Simba Takuva, Azwi Takalani, Kagisho Baenyape (HVTN)
Moderator: Tian Johnson
Complied by: Anna Matendawafa – with inputs from Wilfred Gurupira
Webinar Recordings & Supplementary Materials:
Date: 29 October 2020
The HIV Vaccine Trials Network (HVTN) is the world’s largest publicly funded multi-disciplinary international collaboration facilitating vaccines’ development to prevent HIV/AIDS. The HVTN conducts all clinical trial phases, from evaluating experimental vaccines for safety and immunogenicity to testing vaccine efficacy. It is a founding member of the COVID-19 Prevention Network (CoVPN) formed to respond to the global pandemic.The COVID-19 Prevention Network (CoVPN) was formed by the National Institute of Allergy and Infectious Diseases(NIAID) at the US National Institutes of Health to respond to the global pandemic. Using the infectious disease expertise of their existing research networks and international partners, NIAID has directed the networks to address the pressing need for vaccines and monoclonal antibodies against SARS-CoV-2. This includes the: HIV Prevention Trial Network (HPTN), HIV Vaccine Trial Network ( HVTN),Infectious Disease Clinical Research Consortium ( IDCRC), AIDS Clinical Trial Group ( ACTG)
QUESTION AND ANSWERS
*This section contains a transcribed account of the Question and Answer Session
Please indicate when the effectiveness of drugs is tested, what is the difference in efficacy and effectiveness in the phases of trials?
I think I’ll take that. Hi Nita, so that’s an excellent question. So when you look at your clinical trials, generally you’re looking at efficacy. And then that leads us to the question, what is the difference between efficacy and effectiveness and when we test for effectiveness. So efficacy really can be defined as the performance of your drug or vaccine under ideal and control circumstances. So but in your clinical trial setting, where is with effectiveness, you’re referring to its performance under real-world conditions. Like for instance, you have demonstrated in those randomized controlled trial (RCTs), that the vaccine is efficacious. But now, you also may need to show if it works in real-world conditions. However, the distinction between those two types of trials is some container rather than dichotomy or to say the clear cut black and white differences. So it may be unlikely, or it may be impossible to perform a p efficacy study or a pure effectiveness study without some form of overlap. So as examples, for instance, in an efficacy study, you’re looking at your control settings, like your clinical research sites, that are well resourced, and in terms of the participants that are participating. This is a homogeneous population, that when you’re selecting your clients, treating inclusion and exclusion criteria, and your providers, these are well-trained providers with multiple layers of safety as we’ve seen, but whereas in an effectiveness study that’s more or less like a field trial. So now you’re saying, well, this is work in with real-world clinical practice. Now you’ve got a heterogeneous population where you’ve got everyone really would like to receive the vaccines. They do not have any exclusions or any concerns, receiving the vaccine, and you have unusual service providers in the healthcare system.And last but not least, you could think of this like in terms of the malaria vaccine, the RTSS vaccine. So clinical trials were concluded, and it was shown to be efficacious. But what is currently happening now in Kenya, Malawi and Ghana, they are extensive, full studies to sort of like inform broader implementation, and those are like effectiveness trials. I hope that answers your question.
Would you find people who have a vested interest in the data being generated by their trials in the ordinary course of work?
Azwi Takalani Um, okay, so I’ll take that point. Thanks. I didn’t get who asked the question. But I think the general rule is that it should not be someone with the best interest, right in the trial succeeding. So having said that, I think one of your points was, would they benefit in their career. And I think that becomes a hard distinction. If you think about it, if you’re all medical practitioners, you know, we would all benefit from the burden of disease of certain infectious diseases, you know, being treated as so in that sort of, like removed roundabout way, then you could eventually benefit, right. But it should be someone who can directly benefit from, from the outcome of the trial, it should be an independent review, I think that’s the one word that we should have added on the slide to say, as independent subject matter experts to review this data, check the detail for us. So while you may need a Data and Safety Monitoring Board (DSMB), these are significant phase trials, you need to be independent. But in the small phases, the trial’s where you are in the organisation, you’re thinking, we move from pre-clinical to clinical, you may have an internal SMB that may look at the data. And at that phase, I mean, you’re not it’s not making determinations about large, large populations, but essentially, a DSM board should not have independent subject matter experts.
Do you have any thoughts to share on how adverse events are communicated and their potential impact on trial participation, the patient and giving communities excited and interested in participating in the trial?
