions, to make sure doctors and patients carefully weigh known but rare side effects against benefits, is to make sure that they have access to timely, complete information about these risks and benefits. For example, it is clear that with the proper resources we can achieve more of our risk minimization goals simply by making more effective communication of the risk and safety information we develop, and leveraging medical professional societies to enforce their own practice standards and approaches to safety. To these ends, FDA has undertaken a significant number of new initiatives over the last two years to improve the quality and amount of information we make available about the safety and efficacy of drugs.

We have refashioned the drug label to make it more accessible, we have made this information available electronically free of charge, and developed guidance on how we aim to make information about emerging risks available more regularly. We are in the process right now of finalizing another new rule that would expand the quality of the information available on drug labels advising woman on the available information about the risks and benefits of medications during pregnancy. But over time, the kinds of resources we have had available to us for these and other safety-related and communications activities have not kept pace with our growing mandate.

Reducing barriers to high quality information will help more people make more informed decisions about the medical products they use. This is quite apart from implementing wholesale requirements that would try to influence how they make productive use of that information to reach personal decisions. Yet the latter is precisely what some propose to do as a way to "improve" drug safety.

I am not trying to say that better communication is going to definitely solve all of the challenges we see, but we need to make sure we have done all we can to make maximum use of better tools for communicating information and partnering with providers before we take more restrictive steps.

We need to be especially careful to consider the unintended consequences of these plans before we popularize them by writing them into new legislation. For example, access restrictions on a new drug can drive physicians to prescribe an older drug that is less effective or has more serious adverse effects. Sitting in Washington it might sound reasonable to limit distribution to pre-qualified pharmacies, but for a patient in Montana or New Mexico this could effectively preclude access because they might have to drive hundreds of miles to get it.

In the end, risk management plans could end up creating obstacles to access for patients who already face significant problems accessing innovative care. For example, some risk management plans could push complicated primary care drugs into the hands of specialists. That puts at real disadvantage patients who often cannot get access to specialists. These are sometimes the very same patients who already face significant obstacles accessing quality medical care. In the clinic where I used to work for example, many diabetics never got to see endocrinologists on a routine basis. They got most of their care from generalists.

On the second point, an impetus by some to stem provider discretion to prescribe medicines for uses that are not part of a product's approved labeling, we need to ask a simple question: Whether the public health, and the health of individuals, is best served when there are limits placed on the exchange of rigorous, peer reviewed information about new uses for existing drugs. This question may be especially important for fields marked by rapid medical advance like cancer where a lot of the most up-to-date prescribing is for off-label uses of cancer drugs that are guided by current research published in leading medical journals.

Limitations on the exchange and reliance on this kind of information could have the potential to impede the ability of patients to access the most up-to-date medical evidence. To see how, I think we all need to have a much clearer understanding of the environment in which many drugs are prescribed "off label" and the circumstances under which new indications are granted by the FDA. Consider the case of a patient recently diagnosed with Cancer.

When we do clinical trials, we often look for homogenous populations of patients with similar characteristics and stages of disease so that we can most effectively see how a drug works over a very large population. In other words, to look for one variable that we might have particular interest in understanding, in this case a drug's effectiveness, scientists are asked to design trials that aim to keep constant as many other variables as possible. The less variability overall in a clinical trial's population, the easier it will be to conclude that the one thing that did change, for example whether or not a patient received the active drug and had their tumor size shrink, was a result of the drug the patients were receiving and not some other characteristics that they may have harbored.

This approach to clinical trials creates an efficient way to obtain rigorous information about a drug's effectiveness. FDA sets a high bar on approval by requiring evidence from these kinds of rigorously-constructed trials to show that a drug is safe and effective and the benefits of a new drug outweigh its known risks. This high bar enables reliable information to be developed that might not otherwise be made available to patients and doctors to guide medical decisions.

The problem is that not every patient fits the carefully defined characteristics of the patients that may have been included in clinical trials. Often patients have very unique characteristics of their disease, or unique circumstances, that place them outside the walls of any one clinical trial. The result is that medical decisions sometimes get made based on medical information that is very different than the kind of rigorous information available in most registration trials. Many patients have far less information at hand to guide their own decisions, or alternatively, have far more information about their particular tumor or disease that gives them characteristics to consider that were not contemplated in a drug's registration trial. The result is that sometimes patients are left to make decisions based on other data sources, or on much less information than what FDA requires, not because they want to, but because they have to.

They are guided instead by incremental information gleaned partly from follow on clinical studies published in the medical literature. Other times, they are guided by new advances in care that have been published in the medical literature have not yet made their way onto a product's labeling. In fact, there is typically a 6-12 month delay between the receipt of medical information by FDA and its inclusion in drug labeling even where there is clear evidence that a new indication for a drug is effective. The delay can be even longer since it often takes a drug company's months and maybe even years to prepare clinical data for submission to the agency. As a result, as a Q&A on off-label use from the National Cancer Institute, posted in 1999, stated: "Off-label use of drugs is widespread in cancer treatment for several reasons…. Some cancer drugs are found to be effective against a variety of tumor types… cancer chemotherapy often involves the use of multiple drugs…. Cancer treatment is always evolving."

