Rolling out a vaccine in Australia with Professor Jim Buttery and Professor Nigel Crawford

00:04 MVEC credits 

You’re listening to The Vaccine Coverage, an educational podcast where we talk about the basics of vaccination in Australia. Brought to you by MVEC, the Melbourne Vaccine Education Centre. The vaccine coverage is recorded and produced on the land of the Wurundjeri people. We acknowledge the traditional owners of the land and pay our respects to their elders, past, present and emerging.  

00:25 Rachael 

Hi everyone and welcome to The Vaccine Coverage, our podcast where we hope to shed some light on all things vaccine related. My name is Rachael McGuire and today we’re going to be chatting about how vaccines come to be recommended and available to people. And whether they can be given for free or whether they need to be paid for. And to talk about this, we’re going to be joined by two of the big names in this area, Professor Nigel Crawford and Professor Jim Buttery. Welcome to you both.  

00:50 Prof Jim Buttery 

Thanks very much Rachael.  

00:51 Prof Nigel Crawford 

Thanks Rachael.  

00:52 Rachael 

Before we get started, I might take a minute or two so that you can both introduce yourselves and share your experiences with our audience. Perhaps, Jim, do you want to go first?  

00:59 Prof Jim Buttery 

Sure. My name is Jim Buttery. I’m the Professor of Child Health Informatics at the University of Melbourne and the Chief Research Information Officer at the Royal Children’s Hospital, and I lead a research group in health informatics and vaccine safety at the Murdoch Children’s Research Institute. And I should add that what I’m discussing here are my personal views rather than that of the TGA.  

01:20 Rachael 

Very experienced. Nige?  

01:22 Prof Nigel Crawford 

Thanks. Rach, yeah, my name is Nigel Crawford. I’m a paediatrician, based at the Children’s Hospital in Melbourne and also the Director of SAEFVIC, the Victorian vaccine safety service and a Professor with the Department of Paediatrics, University of Melbourne. And my main experience here has been a roll with ATAGI, which I joined in 2014, and ATAGI is Australian Technical Advisory Group on Immunisation and I’m the current Chair of that committee, which informs immunisation policy here in Australia. 

01:49 Rachael 

With all of that in mind, might be good to open up with my first train of thought, and that is that when it comes to rolling out a vaccine, it’s quite a complex process with lots of different committees and groups involved. Can you walk us through what is sort of happening behind the scenes before I guess the public really hear about a vaccine becoming available?  

02:09 Prof Jim Buttery 

The first step typically is that once a vaccine manufacturer has gone through preclinical, in other words laboratory based and other trials, they then move into clinical trials. And once they have demonstrated satisfactory safety and efficacy, in other words, does the vaccine work then they prepare a submission to the regulators around the world. And our pharmaceutical regulator is the Therapeutic Goods Administration of Australia or the TGA, and they would consider that application. Essentially on, is this vaccine likely to be valuable to some members of the Australian community, in other words, do the benefits outweigh the risks for at least some members of the Australian community?  

02:56 Rachael 

And then following that process, so if the TGA, once they’ve approved that vaccine, so they found that safe and yes, it does work and valuable, what would be that next step?  

03:07 Prof Jim Buttery 

Yeah, so the TGA process, they have experts within the TGA who prepare a dossier and then that’s considered by the Advisory Committee on Vaccines or ACV, which I currently sit on. And then once that recommendation is made and the vaccine is recommended for licensure or provisional licensure in the case of COVID vaccines initially, then typically what happens is that a preparation is made to both the expert advisory group on immunisation, ATAGI, that Nigel chairs, as well as the Pharmaceutical Benefits Advisory Committee, or PBAC. And they have two very different jobs, the ATAGI considering what aspects of the Australian community would best benefit from this vaccine if at all. And where the PBAC is really considering is this vaccine cost-effective? In other words, does it represent an appropriate investment by the Australian taxpayer to improve health?  

04:04 Rachael 

And so I guess when the PBAC are making those sorts of decisions, they’re taking into account cost of hospitalisations, medications and things like that, if the population were to be affected by the disease. So therefore, does the vaccine, the cost of a vaccine outweigh that cost of treatment?  

04:21 Prof Jim Buttery 

That’s right. So essentially they consider all the costs of implementing the vaccine, including the cost of the vaccine, the cost of people giving it and distributing it, etcetera, versus what benefits are gained in terms of reduced hospitalisations. But importantly, the PBAC largely considers things based on a cost utility approach, which is a fancy way of saying what they incorporate as the quality-of-life integration into that decision-making. And so in other words, does this not only improve health, but does it improve quality of life?  

04:53 Rachael 

Hmm. Yeah. And then Nige, I might go to you. Where does ATAGI sit in that? So if you know PBAC is looking at the cost effectiveness and ATAGI is looking at the population level.  

05:04 Prof Nigel Crawford 

Yeah. So I think for the listeners, probably good to sort of think back pre the pandemic, the processes that Jim’s nicely outlined took a long time, good 5-6 years by the time you kind of had all that process and the evaluation and came to the committee and backwards and forwards to get all information to sign things off. But the pandemic has meant that the expectation is now that all these decisions and evaluations and are happening much quicker, so the timeline is that are short and often happening in parallel. So I think the concept of what’s called horizon scanning, so seeing what’s coming down the pipeline, it’s really important from the vaccine side because it’s other similar groups such as the FDA or the Federal Drug Administration in the US does a similar process to the TGA to approve a product. All that information is seen publicly. You can YouTube and watch those discussions and then the EMA, the European Medicines Agency, does a similar process for Europe. So there’s global sharing of this data and we know at the TGA and ATAGI where these products are coming down the pipeline. Just got to preface some discussion to that I’m talking so my personal opinions here, not on behalf of the committee or groups that I sit on. 

06:05 Rachael 

Yeah, of course. 

06:05 Prof Nigel Crawford 

It’s really important to make that clarification. But ATAGI’s role is essentially to provide advice to the Health Minister as well as provide advice to the PBAC. So we provide written advice to the Pharmaceutical Benefits Advisory Committee to see where the vaccine may sit within our National Immunisation Program, where we have a fully funded program across the life course for different vaccines. The different products and we have to see where this new potential vaccine, if we’re talking about a new product, sits in the pipeline and how it may sit then within our National Immunisation Program. We can’t provide advice until it’s got TGA approval, so it doesn’t get through the regulator, it can’t even be considered. And then there’s a set schedule of timing of when the PBAC may sit to discuss that product. They don’t just look at vaccines at PBAC, they look at all medicines with a similar lens and we’ll provide formal advice across all of those different parameters with the group that Is bringing the vaccine to market, which is usually a pharmaceutical company. If there’s a positive PBAC approval, it can then be considered to go on to the Program, and then there’s a separate tender process with the government that actually has that product come on to our Program. So there’s quite a lot of different steps along the way with opportunities for that to then come into the Australian Immunisation Handbook, which is also endorsed by ATAGI. And consumer feedback and different consumer groups also feedback to the PBAC. So it’s a very open and transparent process in terms of those final decision making. But as mentioned, it’s really trying to get the best value for a vaccine for the Australian population more broadly, rather than decisions being just made at a local hospital or a local state level. This is a national program with an equitable way to provide protection at a community level.  

07:45 Rachael 

And so you touched on this just before, but where does the government then sit in these decision-making processes?  

07:52 Prof Nigel Crawford 

So all of these bodies currently sit within the Health you know, Department within the Australian Government in Canberra. So essentially the ATAGI is a committee that’s appointed by the government that’s independent but is providing advice to the Health Minister, in this case to the PBAC. So it is essentially a government advisory committee in terms of that process. So they’re closely involved, obviously both in terms of how the advice is being delivered and discussed, but then also thinking also the implementation, if that vaccine does come onto the Program, how we can actually administer it? Does it come into our routine immunisation schedule or can we give it the same time as a vaccine that’s already been given to a 65 year old and over for their flu, as an example. So some of those implementation issues are also considered.  

08:32 Prof Jim Buttery 

Similar to ATAGI, PBAC doesn’t make decisions. It makes recommendations to the Health Minister. And the recommendations that may make are that the vaccine is appropriate for funding under the National Immunisation Program, or they may make a recommendation that a vaccine is appropriate to go under the PBS system, where there may be a co-payment for many Australians, and then it’s up to the government to accept or not those recommendations.  

08:55 Rachael 

Mmmm, make that final decision. And I guess that is where it comes into the whole concept of, yes, there’s some vaccines that are on the Schedule, others that it might be recommended for certain populations or you know, what have you. But those vaccines come at a cost.  

09:09 Prof Jim Buttery 

That’s correct. And certainly, it may be that they recommend vaccines for specific indications or specific groups. And often the submissions are aimed at those specific groups that may benefit the most from a particular vaccine.  

09:21 Rachael 

If we think to a specific, I guess vaccine that is currently on the Schedule. So, for example, the HPV vaccine, if we use that as an example, how did that process unfold, getting that vaccine onto the schedule? Which initially it was a three-dose course and now recently it’s been dropped down to a one-dose course. How did that go? What was the process of getting it on the schedule and I guess then changing it to just a one-dose course?  

09:47 Prof Jim Buttery 

I think HPV is a really good example because I think if I’m correct, HPV was the first vaccine to follow this process that Nigel’s described. So prior to 2006, the PBAC was not involved in considering vaccines. So first, clearly there were the clinical trials were done there at the time there were two different HPV vaccines. They were both licenced by the TGA and then they were considered and recommended by ATAGI and then PBAC considered those vaccines. I’d just joined PBAC, but I was excluded from those meetings quite appropriately because I’d been a minor investigator on one of the clinical trials for one of the HPV vaccines, and they are very careful at all of these committees about potential conflict of interest. So, what PBAC then recommended based on the trial data, was that three doses of HPV were appropriate and that was based on the confidence that those vaccines would prevent cervical cancer. HPV is a great example because cervical cancer occurs decades after your first contact with the virus. But you need to be vaccinated before you have any contact. And so, the clinical trials didn’t demonstrate that they prevented cancer. What they demonstrated was that they prevented cervical changes that were confidently linked to cancer later on. And in retrospect, that’s been shown to be a really effective and an evidence-based decision and extremely successful. And those decisions have potentially saved the lives of many thousands of Australian women. Then, as the years went by, the evidence grew. That not only did HPV strongly associated with cervical cancer and cause the vast majority of cervical cancer, since then, it’s also been shown to cause anal cancer, penile cancer and in terms of the number of cases, the most importantly, oropharyngeal cancer, second to cervical cancer. And so, the health benefit potentially of HPV vaccines has increased. The vaccines themselves have evolved, and so we now have a more number of strains that can be prevented. And as the evidence has evolved, it looks like we don’t need as many doses. And that’s something that ATAGI has carefully considered.  

12:04 Prof Nigel Crawford 

Yeah. So just adding to that HPV is taking you back to 2007 when I was working with Jim. So it does reflect the 16 years or so been working in in this area.  

12:11 Rachael 

Your experience. 

12:21 Prof Nigel Crawford 

Just saying too, we actually did some work in special risk groups or those that are immunocompromised. And they’re still recommended a three-dose schedule. So while we’re talking about changes, it’s really for those. that are otherwise healthy young people. Our program at mainly year seven, so 12- to 13-year-olds. And something that happened in the clinical trials was that people recruited into the trial were measuring, did they have detection of the particular HPV serotypes in their testing? So were they getting protection from the HPV and therefore longer-term cancer, but some didn’t get all the doses. So some only got two doses and some only actually got one dose. So actually the evidence around the single dose protection are the people in the trials have been followed up now for that 15, 20 years and shown that they still have protection. So this vaccine has shown, even with the single dose to have very high level of antibody. So the antibody level is tenfold over what you see with natural infection. And it does seem to be sustained and having long duration of protection. So therefore, deliberations occurred at ATAGI is a single dose felt to be sufficient clearly for young people, if it’s just one dose rather than two or three, but we still need to be sure that that is going to be the case in longer term protection. So ongoing monitoring and evaluation of that program is important. And then ATAGI essentially provided advice to PBAC around that single dose. They have a clear agenda and minutes that go out publicly and they deliberated on that discussion and agreed that we could go to a single dose. It doesn’t completely half the cost of the program, because you still need to get to the schools and have all the delivery. So it doesn’t potentially drop it by complete. Just by losing the dose because there’s delivery and other factors that have to be considered, but certainly it is then a cost saving you know for the government, but we still need to be having ongoing monitoring to make sure that decision holds. And the WHO Strategic Advisory Group of Experts, or SAGE who provide their immunisation advice at a WHO global level have also evaluated this and provide guidance. So we’re not doing this in isolation here in Australia. Even though we were one of the first: We’re one of the first to introduce HPV and one of the first to go to a single dose. But that information is you know clearly available out there.  

14:14 Rachael 

When you’re making those changes, did you have to go back to the TGA for changes in regulation or it was simply that advice from ATAGI with that evidence from other countries and trials?  

14:24 Prof Nigel Crawford 

Jim can talk to the Advisory Commitee on Vaccines, but I think normally when a vaccine sort of taking a dose away, you’re not changing the product. So it’s not the product information is changing in the sense apart from the number of doses and therefore the level of protection that you might be seeing. The actual product itself is the same as it’s the safety profile. So I don’t think it’s normally a regulator who needs to make big deliberations on that topic. But I know, Jim, you do want to comment further?  

14:45 Prof Jim Buttery 

Yeah, it’s a good question. So exactly as Nigel says, if the product remains exactly the same. Typically the advice from the TGA will be to use the vaccine in accordance with official recommendations, which is typically by ATAGI and so, so long as the dose that is given each time is the same vaccine, it doesn’t need to go back to the regular. If, on the other hand, when you move from a 4-serotype vaccine to a 9-valent vaccine. That the 9-valent would obviously need to come through the regulator first.  

15:14 Rachael 

Now I know that you touched on this briefly before, but when things were happening with COVID vaccines and rolling out their use, everything happened slightly differently, didn’t it?  

15:25 Prof Jim Buttery 

Yeah. So clearly, exactly as Nigel said, typically the pathway to developing a vaccine takes on average somewhere between 8 and 13 years from the start of development through to it being introduced into a community. And with COVID, we had no chance. That was just way too long. And so at the same time as the clinical trials were happening, they were also building the factories, which normally would happen one thing after the other. Many things were happening in parallel to speed things up before licensure. And then the second component that occurred was there was provisional licensure, or in America, that’s called emergency use authorisation. And what that meant was that the clinical trial still had to be full clinical trials. But instead of the typical 12 month follow up after the last person got vaccinated, they were granted provisional licensure when they had three months of follow up after the full clinical trial last person was vaccinated.  

16:17 Rachael 

And I guess now that we’ve got that much more data and that much more time has passed, we’ve still fulfilled that time frame.  

16:23 Prof Jim Buttery 

That’s correct. And so what you can see is that the original COVID vaccines, many have progressed to full licensure in the meanwhile.  

16:29 Rachael 

And do you think that pathway that moves much quicker, if there was to be future pandemics, we would follow the same pathway? Or do you think there were things that we would consider changing next time around? Unfortunately, if that happened again.  

16:41 Prof Jim Buttery 

I think both those concepts of the parallel development as well as much more rapid techniques in how we make vaccines will remain and probably improve. And I think it’s likely that the provisional licensure or emergency use licensure will continue. We’ve learned a lot of lessons, but a lot of our lessons are really what can we add in terms of surveillance, to continue to ensure that vaccines once they’re introduced, are safe and if there are any problems, they’re picked up as rapidly as possible.  

17:09 Rachael 

That’s reassuring. Nige, do you have anything further on that?  

17:11 Prof Nigel Crawford 

Yeah, the only thing I’d add I think is that it’s been pretty tiring for the regulators to be fair. So I think all these products coming meant that lots of people did get burnt out. And I’ve just been thinking about COVID more broadly, you know everyone working in the field definitely was a big demand both on the clinical trials to get them through appropriately with the ethics, where turning things around normally take three or four months we’re doing a couple of weeks. So, no steps are being missed, but it is a lot of pressure on the teams to progress those thoughts and processes. So I think that’s something that needs to be considered in terms of the expertise to proceed. But yeah, not possible to follow the standard process of vaccines in a pandemic. You can’t wait for the full PBAC. You know, these decisions are being made at a country level and obviously at a global level through different groups. So a different pathway was required, but it’s similar. ATAGI has given advice on every change to the program, meeting regularly to provide that advice and a vaccine cannot be utilised in Australia until it gets that provisional approval that Jim’s outlined. So the processes are still there, it’s just the timing and the way that it’s happened was a little bit different.  

18:12 Prof Jim Buttery 

The other thing I’d add is that the one thing we’ve left out of this, although I mentioned it is, none of these big public health decisions happen in isolation and so if we go back to what we thought was a more peaceful time with the HPV vaccine, even that at the time was considered controversial. There were a variety of concerns around would introducing a vaccine against a potentially sexually transmitted disease in early teenage increased promiscuity? And there were major pressures in some countries against vaccine licensure for that reason. So there also needed to be will at a governmental level to support the decision making by the independent recommendations and to their credit they did. And similarly in some countries, when there were safety concerns emerged that subsequently were shown to be spurious, some governments withdrew their vaccine program, meaning that tens of thousands of young women lost their protection. So keeping that government support has been critical and it’s, and to their credit, they stuck through it throughout the life course of the HPV vaccine have been shown to be correct.  

19:19 Rachael 

Yeah, I think if we can sort of switch tack just slightly, I think that would be great to get a bit more understanding and to I mean, we’ve covered how vaccines are put on to the National Immunisation Program. But there’s also those state-funded vaccine programs and how does that differ? You know, obviously different states have different populations, so they might have different diseases. But can you comment on the process of getting those approved and funded for people?  

