Transcript for CDC press briefing: STRIVE trial begins in Sierra Leone

**This transcript is not edited and may contain errors**

OPERATOR: if you'd like to ask a question during the call, press star 1 and record your name clearly, star 1 to ask a question, and please standby.

OPERATOR: please standby for today's call, it will start momentarily, thank you.

OPERATOR: Welcome, and thank you for standing by. At this time, all participants are in listen only mode. During the question and answer session of the call, press star 1 to ask a question. Today's conference is being recorded, and at this time I'll turn the call over to Kathy Harben. You may begin.

KATHY HARBEN: Thank you, Shirley, and thank you, all, for joining us today to hear about the launch of the Sierra Leone trial to introduce a vaccine against Ebola. This is the STRIVE trial. You'll first hear remarks from Dr. Anne Schuchat, She's the director of the CDC's National Center for Immunization and Respiratory Diseases. We'll then open up the line for questions and answers. I'll turn the call over now to Dr. Schuchat.

ANNE SCHUCHAT: I'm delighted to be able to have this call today with you and to announce the beginning of STRIVE, the Sierra Leone trial to introduce a vaccine against Ebola. The CDC in partnership with the Sierra Leone College of Medicine and Allied Health Sciences or COMAHS and the Sierra Leone Ministry of Health and Sanitation has started enrolling and vaccinating volunteers for the Sierra Leone trial to introduce a vaccine for Ebola. As you know, the epidemic of Ebola has been devastating. Sierra Leone, Guinea and Liberia have lost thousands of people including hundreds of health care workers. Vaccines against Ebola are a potential tool to protect people, especially those at highest risk of encountering the virus because of the work they do. Our study is part of a concerted effort to accelerate the development of vaccines against Ebola aimed at helping to end this devastating outbreak and protect people against future ones. Together with colleagues in Sierra Leone, we worked hard to design and prepare a study that aims to measure efficacy and safety of an Ebola vaccine. I'm hopeful from what we learn from this clinical trial will help us get us closer to finding a safe and effective tool that we can use to keep people safe from Ebola. STRIVE is going to look at two things. Isn't how well one of the Ebola vaccines in development called the RBSV vaccine, helps protect people from getting Ebola, and if that vaccine is as safe as early small studies have suggested. Similar studies occur in other countries affected by Ebola including Liberia and Guinea. In Sierra Leone, we plan to enroll about 6,000 health and front line workers who are at high risk of Ebola disease. This includes health facility workers, like doctors, nurses, and cleaning, lab, pharmacy, security, and administrative staff. Also, burial workers, ambulance and surveillance teams and workers responsible for swabbing people who have died. These worker groups are eligible to participate in STRIVE. With participants enrolled in the study, they will be assigned randomly to one of two time frames for vaccinations. Either immediately or about six months later. All study participants will receive the vaccine and will be followed closely for six months. The studies are being conducted in five districts of Sierra Leone, including in the capital of Freetown. Enrollment in vaccinations have already begun in the western districts, rural, and urban, and the study will roll out in the other three districts over the next weeks. CDC has a team of people in Sierra Leone that's been working with COMAHS, the ministry and the district for several months to help prepare for STRIVE. About 350 local people have been hired and trained to conduct the study. We're working in partnership with BARDA, the Biomedical Advanced Research and Development Authority. We've received early key support from the CDC foundation and their donors to jump start site facility improvements. To prepare, we met with the paramount chiefs, religious leaders, work counselors, and elders in the study areas. We'll continue to keep them informed about steady progress. We've also been working with health facility leaders in study areas to plan for enrollment and vaccinations including at public health facilities, hospitals, clinics, and Ebola treatment and holding units. Through STRIVE, CDC is strengthening the existing research capacity of institutions in Sierra Leone by providing training and research experience to hundreds of Sierra Leone staff, which we hope is helpful to the country in the future. Physical infrastructure has been updated including renovating existing structures and building new ones to be able to enroll and vaccinate participants, to handle data management and properly store the vaccine. New technology will also be available to maintain the cold chain, which keeps vaccines at required temperatures including during transport. Sierra Leone and the international community including the CDC are working hard to get to zero in the battle against Ebola. We hope that our study partnership as well as trials in ongoing in neighboring countries will help accelerate the availability of safe and effective vaccines against this terrible virus, and also leave this region stronger and more resilient against future infectious disease threats. I'm happy to turn things back over to the operator and take your questions now. Thank you.

