FDA's Janet Woodcock's Presentation at 2014 RAPS: The Regulatory Convergence

good morning i'm janet woodcock I'm director of the Center for Drug Evaluation and Research at FDA and I'd like to tell you about some of the important initiatives and changes I see going on in drug development and drug regulation and then talk a little bit about how Tran cell rate that you're going to hear about fits into this this is really an exciting time for drug developers for patients and for health professionals because I think we're seeing a wave of innovation and new therapies coming into clinical development and even onto the market that really have tremendous potential to benefit people and an infectious disease and cancer in a number of other areas there's new hope for patients but we have a lot of problems in the drug development world and recently initiatives have been launched by the FDA by others by trans seller rate for example to try and address some of these roadblocks to translating innovation into safe and effective therapies for patients the problems I think can be grouped in a number of different ways but first of all let's start with science science of course is the engine that drives innovation and the biomedical research puts forth discoveries that then have to be translated the problem is that the translational infrastructure really isn't up to the task right now and so we have very very expensive and prolonged drug development programs and people are concerned about that barrier and the cost of drug development when we're talking about exciting innovations in the laboratory how are we going to get over that barrier and get them into the clinic and of course some people say well we should just relax the standards but that's not the right answer the public health professionals even the payers expect good evidence about how drugs are performing how they will work in pay what benefits they provide and what their potential liabilities might be so we can't give up generating that evidence we need to generate that evidence in a more efficient and effective manner it's also provides more information so what's happening there well as many of you know in the early 2000s FDA launched an initiative called the critical path initiative where we performed an analysis of the various problems that occur in translational science and the barriers to getting innovations on the market and in the scientific world a lot of that those problems relate to the ability to understand the underlying causes of disease and to understand the natural history and pathophysiology of diseases so as a response to that many different initiatives have been launched for example one good way to develop drugs and understand their actions and people is to have good biomarkers that measure the course of disease and then the impact of therapy on the disease so we identified that as part of the critical path initiative and numerous consorcio have been set up to study various biomarkers and to provide better evidence one of the principal ones of course is at the foundation for NIH called the biomarkers consortium and that involves numerous pharmaceutical companies patient groups professional groups NIH FDA and other stakeholders to come together to do projects to advance various biomarker such as imaging laboratory tests and so forth so we can better understand what's happening in people when we try to test these innovations these biomarkers are both on the safety side the most prominent there is a drug-induced Canadian asst or injury and on the efficacy side for example using FD gee Pat as an endpoint for lymphomas so the biomarker consortium is taking on a wide range of biomarker development and qualification initiatives similarly the sea path Institute in Arizona which many of you may know about in the u.s. is started out back with the critical path initiative and they also are doing multiple projects on biomarker development particularly in drug safety which is really important for us have better ways to predict drug safety problems before the drugs are out and in many people and so there to be I think commended for a very robust program they're doing other things that I will talk about later but these biomarkers I think are extremely important now an FDA side we set up a biomarker qualification process and what does that mean well it turns out that there's no formal way that the community biomedical community accepts a biomarker as valid it's just sort of people publish them and then people argue with the regulatory agencies about whether they should be used or not so we thought well it's not really FDA's mission but we need to have a formal process whereby evidence is developed and then accepted by the regulatory agencies so that everybody can know what the status of any given biomarker might be and we are running these processes we have accepted biomarkers we worked with Europe the EMA and they have their own process for acceptance as well and we also work with a Japanese regulator so they are watching this activity so a lot has gone on with biomarkers there's still problems with determining what the framework might pay for qualification what is the evidence base that would you lead you to accept a biomarker say for enrichment in a trial or as an endpoint surrogate endpoint for example in a development program that isn't well work out and we need as a society to have much more conversation about that we really need to have a process to get that done now in Europe the innovation innovative medicines initiative I am I has been going on for about five years and that initiative also is looking at biomarkers as one of its activities and so there's a lot of activity going on around the globe and trying to qualify biomarkers now another problem with the science is that we do not understand very well the natural history of many diseases I mean that seems amazing since we people have had these diseases forever but for a long time of course for example genetic disease and so forth we didn't know what caused them we didn't understand them very well and in fact the funding wasn't available