The question we need to ask ourselves is this: Should a patient receive one or even two-year-old care just because the wheels of my government institution and its meticulous work may take longer to turn than the wheels of clinical science? Some people believe that patients should be treated only according to the clinical evidence included in a drug's approved indications. Yet this evidence may be two or maybe three years old, especially in a fast-changing field like cancer, where off label use of medicines provide important opportunities for patients to get access to the latest clinical practice and for doctors to tailor their patients' treatment plans based on medical need and personal preferences.

Don't take my word for it though. Listen to some of the comments of experts who have weighed in on these matters. The American Society of Clinical Oncology, in a 2003 document, stated that "the off-label uses of approved drugs have been an important tool for advancing the treatment of cancer" and the AMA at one of its recent annual meetings affirmed that "the prevalence and clinical importance of prescribing drugs for unlabeled uses are substantial… Thus the prescribing of drugs for unlabeled uses is often necessary for optimal patient care." The National Cancer Institute, a government agency, recognizes and lists on its web site off label uses of many drugs as "standard of care." FDA also has long recognized the medical discretion that doctors need to retain to make appropriate decisions for their patients — decisions that often include the off label prescription of a drug. In fact we ourselves have said: "The physician is responsible for making the final judgment as to which, if any, of the available drugs his patient will receive in the light of the information contained in their labeling and other adequate scientific data available to him" (37FR 16504 8-15-72)

Now don't get me wrong. There is real value in getting new indications for drugs into labeling and the FDA has taken some steps in recent years to try and get more of the common off label uses approved in cases where there is sufficient and rigorous medical evidence to merit a supplemental indication. At FDA, we routinely encourage submission of supplemental new drug applications. Our goal is always to get new data submitted as a supplemental New Drug Application so that the public can benefit from an independent assessment of the safety and efficacy of that new indication. But we know these submissions are not always timely or even possible, especially in fields like cancer, where individual diseases are becoming highly fragmented based on new insights into the molecular basis of many of these conditions.

In the end, it is very hard for us here in Washington to anticipate and understand everything that goes on in a doctors' office, when patients are confronted with hard and uncertain choices. Many decisions are guided by tiny bits of pertinent evidence, not because people prefer it that way, but because peoples' problems don't fit the clean categories that may be studied in a clinical trial.

Efforts to limit prescription and scientific exchange to indications only specified on a label could retard the most important advances in 21'st century medicine. The development and deployment of drugs is becoming more and more closely linked to understanding of mechanism of action, which means that physicians can use drugs in more sophisticated ways that cannot all be anticipated on a label, or easily or quickly studied in prospective studies. Once again, this is especially true in diseases where the underlying damage results from an often clearly identifiable molecular mistake, diseases like cancer.

More important, medicine is becoming more personalized as tools like genomics make it possible to tailor treatments on an individual basis. Physicians will not be able to always wait for FDA to approve a new label for every one of their patients, and drug companies will not be able to conduct a trial to explore every possible contingency. In the future, personalization of care could mean that we will have much more off-label use of new medicines, guided by the latest literature, at least until our regulatory approaches are able to fully adapt to a different paradigm where treatment is highly specific to individual patients. Yet policy forces are tugging in exactly the opposite direction by placing restrictions on the exchange of some of the most pertinent information.

Even when properly informed, armed with the best medical evidence, and counseled by caring physicians, it must be understood that a patients decision making does not always fit into the careful criteria in drug labeling or wait for the existing evidence to make its way onto those documents. That is why the best we should aim to achieve in our policies here in Washington are tools and approaches that help patients and doctors be fully informed of the best science. We can help people inform decisions, but we should not seek to establish policies that execute those decisions for them or prescribe very narrow criteria.

This is also true when it comes to policies aimed at promoting continued learning about new medicines. They too need to be flexible to account for changes in the way medicine is practiced. Congress and some safety advocates are moving toward multi-decade post-market study commitments. They may be setting society up for failure because the medical and pharmacological landscape will change so much that most studies designed today will not yield useful data — and it will not be feasible or maybe even ethical to complete them. The kind of studies that will be possible or useful over those time periods are simple, observational studies like Framingham, which are well outside the purview of a single sponsor and may be a place where government can play an active role.

As we move forward this year and write new healthcare policy, we need to preserve as much flexibility as possible for doctors and patients to make treatment decisions that match a person's individual needs and fears and aspirations. Limits on how a drug can be prescribed or what it can be prescribed for take discretion away from patients and providers. We need to be mindful of the fact that this kind of meddling does not come without its own price. Most of all, we need to respect the fact that there is a boundary between our own policies and the practice of medicine, and what we do in the macrocosm of Washington should not pierce the private decisions that get made when patients are confronted with some of the toughest and most personal choices of their lives.