OPERATOR: Thank you, at this time, we're ready to begin the question and answer section. If you want to ask a question, press star 1. You will be asked to record your name. Again, press star 1 to ask a question, and one moment, please, for the first question. Thank you, the first question comes from Liz Szabo with USA today. You may ask your question.

LIZ SZABO: Hi, I'm hoping you can talk about how you'll deal with the shortage of patients with so few people now being diagnosed with Ebola, just nine in Sierra Leone last week. Do you expect to get a definitive answer, and what is your plan if you don't?

ANNE SCHUCHAT: Thank you for that question. Of course we're glad that the epidemic is improving in Sierra Leone and surrounding countries and the case counts have come down quite a bit since the time that we've first began planning the trials. We have adjusted our studies design to maximize the chance of success and we plan to collect information on safety and immune response that contributes to licensure pathways, even if we're not able to estimate efficacy. We also have a data and safety monitoring board that's going to be looking at the information as it comes in, conducting interim analysis, and seeing how the early findings go. We know that we cannot be complacent about Ebola. We're pleased that there are fewer cases, but health care workers have developed Ebola in Sierra Leone fairly recently, and they continue to be at risk. We're going forward with the study, but adjusted design to maximize the chances of success, and we'll be able to define success in multiple ways. Next question.

OPERATOR: Thank you. Next question is from Mike Stobbe from the Associated Press. You may ask your question.

MIKE STOBBE: Hi, thank you for taking my question. Doctor, you mentioned the cold chain and some of the other challenges in doing this work. Do you mind saying what is the anticipated cost of doing this trial and who is paying for it, and, also, are the participants going to be offered money or anything else to take part in this, or how are you encouraging participation?

ANNE SCHUCHAT: The study is being funded primarily through the U.S. government, through CDC emergency appropriations. There are also contributions that are sizable from BARDA, as I mentioned, another part of HHS. The CDC foundation donations have been critical because they were available early to help jump start the renovations and some of the equipment that was needed to get the cold chains to be able to handle vaccine management. This is a key partnership. You asked about compensation and whether participants would be paid to be participating. The study I need to say has been reviewed by ethics review board, the institutional review boards at the CDC and also in Sierra Leone as well as with the food and drug administration, regulatory authority, and the Sierra Leone pharmacy board.  Participants in the trial will receive some money that pays essentially for their transportation and the time involved with being part of the study, and the amounts of those compensations were agreed to base on ethics review boards, so I think that that was basically the questions that you had. It is expensive to carry out a clinical trial of this magnitude, and it's challenging to do so, a country which is -- has little previous experience with doing such trials. We have not cut corners on the safety or the high scientific standards, and we are keen to do the trial in a safe and careful manner.

MIKE STOBBE: Could you say the dollar amounts, though? What's the dollar amount of the investment in the study, and what is the compensation dollar amount, U.S. accordingly.

ANNE SCHUCHAT: Mike, if I could get back to you with more information on that, I don't have the specific dollars of compensation with me. The congress appropriation for the trial was about $25 million.

OPERATOR: Thank you --

ANNE SCHUCHAT: Actually, hold on, I do have this, this just in. Participants will receive about $10 after enrolling in the study and after getting vaccinated, they'll be getting about $30 so that's the, you know, in local money, so those are the dollar amounts that we're essentially part of the protocol. Next question, operator.

OPERATOR: Thank you. Next question is from Donna Young with Script News. You may ask your question.

DONNA YOUNG: Actually, that was the same thing that I was going to ask was about the total funding. So, again, you said there was $25 million appropriated for this study, and do you expect to have to go back and ask for more, or what happens to the funding that's not used if you have anything left over? Thank you.

ANNE SCHUCHAT: Sure. Thank you so much for the question. What I can say is that we are working diligently with the implementation of the trial, and have multiple needs that are being met. We are incredibly appreciative for the support for this. The commitment for doing this study is that individuals will be followed for six months after vaccination, and that a key part of this is about offering the vaccine in a very safe and careful manner to the front line health workers of Sierra Leone, so even if there's few cases or it's not possible to measure the efficacy, we're committed to continue to follow the individual who received the vaccine for six months after they are received, so this will be ongoing for a good time to come, you know, in terms of the immediate vaccination, and then six months from now, vaccination needing to be followed for six months. We'll be evaluating how far the resources that we've got to stretch over time. Next question.

OPERATOR: Thank you, our next question comes from Helen Branswell with the Canadian Press, you may ask your question.

