MR. KOJO NNAMDIFrom WAMU 88.5 at American University in Washington, welcome to "The Kojo Nnamdi Show," connecting your neighborhood with the world. For almost a century, the clinical trial was a cornerstone of modern medicine. Before any new promising new drug for cancer or HIV could make it to the market, researchers relied on trials with human volunteers to test the untested and hopefully find new ways to treat diseases in the general public. But today's medical trials present unique challenges for researchers and patients.

MR. KOJO NNAMDIAs our understanding of diseases like cancer deepens to the molecular level. Some worry that traditional trials aren't yielding the kinds of insights and treatments doctors need to attack tumors in new ways. Meanwhile, traditional ethical questions are getting more complicated, especially with the rise of health data technology and social networking among patients. We're exploring the recent, past, present and future of medical trials with Michael Carducci. He's a Professor of Prostate Cancer Research and a Professor of Oncology at the Johns Hopkins Kimmel Cancer Center. Mike Carducci, thank you for joining us.

MR. MICHAEL CARDUCCIIt's great to be here.

NNAMDIAnd Mary Marovich is Director of the AIDS Vaccine Research Program at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Mary Marovich joins us in studio. Welcome. Thank you for joining us.

MS. MARY MAROVICHThank you, Kojo. Great to be here.

NNAMDIJoining us by phone from New York City is Arthur Caplan, Director of the Medical Ethics Division of New York University's Langone Medical Center. Arthur Caplan, thank you for joining us.

MR. ARTHUR CAPLANThanks for having me.

NNAMDIIf you have questions or comments on this topic, give us a call at 800-433-8850. Have you or a family member ever decided to participate in a medical trial? Tell us what your experience was. 800-433-8850. You can send email to kojo@wamu.org or shoot us a tweet @kojoshow. Mike Carducci, virtually everyone agrees that medical trials with human subjects are a critical part of the discovery process for new drugs and new vaccines. Give us a sense of what you do as a cancer researcher and the role that volunteers and clinical trials play in understanding cancer.

CARDUCCIYes. I came in to medicine. My role models were all people who were trying to figure out what we did in the laboratories, how we could bring it to the patients themselves through the clinics. And so it was the whole process of clinical trials that sort of intrigued me. And so as I went through my training, it really was, how could I learn from my patients as well as offer them clinical trials. A lot of times, you know, what I do in terms of cancer, it's pretty frustrating not to have an answer for that patient that day.

CARDUCCIBut knowing that all that I knew was really from patients who had gone before them, and the trials that they had participated in. So that whole process, really, was everything we know, really, is because patients, particularly in cancer, have participated in clinical trials and allows us to provide that therapy.

NNAMDIArthur Caplan, and yet, many people have a certain level of skepticism about clinical trials. I read a statistic that said only three percent of American cancer patients opt to participate in a medical trial. What does that number mean to you?

CAPLANWell, there is a lot of distrust of clinical trials. We hear about people who do not get proper informed consent about the risks and the benefits about being in a clinical trial. Certainly the media and fictional presentations often indicate that, to some extent, drug companies, people out to make money are exploiting, taking advantage of folks who might sign up for a clinical trial. You know, Kojo, we never really have had in this country any notion of a duty or an obligation to be in a clinical trial.

CAPLANIt's something you volunteer to do. It's something you make a gift of, an altruistic if you want to let medicine learn, if you want to try and help others. So, the motivation to participate either is you hope something may happen that benefits you, which is a long shot in clinical trials. You know, the research process, sadly, is slow and hard. And you have to feel, somehow, that you want to help others. And that mix is really producing lower numbers, I think, then that medicine needs.

NNAMDIHow does that three percent number, Mike Carducci, affect your life?

CARDUCCIWell, again, we do clinical trials in all phases of trials, as well as states of disease for our patients. And so when only three percent nationally go on, a center like ours at Hopkins puts about 20, 25 percent of our patients on clinical trials. So it's a bit higher, but we have patients who are highly motivated who come to us. We talk about the promise of our trials and the drugs that we have. The access to novel therapies. The science, all that we sort of put out there, you know, is real.

CARDUCCIAnd yet, we have patients who come in, and we want to make sure, like Dr. Caplan said, not to oversell what we're going to be able to do for them, but sort of sit them down and talk about sort of here's where we are. Here's what we know. And this is why we're asking you to participate.

NNAMDIMary Marovich, kind of by definition, Mike works with people who are already sick, which presents all kinds of ethical questions, but you're working to develop an HIV vaccine which means you work -- you're working with healthy people. Tell us about that.

MAROVICHYes. It's an entirely different population with different motivations for participating in clinical trials, certainly. One of the most difficult things for volunteers, who are considering participating in an HIV vaccine trial is the risks and benefits to them. And I spent time trying to understand why people volunteer, because it's such a big deal. It's such a big sacrifice. And often, people know someone who've been stricken with the disease, particularly from this area. And they're motivated to try and do something.