often to do a very careful look at what happens to people over time who have various diseases as you know like the Framingham study which is a very long longitudinal study has yielded a treasure trove of information about diseases that happen to ordinary Americans and help us figure out how to design trials better to treat those diseases but we don't have a Framingham study for most diseases so we have been working at FDA with other parties to develop natural history registries studies and other things and the National Organization for rare diseases has set up a program a computer program that patient groups can use to follow the natural history of rare diseases and this is very important because that kind of information is really lacking on very rare diseases because they're just haven't been enough people to know and of course as you all know as regulatory professionals to power trials and determine the feasibility of a development program you have to have a pretty good idea of what happens to the people you're intending to treat before you go and launch a whole program so that is good that that's going on now another whole set of problems is the clinical trial enterprise and many people have talked about this and it's one of the focuses I think of the trans seller eight project right now as you well know a clinical trial people think of it they have a specific drug in mind they gather together investigators they get thought leaders they try to find out what happens to people with the disease and stage a disease then they have a long protocol writing activity and then they have to get sites and have to sign up the sites and they have to make agreements with the sites and sign contracts and then they have to get IRB approval and then sometime way down the line they may be able to launch the trial and yet they may not get a cruel sites may languish trial may not be completed and there's a lot of time and money sunk in these type of activities and then when the trial is over everything is dismantled and later start over again this is a very inefficient way of trying to generate evidence about medical interventions and we can do better than this so tranh cell rate is one example where the pharmaceutical industry itself got together and is trying to change and improve targeted parts of the clinical drug development process and you'll hear about that in more detail other activities that are going on include trying to develop master protocols or standing trial networks both of which sort of flip the paradigm on its head and instead of using designing a single trial for a new drug that's in development you have a standing network that's capable of evaluating many drugs and most recently the friends of cancer research the foundation for NIH at NCI working with a lot of pharmaceutical companies in FDA set up a master protocol for advanced squamous cell lung cancer and currently they're testing five different investigational agents in that trial but the point is that trial has capacity to incorporate new investigational agents and keep on going and that is a design that's very desirable that we keep evaluating this stage of lung cancer which is usually incurable until we have major results until we make a major improvement in that disease and we get better and better therapies that we can continue to test perhaps in combination until we start seeing acuras of this stage of lung cancer so that's an important area which is the reform of how clinical trials are done a whole other area we're working on is looking at endpoints what are you trying to achieve when you do a trial or a drug development program and of course we have the payers playing much more now on whether or not drugs should be used and how much value they add and so there's a lot more emphasis on value-added and drug development and assessing that and that's where the patient comes in front and center really you want to improve how people feel function or survive right and to do that especially the feel or function part you have to know what is bothering them about the disease and you have to know the negative impacts of the disease what the most serious symptoms are from the patient's point of view and you also have to know how they feel about existing therapies of any are available how beneficial are they what are their downsides and so as part of the padutha negotiation last time most recent one FDA an industry put forth the concept of patient-centered drug development and that we would have a series of 20 meetings over a five-year period with different patient groups disease groups to learn from the patient's themselves what is the burden of disease and how are the therapies currently working and what's symptoms would they like to see address in their disease our first workshop was on chronic fatigue syndrome which is currently has no approved therapies and we heard some very heart-rending stories about the devastating effect this condition has on people's lives and what they would need to have it improved and subsequent to that FDA issued a draft guidance on chronic fatigue syndrome which we hope would drive development in this area by laying out end points it could be used in trials for chronic fatigue syndrome since that time we've had multiple additional meetings and we you know intend to keep running through this closely linked to this activity is the idea of patient reported outcomes those haven't been used that much in clinical development programs except for symptomatic diseases where you have pain for example the endpoint is relief of pain and that is a patient driven outcome but for many diseases say cancer chemotherapy we haven't recorded very well those effects on the patient some of which can be devastating so now we have many groups including the C path Institute and many other groups working on developing patient reported outcome measures that could be used in trials and then put in labels as claims so that we really incorporate the viewpoint of the patient and this process is ongoing and FDA set up a similar qualification program for patient reported outcomes where people can submit to us and we will eventually render a qualification decision publicly so that people can use this outcome measure in disease trials there's been great enthusiasm by patient groups and professional groups in participating in this process and it's robustly subscribed so that's very important now that raises the question then about how to incorporate all this information into a regulatory assessment we've been piloting it's cedar for the past four years i think a structured benefit risk assessment this is intended to be completed by the medical folks who clinical people who do the evaluation of the drug and is in a formal structure that would be in the front of the review it should incorporate the patient's point of view in the beginning of it talking about the burden of disease because unless you have a good idea of the patient burden of disease it's hard to quantify or even qualitatively assess the benefits of the drug so we are currently piloting that we're going through a cycle of implementing it in reviews we will assess that and then we'll have more public discussion about how to do benefit risk assessments in a regulatory setting this is very important because of course the payers want to know for their customers the patients they really want to know to these new interventions add value and what kind of value do they add and they're very interested in the patient point of view so I think this is a synergy across various sectors that we really want to know from the patient as this drug benefited you what are its liabilities what are its downsides and this will help doctors and other prescribers and counseling patients about whether they should consider to take a drug or not so I think all of these activities together will begin to help streamline the drug development process particularly as we're savings go would be the use of trial networks master protocols and other things that actually streamline the the actual setting up of the clinical trials in that process which usually can take many years we have many other activities going on at FDA cedar that are aimed at improving our understanding of drug development or ability to assess drugs one of the very interesting programs that was put in place with the food and food and drug safety and innovation Act orpha daisya is the breakthrough therapy designation program this program was born out of the observation that a number of new drugs are really game changers for serious diseases so that perhaps before no treatment was available for this disease or stage of disease and along comes a treatment that doesn't just have a tiny bit of benefit but actually has a major impact on the disease and so we the designation program was put into the statute and we have begun implementing that and it's been wildly popular to our surprise we've designated I think around 50 breakthrough drugs in different stages of development this is a developmental designation although people are permitted to apply up to the time of approval for designation but it really provides the most benefit we think in drug development where once a designation occurs then we work with a sponsor very closely to try and streamline that development program because of the promise it shows so it's only for serious and life-threatening diseases and the sponsor has to come in with clinical data not laboratory promise which you know pertains to a large number of compounds but actual clinical data that suggests the drug may be a game-changer in one of these terrible diseases so that's good news that we have so many of these under development of course not all of them will prove to be what was hoped and that of course is a downside for patients because it may raise their hope and then further evaluation shows the drug wasn't as good as we thought but we've approved a number of these already based on really significant patient benefits this program is causing a lot of effort on our part but I think as physicians this is something that we really care about is to get drugs that really make a difference to people who are very ill so there are many other activities going on at Cedar we also have a huge drug program the user fee program that we're implementing we're in the third year of that program will beginning the third year October one that's a huge push for the center and we plan to deliver on our commitments under the dufaux program we also are doing a new effort on regulating pharmacy compounding that's taking a great deal of resources and effort to try and put together a scheme for how pharmacy compounding would be regulated it includes a new category of industry called outsourcing that will that will be subject to gmps but will not require applications and we'll have to see how this all plays out over the next couple years we also are doing a huge quality initiative where we're planning to change how we regulate the quality of pharmaceuticals and this we hope will play out over the next six months and we'll get a new organization stood up and we already have changed many of our approaches to pharmaceutical quality and we think this we hope will bring the regulation of pharmaceutical quality well into the 21st century and really finish the efforts we began in the early 2000s in this area so in sum as usual there are many exciting activities going on in cedar there's a tremendous amount of excitement and effort in multiple different areas the drug development process that trans seller eight is focused on for example has a lot of attention and effort I think many of the initiatives we have begun or beginning to pay off as well as transyl irate efforts and by the other consortia to streamline this drug development process so it's always exciting and very challenging to stay ahead of the science and the social changes and the whole milieu in which drug development operates but I think because the science has moved ahead so far we're going to see a really exciting new era of drug development and as regulatory professionals I think we all need to be ready for that thank you

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