HELEN BRANSWELL: Thank you for taking my questions. I have a couple. Dr. Schuchat, what you just described, sort of the generation of both benefits for Sierra Leone and important safety data on the vaccine sound great, but they also sound more like a phase two than a phase three trial. Can you talk about whether or not any consideration was given to either not proceeding or turning this into a phase two at any point? Does it still meet the futility test? I take it you have to -- the data safety monitoring board or IRB has to sort of assess whether there's a likelihood of getting an actual efficacy answer, and at this point, I'm just wondering if that's likely to happen, and, also, if you could explain a bit about how you adjusted the trial to increase the chances of getting an answer, please.

ANNE SCHUCHAT: Sure. You know, this trial was designed as a phased introduction study that would have careful evaluation to maximize the opportunity to measure efficacy and safety. Part of the discussions in country about carrying out such a trial were that the front line health workers would have a chance to receive the vaccine under the study's circumstances over the course of the trial. Obviously, health workers and other front line workers have been through a lot in Sierra Leone, and it's a pretty frightening thing to provide that front line health care in the context of such dangerous virus, and so we did not really consider the idea of not carrying out the trial when case counts decreased. However, we did decide it was very important to adjust our design to maximize the chance that we would be able to answer key questions. Instead of conducting a classical step wedge design, which is what our initial intent was, we changed to an individually randomized trials, where individuals would get either a vaccination now or a vaccination six months from now. And that provided more flexibility with the numbers of people that could be enrolled and the pace with which we would be able to vaccinate people as well as evaluable time, a person time you could analyze. We essentially adjusted to have this randomized individual trial for yet a based introduction, where everyone eventually would be offered the vaccine. I think in comparison with phase two trials, this intended to be a bit larger in terms of the 6,000 workers we're anticipating. In terms of the futility, we did not include futility as part of the interim analysis. We do, of course, have important regular looks for safety and the trial could be stopped early if there were safety problems of great concern. The other reason the numbers -- the trial might be stopped early would be if interim analysis identify efficacy earlier than expected, and so even with relatively low rates of disease, our trial's actually designed around an efficacy of 50 percent if the vaccine is much more efficacious than that, which we have reason to believe it might be, than smaller numbers are needed to be able to confirm efficacy. The last point is that if we are able to vaccinate about 6,000 people and diseases is rare or has gotten to zero, it's possible that those people might be exposed in the future. The virus could be reintroduced into the human population or outbreaks could reemerge, and then it would be possible to do essentially post marketing case control study types of vaccine efficacy studies. The -- a disease like Ebola was never expected to have a large scale phase three study done of vaccine efficacy, and regulatory authorities before this epidemic were considering what they called the two animal rule where studies and animals together with immunology and safety data are contributory to the license pathway. If the efficacy estimate is not possible in this trial or in the other trials ongoing, it is still possible for there to be a licensure pathway for this and the other candidate vaccines. I think I covered most of your questions. Next question.

HELEN BRANSWELL: Yes, thank you.

OPERATOR: Thank you, and, again, if you want to ask a question, press star 1 at this time. Our next question comes from Kai Kupferschmidt with Science Magazine. You may ask your question.

KAI KUPFERSCHMIDT: Thank you for taking my question. I have two, if I may. Dr. Schuchat, I don't quite understand what you just answered to Helen about how exactly conducting the trial as an individual randomized trial as opposed to a classical step wedge trial. How exactly does that help you improve your chances of getting an answer on the efficacy? How does it make it easier or faster? I didn't quite understand that. And then the other point, is there any -- do you have any numbers on the power of the trial? How many people would you expect in the delayed vaccine group to have to develop Ebola in order to see -- to see the signal of efficacy if it is indeed 50 percent for instance?

ANNE SCHUCHAT: Right. The difference between a stepped wedge and an individually randomized trial with vaccination at zero or six months' time is there's a larger person time valuable in the individually randomized design. Essentially, you have six months at least of evaluation between those vaccinated now and later, and in a stepped wedge, the way we were thinking of it, it would have had a much -- a much lower number of person months at risk. The issue of number of subjects needed actually, the trial is designed around events, and for a 50 percent efficacious vaccine, we estimated needing about 67 events to be studied, but if the vaccine were 90 percent effective, one needs about 17 events. Obviously, there's a lot of assumptions that go into that, and much is changing. Another thing to mention, though, in terms of where we are with the epidemic. We are thrilled the disease counts are way down, but people are continuing to get the Ebola virus disease, and we know the outbreaks in the past have had long tails associated with them. They have not been snuffed out, but they have taken quite a while to really end. We know health care workers will be under continued risk during that period. Next question, operator.