Simba Takuva Thanks, Tian. So Azwi I can go first, and if you’ve got adds, you can jump in. Yeah. So that’s a great question as well. So, when one thinks of it again, you think of it as a continuum, right from this time, from the time that you are drawing up the protocol, it needs to be clear that adverse events like for instance, your phase three or phase two, your phase one, safety is a priority. So, if you look at all protocols that we work in, beyond efficacy, one of the key primary objectives is to establish and also to test safety. And then with that protocol, within moves on to your informed consent document. So again with your informed consent form (ICF), this is a very important document safety adverse events, expected adverse events begin solicited or unsolicited, this needs to be laid out clearly in the ICF. So that participants can be able to, to have a good sense of the type of side effects or adverse events that are involved. And then when it comes to communication with the general public, so that’s outside the clinical trial setting, beyond your subjects, it is important with regards to improved transparency. And I think we’ve seen that in the past few weeks, where they’ve been maybe some adverse events that have resulted in trials being paused because there’s been transparency to sort of like, report this to the general public, but at the same time trying to balance the rights, the privacy confidentiality of the participants that are involved. But yeah, there’s room to always do better with regards to that.
Azwi Takalani I think you covered it well Simba. But maybe just to add to that, for the trial participant. That’s why I believe it is important that the ethics committee also reviews the informed consent and informed consent in the procedure. So if you think about it, we’re doing global multi center studies. And adverse events that may seem minor in one setting may have a cultural bearing in another setting or more important. And so when we do our informed consent process when we try to put as many adverse events, the but we also encourage the staff that will be taking the participants through the informed consent procedure to highlight those adverse events as far as possible. The ethics committee can again come back and say, well, we think that in this context, you need to communicate these adverse events more to the participants or the community, before you even starting with the enrollment of participants. So those are some of the communication mechanisms that we try to use or that are in place to ensure that adverse events are communicated well, to the trial participant. And then like Simba said, after that, it becomes an issue of the people who will then this is post-trial, the clinicians, are you explaining these things? Well to the participants, before, you know, post-licensure does the community aware. With time, it’s becoming more apparent that lack of adherence, even trial loss to follow up on trial is because participants in the community, we’re not aware of specific adverse events. And when they happen, they become shocked and be pulled back. So the chat is increasing to be more transparent and to have better and better communication strategies.
Could either of you briefly describe what discussion happens with researchers in terms of access? So are researchers having access discussions, when trials are designed conceptualized? Is that forefront of in your mind the access issue, the eventual access of the product?
Simba Takuva Okay, thanks. Thank you for that question. I’ll have a go first. So like, for instance, by the time you get to your late phase studies, your phase three studies, there are lots of investments that have come in and effort time conversations around access, usually are already fully established. Like you have to prepare for success, right? Should you succeed in coming up with a vaccine that helps and works, what happens after that, and also you have to prepare for failure, so thinking of a hypothetical situation where you’re preparing for success. And that means talking about access, how do you roll out the vaccine who gets the vaccine etc. So one of the things really to highlight is that the concerns that usually come out are mainly bent on the fact that you have your less-resourced nations or countries, that’s probably unable to fund some of the studies may be or even buy some of these vaccines. But thankfully, due to the current global initiatives, be it in HIV, be it in COVID-19. Some models are working well, like your public privates, products development partnerships, where you have well-resourced funders are well-resourced countries that throw in resources or putting resources into the kitty back so that they can be equitable access for all An example would be an organisation like for instance, the GAVI Alliance. And we simply I’m sure you’ve heard of this, WHO has been putting together a facility with different organisations, which is known as I think it’s called COVAX access to COVID-19. So it’s a framework whereby the WHO has developed that sort of like guides and gives guidelines for equitable and affordable access to safe and effective vaccines. So the whole aim of this framework is that at the end of 2021, should there be a vaccine? There should be enough resources to deliver, beyond 2 billion vaccine doses globally, regardless, regardless of how wealthy your nation is or how poor, your country is so vaccine allocation will also be driven by public health needs for priority groups, which might represent close to half of the population. So yeah, there is a structured compensation going on. And there’s a lot of effort behind the scenes that are going on that’s setting the stage for a large success
Ntando is speaking of varying cultural settings, how well is the field doing and innovating informed consent processes? Do Simba and Azwi think the opportunities for improvement will help how we currently do informed consent?
Simba Takuva That’s a great question as well. So Azwi I think I can go first and you can add on, and then I believe we have Kagisho as well, so feel free to jump in? You know, that’s a great question Ntando. And I think, as the times progressed, we also have to be innovative and also have to sort of like adapt and unwind to the different environments that we work in. So perhaps what immediately comes to my mind is the way informed the informed consent process has sort of like, adapted to the current status quo, which is like a pandemic like COVID lockdowns, where persons cannot then travel reliably, etc. So, there have been some innovations, like for instance, being able to go through informed consent, not in a face to face environment, but perhaps like remotely, whereby you can be in touch with a participant and then take them through the informed consent process. And then they can, for instance, maybe electronically, electronically sign that. So that’s the kind of information that I can think of that’s sort of like aligned to the current status quo. But then, of course, they are cultural caveats that you do raise, and I’m sure, maybe more examples to that. So Kagisho do you want to add a bit more to that?
Kagisho Baepanye Thank you. Thank you for unmuting. So one of the things that are done in terms of the ICF like Simba said, there are different ways that we are trying, but, like issues of new where ICF is on devices, but also it, we need to give participants a chance to like, for example, take the information home to consult with a doctor. But the question that Ntando asked, it’s essential, because we need to have also to have new ways because then we can be doing things as we have been doing before. And one of the things that sites are doing that, for example, they will have flip charts. So we’ll go the whole ICF on a flip chart to discuss with the participant. Besides giving the participant the document to take it home, they will have like, videos where ICF is narrated, on a video, but still, the participant has to take will still have to sign it on a paper form. But what is important is that a participant is not required to sign the ICF the same time, if you want to take it home, you can take it home. But I think this time, the times that we’re living in now are pushing us to innovate new ways of doing an ICF than what we normally used to do. And thanks, Ntando for asking that question. I think it makes us think what other ways that we can do are, but these new studies are trying to check if we can’t use those devices for ICF, for example. Yeah. Antibodies or vaccines for COVID-19, which shows more promise? Azwi Takalani I’ll go first. And then I’ll give Simba opportunity to add. I think the way we are thinking about COVID; it’s a pandemic, millions of people all around the globe are affected. And so the target is to have at the end, probably a multi-pronged strategy. So having said that, both antibodies and vaccines are showing promise. But the question should be more of which target groups do we think we will work for the other. And in terms of that, we will be showing more promise. So for example, I’m looking at giving antibodies to maybe more the elderly, is that shows like it’s going to show more promise of really preventing severe disease. But if we think about a younger population cohort, will the benefits of those antibodies be sustained enough for a long enough period? For us to believe that this is a good preventive strategy? So I think the question is like saying it’s straightforward, but deep because it needs to be thought of in different layers. But we just so happen to be the answer of the approach towards COVID prevention strategies, that there should be multi-pronged targeting different population parts to achieve a different result. So both shall perform at different levels. Simba do you want to come there? Simba Takuva Azwi I couldn’t anymore? I think you’ve captured it very well. Maybe I could just add like an example in another therapeutic area if you think of family planning. Your ideal scenario is you want to have a toolkit of interventions, right. For instance, in family planning, we have the pill and the pill really may not be suited for everyone. I might be forgetful. So maybe taking a pill every day might not be the best. I might need something that is a long term like an injection that I have every three months, and then someone might want a copper IUD or something like that? Yeah. So at the end of the day, you’re developing a toolkit or a box that has a lot of those different interventions that might be appropriate for different people in your population, just as Azwi well-articulated it. Thanks.
So this question speaks about the halt and the pauses that we’ve seen globally, and of a range of COVID trials. Have you seen this impacting at all? Your ability to recruit participants for your trial? Have people shown something hesitance regarding and being enrolled in your trials because of this?
Simba Takuva So maybe I can go first. So from what we hear with the colleagues that have already started, those trials, or colleagues that have had holds and pause already, I think what happens is, you tend to get more questions. And this is where the issue of transparency becomes very important. So what is important is to inform then your volunteers inform your subject, inform your population, inform your collaborators, if there is transparency. The information is out there, and then folks people can take in the information comprehend, ask further questions if there’s need to. And usually, that even instills more confidence in the clinical trial system to say those safety guards or those safeguards are working, and are in action. So it comes back to communication and transparency.
What is your take on how different community engagement has been in COVID research compared to HIV prevention trials, has there been a difference?
Thank you for unmuting to me. Yes, I would say there has been a difference in terms of how COVID-19 community engagement, for example, has been done compared to HIV vaccine, so, or HIV ……….. So, one because of the challenges that we are faced with COVID, and then the ability of people to meet access to some of these things. But we also want to appreciate that it has not been easy. But a few things that had to change; one of the things was that the issue of time was an issue, for the engagement to be done as we would have wanted, compared to each a vaccine. But what we are happy and encouraged about is that we have managed to speak to people on the ground and engage with communities and our sites have given us a good rapport in terms of how their communities have engaged with them. So like we said previously, one of the questions that you asked me and that COVID is actually and pushing us to look for new avenues on how we can communicate and improve on our engagement and which is also what GPP has been a teaching us your broader stakeholder engagement. And this is what we also find an example in every conversation that we have with community educators is to ask, how broad are we moving? Are we moving beyond our traditional engagement areas? So it is what it is, and it is pushing us to change, And I believe it is changing for the better and in the right direction to ensure that we continue to engage in communities broader. And broader means if we have engaged different people today, tomorrow, you will engage a different stakeholder. Still, we would continue to engage different communities that in some instances, we have never engaged or stakeholders that we have never engaged with before. So what is nice about this pause is that it has pushed us to talk to groups of people that we have never had an engagement within previous engagements.