 Okay, so Welcome everyone to the October health policy and bioethics consortium Our our topic for today is on drug shortages. Thank you for joining us We want to let you know that today's event is being recorded and live streamed via Facebook the event video afterwards for people who can't make it will be posted on the Center for Bioethics and The program on regulation therapeutics and law web pages You can submit any question you can submit questions at any time using the Q&A feature And we will discuss those questions after the presentations in the broader Q&A section of the of the discussion You can also Continue the conversation on Twitter using the hashtag hashtag Harvard Bioethics or the hashtag Policy ethics, which is the hashtag that we've used in past months as well If you have a technical issue use the chat feature sending it to the the message all the panelists and we'll try to help you with that and You are welcome to check out future events at the bioethics web page or at the portal web page as well Oops, let's see so So I want to welcome everybody my name is Aaron Kesselheim I'm a professor of medicine at at Brigham it's hospital and I run the portal research program at At the division of pharmacokinemiology and pharmacokinomics. It's my pleasure to be able to To be able to host these events with my co-teacher Leah Rand These this series of health policy bioethics consortia run on the second Friday of every month And we are always excited by the high quality of experts that we have and today in talking about drug shortages and managing Allocation in the supply chain. We also have again two national experts on this topic to talk to us today The goal of the consortium as always is to articulate key issues in the health care system and public health that involve ethically challenging policies or practices Bring together experts with different perspectives who work in different You know who work on the topic at different levels or different areas or take Different approaches to the topic to come together and think about the issue and propose solutions And to stimulate conversation and further academic study the topic to help advance the field If you are interested in the work that we do at the program on regulation therapeutics and law You can follow us on Twitter at at portal underscore research or check out our website at portal research org If you were to do that you would know that the last week has been a particularly prolific week for Work coming out of portal here. You can see a selection of the Multiple research papers and commentaries that that have come out of the group just in the last week Studies of biosimilars looking at public funding of transformative drugs comparisons of health technology assessment approaches All of these topics and more are the kind of stuff that we work on and so if you're interested, please please come by and then as always just want to give you a little bit of a update of what's coming next in the in the consortium series in November We're going to talk about concussions and youth sports. How much is too much risk? And then in December discussing Experimental drugs, which has been a topic that has been in the news over the last week or so Do a substantial degree and we're going to talk about that in December with again a couple national experts on the topic But so today to bring us to our to introduce us to our topic I wanted to Turn the floor over to my friend and colleague. I meet separate worry Who is an assistant director of the pro or the portal program? He is a lawyer and epidemiologist and and does a lot of research on Pharmaceutical policy issues focusing on on FDA biosimilars and biologics and is here today to talk to us about Drug shortages why this is an issue and to introduce our our two guest experts for the day. So I meet Thank you very much for for joining us My pleasure. Can you hear me? Yes, I can great. Okay. Well, thank you Aaron and thank you. Leah for Organizing this session and I think we've got some great experts who I will soon introduce on this topic But as Aaron mentioned, I'm a lawyer and epidemiologist and I work in a portal program And this is a topic that's definitely near and dear to my heart drug shortages It are definitely an increasing subject of National and international concern and so when we're talking about what we mean by drug shortages There are two sort of primary definitions and they largely overlap But there's a slight difference and I think it's important to cover that so what does the FDA define as a drug shortage? It defines as a period of time when the demand or projected demand for the drug within the United States exceeds the supply of the drug And then you go to the Ashby definition the American Society of Health Systems pharmacists a supply issue that affects how Pharmacy prepares or dispenses a product or influences Cropation care when prescribers must use an alternative agent And so if you're looking at how these definitions overlap Usually the Ashby definition is a little bit larger And so when you look at counts as to what FDA and Ashby say how many drug shortages there are Usually the Ashby count will be a little bit higher And when we take a look at the Ashby count, which is built on information from the University of Utah Drug information service data, which is led by Dr. Aaron Fox one of our experts you can see in this first figure on the left the drug shortages new drug shortages by year and You see a sort of uptick from about 75 in 2006 to over 250 in 2011 and then a slight decrease but out of those shortages the majority are Injectable products and we'll discuss that in future presentations during this session But since 2007 you can argue that there's been a decrease of new shortages At least a trend of a decrease in new shortages But when we actually take a look at the number of active drug shortages by quarter, that's remained relatively stable And so what it pretty much means is that? Problems that have occurred new problems aren't always being solved and so while Perhaps a smaller number of new problems are emerging. We're not doing all that we can to tackle existing problems And when we're talking about what classes that these exist in Some of these older injectables commonly include anesthesia drugs pain drugs antibiotics Nutritional or electrolyte products or chemotherapy agents Now COVID-19 has exacerbated the crisis. So we've seen a surge in use Sort of things that we would predict So shortages of drugs associated with ventilator use You see the stat news article headline from April 2020. We see Non-evidence-based use. I think the classic example is to run on hydroxychloroquine and this is a graph that you see from the CDC Showing the uptick in prescribing or dispensing of hydroxychloroquine by non-routine prescribers of the drug hitting right at April at March in April 2020 and The downstream consequence of that is the non-evidence-based use of hydroxychloroquine for which the recent knee gym study has hopefully put one of the final nails in the coffin for its importance in COVID-19 has resulted in Nupus patients lacking the ability to access a critical drug for their care and then we've also seen a lack of new drug manufacturing capacity and most Relevantly in the context of remdesivir again a study came out yesterday showing That it does have a mortality benefit But over the summer we've seen problems from Houston to Miami of hospitals running short of remdesivir for COVID-19 patients And such proposals difficult decisions in terms of allocation of these products To a proposal that perhaps a fair way is through a lottery system So we've got difficult questions that are now arising that have been there but are Being put in even more of a spotlight in the context of COVID-19 and we're hoping to address some of those in this session today So what is it really that we want to drill down in in today's session is well What has been the impact of these drug shortages? How great of an effect have they these shortages had on clinical care? Within that how our scarce drug allocation decisions currently being made and we know that there's variation In how they're currently being made, but what is the broad spectrum of the decision framework? that's currently being used and How should those scarce drug allocation decisions be made? We also want to understand the causes of this problem. So what factors are contributing to the drug shortage problem? And what have we done about them? So how have these factors changed over time? And then in terms of solutions what corrective actions have been taken to address the drug shortage problem and What further steps are needed? And it's really a pleasure that we have two wonderful experts who are going to weigh in on these topics And provide some insights that can hopefully advance the dialogue and show us where we're headed And so it's my pleasure to introduce these two experts and the first is Dr. Yoram Nguru a pediatric hematologist oncologist with joint faculty appointments at the Johns Hopkins Berman Institute of Bioethics And the Hermann and Walter Samuelson Children Hospital at Sinai Hospital where he chairs the Sinai Hospital Ethics Committee He's also an assistant professor at the Johns Hopkins School of Medicine A primary focus of the scholarship has been the allocation of scarce life-saving medications Dr. Nguru has served as an ethics consultant to national organizations including the American Academy of Pediatrics and the American Medical Association Sits on the editorial board of Pediatric Ethoscope and leads a multidisciplinary transnational working group Examining the ethical and policy implications of chemotherapy shortages and childhood cancer And our second expert is Dr. Aaron Fox who is the senior director of drug information and support services at University of Utah Health which provides content for the American Society of Health System Promises drug shortage research center a Patient advocate Dr. Fox has testified before Congress and published multiple peer review articles on possible changes to improve the ongoing drug shortage crisis She has been honored for her work by the American Society of Health System Pharmacists in the Institute for Safe Medication Practices So it's a pleasure to introduce both of these speakers and we'll start with Dr. Nguru And I'm privileged to hand off the floor to him Thank you, Amit and just to verify you all can hear me. Yes. Yes, we can wonderful. Okay. That was a lovely introduction I would have been satisfied with wannabe tennis player Hopefully you guys can see my screen Hope can you see that as well? Yes, we can wonderful. Okay. Now that we've done that out of the way I want to thank Aaron, Amit, Leah for the opportunity to be here today. Thank you all for zooming in. I hope you're well I've been involved with drug shortages in particular chemotherapy and supportive care Drug shortages for a number of years both as a clinician and as a member of the children's ecology group steering committee on bioethics Not something I anticipated ever having to do And so in the time that I have I'm going to give you guys some background about the shortages and discuss the unique ethical issues They raise for clinicians and institutions and we're going to try something a little bit different I'm going to give you guys an opportunity to come up with your own allocation schema for scarce life saving chemo for kids with Cancer and in the Q&A if there's time I'm happy to tell you about an approach that a task force that I led has come up with so Disclosures there's a group participation participation part in this so Hopefully you guys can recognize some of these people and if you want to type into Q&A or chime in We've got Tanya Harding. Many of you are in Boston anybody Amit, do you know who this is Aaron? Do you know who this is? I don't I don't remember her name. But is that the Rosie Ruiz? Oh, you are good man. Yes The 1980 Boston Marathon by entering the race a half a mile before the end One of the things that gave her away was that was water that was on her shirt not sweat because she hadn't broken up a sweat Here we got Rick singer the mastermind before the behind the college admission scandal and most people know who these two folks are Felicity Huckman and Ampecky. So I'm a pediatric oncologist and bioethicist. I got no disclosures people. I wish I did So drug shortages are not new One of the first large-scale drug shortage was insulin in the 1920s And this was followed by penicillin in the 1940s that affected far greater number of patients But over the past decade or so these shortages have become increasingly more common and this includes chemotherapeutics And this is primarily a US problem shortages do happen in other countries But they don't happen like they happen here. In fact, I like to say that we own this problem And I think Michael Lane captured this most aptly Michael is a pediatric oncologist at Stanford and past president of the American Society of clinical oncology And you can see what Michael has to say here, although we've had shorted before they never lasted as long or involved as many drugs as they do And if you look at the data that Aaron was a E my co-panelist Publishes Religiously every quarter. Thankfully currently there's about 270 drugs and short supply in the US So let me just repeat that for effect 270 drugs and short supply in the US and there's two main sources as a me told us in the beginning You can get up to date info the American side of health systems pharmacist and the FDA But my focus today is going to be really in my part on the chemo and supportive care drugs So when it comes to the chemotherapy Most of these affected drugs belong to this class of sterile generic injectables But when you look at all drugs on the US shortlist not just chemo up to three quarters belong to this class of sterile generic injectables and it's important to appreciate that these injectables They make up the backbone of proven and life-saving regimens not just for kids with cancer, but adults as well But because in pediatric oncology, we are so dependent on these injectables when there's a shortage We're especially hard here While the reasons for the shortage are multifactorial Most experts agree that the primary causes are economic manufacturing quality into a lesser degree regulatory Following a two-year investigation at the end of last year the FDA published this report that you see here And the FDA concluded what other experts had been recognizing for some time that the primary drivers are Economics and they went on in the report to state this right here unless we're willing to make some change to our marketplace We shouldn't expect these shortages to go anywhere now Aaron Fox and I were fortunate enough at the end of 2018 to testify at an FDA public meeting on the shortages and I Was surprised to see this included in the report during my comments I tried to drive home the the point that what we're seeing are shortages of decades old drugs drugs that are reimbursed at dollars per Dose that are life-saving and often for which we have no alternative what we don't see are shortages of blockbuster drugs drugs that are Reimbursed six seven figures that may be extend life for a few months and it just doesn't seem to make much sense to me And if you're still not convinced it's the economic drivers Maybe hearing from an insider if you will will help so at that same meeting Martin Ventrest was there and Martin's a former VP and senior chief quality officer and Jen and now he heads up this outfit called Civica that Aaron's gonna talk about and just a bit and here's what he had to say all drug shortages all Are the result of economics financial and management decisions, but this isn't only a cost issue Why is there a state so let me give you some real data because we're only as good as the facts and the data This is from the New England Journal of Medicine back in 2009 There was a shortage of an old tried and fruit chemotherapy called mechlorethamine used to treat some young kids and young Adolescents with Hodgkin lymphoma and at the time evidence suggested that another chemotherapeutic Cyclophosphamide was as effective so 40 out of 181 of the kids got the alternative with the cyclophosphamide Well the two-year event free survival for those kids who didn't get the standard of care who got the alternative was 12 and a half percent lower And while there was no death these kids got exposed to considerably more rounds of toxic chemo including stem cell transplant The long-term effects of which still are entirely clear and that prompted the authors of that study to state What you see here in the middle even promising substitute regimens should be examined carefully before adoption What might appear to be a suitable alternative regimen may result in inferior outcome and for those of you who like to see that Schematically you can see that in this graph and It's important to appreciate that it shortages of chemo more than any other class of drugs that affect patient safety Suddenly we're using drugs We're not as familiar with in combination with others and that results in a whole slew of problems And this issue of safety is one of the downstream effects of the shortages that I don't think gets enough attention So I just want to take a second and walk you through what this really is about So what you may not realize is that nearly 90% of the raw ingredients for the drugs We rely upon here in the US come from places like China and India and over 25% of the drugs that are labeled is made in the US actually are made Offshore and plants inspected by the FDA and FDA is Overwhelmed and understaffed and so in 2015 FDA faced a dilemma There was a shortage of a chemo therapeutic called doxorubicin and we use that to treat plenty of kids But even more adults with various cancers and FDA had to make a decision Do we allow these patients not to get the life-saving drug they need or do we allow to import the ingredients that we need to Make that drug from the Chinese plant that they previously censured for poor quality and what do you think they did? They did the latter and you probably didn't hear about it Further complicating matters is that drug companies are required to disclose to the public where they get their ingredients from and if they're getting them from a manufacturer that has had poor quality and then the companies are supposed to do the right thing They're supposed to check the ingredients for purity quality and strength some do some don't Because it costs money and so it ends up happening as you've seen these important contributors here Including my colleague Aaron has said that the FDA ends up relying upon an honor system to make sure that the drugs we're getting are up to speed Not sure that's really how we want to move forward Here's some more data from you also from the New England Journal This is a paper published that was a study of medical or adult oncologist asking them What the impact of the shortages were over a six-month period and the staggering 83% Said that they weren't able to prescribe their preferred chemo therapeutic over three quarters Said they had to make a major change in their treatment such as picking a different drug or a different protocol and over 40% said they had to delay the start of treatment because of a shortage imagine you're told sorry, Mr. Smith You have cancer, but I can't start treating you because they don't have a drug in stock Now what I find really concerning is even though these shortages have been around for over a decade 70% of the respondents said that their hospital or group lacked guidance about how to ethically allocate these drugs What about on the pediatric side? So here's a study published in pediatric blood and cancer This was a survey of children's oncology group principal investigators and pharmacists Asking what the impact of the shortages on clinical research and clinical care was over a two-year period And at the time of this survey, these were the drugs that were primarily in short supply But take a look at this data 50% of the COGPI said that at least one of their patients participation in a trial was affected by the shortages and over two-thirds Said that at least one of their patients clinical care was affected this data from the pharmacists is damning A third said that there was either a near-miss or actual medication error attributed to the shortages And what you see on the far right over here is what they did to deal the shortages Now I told you the 70% of the adult oncologist lack guidance exact opposite was true on the pediatric oncology side 73% said there was center-level guidance But I'd argue just because they're center-level guidance doesn't mean that it's necessary ethical or uniform And then here's a national study just from last year This was a survey of over 800 US pharmacists asking them about the shortages without exception 100% said they'd had shortages Now what I find concerning is it just over a third said that at their hospital There was a drug shortage committee a body tasked with deciding how to allocate them And when there was a committee fewer than 5% included an ethicist to me. That's that's somewhat troubling And I could go I could talk to you guys until you're blue in the face until I'm blue in the face about the shortages and their consequences So they're they're very very diverse So this raises a host of ethical questions for us. What do we do? Do we delay treatment? Do we skip a dose? Do we give a lower dose? Do we prioritize and if so who gets to make that call me the bedside treating physician Or maybe you guys an independent panel and if we do do that, what does it look like in practice? Well, let me give you an example I talked to you about the methotrexate the drug that's been in short supply before We use it to treat kids with acute lymphoblastic leukemia the most common childhood cancer Counting for almost a quarter of all childhood cancers. We use it to treat kids with osteosarcoma the most common bone tumor So the average adolescent with osteosarcoma requires 20 grams of methotrexate for one cycle And 360 grams over the course of his or her treatment That same 20 grams to treat one kid with osteosarcoma for one cycle could be used to treat anywhere from 1300 to 2000 kids with ALL For cns prophylaxis. Does that mean that the kid with osteosarcoma's life is worthless than the kids with ALL? Maybe we prioritize kids over adults. Hey, I'm a pediatric oncologist works for me Well, that's what happened at Sloan Kettering a few years ago And they prefer to divert their limited donna rubison supply to kids over adults What about first come first serve seems to do away with some of the sticky ethical issues? Well, not so fast Let me tell you about some of my concerns with first come first serve The first really is information for better or worse by virtue of you all being here today You know about these shortages where someone who wasn't here doesn't i'm not sure we want to allocate based on that The second is access so let's say that there's one drug dose left and both a meat and I need it And let's say that a meat cares about the environment. He rides his bike to the hospital It's going to take him a little longer than me because I drive like a good israeli. I'm coming hard and I'm coming fast And I guarantee I'm going to get to the hospital before a meat I'm not sure we want to reward me because I drive like a maniac But really the biggest problem of first come first serve is need it doesn't account for need We can have two patients with the same disease but in very different places. So not the way you want to allocate I've given you plenty of examples about how these shortages affect clinical care We also need to remember how they influence our ability to conduct research In pediatric oncology, we're very proud of the fact that each decade We've seen more and more kids with cancer survive and that's because we do Cooperative group clinical trials these drugs that are in short supply. They're the backbones of our research protocols How are we going to continue to make substantive observations in their absence? We saw that when even when we do have an alternative like with the cyclophosphamide and mechlorethamine it may not pan out Now this notion of cooperation coordination This is one of the solutions to the shortages not the focus of our talk But happy to talk about it in the q&a if it comes up I wouldn't be remiss though if I didn't mention the gray market So I'm sure some of you have heard of the gray market for those who may not have the gray market are a group of Unauthorized secondary drug distributors who profit from the shortage The average markup of a drug sold on the gray market is 650 And take a look at this data. This is years old data But my pharmacy colleagues tell me it's still pretty relevant What you see here are the top 10 highest marked up drugs sold on the gray market and three of the top four chemotherapeutics The drug called citerabine and dexamethasone, which you've heard about I'm sure a lot this week marked up over four thousand percent lukewarm over three thousand percent remember economics business management financial This is a screenshot of the children's oncology group drug shortage page the fact that we have to have a drug shortage page Boggles my mind, but I want to tell you Hopefully to drive home how impactful these shortages are Back in february 2018. We had a shortage of a drug hub in christen and at the time there were two manufacturers That same week we had another shortage of a different chemotherapeutic called the toposide The combination of in christen and a toposide are used to treat About 95 to 98 of all types of childhood cancer within one week Within about a year later at the end of october last year or beginning of october last year We had another vinkristen shortage This one was really impactful because now we only had one manufacturer And I think erin's going to talk about this a little bit later And the thing that really is bothersome is as you can see we have no substitute. This is not an antibiotic It's not like I can swap out a moxicillin for penicillin. There's no substitute for vinkristen And then just earlier this year yet again We had another shortage of this drug called urinias And I say yet again because we have shortages of urinias every few years because there's only one manufacturer And this was a paper that was just published a few months ago in journal of clinical oncology talking about how important This drug is to children's survival and you can see if they don't get it They have an inferior disease free survival. So again, we're talking about children's lives Solving the drug shortage problem will require major policy shift one that's grounded in coordination cooperation But until that time comes as a society We need to be able to make the difficult decisions about how we want to divvy up scare slice saving resources among equally deserving kids Now when I talk about prioritization, I think here in the u.s. In particular It's a four-letter word or the proverbial third rail. I say prioritization and oftentimes the next thing I hear people say is Allocation rationing and death panels and here you see two opposing views John eras was a philosopher and bioethicist. Unfortunately, john passed away a few years ago I'm sure some of you may be familiar with this work and as you can see from these quotes John talked about the importance that we'd be able to prioritize and ration in the middle You have sarah panellin is now infamous facebook post from 2009 where she talked about death panels But what we need to remember is rationing happens every day in the u.s. Healthcare system Insurance companies ration all the time when they approve or disapprove or treatment or a procedure And in ethics is what we talked about as implicit rationing Another form of implicit rationing is a patient's ability to pay Explicit rationing is things like allocation of organs, hemodialysis, PPE, etc All right. Now, hopefully you guys are going to be able to participate Otherwise, it's going to be very quiet and the meat and I are going to stare at each other So I want each of you guys to imagine that you're a pediatric oncologist And you work at a busy center that provides both inpatient outpatient chemo and so far you've been lucky You've been able to have adequate drug despite the shortages But when you come to clinic this morning, you're told by the end of the week we're done We have no more than christen and to make matters worse The chemotherapy pharmacy director tells you that the usual avenues Through which he's able to get additional drug aren't available because the primary supplier's halted production Resulting in a national shortage. Now what you need to understand about vincristin is it's kind of like our water Chances are I'm writing an order for it before I even know what you have because we use vincristin treat it in leukemias, lymphomas, bone tumors, brain tumors So vincristin shortage would have a far-reaching impact on countless kids with cancer And that's exactly what you realize when you review your census of who needs it Now all of the kids are going to be getting the same one and a half milligram per meter square dose of vincristin But because of their different body surface areas, which is used to calculate that that dose Because of their different diseases or different protocols Some of the kids are going to get a higher dose some a lower dose Some are going to get a more frequent dose some are going to get a less frequent dose And to further complicate your decision-making calculus Some of the kids are getting vincristin as part of a standard of care and others as part of a clinical trial So my fine My question for you fine folks on this one o'clock afternoon on friday is How do you want to divvy up your scarce vincristin and you can think about yourselves Much like this group and as you're starting to think I think we can all appreciate that the wrinkle Or dilemma if you will of having to make the decision was appreciated in this paper published over 50 years ago So i mean i'm not sure what the best way is but i'd love to be able to hear what people say Can they talk and they just put in the q&a? What do you think? It would be great if It'd be great if you do you want to post specific sub questions from this larger topic And then we could perhaps take some votes if that's possible. I i'm hopeful the Administrator on here can facilitate that if sure and I apologize for throwing talk about a wrinkle or dilemma Oh No, that's great. And I I think if we can also I I have the participant list if if hands can go up I can have people Allow them to voice an opinion as well, but I I guess it would be helpful to start with just a I guess a more narrow question to to open the the door to conversation Absolutely. So I guess the first thing that I would say is Um You first of all you can say whatever you want you can have an opinion about how you want to allocate who gets what which kid But you got to justify it, right? So you can't just say like my daughters do because well because well, I don't know just because so Let's drill down a little bit. Um, is there a particular? Type of patient disease based perhaps that you would consider or would you consider allocating based upon The child's age or are there other specific factors unique to The protocol that the meaning the cocktail of drugs that the child is getting that you would want to consider Maybe that's a starting point So I see Jonathan Darrow has his hand up and I'm going to allow him to talk All right, am I waiting for my image to come up here? I think we can just hear your voice. I think that'll be great if that's fine I don't know if an image is going to come up. All right. Well, thanks very much for your talk. I appreciate it I was struck by the focus of the conversation which seemed to be to me to be very much clinician oriented We have this shortage. Oh my god. What do we do now? and Sorry to take this in a different direction, but I think this is the more important direction. I think that's the wrong question That might be the right question if Like covid we've never had a shortage before and we never thought that we might have one But as you pointed out at the beginning of the conversation, these are not only decades old They're at least a century old We know these shortages are coming What should we do about it? And I guess the first question I would ask is what is the shelf life of some of these Products and is there a reason Why the question isn't dear hospital administrator? Can we please have three more months of been christine in stock? Is that not possible because of the nature of the drug? Great question and and your your observation is spot-on And you're wrong before you you keep on going I'm going to say for other participants who want to weigh in on this specific question Please do raise your hands and we will be able to bring in your comments and and also just a reminder that some of the Clinical focus questions that have been brought up in this will be focusing on some of the more systemic and policy related questions in the second talk that erin will give but Sorry to interrupt. No, no, absolutely. Thank you for clarifying that And and the the clinical and the policy are intimately related but I I preface my remarks by saying I'm a clinician and We need to be able to help our clinical colleagues as you noted not just with covid but with these issues and On the ground they need concrete guides. They need explicit recommendations and The the the idea here of shelf life is is critical. I know that erin's gonna address that so I don't want to steal her thunder There are there are many options that we oftentimes overlook But this does certainly require Taking a step back and rather than Being reactive we have to be proactive. I think that's what we're seeing When we're tying this into the current crisis with covid that rather than than weight We're trying to get out in front of the the moving target and come up with Appropriate ethical transparent allocation schema that have public buy-in And so if you'll if you'll allow We I promise you we will get to your your larger question Which is the right one over the course of the coming minutes here But I would I would be curious just to hear if there are folks who have an idea about you've got two kids Who are right in front of you and only have enough drug for one of them. How are you gonna make that call? Neeraj Why don't you introduce yourself first and then I ask your question Uh, hi, hi, my name is neeraj Patel. I'm a research assistant at portal. Um I think that the first Thing that sort of came to mind if I were Faced with this sort of seemingly really difficult decision would be to try and This is a very I guess Utilitarian approach but to try and think about which of the two options would maximize the number of life years Saved. Um, and so I think part of that might be Trying to figure out a way to calculate Expected benefit of receiving the drug for each of the patients and then sort of subtracting that from The level of severity of disease in each of those patients to try and sort of balance those two factors to come up with An answer although it I am kind of cringing while I'm saying that because it is I think a little bit difficult to talk about in those sorts of terms Before like you're on if you want to is samson is yours Is your comment directly related to this because we could take that too and then and then turn it back to your arm Yeah, so it's somewhat related. Um First of all, I'm a medical student from hong kong Which is where there is a centralized drug formulary and the way we Tense to deal with this is we we calculate Like we do a cost utility analysis based on quality adjusted life years and then we depending on It's the same which is we we maximize the quality adjusted life years To to allocate these resources So I don't know if that will work, but I don't know I don't know the intricacies of the US healthcare system So that might be why it doesn't work. Sorry. No, thanks for your insight. I'm bringing that So both both are great points. The one the one thing I'll go back work. I'll start with samson We don't have great pediatric data on qualities. That's a little bit more fleshed out. I think in the adult world But but both of you raised important points about this this threshold of curability and getting the most bang for your buck You know the problem with qualities in a pediatric Population in particular is If you've got a four-year-old and a 14-year-old But you still have the ability to cure both of them and they're otherwise able to live a normal life expectancy You're still looking at 60 70 years for each one and is that really where we want to make that decision So the degrees of precision That is required are are much much higher And it's a little bit harder to do but absolutely We don't like to think about it because we are able to cure so many patients But having some prognosis based threshold probably makes sense The the concern here is though that kids who have more aggressive disease and who may need that drug need that drug really They don't have any other options. And so there are some other you can flip it on on its on its side actually There are probably diseases that we use drugs that aren't as critical But have just historically been part of protocols that you can withdraw and use those for kids who need them more So an example here would be a kid with a rabdomyosarcoma or a bone sarcoma Who needs a drug like a doxorubus that I mentioned before or as a kid with a Hodgkin lymphoma Probably doesn't need that drug to save other options in their armamentarium I I want to certainly continue to move forward and allow Erin to do her talk I don't know if there's any one other person maybe has a comment and then maybe later we can continue if there's time Or we can just move forward and if anyone has a comment that they'd like to make Please feel free to raise your hand now. Otherwise we can address this in the q&a. Definitely Give it another five seconds and then Don't be bashful Okay, okay. Why don't we And I'm I'm wrapping up here. So We've talked about kovat and I just want to drive home what Amit noted because I think a shortage is a shortage and this isn't just related to my particular world of pediatric oncology So here we are at the end of February and there's this notice and then the next day in the times There's a story and I think one of the problems about the shortage is that erin's gonna I think talk about is The lack of transparency the opaque nature We we can say there's a shortage but we can't tell you what the drug is or where it's made and then you have Commissioner Han with this statement You know the next day, it's not just that we have a shortage But we're starting to see price hikes and in part this is related to where we're getting the active pharmaceutical ingredients Within a couple weeks It's the shortages of the paralytic sedatives and anesthetics And then you have this story in the new york times in early april where sherry fink is quoting A critical care doc talking about the medication shortages and really down here on the bottom Then you see the statement by senator tina smith who's one of the Sponsors cosponsors of the meds act and talking about yes, we're worried about shortages of PPE But it's really the drug shortages that are going to break our back And so i'll leave you with this statement that came from that fda report It's not the shortages can harm patients and impose burdens. I would actually argue that they do So thank you guys for your time Thank you for participating and i'll uh, i'll turn it over i'll stop sharing and i'll turn it over to erin We've got you on mute amit. I think you're Great, thanks very much around erin the floor is all yours. If you have any issues letting your sides just let let me know but Looking forward to The next phase of the analysis of the problem Okay, and slides are good Yep, we can see them. Okay, perfect. All right. Um, I want to echo um, uh your arms. Thanks. Uh, thank you so much to the portal folks erin and amit and lea and everybody For for this invitation and to get to talk about something that i'm i'm really passionate about um super quick disclosure, um You know just our university wants to make sure that I'm speaking on behalf of myself and and not the university of utah and then uh, you know I am an unpaid volunteer for for civica and um, we also do some work with vizient, um, but no funds are paid to me So I want to talk a little bit, you know You're set up a great clinical dilemma, right and and it is uh, just um heart wrenching to think of these decisions But I want to take us back to think about how we got to this place Where the united states has so many drug shortages and One of the problems is that for injectables especially for generic injectables We've got a really fragile supply chain and and part of the reason for that is There's a lot of concentration in the market. So Usually a product maybe has one to three suppliers And you know three suppliers sounds good, right? Like one one person could take over for the other But you know thinking about that ben christian example One company had 97 percent of the market share Rather than You know kind of an even split and that's the usual case one company usually dominates and That market share data is not publicly available. And so it's it's not transparent who has the most We also have a very limited capacity Many of these products are all made on the same manufacturing line. So you could have one line with maybe 20 or 30 products rolling off of it And it's you know any any kind of a glitch there doesn't affect just one product. It affects multiple Um, there's also, you know in the united states, we have no requirement for any company to make anything We have this free market and no matter how life saving the drug Doesn't matter. Nobody has to make that product And you know when you think about this about how drug manufacturing is a business These decisions actually make sense. It makes sense to to make your decisions based on profitability And how much would it cost to fix something? Um, is it more efficient to run your factory 24 7 or to expand and have some additional capacity? These things cost money and you know, unfortunately most of the time We've got shortages because of a serious quality problem at the factory and That's that's just the bottom line Um, the economics are real You're not going to invest in your factory to make really cheap drugs This this chart from FDA Notes that most of these products that are short of are less than nine dollars a dose You know the investments required to maintain your factory to maybe invest in redundancy Invest in a continuity plan invest in a backup plan It's just not built in with with this pricing structure So, you know again, I really want to make sure that people understand that the reason we have shortages Are quality issues now, certainly, you know, what is the root cause of that quality issue? Um, I I fully believe it's an economic issue. Uh, these these companies have not invested in their factories And thus we have quality problems And so, you know quality problems are actually a really um A really interesting hot topic for for probably the past couple of years If you haven't Read it already read Anna Edney's series in Bloomberg about America's love affair with cheap drugs and the hidden costs And it is a bone chilling expose of drug companies Lately flaunting the manufacturing rules Latent contamination Shredding documents ahead of time It actually even resulted in a commissioner got leave at the time issuing a quick statement In in response to to this expose If you also haven't read it, I get no no royalties or fees from from recommending this but Read Catherine event book It is reads like a thriller and it's a quick read. Um, and I think it should be mandatory reading for any healthcare provider So, you know, when we talk about quality issues, even a really small quality hold can be devastating This vinn christian example, uh, that we talked about earlier Um, with one company having 97 percent of the market share. What happened? Uh, Pfizer had a quality control issue that they needed to investigate But because they had so much of the market share and they didn't have additional stock on hand It's all just in time. Um, you know, it really held up therapy And they also didn't communicate well at all, you know, uh, hospital viruses were hearing you won't get your order, you know, until, you know, three months from now It created a massive panic massive, um Allocation decisions that that maybe didn't actually need to be made. Um, and you know, the most frustrating part about this was These market shares didn't come out until Probably three or four news stories in Um, you know, the Tevin really got thrown under the bus for discontinuing their product But with a three percent market share Why wouldn't you just continue that product, right? Does it even make sense to invest in in making a difficult to make product? Um, when when you only have I have a small amount amount of the market share. So, uh These small quality holds, um, when not communicated correctly and without a backup and redundancy plan are devastating We also see problems of quality in our very common, uh blood pressure medications Um, it has been very interesting to talk, uh with congressional representatives about Their concerns with with their own medicines being contaminated being recalled having drug shortages We are over two years into this thing with with the arbs And we still don't have a good list of of everything that that is effective And you know, you can say well, you know, shortage is one thing but The quality problems actually also can cause direct patient harm when the products are contaminated And this, you know Kaiser health news story by seny lepkin is absolutely worth your time to read You can read about, uh, anderson marino and how his heart transplant was delayed because he had a burkholderia infection from docu state liquid Docu state liquid is basically so it is, uh A useless product, um, but it is frequently frequently used in In clinical settings as a stool softener This is what part of the problem is with the lack of transparency that we have this is what it looks like When we're trying to remove contaminated products off of the pharmacy shelves In this case FDA didn't even have a complete list on august 8 and 2017 of all the products that were affected Affected by contamination with bacteria. I want to add And so it took, uh, almost a month to get that full list of all of the products that were were contaminated with bacteria Meanwhile, patients are being exposed So I left the question earlier. You're thinking about the wrong problem. You're clinically focused, but how can we fix this? I absolutely agree We the clinical problems are so important to solve on a day-to-day basis But we have got to be thinking about How we fix this this problem so At the FDA meeting that that you are mentioned and that we were both at The report came up with kind of three Main solution ideas and you know, they're they're they're pretty good to work on What I'm fascinated at is, you know, almost two years later not much has happened on on these at all Um, there's been a lot of discussion about on-shoreing, right? Let's move everything back to the us Especially with with all the covid concerns folks are are wanting to onshore everything Will that fix shortages? I say no not for drunk shortages And the reason I say that is because year after year all of the data that we have For all of these injectable products that are affecting our our clinicians every day. These are made up factories inside the united states Inside the us. They're already on shore, right? They just have bad quality problems. So that's not going to fix the problem Uh, certainly there's a discussion about on-shoring for raw materials. Um, if you want to prevent national security risks Yes, there is absolutely a roll roll roll for that But to add to say that on-shoring will truly fix shortages That that is not the case and when we look at these data from FDA Um, you know, how good are the us factories? Look at these These these show the percent of manufacturing facilities that that need to have some kind of action after an FDA inspection And the us is not number one You know, we we have some quality problems here in the us There is a tremendous amount of attention right now on increasing transparency and i'm so glad to see this because You know, it's it's really a situation of Almost like online shopping, but without any, you know, seller Ratings any information about who even the company that makes the product All of this is is is not available to the people that are purchasing medicines And I want to spend a second to to really hammer in this this transparency recommendation because Janet woodcock and and martin wassenska Laid this out in 2013 so seven years ago It was the best argument and really lays out that the reason we have poor quality Is because there is absolutely no incentive for manufacturers to have high quality We have a pass fail system in the united states Now fda sees a fully graded system fda sees, you know, a plus to to f Um But the problem is the passing grades, you know, a c-minus factory is is going to be the same pass fail system as an a plus factory There is no Incentive for any company to invest the money to give themselves an a plus factory Everyone is just going for that c-minus barely passing grade And because that's not transparent people that purchase drugs have no way absolutely no way to Preferentially buy from from a company that has an a plus factory I am in charge of all of the purchasing for our health system almost half a Half a billion dollars of almost 500 million dollars comes through me I want those dollars to go to high quality medicines I want to know but unfortunately we have such capacity That it's it's impossible And, you know, jennet woodcock came out even last year talking about really If we're going to fix shortages, we've got to have manufacturers focused on quality. It's the only way forward And so, you know, there are quality metrics goals Things about, you know, really modernizing quality oversight And and I think, you know, some of the ideas that have been thrown out there are like a star rating scale for manufacturer What things do you buy without looking at the ratings? You know, if you go to a restaurant, uh, if you're purchasing, you know, a new wireless router You want to see what are those ratings? And that is something that we absolutely don't have In in the pharmaceutical world I think, uh, this quote is very telling again. This is from almost six years ago These are FDA folks talking about To really eradicate the problem and and FDA really sees what what the problems are to eradicate the problem We've got to have companies invested in improving their manufacturing and modernizing Their their quality systems otherwise We will continue to be in this, um, you know, hamster wheel of constant drug shortages So I wanted to take a minute and and when when I was at the FDA public Meeting, um, there were kind of three buckets of of wish lists of of what people felt like Would help their group the most so the FDA wanted more information about reasons Believe it or not until very very recently companies didn't even have to tell FDA why they were having a shortage FDA doesn't have a lot of information about how much product A given company can make The types of contract manufacturing organizations that they're using They also often don't know if their company is using A different source of api if more than one is approved Um, it was very interesting to hear from the manufacturers manufacturers said, you know what? If we're going to keep making these cheap drugs and we don't want to because you know We don't make any money on this and it's really expensive But if we're going to do it We need to have a guaranteed volume and we need to have a long term contract The way that, uh, products are purchased right now Both of those do do not exist. So, um, with the group purchasing organization contracts or even, you know, individual term contracts Most of the time you you don't have to buy from a specific manufacturer You can you know, you can switch tomorrow if if something is five cents cheaper And unfortunately that is the mentality of a lot of pharmacy purchasers If they find a cheaper product, they buy that one everything's equal Um, we don't have any quality, you know, everything's pass fail. So why not go for the cheaper product? We also don't have long term contracts. Most of these contracts are for a year and you know, when you think about investing a lot of uh effort into your factory to make sure that you are doing a good job for for a long time A one year contract doesn't cut it and then You know, the the people that are buying the drugs they really wanted Um, certainly a consistent supply. Um, it is One of the biggest waste and healthcare that we have Is the the huge amount of labor that goes into all the workarounds that are required to deal with these shortages And they also wanted information about the quality of specific products so they can make a better purchasing decision The idea is I want to buy from a company that has a good record They're not going to be recalling their products and they're probably going to be able to supply me But with the current system, we don't have that at all And so those are those are kind of the gaps that the that we really need to work on fixing um Dr. Ungaroo Mentioned the meds act. Um, that is is potentially still in play, but the cares act was passed And we actually got quite a few shortage provisions in that cares act Not folks folks may not be aware of this and so You know, we we got a variety of concessions. The big thing that's missing though is transparency Nothing in here around transparency And so if we go back to our our gap analysis, what did cares get us? Well, FDA got got quite a few things. Um, they got more information about reasons They're going to get more information about the raw materials the active pharmaceutical ingredients They're going to get more information, uh from from those contract manufacturers And there is a concession in there That manufacturers should have some kind of business continuity back up plan So purchasers got a little bit manufacturers didn't get anything so It's like we're not fixing the problem, right? We're not close yet. We're getting there so What about new companies new ways to think about things? Um Civic rx is one model. There are other models out there. Um, civic rx is a not-for-profit Company again. I am an unpaid member of the advisory board. Um But their goal is to really improve supplies and what is unique about this venture Is that they're actually giving the manufacturers What they say they need to do a good job So it's a long-term contract So I have to tell civica how much of a specific product i'm going to buy for five years And I am absolutely bound to purchase that product Even if the drug doesn't come to me I say I don't want it. I still have to pay and so I've got skin in the game To to really do a good job of making a good estimate And so the manufacturers get a long-term contract and the guaranteed volumes so We're still in the experimental stage with with this company though. Uh, there are over 20 products available Will it work? We don't know Hopefully it will be We've already seen one of their products on backorder and that stacks them up the zone And one of the companies that that is making this product for them Is is having a quality hold and so We will see we will see if this truly this this model truly does does shake out and and fix things So just a couple key points and then I'm really excited for the discussion Um This is a really good time for action There's a lot of interest COVID has has really elevated the problem of drug shortages. We've had these shortages forever Almost every drug shortage that we've had as a result of COVID the the spike in demand for patients All of those products were short before COVID hit with the exception of propofol Um, but but all of the neuromuscular blockers all the pain medicines everything was short short already And so COVID just really exacerbated that The missing piece that we do not have in legislation It's not in the meds act either Is this need for transparency and it's something we we have to demand There's nothing else that we buy that we have so little information about than than our medicines And you know, of course working together on all of these problems Hopefully we can mitigate the the the actual patient harm that that is happening So with that, uh, thank you so much and uh, let's let's discuss Sounds great. So I see some hands. Um, please feel free to put more hands and feel free to also type questions in the q&a if you'd like But i'm gonna take my moderators privilege first and ask two questions to each of the speakers and I I guess To dr. Fox. This is incorporating a question that was on that chat plus one that I had or that was thinking about but I think you've alluded to this But do you think the FDA has recommended solutions for the shortage crisis get to the root of the issue or is a solution like California's recent decision to begin public manufacturing preferable and we know that california is working with civica On on that and I guess this builds into a larger question I have and of course you've already disclosed your role with civica, but they Do you think they I mean it's met with early success. You've noted that it's in the experimental phase But are there aspects of the business model that give you concern Over the long-term vibrancy of the generic market I guess how have the for-profit generic manufacturers responded to the growth of civica Those are really good questions. Um So I think FDA's solutions are are good because they really are trying to get at some of the economic issues Especially looking at contracting practices. Uh, that that's where civica can you know, this this issue of a lot making a long-term contract Is is different FDA also really recommend this this quality rating more transparency about The the medicines that we're buying this improving transparency to improve the quality That that is that is a key recommendation and and unfortunately it's just it's not being worked on Civica is being transparent. Um, I will I'm very happy with that They will tell you which contract manufacturer is going to make their product. Um, but These are contract manufacturing companies, you know, we we have a fairly limited number of companies that can make injectables and They almost every last one of them had some kind of a quality problem over the last 20 years So it kind of depends if they're going to fix it or not and and how much how much money they're they're going to invest I think um potential downsides to this would be if a company Preferentially made product for civica and then shorted the rest of the market Certainly hospitals can it's it's not a it's not a huge fee to be part of civica But not everyone wants wants to do that and and invest in these five-year five-year contracts. So That that is certainly a concern. Um, and I I don't want to dominate the the discussion but um, uh It's it's gonna it's we're gonna have to see if these companies can really uh anti up the quality or not And there's two follow-up questions here that relate to this but I want to give You're on if you did you want to weigh in at all on this question? There's more coming for you a little bit later, but uh, so I I saw the q&a I peaked and um I mean erin answered that more comprehensively Than than I will so I'm happy to to to feel the next one Sounds great, so I I guess I'll come back to a few questions to you erin But I want to give your on a chance to answer is a chemotherapy related question that's come up It's uh, it's from josh hyac especially in chemotherapy medications because of the cost and research implications and pediatric dosing Is there any indication that the higher level of accountability and transparency of drug manufacturers marketing practices required by open payments correlates to increased rates of drug shortages That's a good question. Um, and the honest answer is I don't know. Um, I'm not aware of any data The points to that now that could partly be in fact because we don't have a clearing house We don't have a central repository of information and disclosure requirements being what they are not Um, I'm not I'm not sure that there is any data on that. That would that would be interesting to to know Um, erin are you aware of that? Yeah No, that's that's a great question And to to build off a I mean a related question in the area is just you talked about There to be a lack surprising lack of ethics committees at the local hospitals to make these determinations of scarce drug allocation But in the case of covet 19 at least certain states have established scarce resource allocation guidelines um Do you think those guidelines first of all? Do you think all states should do that and do you think that those guidelines should be mandatory? Or is this something where you would afford the local institutions? An amount of discretion Very very thoughtful question So I think you know in the absence of a national policy advisory statement local jurisdictions are going to have to Be able to step in Because we can't sit on our hands and just hope for the best because we're seeing this every day that that's not appropriate as far as the Mandatory nature of that I think the the honest answer is it depends in other words if there is appropriate stakeholder Engagement if these policies have been appropriately vetted if they're transparent one of the things that We and many other groups and individuals talked about is hospitals need to be willing To be more transparent and post information about shortages So you come to Sinai hospital johns hopkins hospital the university utah Dana farber whatever did there should be somewhere in the public domain These are the drugs in a short supply because we have not been effective at our level enough In fermenting change and i'm not kidding when I say hell hath no fury like an angry mama bear We need to get patients patient advocates Involved and one way to do that is let's arm them with the tools that they have So it's a somewhat circular kind of way to get to it to address your question about should they be mandatory? I think if it's appropriately representative And it has the the necessary transparency Nuanced approach That is explicit and that is public i'd be more willing to step out and say yeah, that should be mandatory But if it doesn't I think we need to take a step back And I realize that there's all sorts of civil liberties issues and others at stake here And I'm going to stay with you for One and a half extended questions one you said as long as the proper stakeholders are at the table Who who are the proper stakeholders who need to be at the table? Would you say at a minimum and then second was just a question that was posed in the in the chat which is You know you would pose the question to us about how we would decide And uh an audience member was curious about how How you react in those decisions and what are the most important factors you consider and realizing that that's hard to summarize in a very short space But uh, I guess I'll I'll pose those to to you before erin there's there's plenty of more coming back to you in just a second Sure, so question number one was who should be at the table if i'm if my memory serves me right with my one cup of coffee so far today So, you know the the people who need to be at the table in my mind Should resemble in many ways what a typical ethics committee looks at these should be folks from all walks of life So you should have clinicians of all flavors. You should have policy folks. You need to have community representatives I mean, I think that is key people who have zero affiliation with the hospital the pharmaceutical company Whatever There really needs to be as broad as possible and and patients need to have a Say in this more than anything That's a little bit harder. I think when you're talking about pediatrics, but but my my this does not relate specifically to peas This is more in general. So that could be that could be a parent And and this needs to be A committee that is meeting well in advance that is coming up and then a sharing whatever processes are coming up with to get public buy You know as far as how do I make this decision? There's a lot of really good work out there that many different groups have put out One of the most well known is govind presides zika manual 2009 lance of paper There's phil rossoff and his group down at duke in 2012 The canadiens out in toronto have really good work We've added to that and I think what all of these all of these approaches Recommend to something that samson brought up I think it was samson who noted there's there's a utilitarian approach I mean we have to focus on moving away from the personal patient Clinician relationship to the greater public health one. That's what we're seeing now How you do that? I think is is in the is where the critical role is so things that we've recommended are Focusing on a threshold of curability where appropriate meaning you've got an 80 percent versus a 40 percent Perhaps you divert in that way Focusing on how important that drug is to that particular disease looking at the data in pediatric oncology You know we talk about clinical trials all the time But we also are very keen to using drugs in a research setting We shouldn't do that because we still haven't had data yet that's finalizing We've seen where a drug can look promising and not so unless it's a tried and true drug We shouldn't be prioritizing research over standard of care cohorting patients Maybe thinking about lower dose and then we need to really think outside the box You know, maybe we we extend use of a drug beyond its shelf life. That's not legal That requires a really informed and transparent discussion with the patient the patient's family But you know, I've had many times I've taken a swig of the milk at 12 0 5 a.m When it expired at 11 59 and I'm still here to tell about it and I'm not I'm not joking I mean, you know, nothing happens miraculously, you know a day after the drug expires So I don't want to like Darren said dominate, but those are just some of the ideas Yeah, that's wonderful input. Thank you. And I'm going to move to another question on larger Drug manufacturing issues. It's what is the role of the federal government in assuring supply? By directly entering the manufacturing space ie government run drug labs and I'll Couple this on too. So we've seen proposals by Elizabeth Warren to enter the manufacturing space Now she her proposal would say that that could be contracted out, but it could also be a government run Manufacture and I'm curious Erin what you think and then you're wrong if you want to weigh in after that's fine But is that is that a solution we be we should be looking towards? particularly in light of all of the quality issues that we've been seeing as being the primary driver of some of the shortages Yeah, that's it is an interesting question Because of of course with the federal government right now, we have no requirement for any company to make anything but I'm really hesitant about having federal drug manufacturing facilities in part because of the way the federal government is funded And and the long-term Needs of a manufacturing facility, you know, you can imagine we'd have shortages during shutdown You know as we have these, you know, chaotic budget cycles Would that agency have enough money to to do the work that it needs and it's going to need long-term funding You know, I think the federal government really could play a role in enhancing Drug manufacturing if we had these quality ratings you could imagine that cms might only pay For products with with a higher quality rating There's your incentive right there. I mean, it is a bit of a stick and a carrot, but That is one one way federal regulation could could really help. I am nervous about Setting up specific factories not only just because of the the length of time in the and and just It's yeah, I don't know. I don't know about that And I guess this builds a to your um, I don't know if you want to weigh in are you skeptical or I Perhaps not surprisingly. I agree with Aaron. The one thing I will say is The pharmaceutical company exists for a very important role and they deserve to be fairly reimbursed and appropriately reimbursed for the hard work and the drugs that they They provide for for the for the world There has to be a happy medium And we haven't struck that the other thing I will say is, you know, the federal government has stepped into bailout fanny and freddy They've stepped in to bail out the auto industry There's many ways that could happen. I am not a a policy wonk But I do feel that the government has to take a more Important role, you know, we we have other public utilities if we view these drugs as critical infrastructure Which the AMA has said which ASHP has said which many people have said if we view these drugs As essential medicines as critical infrastructure, then there has to be an obligation on somebody's part and this I think it would be the government To somehow make sure that they're provided. And so if we view these as a public utility much like water much like electricity And there's a nice marriage between Public and private That's one model. I think that we could potentially consider not claiming that it's, you know, the silver bullet by any stretch But something to to dwell on And this follows up on I think Erin you spoke to this point a little bit in terms of CMS perhaps only buying from those manufacturers that have high quality ratings, but This was a question that was posed Which was You know, what regulatory structures are in place or could be in place to effectively incentivize companies to make these admittedly cheap drugs And to do so at high quality. Are there other ideas out there? That are being floated around or that you think should be given more weight Yeah, you know, I think um, you know, it's it's interesting to think about why these products have been driven down and in price so low Much much lower than than you know, some of the generic counterparts in europe and you know part of that is the the drg reimbursement that hospitals have um, you know that really forces Inpatient settings to just look for the any tiny cost-cutting measures measures that can happen We may need to kind of think think about that. Think about the The way that we might need to pay more for these products if we're going to ensure Accessibility and you know, that's a little bit that that's civic a model. Certainly I will be paying a little bit more for for some products But I have this five-year plan knowing that I don't have to worry about about that product and so It's it's complicated, but but I think I think it's it's worth thinking about the reimbursement structure for sure And Rom do you have anything to add to that or I mean that's what happens in other countries There's the ability to negotiate directly with the drug company something that oftentimes is not allowed It does not happen here in the u.s And it's more of a level playing field You do pay more for of in christen. You do pay more for a dexamethasone than what is paid here, but you pay a heck of a lot less for a You know ms. Susamab or the sexy designer drugs and things like that And so it does allow for some more parity. So absolutely. I think that the the reimbursement the average sales price Plus six percent old model that was passed is something that needs to be looked at Thanks and for the all the all the wonderful questions coming in. Thanks for your patience I'm trying to sort of find natural ways to group them together and Here's one more that I'll pose again for both of you, but One is just this general question Comparative to the world stage. So is the drug shortage issue in the u.s. Unique or do other countries have similar shortages? And that relates to another question that was posed, which is Is there a model country that you guys know of or that you guys hold up that has been particularly effective in recent years at mitigating and managing the effects