OPERATOR: Thank you, press star 1 to ask a question. Next question is from Lisa Schnirring from CIDRAP News, ask your question.

LISA SCHNIRRING: Dr. Schuchat, thank you for taking questions today. I'm wondering if front line health care workers who are slated to get the vaccine are mainly Sierra Leone people or if there's foreign medical teams or nongovernmental organizations in the area who may be getting that. Thanks so much.

ANNE SCHUCHAT: Yes, you know, the eligibility criteria for the trial are that both Sierra Leone workers and international workers would be eligible if they're planning to be doing the kind of work they are doing and staying in Sierra Leone for the next six months, so we have already encountered individuals who were not planning to be remaining in country during that period, so that is an exclusion criteria. We think the evaluation of the subjects or the participants in Sierra Leone is important, and so those international or other workers in the country are certainly eligible for the trial if they're in one of those districts and they're carrying out the kind of work that I described if they are intending to stay there. Next question, please.

OPERATOR: Thank you. Our next question comes from Helen Branswell with Canadian Press. You may ask your question.

HELEN BRANSWELL: Hi, I apologize, you may have addressed this in the opening remark, some of which I missed, but are you -- you're doing some sort of sub studies, aren't you, on reactogenicity and immunogenicity. You're drawing bloods, pre and post, are you? Could you talk more about that?

ANNE SCHUCHAT: We've already initiated a sub study of safety and reactogenicity as part of the full scale trial, and that is looking more closely in active follow-up of people, of the first 400 subjects that are being enrolled. We intend to do an immunogenicity study as well as, and that is not yet up and running, but the sub study on safety is.   

HELEN BRANSWELL: Okay, and how big will the reactogenicity study be?

ANNE SCHUCHAT: We're still working out the agreements about that with authority -- the approval groups, and so it'll be at least several hundred.

HELEN BRANSWELL: Thank you.

ANNE SCHUCHAT: Next question, please.

OPERATOR: Thank you, again, if you want to ask a question, press star 1 at this time. Our next question comes from Kai Kupferschmidt with Science Magazine. You may ask your question.

KAI KUPFERSCHMIDT: Thanks. I just wanted to clarify two numbers. So when you talk about events, the 67 events, for instance, in the 50 percent efficacious vaccine, that would be people who develop Ebola? What else constitutes an event, and the 25 million earlier, is that the overall price tag for the whole trial or higher?

ANNE SCHUCHAT: The events are laboratory confirmed Ebola virus disease. And the dollars are not necessarily the price of the trial. The $25 million is what the emergency appropriation provided for the study. So the price tag, when everything is pulled together, maybe more than that. The -- or less than that, but that's what the appropriation was. As I mentioned, we've already really benefitted from the partnership from BARDA and the CDC foundation which had resources early and was able to help focus the renovations that were so critical to get sites ready to go in the cold chain upgraded.

KAI KUPFERSCHMIDT: Right. But the 25 million is a rough estimate of the price tag or can you give a better one?

ANNE SCHUCHAT: I don't have a better one, so that's why I gave you that one, sorry. You know, large scale trials can be quite expensive to carry out and are often more expensive than that, but that, you know, we are extremely grateful for those resources and we are managing them carefully. Next question.

OPERATOR: Thank you. Next question is from Alex Otto with Internal Medicine News. You may ask your question.

ALEX OTTO: Hi, I have questions about vaccine safety. Have you seen any safety issues with this vaccine and the people who got it so far, and, number two, how many people got the vaccine so far? Thank you.

ANNE SCHUCHAT: So the vaccine has been studied in phase one and now two studies, about 800 people have gotten the vaccine, and other trials so far, and to date, there have been, of course, local short term local reaction, pain and so forth, but the common side effects do include fatigue, headaches, fever, muscle ache. Those can be relatively common. There also have been reports of some mild pain and swelling of joints that is self-limited and improves. So we are looking for those, of course, in this trial, and we are at too early a stage to know what we're seeing in this particular trial. In terms of numbers, so far more than 200 people have enrolled, and more than 90 people have been vaccinated.

ANNE SCHUCHAT: Next question.

OPERATOR: At this time, I'm showing no further questions.

ANNE SCHUCHAT: Okay. Thank you. Let me just say before we end, then, that the Ebola epidemic has been devastating for West Africa, and I really hope is the beginning of a new positive chapter for Sierra Leone and the story of battling this virus. Thank you so much for calling in and for covering this important update.

OPERATOR: Thank you, and this does conclude today's conference. We thank you for your participation. At this time, you may disconnect your line.

**This transcript is not edited and may contain errors**

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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES