Schuchat Vaccine Transcript

SCHUCHAT: From that weekend on was an evolution or a journey of thinking about how to try to test a future Ebola vaccine in the middle of an epidemic in a place that had never--that had not got a vaccine field site going. The next several months were--we can go into however much detail as you want, but developing, recruiting a couple people to work on this fulltime, to develop it out. Then many changes in our design and plans.

Q: What are some of the most important of those changes of those decisions?

SCHUCHAT: We initially proposed a stepped wedge approach. You may, you probably heard. There was a lot of discussion about, can you test--a randomized controlled trial is a pretty hard thing to pull off. Double-blind, large numbers, everybody involved needs to--you have to follow incredible protocol, details, of course. But also the idea of placebo and blinding is pretty complicated when you're--even just an investigational vaccine is pretty complicated. We thought, well maybe we could do a stepped wedge design which would be a way that everybody's eventually going to get it, but they don't all get it on the same day. You use the observation time before you get it of what's going on, but it takes a huge population and you actually have to get everything ready to go in terms of enrolling the whole population and tracking disease in them before you start giving vaccine, or there's problems.

We started off with that plan and we started developing sample size calculations doing the paper version of the protocol. Then October 23rd, 2014, there was a meeting at WHO [World Health Organization in Geneva] about vaccine trials. I went for CDC and there were folks there from NIH and there were folks there from a number of academic institutions. Then there were people from the [affected] countries, as well as a number of donors. We were talking about what could be done. There were manufacturers there about their candidate vaccines. Where are we? Because frankly, we were talking about stuff but [products] hadn't really gone into people very much at all at that point. That usually takes--it takes multiple years [to go] from animal [trials] to people for the small studies in people, and we were talking about doing a big field trial.

October 23rd was the first time that we offered. [CDC] had folks in West Africa already for the emergency response, but at that [Geneva] meeting we started to talk about this idea and if Sierra Leone was interested, or others were interested, we would be interested in working with somebody on this. Then the next week, or the last week in October or first week in November, we sent three people from CDC Atlanta to Sierra Leone to start meeting with counterparts and start talking about possible studies. Initially the possible study was this stepped wedge design. The folks--you'll probably talk to different people. People who went to the field in November and December--I'd made my first trip early December and by then we had a lead from the Sierra Leone College of Medicine and Allied Health Sciences, our principal investigator. We had a lead from the Ministry. They had been doing a lot of outreach to try to understand what was important to people. If we were going to do a study, what needed to be considered? They were looking for possible sites, trying to figure out where would we do it, trying to match what was going on with the epidemiology with the logistic needs that we have.

December, early December, it was still quite hypothetical, but it was still quite urgent. I think the week I was there was actually, looking back, the peak week of disease in terms of the number of cases per week and so forth. An overarching principle for us was not to distract from the response. CDC's staffing really had to go for emergency response. Staffing for our trial team couldn't take people who were going to be working on the response. We needed a lot of different kinds of people, but we had to make sure. It was kind of exciting to work on a vaccine trial, but [we couldn't reassign people], no, no. You've got to fill the spots in the response [first] and then we can get people, although we needed people with certain skills.

In any case. In December, we were having leads here in Atlanta for the design, or for the trial which at that time was a planning [activity], and leads in the field who were figuring out [logistics like] who were the counterparts, where might we do it, what's all involved in this? Just to jump ahead. I think we've had over three hundred CDC staff involved in this trial, because people were rotating through both in the field and in Atlanta. I may be the only person who's been involved since September [2014]. We changed the design, we had to select a vaccine, we had to identify who would be eligible, we had to develop a cold chain. We had to do this in a way that would be acceptable and that would be, have both short-term and long-term acceptability. Our leads in the field from Sierra Leone, as they went out talking about this project, learned that when you talk about an Ebola vaccine people think you're talking about a vaccine that gives you Ebola. We learned that CDC didn't necessarily have a good reputation in Sierra Leone before the Ebola outbreak and that there were concerns that that field station CDC had in the eighties might have been where Ebola came from. It was really important to us that there be country ownership and a country voice and face for the trial, and that CDC work on this in a collaboration. My first trip in December, our lead from the university, we had a really good discussion and he said that the most important things from his perspective were transparency and mutual respect. I said, perfect, because those are really important to me, too.

We had multiple objectives. Our overarching objective was to accelerate use of a vaccine while simultaneously evaluating its safety and efficacy. We didn't want to [roll out] vaccine that was unsafe. We wanted to find out if it worked quickly, because it if it worked quickly it would be important to scale it up. We didn't want to just answer a study question and then stop. In Liberia, their goal was really good science of randomized, controlled, placebo-controlled safety and immunogenicity of two different vaccines against placebo. They didn't really have the phased introduction idea. In our study, we didn't stop when we realized we're not going to be able to measure efficacy because part of [our purpose] was accelerating availability and we were targeting high-risk healthcare workers and frontline workers. We ended up pretty much vaccinating anybody in the five districts we targeted who met the criteria, who could be enrolled. Essentially, [health workers in] those districts pretty much were eligible. We got over eight thousand people vaccinated with what I think is probably a very effective vaccine. The vaccine's [still] not licensed. It's 2016. As there are new cases and we do outbreak response, [vaccine] still [has to be used] under a research protocol [in order for] people to get vaccinated in the rings. We had from the beginning that goal of quickly figuring out if [the vaccine] works or if it's harmful while [if it's not harmful] making it available as quickly as possible.

The second overarching goal was to strengthen the capacity of Sierra Leone. We wanted to do this trial in a way that not only was safe, ethical, scientifically rigorous, but that had a long-term benefit for the country even if the vaccine didn't work, or even if the vaccine was harmful.

I think it's really hard in 2016 to fully remember or understand that this was a pretty scary enterprise. In December of 2014, a little study in Switzerland found unexpected side effects of one of the two vaccines. We had to decide which of these two vaccines are we going to use. We said, one of them has a better [chance]--we think theoretically it might be more effective. We didn't know. Just based on the nonhuman primate [results] and the immunogenicity, you couldn't really tell. We think the one that might be more effective is the one that might have unexpected side effects. We're talking about a community that has--is dealing with an epidemic, has very limited healthcare, all those things. We had to go through all this expert review to figure out which of the two vaccines to propose. Then we needed the country to decide, what do they think? They agreed with us and we went with the one vaccine [vesicular stomatitis virus, VSV]. The first doses [were given] when Jane [Seward] was there--that was intense. In January of 2015, we got the first dose response results from the human immunogenicity studies done elsewhere and instead of this dose [that we had expected], we needed a higher dose. Instead of a dose we were expecting, we needed an even higher dose and that meant that the bottled formulations had to be diluted in the field in a different way. It's a live replicating vaccine. Just the quality control of dilution. The vaccine had to be kept at minus eighty degrees. We had to get that to happen in a place with a very--where the power--just to have power and a backup generator and everything was really complicated. We had to transport [vaccine doses] to all these different sites that we were going to be using. The logistics [reality] and the rigor [needed] were always in tension, just to make sure that we could do this carefully and well.

Then we had an extraordinary communication plan, because it was really important to us that people voluntarily participate, that they understand we didn't know if this [product] worked or not, that they didn't put themselves at extra risk because they thought they were protected with the vaccine. One of the reasons we didn't use a placebo--we changed our design, but we didn't ever use a placebo--was our principal investigator felt like people won't believe if you just give them a shot, they're not going to believe it's not real. Whatever you tell them, they're not going to believe it. We counseled everybody on continuing to use protective equipment and so forth. Anyway. We had to pick the vaccine, we had to change the formulation plans and really try to do everything as safely as possible.

Our communication program, the folks in Sierra Leone and our team from CDC really worked hard on stakeholder engagement, visiting the chiefs in the districts, visiting the health leaders in the districts, meeting with all the healthcare workers before they could enroll to really understand how we should design this in a way that was going to be acceptable. Then had to do the training, very short notice because it was a race against time to get the trial going. Both because we wanted it to be useful and because the cases were starting to go away, which was good.

My role was--there was many funny things about this trial, but my role was cheerleader because almost every day additional problems emerged. The two leads in Atlanta would meet with me every day, tell me what they were hearing from the field, what was the latest catastrophe, and I would reflect what we ought to do or help give them feedback. Then I had these pom-poms and I would bring out my pom-poms to say, we're going to get through this. It looks like there's no way out of this, but we've gotten through worse before and we'll keep getting through it. I think nobody believed it was going to happen until it started and then when it started, of course, there were so many other additional challenges. Whenever we thought it was about to slow down, something else happened. It's been a big journey. Very, very meaningful to be part of […]