MAROVICHAlthough they are concerned about risks, and so we have to go over that in great detail and emphasize the measures that we take, the safeguards to reduce that risk.

NNAMDIYeah, because what you are really talking about in your situation is presenting a stranger with a proposition that, in this case, is mostly a risk without much chance for reward. So people have to come in motivated, so to speak, huh?

MAROVICHIt is true. And what I would normally do, when I'd interview them, is try to understand why they came in and what concerns they had. And what -- address those concerns up front. Mostly, the concerns would be could I get HIV from this vaccine by some big mistake? Or will it look like I have HIV infection from this vaccine? Those were the two major concerns, and we'd have to spend a lot of time addressing those concerns. And what I found at the end of the day was really, if the volunteer trusted the investigator, they were willing to participate. It was a big matter of trust.

NNAMDIIn case you're just joining us, we're talking about the future of medical trials and inviting your calls at 800-433-8850. You can also go to our website, kojoshow.org. Ask a question or make a comment there or shoot us a tweet @kojoshow. Arthur Caplan, and you, Mike Carducci, on the topic of working with sick people. Many people actively seek out medical trials because their prognosis is bleak. Maybe they have an aggressive form of cancer and it's pretty clear that they can see an early stage experimental drug as their best chance. Starting with you Arthur, how do you unpack the ethical issues at play here?

CAPLANWell, we have a notion, Kojo that is very important in dealing with very sick people. People who are facing terminal illness or serious disability. And that is what we call a therapeutic misconception, that, if we recruit someone to a new drug or a cancer vaccine, that they will benefit. It's still research, even though it may be the only option that someone has to try a new drug. To try something in the early stages. So we really have to try and explain carefully that we're still testing.

CAPLANIt may be a safety test early on. It may be trying to figure out what dose to use or what mode of administration works best for the drug. So, you're really trying to take people who are hoping for someone to throw them a life preserver and say, look, may not be able to do that. Sometimes the best we can do is learn from you and would you be willing to offer us that? And that is a very, very tough situation to put a desperately ill person in.

NNAMDILater in the broadcast, we'll be hearing more about this from a patient perspective, but Mike Carducci.

CARDUCCIYeah, my sense is it really -- I remind myself every time I'm with a patient that it's an experiment. And really just going to the basics, explaining to patients how trials get developed and the phases. You know, a patient who's coming to me for a phase one trial, so I'm looking at that study, really, to sort of, is this drug safe? Okay? That's all I need to know. Is it safe, so that I can figure out what dose is appropriate for subsequent studies. For the patient, they're looking at it, well, is it gonna work? Is it gonna help me?

CARDUCCIAnd we did one study where actually, you know, we're as honest as possible, saying we don't think this is going to help, but then we use a language that says, after a little while, we're going to evaluate you with scans to see whether it's helping you. So they automatically hear help, so it's going to work. And so that whole process has to sort of be discussed with them. But with our newer clinical studies and drugs that become more and more targeted for specific cancers, we feel like the response rate actually is going up. So that therapeutic intent seems to be higher, at least in our minds, whether it really translates for patients.

CARDUCCIPhase two is really, we have a drug that's safe. Now we want to know does it work? And so patients coming in in that setting are much more open to sort of say, okay, you know you have a drug, you know it's safe, but I just -- we're trying to figure out how often does it work? So that the next patient, I can say, when we give this drug, it works 20 percent, 30 percent, 40 percent. And those studies are often randomized in terms of patients have a flip of the coin as to whether they get the drug or it by itself with another agent. So those patients are often usually getting the drug.

CARDUCCISo those are often easier to accrue to. And finally, the phase three studies, which is the one right before approval, is we have a new drug. We know it's active, but is it better than what we currently do? And the idea is if it is better, then it would become a new drug on the market.

NNAMDIArthur, you've been involved with a program at NYU called the Compassionate Use Project. How does that work?

CAPLANSo, as we think about those stages that were just described to put drugs through. And they're slow and careful and important, because they guarantee both safety and efficacy to the majority of people of who are gonna wind up using drugs or vaccines or medical devices. We also know there are people who can't wait. Who are dying or going blind or becoming demented, and they have weeks or months. They often, we see them in the media these days, or social media, they're often saying I can't wait for a trial.

CAPLANI can't wait for that phase three trial to be done. I can't even wait for it to be started. I'm going to die from my tumor, I'm going to go blind from my disease within weeks or months, my doctor says. I need to get access to something and nothing is around that's proven. I want to try something experimental. We call that situation compassionate use. And it raises enormously interesting, difficult and important ethics problems, because it's not as if there's a cure that is known out there, when someone says please let me try something.

CAPLANIt may only have been tried in mice and rats. It may only be up to that phase one trial that Mike was describing, where human subjects have been given some of the drug to see if it's safe, but that's it. We don't know if it works. Still, I think there is a moral duty to try and rescue, that people have an opportunity be given to them to try something if they're very, very sick. But at the same time, you don't want to exploit them. You don't want to take advantage of their desperation and just say, oh, we'll try anything on you, you know? If it looked good in a mouse, then maybe we'll try it on you.

CAPLANAnd you also don't want to undermine your regular development of the drug, so you don't want everybody rushing over to use drugs compassionately rather than going through the process of trying to prove that they work. So we have a social need to get drugs out there. We have an individual need for people who are very, very sick to say, I want something right now and I can't wait.

NNAMDIOn to the telephones. We start with Joe in Washington, D.C. Joe, you're on the air. Go ahead, please.

JOEHi. Thanks for taking my call. I kind of wanted to tie this into -- for your panelists to the Ebola outbreak that's going on in Africa. I've had several friends say that they don't think it's fair that the American volunteers or doctors were given this trial drug first before any African people that have been infected were allowed to use it. And I know there's limited supplies in that issue. And I just wanted to get panelists thoughts on that, especially like as far as compassionate use and, you know, the ability to provide informed consent.

NNAMDIWell, ZMapp is the treatment we're talking about. Arthur Caplan, it was used on the American doctors who were flown back to the U.S. The WHO World Health Organization has said this is ethical. Can you walk us through the issues at play?

CAPLANA lot of tough questions here, good question from the caller. So remember Ebola is a frighteningly dangerous disease, also communicable, not easy to communicate. But that shifts some of the thinking. It's not the same as when you're trying to give compassionate use to a cancer patient. They're not going to give that to somebody else.

CAPLANAll that said, the two Americans who got access to this experimental drug which had been showed at least safe and a little bit efficacious in a few monkeys -- that's as far out as that drug was -- a small company made it in San Diego. Ten people working at the whole company. And I should add, the only reason they were working on that drug is they had a contract from the government to try and develop something along with the Canadian government in case of bio-terror. That's why that drug even -- ZMapp even existed at all. There's not really a market for it in the pharmaceutical industry because Ebola's too rare and it effects very poor people I'm not sure could even buy a drug or a vaccine.

CAPLANBut in any event, the Americans got the drug, and I tracked this down myself, because the evangelical organization that sent them over asked for it. It's as simple as that. It wasn't rationed to them or they didn't get preference. They just were the first to ask whether something existed. The FDA told them there was this little company. They approached the little company. The company gave them the drug. In fact, there was one other person who got access early, a Spanish priest. There was a drug deployed there in Geneva just in case a European health care worker got Ebola. And this guy did and he went back and he got it. He died by the way.

CAPLANSo a few crucial points. Do we need to have a system to better allocate experimental drugs for compassionate use? I think we do. The way that all that unfolded may not have been fair so we could probably come up with some criteria or a system that does a better job. Did the drug save the two people, the two Americans? Not clear. Again, we're not studying it. We're just basically giving it out compassionately. Some people do survive Ebola. Some people survive Ebola better if they get to Emory Hospital and get good fluid care and good intensive care and get their bleeding controlled and their clotting controlled.

CAPLANSo we still haven't really learned, is that a drug that really can help? But overall I don't think it was an issue of bias. I think it was an issue of the people who got the squeaky wheel going first got the drug.

NNAMDIMary Marovich, you're in AIDS research and not an expert on Ebola, but can you talk a little bit about how these vaccines work? What are they trying to do with these treatments? And how does a virus like Ebola compare to HIV or, for that matter, rabies?

MAROVICHOkay. The -- excuse me -- the drug that everyone is referring to for Ebola that these folks received, my understanding is that it was an antibody. And it's -- generally what vaccines will do is we give vaccines in the effort to induce the immune system to make an antibody response, which generally will neutralize the virus and prevent it from infecting cells and then mitigate disease.

MAROVICHFor Ebola, antibody-based protection has been found to be extremely helpful in the animals, especially the primates. And that is the goal for human studies as well. So there was good pre-clinical data for using that type of approach. But it was a so-called passive delivery. Normally with vaccines we would give some type of an agent that would actually induce the individual to make those antibodies within their own system. And that's what we're trying with HIV.

MAROVICHHIV is obviously a very different virus. It is communicable though it's not very efficient at transmission, believe it or not. And it takes very, very long for someone to get sick unlike Ebola.

NNAMDIMike Carducci, we got an email from Jonathan who says, "Are there risks of making a disease worse when conducting trials by experimental therapies changing or strengthening?"