of shortages when they occur So I can start with Aaron if you want Difficult questions, but great question It's a really interesting question. I had the opportunity last year to go to belgium there was a conference of with with europe and the south america and um All of these different countries talking about the way that they handle shortages one of the things that I was struck by is um The companies that do this negotiation and you know, I really prefer maybe one single product They are much more likely to have a shortage where they are completely out of of something That's actually pretty rare in the u.s. So it's usually we can't get enough of something or the right formulation But but these countries are much more likely to um have You know just just be completely out and have very difficult Time accessing another alternative because of that negotiation That that was a surprise to me the other thing That I will say that I learned i'm not sure if it's a model that could be implemented in the u.s. But in belgium there is one central shortage committee They have one emr and they make the decision it floats out and and that's how they they handle things Clearly that is far from reality for the u.s. And did you want to add anything you're on? um The only thing I would say to add to that really is is an aside um I think we need to we need to go upstream a little bit and first decide on what is truly essential and critical that will then help us alleviate some of these shortages in other words, let's come up with an absolutely must And again, this is what suffocates trying to do and others But I don't think we have agreement on that and we we use we use lots of different drugs not necessarily based on data Let's go back and and make sure that we're looking at the evidence I will say that the national academies of science has a new committee that will be focused on um Kind of looking at that. What is the essential list? Uh a little bit later on this year Great now. I want to come back to something uh, Jonathan had mentioned before earlier Jonathan Do you want to follow up on your question from before? sure, um, so Thanks again for some excellent presentations and for all of your expertise that you're sharing with us I just wanted to re-ask my question from earlier which is Why can we not go? to the hospital administrators and say Please have an extra three months or whatever the median period is for drug shortages Of drug x. Is there something special about vincristine and other Drugs that have been in shortage that we cannot do that I'm happy to jump in there um and try to answer, uh, Jonathan You know one of the one of the problems with the way these drugs are made and particularly sterile generic injectables is What would they call just in time production? um The companies don't Aren't able to it's it's hard to run these these production lines. They don't have enough drug on the shelf It's not like you can go to amazon and they have you know a thousand copies of bottle of lyes You know they keep just enough for for a week or two and and I'm not a um, I'm not a a pharmacist or a or a chemist to speak to what the What the scientific rationale for that is but from a business perspective, it's very hard for them to Commit to keeping more. Um, I think by increasing the number of producers, which would obviously be low hanging fruit of seams, but it's not because of the the economic considerations because of the difficulty maintaining these quality Lines that makes it even harder. And so you have one or two companies that is unable Uh and or unwilling to make them and so I don't think this is a question for our hospital administrators I think it's farther up the the food chain where the problem starts And I think the other thing to think about is um The the average length of time of a shortage is about a year and so There are storage capacity uh issues. Um hospitals don't have a finite Uh, let's say that you decided to go with the who essential medicine list 200 things Keep a year supply of all of that on hand. Um, it's it would be very very difficult to to actually do that Um, I think the the other thing to think about um, even with the civica model They have six months extra kind of buffer stock on hand but What happens if if if something lasts longer than than a shortage of six months And so so that's the other thing to think about and then injectables in general The companies don't have a lot of incentive to have these products To do the research to to give them longer expiration dates. They will During a shortage and fda will extend those those expiration dates, but Most of these products expire in about two years so and so now I want to transition over to reputational The reputation of pharmaceutical companies and also their own allocation Decision so there's two questions here So I guess I'll start with the allocation one Which is that could you speak to the allocation mechanisms that drug companies themselves Have used during shortages for my anecdotal experiences It seems to range from no allocation mechanism to hospitals needing to submit individual requests for drugs And then the follow-up is perhaps a larger question is I'm interested in the proposition that pharmaceutical manufacturers attend to the reputational implications of their decisions Are equality or occurrence of shortages? Is there evidence of this? How does reputation or reputational loss impact or matter for manufacturers? I can just jump in there very very briefly I mean as far as reputation, you know the FDA safety and innovation act the president obama passed in 2012 One of the requirements was that if a pharmaceutical company notified the government about hey, we're going to have a shortage and We're giving you a heads up and one of the steps that Existed was if they failed to do that there would be a public letter essentially shaming And that did nothing like Aaron like you showed in the beginning like Aaron talked about we've got these shortages And nothing's changed. So I'm not I'm not so sure That's the the where we want to put all of our eggs in that one basket As far as Allocation and what the internal company do the companies do internally You know some are very forward thinking Jazz for example the company that the one company that makes our winnias this really important drug for kids with leukemia and certain types of FOMA they actually convened a group of Folks to try to figure out a way that would help them allocate their limited supply. Unfortunately Not much came of that others don't and so It would be really important to know that companies have a mechanism in place And again that they're transparent. It doesn't have to be it doesn't have to be a perfect policy, but Many wait too long and and then kind of get surprised when there's a huge backlash and I think if anything we're seeing now That's not the way that we want to deal with these shortages You know, those are those are great points. I think um, it's important to realize fta also has Zero input into how things are allocated. We can recommend but drug companies don't don't for for instance Have to ship product only to children's oncology centers for for example and then You know the the other thing To think about is is the role of the wholesalers? so There are three large wholesalers and they all allocate product very very differently and Many drug companies actually don't have the capacity to directly ship They work through the wholesalers and so there's another layer there that that that often Gets gets missed with regard to reputation. Unfortunately these companies Don't get a bad reputation for having shortages Their bottom line is not affected because they're so cheap. So the stockholders don't care And unfortunately many hospitals are reluctant to speak out about shortages No hospital really wants to be out there saying hey, we're out of this, you know and so it's very underground and so Um fda gets a tremendous amount of blame You know the pharmacy administrator gets gets blamed for for not ordering enough but Nobody blames the company that for six years chose not to fix the quality problems and and now has to close down Thank you both and I know we're at time and I know some people have to leave This question is more towards erin on the line. Can we go for five more minutes on q&a or should we cut it? Uh, I do think we have to cut it just because of other people's schedules But if there's a yes no question you wanted to ask we can do that No, I think that that's fine. So apologies to the people who have uh posed some other very nice questions Unfortunately for time we have to cut things to a close But I do want to give in the in the in the minute or two that we have last Both erin and yorama chance to uh say any closing thoughts on the issue So I'll start with erin if you if they if there are Um, yeah, just thank you so much and um This is a really important topic. Um, please please keep talking about it. Um, make make sure that the people Are hearing about the short shortage problem. A lot of it gets Uh swept kind of underneath the the rug and it's not not why they talked about important And and I would just also echo the thank you for covering this this issue. Um, I often times feel like I call myself a drug shortage prostitute. I'm happy to talk to anybody Who's interested in this but this is a really important A platform that you all have And and get out there and let your parent your patients know let your community know It's shocking how many physicians don't know about drug shortages Our pharmacy colleagues know and they keep us honest, but um, I did a An informal poll in my hospital. It was shocking that the doctors and nurses didn't even know about drug shortages So clearly there needs to be more pounding of the pavement Thank you both again sharing for sharing your expertise. I think this was a wonderful session I think we learned an incredible deal. We will keep these ideas going and I hope you guys continue your work in the space and Um, we're looking forward to some solutions and we know that they're not going to be easy But to the audience in particular, thanks for wonderful questions as well again, a very engaging session and We look forward to the next one next month, but I'll hand off to Aaron now through the final. Good. Bye Okay. Goodbye There you go. Have a good one everyone. Have a good afternoon