Print BCTV: Compassionate Access -- Josh Hardy's mom, Kids v Cancer, FDA,Brookings on social media, medicine

Compassionate Access

Transcript of BioCentury This Week TV Episode 186




Aimee Hardy mother of 8-year old cancer patient Josh Hardy

Richard Klein, Director, Office of Special Health Issues, FDA

Nancy Goodman, Founder and Executive Director, Kids v Cancer

Darshak Sanghavi, Fellow and Managing Director, Engelberg Center for Health Care Reform, Brookings Institution




Chimerix, Inc.

Kenneth Moch former CEO and president, Chimerix, Inc.

Brincidofovir, (CMX001)




Steve Usdin, Senior Editor




STEVE USDIN: A family's successful social media campaign to save their son's life raises tough ethical questions. We'll hear from Josh Hardy's mother, and get some other perspectives. I'm Steve Usdin. Welcome to BioCentury This Week.


NARRATOR: Connecting patients, scientists, innovators, policymakers to the future of medicine -- BioCentury This Week.


STEVE USDIN: When Josh Hardy, a seven-year-old recovering from cancer treatment, developed a deadly infection, doctors said his best hope was an experimental drug. The only clinical trial was testing a different virus and was only enrolling adults. The drug's developer, Chimerix, denied the Hardy family's request. It had already turned on hundreds of similar requests, saying that granting access to a single patient would open floodgates to demands that would swamp the company and delay FDA approval.


The Hardy family took their case to the internet, launching a Save Josh campaign on Facebook and Twitter. Josh's plight went viral. Celebrities with millions of followers tweeted support, and thousands of people used social media to criticize Chimerix. The Save Josh campaign was featured on national and local television.


TV coverage got FDA's attention. In 24 hours, the agency and Chimerix agreed to create a new clinical trial with Josh as the first patient. The virus was quickly defeated, saving Josh Hardy's life. Kenneth Moch, Chimerix's CEO, resigned last week. The case raises important questions.


Is social media a fair way to allocate scarce medical resources? Who should get unapproved drugs? Who should decide? Who should pay?


I'm pleased to be joined by Josh Hardy's mother, Aimee Hardy. Aimee, thanks for taking the time to talk to us today. To start with, I of course want I ask you, how's Josh doing?


AIMEE HARDY: He's doing very well. We're very encouraged and excited about his progress. He still has a long ways to go, because he has endured quite a few complications. But we are definitely out of the danger zone with his health. And we actually anticipate hopefully getting out of the hospital very soon.


STEVE USDIN: Well, that's great. I'm wondering if you get back up for us and tell us the story of how you first applied or asked Chimerix to get access to the drug and how the story unfolded from there?


AIMEE HARDY: OK. Well, at the end of January, we realized he had the adenovirus, and our doctor said that they were going to ask this drug company if they could have compassionate use of this drug that they were trying to get. And we were like, OK, great, the levels were low, we weren't overly concerned. We thought it might go away on its own.


But his immune system was very compromised. And with every week, it just got a little worse. And every week, our doctors asked them. And finally, in the first week in March, they came to us and said, if we don't get this drug for him, he's not going to make it.


My husband and I each on our own individual Facebook pages just said, does anybody know anybody that works for Chimerix, anybody with any influence or anything? We need to get this drug. It is a matter of life and death. And the response was incredible.


And our family gathered around us, and they made the Save Josh Facebook page. And they know how to Twitter, which I do not. But everybody worked together trying to get the word out and try to see if we could find some way to make it happen.


STEVE USDIN: So you had this fantastic outpouring on social media and then on television. And it turned it around. Do you know what it was that put it over the top that led the company and the FDA to grant access to the drug?


AIMEE HARDY: I really can't say for sure. It was a lot of social-media pressure. I know a lot of people were calling the company and asking them on Josh's behalf and sending letters. I know there were a lot of people were talking to the FDA. I can't say for sure exactly what made it change.


But I do feel like the attention that it got and the fact that we were on news outlets, I think they wanted to try to make it happen for us.


STEVE USDIN: This was tremendous news for Josh. But obviously, there are a lot of other people who asked for access to the same drug and didn't get it. And there are other people who need access to other experimental drugs and don't get them. Have you thought extrapolating from your own experience, about how you think policy might be changed to improve access for other families?


AIMEE HARDY: I have put a lot of thought into it, because I think about us and our fear of losing our child when someone was holding the medicine in their hands. But I understand on the drug company's aspect, I've seen drugs put out to market too soon and did not know that the ramifications. And then they have to back pedal and try to fix what damage was done by a drug.


So I understand the hesitation, and there's rules and regulations to try to protect the public and the drug company. But I think when there's a life or death situation, I know in our case, we were willing to take the chance of any adverse side effects just to get more time with him. And I believe any family in this situation would say, yes, please let us try the drug. We understand this is an untested drug and that it could have possible side effects. But please, let us have it.


I've thought about it before. I've seen a family member go through a heart transplant, and I know that there's different levels of when you're on the transplant list, based on the severity of your situation, if a heart becomes available but you're not the most serious person that matches that heart, you're not in line for it yet. And I almost think on a compassionate-use level, that might be an idea too.


If someone is in a dire circumstance, that if they don't try something new that they're not going to make it, I feel like that should be something that would allow them to be eligible for the compassionate-use drug.


STEVE USDIN: Well, thanks very much. And good luck to Josh. We'll be back in a moment with more on compassionate access.


NARRATOR: You are watching BioCentury This Week.



STEVE USDIN: I'm pleased to be joined by Richard Klein, director of FDA's Patient Liaison Program, Nancy Goodman, founder of Kids v. Cancer, and Darshak Sanghavi, a Brookings Institution fellow. Chimerix and the Biotech Industry Organization declined BioCentury's invitations to participate in today's show.


So I want to start out and maybe throw it out to all of you -- is social media a good way to make decisions about who should get access to experimental drugs?


DARSHAK SANGHAVI: I think social media's use indicates that there's probably not a established strategy that many people have. And so they turn to really the only thing that's available, which is talking to their friends, talking through social media. So I think, at least in my view, this indicates or is an indication that there is a problem that needs to be addressed.


NANCY GOODMAN: I agree. One thing, though that we can say about social media is who's successful in the social-media context. With respect to Josh Hardy, it was a child. I think that people in particular care about kids getting access to drugs.


STEVE USDIN: And I guess it still begs the question, even in the case of this one drug and this one company, of the hundreds of people that came before him who didn't get access to it, presumably because they didn't have those kind of social media campaigns. And I'm wondering, to start with, how is the process supposed to work, Richard, from FDA's perspective?


RICHARD KLEIN: Well, let me just give my opinion about the social media. I don't think it's the best way to make healthcare decisions, and I don't think that the people who are participating in it really know all the ins and outs of the questions. The way that the system works now is, FDA provides essentially, I guess, it's a pathway or a mechanism that patients, doctors, and the companies use.


FDA has a very minor part, really, in that decision making and really is the mechanical part that allows that drug to be shipped to that patient if everyone agrees that the risk is reasonable, that people are willing to accept that risk, and the company's willing to provide the drug.


STEVE USDIN: The proviso there is, the company has to be willing to do it. And so ultimately, the decision making is in the hands of the companies now. Does that make sense, and do they have good ways and transparent ways of making those decisions?


NANCY GOODMAN: That's right. And to that extent, I think social media is really OK as a response to the company being the actor who decides whether a person or, for example, Josh gets the drug. Companies have their own goals and objectives. They are for-profit entities with fiduciary duties to their shareholders.


Should they be the actors deciding whether a seven-year-old boy receives a viral -- anti-viral -- drug, for example?


STEVE USDIN: And one of the things that Chimerix said, for example, is that they had a policy in place not to grant compassionate access to drugs because they said that doing so, they would have been swamped. And that would have prevented them or delayed FDA approval for the drug, which ultimately could have helped a lot more people. What are the kind of reasons that all of you think are legitimate for companies to say no to those kinds of requests?


DARSHAK SANGHAVI: Part of the issue is the one looks at what is the role of a pharmaceutical company. And their role is to try to bring a product to market. And in addition to that, many of them feel like they have a societal responsibility. We as society pay for a lot of these drugs. And perhaps they then especially also have a moral responsibility to try to make sure that people who are desperate, who may not qualify for trials that are really geared towards approval and selling the drug, is there really a responsibility to do that?


And some companies probably interpret that as having responsibility. They have a plan, usually the larger ones. And maybe some of the smaller ones feel like they may not have that or that's probably not part of their central goal. So I think you're going to see a lot of variation as you look at different companies.


And I think that's born out by patients who try to get compassionate use. Some of the companies you'll find have a very explicit pathway, they have a website, they have a video you can watch. It's clear who you contact. Others, it may not be entirely clear who you even call to try to get compassionate access.


STEVE USDIN: Nancy, no patient is ever going to be happy, nobody's family is ever going to be happy with the decision if it's no. But from your point of view, what would be the legitimate reasons why companies or FDA should say no in some cases?


NANCY GOODMAN: Well, let me back off and say, I think that the company is not the right entity to make the decision in the first place. So the question is, what is a reason for whomever the appropriate entity is to make a decision? I think the first question is, does this drug have a possibility of helping the patient?


And that should be just your baseline question. And where's the drug in the development process? Is there a reason that patient population has not been studied for the drug? And is that a reason that this drug should be withheld from the patient?


STEVE USDIN: And one of the criteria that FDA also applies in making decisions is, is there a clinical trial available? Because the idea that compassionate access shouldn't be a way to avoid, for example, being randomized to placebo in a clinical trial.


RICHARD KLEIN: Exactly. And the primary goal is to get people into clinical trials so that you can get the kind of information to determine how effective is a drug for a given indication, how safe is it, how do you balance the benefits and the risks, and how do you manage whatever toxicities you have. Then you put that in the label. It's available to everybody. Usually, third party payers, insurance companies will pay for it. It's a much broader access in the future.


STEVE USDIN: Thanks. And in fact, FDA's decision making isn't what usually leads to people not getting access to drugs. We'll talk about that and more right when we come back.




NARRATOR: Now, back to BioCentury This Week.


STEVE USDIN: We're back with FDA's Richard Klein, Darshak Sanghavi of the Brookings Institution, and Kids v. Cancer founder, Nancy Goodman. Nancy, you were saying that you don't think that companies should have the ultimate decision on making compassionate-access decisions. What would you think what would be a better way to do it?


NANCY GOODMAN: Well, there are so many other ways I think that would be preferable to the companies making the decision. And I suspect, frankly, that there are fewer compassionate uses issued than we as a society might want. So who could that be? It could be a third party that would be responsible for reviewing every case on an expedited basis, understanding both the challenges and limitations the company faces, and the probability of a particular investigational drug assisting a patient.


STEVE USDIN: So one of the other things that comes up that wasn't the case, as I understand it, with the Chimerix drug, but it comes up pretty often in these cases is that companies simply don't have enough drug supply to give everybody who would want it on compassionate access use to it. What should they do in those circumstances?


DARSHAK SANGHAVI: First of all, it's going to depend on the type of drug. So that's right. Certain manufacturing processes, biologics, you have a limited supply. And you don't have as much as you need. And that's really where there's no easy solutions, because even if you have a third party, that decision might be appealed by a family as well. They may not agree with that.


And so there's a variety of innovative ideas. Some people say maybe it can be a lottery. You have a limited supply. You have a legitimate number of potential people who want it. You should just give it out randomly. Others might say it's in terms of severity, maybe those who are sickest.


And others would say, well, how about we think about the biology? It should be those who are the most likely to benefit. Those are all questions that we don't really have the answers to. I do think that, as you said, maybe having at least some equitable way of deciding who qualifies rather than social media or who's the most popular. Maybe that would be a first step.


And then once we know how often these issues come up, then we can try to develop strategies to help.


NANCY GOODMAN: Just to go backwards one step, Dar, maybe we should require companies -- I'm just throwing it out -- to have a larger clinical supply. I do want to note that when companies develop an investigational drug, they have intellectual property rights over that drug, which we as a society give them so that we can encourage them to develop that drug and provide it to market.


STEVE USDIN: So your idea is basically saying, part of their responsibility should be they should build into it having enough supply to give people outside of clinical trials.


NANCY GOODMAN: That should be part of the analysis that Dar has proposed.


STEVE USDIN: Some of the other issues when you get to FDA -- one of the proposals that's been floating around I know in Congress is the idea of requiring the companies tell FDA about compassionate-access requests. I guess, all three of you, what would you think? Is that a good idea?


RICHARD KLEIN: Are you talking about the total number of requests that they get?


STEVE USDIN: Yeah, every time they get a request, they have to tell FDA about it.


RICHARD KLEIN: Well, if the company were not willing to provide that drug to patients, I don't know what the purpose would be, other than to get numerical picture of the landscape. But FDA doesn't have any authority to decide what the company's going to do with their intellectual and physical property.


NANCY GOODMAN: And there are certainly many very good reasons for a company to decline a request for compassionate access. But I respectfully disagree. I think that FDA officials do sometimes reach out to companies and say, I understand there have been numerous requests for compassionate access. Let's do an expanded-access trial.


It gives the FDA an opportunity to engage the company and to identify other solutions.


RICHARD KLEIN: I think that actually happens more than people probably realize.


NANCY GOODMAN: But it can only happen if the FDA knows.


RICHARD KLEIN: Well, a lot of times FDA sees benefit in the clinical trial results as they're coming in. They're looking at what's happening in the study and decide, this is a drug that's showing some efficacy, we don't have tremendous concerns over safety. There are a lot of people who could benefit from this. And they'll go to the company and encourage an access program.




DARSHAK SANGHAVI: I think we can all agree that somebody should be counting and in some way to keep track of how often these requests are being made. And that would make a lot of sense. If we don't even know the magnitude of the issue, then we really can't even decide how we're going to fix it.


STEVE USDIN: Richard, FDA almost always, more than 99% of the time, approves requests for compassionate access to drugs. But you said an interesting thing to me when I interviewed you for a story that I wrote for print, which is that you think that people have an exaggerated sense of the value of experimental drugs and their efficacy.


RICHARD KLEIN: Right, Steve. I think almost all of these the applications that come into FDA are approved to go forward. One of the big problems is, it's very hard to get the outcome data, particularly for single-patient applications. So we really don't know how effective most of those drugs are. But I think that people have an exaggerated opinion or a view of how effective they are in thinking that if I can get access to this drug, this might be the cure, or this will keep somebody alive for a long time or cure them.


I just don't know for sure what the outcome is for most of those people. That's why the trial is so important.


NANCY GOODMAN: Richard, I agree. A trial is so important. But when you're faced with, as I was, a dying child, and you know that there is a very, very small probability of success of a drug -- I applied for eight compassionate uses for my son, Jacob when he was in end-stage pediatric brain cancer. I know the probability of success of any given drug was infinitesimally small, but it was better than death. That was what was motivating.


DARSHAK SANGHAVI: I'm a periatric cardiologist, and I'd like to compare this discussion to surgical techniques. We often deal with kids who are desperately ill, dying. And the parents or their surgeons may want to try something entirely new. And we let them do that. And we believe that as long as the family and the physicians have a discussion and they agree to this, that that's enough. Yet we treat drugs a little differently.


And I think that that's kind of a difficult problem to fix. But there is some precedent for that.


RICHARD KLEIN: But I think the track record at FDA does point to the fact that people at FDA feel and think the same way. But there needs to be that supply, and it needs to go through that pathway. But for the most part, most of them are approved. If there is hope that this is going to be useful, people want to give the opportunity for people to use it.


DARSHAK SANGHAVI: And ideally, that we learn something from the experience.


STEVE USDIN: Is there a problem with false hope? I mean, if you go out there and look at some of the petitions that are online for drugs that some people want access to, there are things that the medical establishment would say was quackery.


NANCY GOODMAN: That is a problem. I think if we had a third party making the decision, then we would certainly address that problem. That someone is asking them at their request is not well reasoned or should not be honored doesn't mean that they shouldn't ask and they shouldn't give the most persuasive ask that they can for compassionate use.


STEVE USDIN: We're going to be right back to talk about that and other issues about compassionate access.




STEVE USDIN: We're wrapping up our conversation about compassionate access to experimental drugs with Darshak Sanghavi, Nancy Goodman, and Richard Klein. Richard, I wanted to start with the question about who pays for drugs that are given under compassionate access. Right now, FDA has a mechanism to allow companies under certain circumstances to charge, right?


RICHARD KLEIN: Correct. And usually, it's a sponsor, the developer of the drug who would pay for the drug. But if a company cannot do that, cannot swing the cost of the drug, they can appeal to FDA or file an application for FDA for getting paid for that drug. But it's very limited to the cost of manufacturing that particular drug, not the background industry cost, the overhead, but the cost of the pill itself.


STEVE USDIN: And it's very rarely used, because one, the incremental cost of the pill isn't usually what the issue is. And two, of course, companies don't want to have that information out there public. Nancy, do you think that there's a case for having some kind of public funding for helping give access to experimental drugs?


NANCY GOODMAN: Absolutely. In the case of Chimerix, it's a small company of 50 people. And it's not only the cost of the drug that's a burden to them, but all of the dislocation of staff who are focusing on thinking through and evaluating compassionate-use access, communicating with the families, communicating with oncologists. It's a huge burden for them, and they should be supported, if we're going to, as a society, ask them to expand these programs.


DARSHAK SANGHAVI: It seems to me that the biggest cost you said is really the evaluation, the paperwork, maybe tracking them, not really the manufacture of the drug, at least with limited exceptions. Perhaps if that was a third party, as we suggested, that would decompress this from the companies. All of us can agree that the last thing we want to do is to impose additional regulatory burden and cost on people who are trying to make life saving medications.


And so I think there would have to be a balance. And perhaps a third party would be one way to make that suggest a solution.


STEVE USDIN: And one of the other things I'm wondering is, I don't think anybody would say that compassionate access or what FDA calls expanded access is the best way for people to get access to drugs. And having an approved drug is obviously the best. But beyond that, having some kind of a program where there's information that's generated about it so that when the next person comes along, you have some basis for knowing whether it's likely to help them, what the side effects are, something like that. Are there ways that we can expand the clinical trial so that more people are in clinical trials, unless people are desperate and seeking drugs through expanded access?


DARSHAK SANGHAVI: I think one of the things that we have to keep in mind, particularly in oncology, is that the vast majority of patients are not enrolled in clinical trials. We're not learning as much as we should from their experiences -- very different than in pediatrics, where almost all children are enrolled. And I think that if we focus on that as an additional issue, learning as much as we can from people that are already out there getting all kinds of treatment, I think we can all agree that is a noble goal, probably different than compassionate use, something can be [INAUDIBLE].


STEVE USDIN: But it would release the pressure. Nancy, very quickly, we're just about done -- is that really true that most pediatric cancer patients are in trials and getting access that way?


NANCY GOODMAN: 2/3 of all kids with pediatric cancer are on trials. So that is true. But that being said, pediatric-cancer trials start many, many years after adult cancer trials. So the reason you see kids requesting compassionate use is because they don't have access to investigational drugs through the clinical-trial process.


STEVE USDIN: That's this week show. I'd like to thank my guests, Aimee Hardy, Richard Klein, Darshak Sanghavi, and Nancy Goodman. For more information about compassionate access, including BioCentury's reporting, and a proposed framework for decision making, log on to Have a thought about today's show? Remember, you can tweet about it using the hashtag #BioCenturyTV. I'm Steve Usdin. I'll see you next week.