CARDUCCIWe certainly hope not. I mean, but that is a question that patients do ask. Can you make my cancer worse? We worry more about the side effects of the drugs making the patient, the host themselves debilitated in some way for subsequent therapy if the drug is at the wrong dose or not the right drug. But most of the biology would say we're probably not making the cancer worse. It's more about the toxicities.

NNAMDIArthur, are there different rules or practical approaches when it comes to research abroad?

CAPLANGreat question. When the research is sponsored by U.S. money, say the National Institutes of Health, we follow U.S. standards wherever we go, so they govern. But when it's a drug company sponsor or some other sponsor, there may even be an Indian government sponsor or a Singapore government, then local standards apply. The short answer, Kojo, is that the world has kind of bought into minimal standards of what they expect in terms of informed consent, in terms of review by committees. But not every country is set up to really carefully monitor what's taking place. Some places are just poor and they don't have a lot of expertise.

CAPLANSo there is a little bit of research shopping that goes on out there where a company may say, let's try the drug here as opposed to over there. We think we can get it through faster and we think we'll have less hassle if we do it there than if we did it say in a European or North American country.

CARDUCCII'll say, Kojo, one thing about the international studies is a lot of the newer agents in cancer therapy are getting done in the developing world because a lot of those patients don't have access to the drugs. And so the only way for them to get access to drugs is to participate in the trial. So we feel like they're accrual rates are higher. So if it's 3 percent of the states and if you go to Eastern Europe, South America, some of those countries have much higher accrual rates. And the FDA has sort of said, as long as a lot of the patients are U.S. we can sort of make it attributable to our population. But the world really does help us get the clinical trials done now.

NNAMDIHere now is Marie in Arlington, Va. Marie, you're on the air. Go ahead, please.

MARIEYeah, I'm a medical doctor in Arlington, Va. And I went to medical school locally and took an ethics class that took me up near NIH and the (word?) medical school. And at that point a question came up, you want the patients to commit to your trials and to volunteer but I'm wondering what is your current commitment to the patient? When I was in school, I got the impression that you would hold onto the patients as long as they were useful to the trial. But when they were no longer useful you would cut them loose even if it meant they had no other options. Could you please comment on that?

NNAMDIIt sounds like it might be in violation of one of your seven basic principles Mary.

MAROVICHYes.

MARIEI would think so but this is research so they don't have to stay in commitment.

NNAMDIWell, the NIH has seven basic principles.

MAROVICHYes. Thank you, Marie, for that question. We do go to great lengths to define four examples of length of any given study. It's required, that that's indicated in the protocol which is the roadmap for every study that is conducted. There are a series of standards and regulations that we use that we need to follow to conduct these studies. And volunteers are informed in advance prior to committing to enrolling in the study, the length of time the study would be conducted, whether the vaccine or the drug would be provided after the study's completed or for example if they're in the placebo arm, could they roll over and receive that? So those items are discussed very clearly with the volunteer and are regulated.

NNAMDIMike?

CARDUCCIMy sense is, you know, I have patients that I share with people that are -- individuals that are treated at the National Cancer Institute. And those patients certainly have both of us. So I think patients on research get better care, the better follow-up and have a greater team of doctors. It may be in different situations that the patient does move from one doctor to another based on sort of where they are in that clinical trial. But it probably sounds like you, Mary, and myself, you know, we're there for the long haul for the patients whether they're on the trial or not.

CAPLANKojo, one other point about this, when the studies are done overseas we do try, when the emphasis are around, to get the sponsor of the study to commit to make the drug available once the study is done at an affordable price. So that becomes a challenge. In some very, very poor countries you may find something useful for diabetes, cancer or whatever but the local folks who are in the study couldn't afford it once the study ends. So we watch. And that is an issue of justice about are we exploiting a group if we don't stay there and at least try to make it available once the study concludes if the study's positive.

NNAMDIArthur Caplan is director of the medical ethics division of New York University's Langone Medical Center. Arthur Caplan, thank you for joining us.

CAPLANMy pleasure.

NNAMDIWe're going to be taking a short break. When we come back, we'll be continuing this conversation on the future of medical trials so stay with us. If you'd like to join the conversation, call 800-433-8850. The lines may be tied up. In that case you can send an email to kojo@wamu.org or send us a tweet @kojoshow. I'm Kojo Nnamdi.

NNAMDIWelcome back. We're talking about the future of medical trials with Mary Marovich, director of the AIDS vaccine research program at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Michael Carducci is a professor of prostate cancer research and a professor of oncology at the Johns Hopkins Kimmel Cancer Center.

NNAMDIAnd joining us now by phone from Boston is Jamie Heywood, co-founder of Patients Like Me, a company that runs a data sharing platform for patients. He started the organization when his brother was diagnosed with amyotrophic lateral sclerosis, ALS, also known as Lou Gehrig's Disease. Jamie Heywood, thank you for joining us.

MR. JAMES HEYWOODIt's great to be here.

NNAMDIJamie, we've been discussing some of the ethical and practical challenges facing researchers during medical trials but patients have a strong vested interest in these trials. You covered these issues as a researcher but also as an advocate who has dealt with a devastating illness in your own family. Tell us about the company PatientsLikeMe.

HEYWOODSure. So, you know, it was interesting, as I was listening to the conversation, which I think was extremely thoughtful and went over many issues, there was the perspective of what a drug development person needed or what a provider or a system needed or the health system itself needed. And I do think that patients look at this very differently. So when Steven was first diagnosed, you know, ALS is one of these diseases like, you know, some of the more terminal cancers where you get two to three years to live as the projection.

HEYWOODWe went through the process of trying to figure out what to do. And my brother participated in formal clinical trials for drug companies. We did a number of compassionate use exemptions that we filed with the FDA, as Arthur Caplan had described. And then actually we discovered our own treatments. This is at the ALS Development Institute that I also started, to work on that.

HEYWOODAnd as I went through that process, what really struck me was that at some level in medicine we're almost asking the wrong question because trials are designed to solve a particular problem, which is does this individual intervention for this group of people make a difference? But the problem a patient really faces for me as an individual against, you know, all of my own individual background and history and individual pathology and health behaviors, what's the right course of action for myself, for me?

HEYWOODAnd in order to build a system that does that you really need a surveillance system. It's not something where you design a single experiment but where you really measure everyone in the real world context in really rigorous ways. And PatientsLikeMe was sort of built to do that was to allow patients to share and connect using, you know, rigorous measures, initially self purport now increasingly connected to the medical system to allow us to sort of begin to take apart what works and what doesn't work. So that as an individual you can find out how things work in the real world.

HEYWOODAnd we know that one of the real challenges of trials is that there are many sort of initially positive signals that come out of that context that tend to not bear up when used in the real world. And I think that it's sort of a complimentary form of evidence here. How do you give patients a chance to contribute all the time, not just in one experimental context?

NNAMDIMike, for at least 20 years we've been hearing a lot of promises about the future of cancer care. We've been told that gene sequencing might allow for new kinds of cancer treatment and that someday a new class of drugs might be able to better target tumors. But the reality is a little more complicated, isn't it? Why has there not been a magic bullet?

CARDUCCIThe foe is cancer. So the only good cancer cell is a dead cancer cell. And I think that's what we're all targeting with our therapies. And yet sort of, you put it into a host and you take cancers that come by very different names. I think it becomes a much greater challenge. So I think, you know, there's two approaches that we really are looking for. I think the American Society of Clinical Oncology or ASCO is taking the lead in a rapid learning process I'll call cancer link.

CARDUCCIThe idea really is that you take all the practices that are practicing oncology, follow what patients do, follow their outcomes and maybe we can have a real world approach to cancer so that we can give that information back to patients. I think that's going to be one of the major future changes for our field.

CARDUCCIAnd the rest is now that we have patients who are really -- the ethical issue is we're asking them to get more of their tissue. So they're well and biopsying parts of their body that have never been -- had access to get tissue so that we can do molecular characterization, look at their genes and what are the changes so that we can pick the right drug for them. The idea is we need more drugs and the genes are so diverse that we really have only got a handful of them now. But I think that's going to grow.

NNAMDIJamie, at an individual cellular level, a tumor in one person's pancreas might behave very differently than another person's tumor. Some people have questioned whether medical trial scan be adequately representative or can generate enough information that can be applied accurately to other people. That would seem to me to be something that you're particularly concerned about.

HEYWOODYeah, an example I sort of like to think about in this context is if you went to Toyota and you asked them, how well do the water pumps work in the vehicles that you made in 2004, they would basically be able to give you a precise answer for this $25 part for millions and millions of vehicles ten years later to the degree that what are operational and non-operational. And yet in hospitals, you know, we will put a $3,000 knee into millions of people without actually figuring out whether any of those people can walk six months later, two months later, three years later, let alone whether they're alive years later.

HEYWOODAnd I look at that stark contrast where we take a trial based on a couple thousand people, extrapolate that to this enormous market, we sort of presume it's working as the trial designed and think that that system is insured. And I think, you know, what Michael just said about, you know, ASCO's approach to cancer is the right one. The trick that's really important here is there's two really things that are necessary for this to work.

HEYWOODThe first is, you have to really democratize access to this information. And I think patients, you know, and as a patient advocate, are sort of tired of the day when people say, well, after we analyze this you can have this information later or afterwards you can look at this in this context. There isn't a reason in this modern networked age when you can order a car on your iPhone or, you know, tell your friends what's going on on Facebook that we can't have democratization of the analysis of data. And there will be many people that are wrong but there'll be many, many more chances to be right in that context. That's one.

HEYWOODAnd the second thing is you've got to get the right information. And I think, you know, what you talked about, the component of a tissue, a cell that's wrong in someone's pancreas is right. And, you know, you look at the host immune system, you look at the margin around the tissue. These are all the things that Michael knows well. These are questions that we need to have a competition to get better and better information into the system.

HEYWOODAnd one of the problems with medicine is it sort of tends to lock down and run these very long experiments on sort of older approaches and measurement. The current one will be, you know, term in genomics. But we need to have a system that leans about the most advanced diagnostics in the real world, in real time, and supports that. And it's just stunning to me how little, as a medical system, we spend on this from an information standpoint and how much little time we spend on this.

HEYWOODAnd I think that's a lot of what drives patients to come to our systems, at least from the diseases we cover in PatientsLikeMe. Like, you know, I get a lot of sort of depression or multiple sclerosis. These are areas where you can really get the kind of data that's not available anywhere else.

NNAMDIMary, we've been trying to find a vaccine for HIV for, what, more than two decades now, right?

MAROVICHYes. I wanted to just draw on a comment that Jamie brought up as well, as far as research. We always like to say that research has to be generalizable to some extent. So particularly in the area of vaccines, we really need these vaccines to work on the majority of the population or at least 50 percent, say, of people that are tested to make an impact on the epidemic. I will say that about five years ago, there was an efficacy signal. It was the first time for an HIV vaccine that had been demonstrated to prevent infection, and that was the RV144 Thai trial.

MAROVICHYou may remember, about 16,000 people were studied in Thailand. And there were 31 percent reduction in infections in those people given the vaccine. It was a collaborative study done by the Royal Thai Army, the U.S. Army and the National Institutes of Health. And since then, we've now known that it is likely that we could prevent infection using vaccine. And there are plenty of follow-on studies planned to address that.

NNAMDIAre there many different kinds of AIDS?

MAROVICHYou mean are there many types of viruses that cause AIDS?

NNAMDIYes.

MAROVICHYes. HIV is -- I believe it is the most diverse virus. It rapidly mutates. And that's how it evades the immune system. What we call these many different flavors of the virus -- they are different clades or subtypes. And they tend to be geographically restricted. The most common is subtype C that occurs in sub-Saharan Africa and other parts of the world.

NNAMDIOn to David in Hyattsville, Md. David, you're on the air. Go ahead, please.

DAVIDYes, I'm David. I'm at NIH in a protocol. They don't use experimental drugs, but every year of the eleven years that I've had this rare ailment of parathyroid cancer -- not thyroid, but parathyroid cancer -- they've learned better how to treat me. I've had about five operations removing inflamed tumors that put out too much calcium. And Dr. Electra Kebebu (sp?) , an outstanding surgeon from Ethiopia, who's been at NIH for three years, has operated on me several times. NIH is a phenomenally able place.

NNAMDIOh, David, thank you very much for, well, not just your call, but your testimony, if you will, about what you've been experiencing at NIH. We've got to take a short break. When we come back, we'll continue this conversation on the future of medical trials. You can still call us at 800-433-8850. Or send email to kojo@wamu.org. You can go to our website, kojoshow.org and ask a question or make a comment there. I'm Kojo Nnamdi.

NNAMDIWelcome back. We're talking with Mary Marovich, director of the AIDS Vaccine Research Program and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Michael Carducci, he's a professor of prostate cancer research and a professor of oncology at the Johns Hopkins Kimmel Cancer Center. And Jamie Heywood, co-founder of PatientsLikeMe, a company that runs a data-sharing platform for patients. He started the organization when his brother was diagnosed with ALS, also known as Lou Gehrig's Disease.

NNAMDIJamie, earlier this year you wrote an interesting piece about ALS research in the BMJ, formerly known as the British Medical Journal. You wrote about an off-label treatment for people suffering from Lou Gehrig's Disease, which was quickly adopted by people suffering from the disease, without consultation and indeed despite the traditional research community. Can you please explain?

HEYWOODYeah, actually, it's a very interesting case. So ALS, you know, obviously being a very desperate disease, a lot of individuals try things that are really inventive. And in this case, what had happened is there was a drug trial by a company called Neuraltus that had been running a clinical study on a compound. And the patients -- some of the patients in the trial had felt the drug was quite effective. And there was some publications later that said that it was. And they were so desperate for the drug that they read the original patents and found the active ingredient and were drinking it. In this case the active ingredient was sodium chloride, so it's a chloride salt.

HEYWOODAnd they were -- they were drinking this, essentially, you know, an industrial chemical, to treat their disease. And what often happens in this case is that people go on messaging boards and they report on the Internet that they're feeling better. But what we do PatientsLikeMe is very different. We actually measure functionally how each patient is doing. In this case, we use a scoring system that measures the functional state of the patients.

HEYWOODAnd we showed in this paper that the patients that were, you know, drinking the sodium chloride instead of, you know, using an I.V. the way the drug company were recommending with some other stabilizing ingredients, were actually getting significantly worse. And that stopped hundreds and hundreds of people from using this and making themselves worse. Now the other thing about the paper that was interesting is that the same technique we used, which was to compare the patients against a predicted outcome -- in other words, our computers predict how everyone will do and we compare the people against the prediction -- also was able to call the results of two clinical trials that were going on.

HEYWOODOne that we said wouldn't work in the end and one that we said looked like it would work in the end. And we did that by independently monitoring the patients in the trial. And a lot of the paper is about, how do we handle the ethics of this? Because we're coming into a networked age, where essentially everything that can be known will be known. And with technologies like the ones at PatientsLikeMe that has monitoring and modeling, you can begin to make medicine real time. And, you know, given that clinical trials require blinding -- they require this sort of safe assumption that people don't know.

HEYWOODAnd that may not be possible in our modern networked age. We asked about how we approach that. And that was a lot of -- the dialog we're trying to start with the research community. And I think that's the real challenged now, is that where does medicine go in the Facebook age?

NNAMDIAllow me, Mike Carducci and Mary Marovich, to reiterate what Jamie just said, and that is the traditional model for medical trials is to keep patients separated from one another or blinded in order to make sure the results are not tainted by bias. But that's getting really hard to maintain in this era of social media and virtual communities of people suffering from diseases like ALS and M.S. Many advocates and researchers also seem to think it's important for patients to be able to talk with each other. Is it possible to reconcile these ideas? First you, Mary.

MAROVICHYes. Actually we think it's really important that volunteers network. And this has been a very effective means to encourage people to join studies and find support groups. So, and I completely agree, in this day and age of social networking, that it would be unlikely that people wouldn't connect. So we think it's actually very important for the research process.

NNAMDIMichal Carducci.

CARDUCCIYeah, I mean, doctors still have waiting rooms. So our patients are out there chatting with each other. So Tuesday at John Hopkins is prostate cancer. Everybody out in the waiting room is -- they're talking to each other about what they had. Did you get it? What did you -- how did it help you? So I think it's important because it only brings up questions that they bring back to me when we're having our one-to-one interval. And I think when we're designing clinical trials, we are looking for those trials that we don't really have to have a blind. If the drugs are so different and they're going to have so different side effects, why do we not tell the patients what we expect?

CARDUCCISo I think that has gotten better. But sometimes the fastest way, the safest way is to really have the blinded study where there's placebo or sugar pill in it, so that we can get the answer faster. And I think patients appreciate that when they're participating in it, particularly even in their vulnerable state.

NNAMDIOn to the telephones. Here's Rita in Vienna, Va. Rita, you're on the air. Go ahead, please.

RITAHi, I'm glad to call in. I started doing clinical trials years ago because I had pretty bad asthma and I've benefited enormously from them. Since then, I've -- like, I did a clinical trial for Advair. And now that that's come out, my life is a lot better. I've done clinical trials -- I did the HIV vaccine back when a friend of mine had died of AIDS. When they were doing anthrax vaccine at Walter Reed, I signed up because I worked a few blocks from the White House. And this was right after, you know, 9/11 and the anthrax scare.

RITASo I thought, well, you know, if I'm getting the real vaccine, it wouldn't hurt me to have. You never know what's going to happen out there. Anyway, I'm in the Human Genome Project and a bunch of other things over the years. And I really...

NNAMDIIn your apparently vast experience at participating in medical trials, how have doctors with whom you've consulted explained both the possible benefits and especially the possible risks?

RITAThey are really good at that. I've been able to compare, you know, Johns Hopkins and Walter Reed and NIH and a couple places. They really have a very good protocol. They answer all questions. They make clear at any point, you can drop out. You don't need to feel guilty.

NNAMDIOkay.

RITAI've been -- I've felt that I could really trust these folks, as somebody mentioned earlier.

NNAMDIRita, thank you very much for your call. Rita is talking about the upside. Victoria in Washington D.C., I think, wants to talk about the possible downside. Victoria, you're on the air. Go ahead, please.

VICTORIAHi, yeah. Great show. I wanted the panel to talk a little bit about the risk of generating mistrust when a drug or a vaccine trial doesn't go well, particularly in a low-information population. And I'm -- I'm not a doctor. But I'm a novelist and wrote about this in the Native American population in the 19th century, when the smallpox vaccination wasn't being distributed to Native Americans. And part of the reason was because it wasn't reliable and there was a risk of generating, you know, wrath and disease and making everything worse.

VICTORIASo in that novel, "Devil's Paintbox," my second to last novel, I did a lot of research with this. And it was, a big question with measles, with a lot of the early vaccines. So I wonder if the panel would talk about that a little bit.

NNAMDIMichael Carducci.

CARDUCCIYeah. First, I want to thank Rita. She's a true hero, as of anyone who sort of has that openness to participate. So I think trust is a key element for what we're doing and making sure that patients are aware of how the trial goes on, things that we learn that sort of impacts why they want to continue to participate is a key element. And I think, you know, as Jamie said, you know, the more that we know and communicate as research teams with our patients, we can have a sense of signals that are going awry for different patient populations.

CARDUCCIYou know, it, you know -- all these studies have data safety monitoring boards who are looking at the data behind us and say, okay, it's still safe, you can keep going, or there's a trend. And it's important to sort of make sure that those are ongoing so that we aren't doing harm and we maintain that trust.

NNAMDIJamie.

HEYWOODYeah, I was going to say, we've studied this actually. Because I mean one of the other things that PatientsLikeMe is trying to do, besides provide new evidence, is to support the existing trial process. And we did a large-scale study this spring on trial experience. And, you know, on average, you know, only about 55 percent of the people that participated in a trial would recommend doing it to someone else. And that's -- that's called the promoter score. That's a horrendously bad number for a customer service experience. And in fact, you know, 20 percent kind of ranges who really just thought it was terrible.

HEYWOODSo I think that, you know, while, I know Hopkins and I know that some of the studies that are done, you know, in many contexts are very good, there are still huge gaps in the quality. You know, some of the other data that I've seen shows that, you know, we only really thank people 10 percent of the time, send them the results of whether the study had any impact in that, you know, that framework. And again, you know, this is stuff that PatientsLikeMe is very committed to. We do things -- we send everyone the research papers that come out of it. We send them summaries of the studies as soon as they're done, in real time.

HEYWOODYou know, and a lay summary, you know, written for the patients, as well as a technical one. So I think that there's a -- the big perspective here is that you have to really involve the patients in the design, as sort of naïve individuals that are trying to figure out what's the value to them. And I don't think we do that enough. I think that, you know, we still treat patients as subjects and not as partners. And that has to change if we're going to build a learning health system.

NNAMDIMike, American medical history has its share of tales of unethical scientific research, particularly research conducted on African-Americans. Two examples, the Tuskegee syphilis experiments, where African-American men were denied treatment for syphilis, and the case of Henrietta Lacks, the African-American woman who died of cervical cancer and had her cancer cells taken without her consent. How do those bad examples weigh on the work that's being done now?

CARDUCCIYeah. I think you have to address some of that, particularly with various patient populations, sort of where, you know, certainly Johns Hopkins is located in East Baltimore. We have a lot of patients who come in with some mistrust. And talking about it as to why we participate and making the culture sort of feel like there are people that they can talk to that sort of have either participated in clinical trials, somebody who can navigate and follow with them so that they feel like they can have their questions answered. And so that there's not this sense of mistrust. So if we get past that barrier, I think the experience has been generally favorable.

CARDUCCIBut those are the things that we start with, knowing that there could be issues. We're all now going through cultural sensitivity and training so that we all, you know, how to speak a little bit better so that we can communicate more effectively.

NNAMDIAnd we're running out of time very quickly. But Mazar in Vienna, Va., raises an issue that we didn't get an opportunity to talk about so far. So Mazar, it's your turn. You only have about 30 seconds.

MAZARAll I wanted to say is that, Anandi (sic), is that there's a doctor in India that supplies drugs to African nations for 50 cents a day for AIDS, and American companies are charging $30,000 a month. Pharmaceutical are one of the biggest crooks in the world. Sorry.

NNAMDIProfits over care. Does that also play into medical trials? Of course, both of you work for institutions that are either government or universities, but a lot of this is being done by private pharmaceutical companies for profit. Does that factor into this, Mary Marovich, in 15 seconds or less?

MAROVICHYes. I think that there's probably a reason why not very many large companies are involved in developing an HIV vaccine, because it's not very profitable for vaccines as opposed to drugs.

NNAMDIMary Marovich is director of the AIDS Vaccine Research Program and the National Institute of Allergy and Infectious Diseases. Michael Carducci is a professor of prostate cancer research and a professor of oncology at the Johns Hopkins Kimmel Cancer Center. And Jamie Heywood is co-founder of PatientsLikeMe, a company that runs a data sharing platform for patients. Thank you all for joining us. And thank you all for listening. I'm Kojo Nnamdi.

NNAMDIComing up tomorrow on "The Kojo Nnamdi Show," new rules for new technology. Personal drones can capture images from just about anywhere. Tech Tuesday explores how national parks and others are responding to privacy concerns. Then at 1:00, the case for free money. Why some Libertarians and others advocate the radical idea of giving everyone a basic income. "The Kojo Nnamdi Show," noon till 2:00 tomorrow on WAMU 88.5 and streaming at kojoshow.org.