19:45 Prof Nigel Crawford 

I’m happy to start first. I think everyone going back to COVID, we are a federation with jurisdictions and our borders closed and opened at variable paces and there are decisions made of those jurisdictional governments that can build roads or do different components and often with collaboration nationally. But they can make their own decisions and good example maybe is the rotavirus vaccine, which is protecting against gastroenteritis. That’s a much higher prevalence in our First Nation Aboriginal Torres Strait Islander and the Northern Territory actually started a program before we had a national program. So they wanted optimised protection in their group. So there are times when jurisdictions might make a decision, hoping obviously that will then progress into a National Immunisation Program. And maybe a second one to flag is meningococcal disease. People might recall there was an outbreak of a couple of different strains of meningococcal that also some of the jurisdictions led a program as the wheels were turning for our national program in some of these decisions. So there’s certainly, you know, opportunity and scope for that to happen. But the communication of that needs to be open and ideally as mentioned, you really want to land at the end of the day with an equitable program that all Australians have access to, as opposed to being the postcode or jurisdiction necessarily of where you live. Acknowledging there may be some variations at that level, particularly early on in the programs.  

21:00 Rachael 

So I guess those vaccines still go through that sort of PBAC TGA process, get recommendations by ATAGI as to how they should be used. But the funding themselves are from the states?  

21:14 Prof Nigel Crawford 

A little bit different, so they there may be a PBAC process happening but they’ve not necessarily waited for that. For the PBAC, it’s really looking for the National Immunisation Program support. So they may be hearing about those decisions and discussions. But essentially the PBAC is required to go into the National Immunisation Program. It’s normally when those decisions haven’t quite been made or there are cost effectiveness discussions that are happening that a jurisdiction may decide to run alone with their own program, and Jim, you wanted to expand on that.  

21:42 Prof Jim Buttery 

Yeah, that’s right. So any vaccine use in Australia has to be a licenced vaccine typically or at least go through the regular. Whereas the jurisdictions can choose to implement a vaccine that may or may not have been through PBAC because they’re not bound for their decision making to for on PBAC’s recommendations. And so it may be that they decide to respond to a local issue, whether it’s an outbreak or whether it’s a higher rate of disease within their population, there may not be enough to have reached the national considerations yet.  

22:12 Rachael 

That’s great. I think it’s really good to make those distinctions between the different state programs and the national programs.  

22:18 Prof Nigel Crawford 

So I think one thing we haven’t touched on is there’s a sort of a private market of vaccines as well. So that will classically be your travel vaccines. So if you are planning your trip to Bali or post the pandemic moving, there are sort of vaccines that are available, some of which are jurisdictional funded. So, BCG an example, protects us against tuberculosis, there are some state-based programs that will protect particularly young infants from tuberculosis with the BCG vaccine, which are state funded. But other ones you will need to purchase privately. So there are lots of vaccines that have gone through the TGA regulator that need to be purchased.  

22:51 Rachael 

Before we go, I’m just hoping that you might be able to answer some of the questions from our audience, if that’s okay? Can either of you comment on some other vaccines that may be in the pipeline and available in Australia in the future?  

23:04 Prof Jim Buttery 

I think, clearly locally RSV is probably the, if you like the next off the rank. Regionally, I guess some important vaccines which is quite exciting, that may well be implemented soon are important infections like vaccines against Dengue fever, another viral infection called Chikungunya that affects many children regionally. And I think with the mRNA platform technology, we’re probably going to see increasing numbers of mRNA vaccines, either against an existing infection, so we’ve got some vaccines for, like influenza. But also other snot-producing viruses that parents of kids in childcare are so frustrated by, and they may include other viruses like human metapneumovirus and other of those viruses.  

23:45 Rachael 

I think as a parent of young kids, I would very much welcome that. And I guess the question for the healthcare professional, what should providers do to stay informed on changes to the schedule, storage guidelines and just general good practise around vaccines and vaccination?  

24:01 Prof Nigel Crawford 

I’d throw them to the Melbourne Vaccine Education Centre website and the team here can provide them with all the links that are required and obviously we, as mentioned earlier, we do have the Australian Immunisation Handbook that provides advice as well as our Victorian immunisation service and team, as well as the national resources.  

24:15 Rachael 

And just lastly, another question after childhood and adolescence, how should you stay informed about what vaccines are recommended for you or which ones you can access for free? And I think there’s probably comes about more, so you know, I think once we’re out of our childhood and adolescence, we don’t tend to go to the doctor much or you know, rely on our mums as much.  

24:34 Prof Nigel Crawford 

So I recommend TikTok. I think that’s the place to find things. I know Jim’s got a bit of experience and some education through that mechanism, certainly my kids, that’s all they’ll listen to. So maybe we need to get some TikTok resources to remind you where you’re up to, when vaccines are required. Jim?  

24:49 Prof Jim Buttery 

I mean, clearly there’s excellent web resources in in Australia and the WHO actually accredit two different Australian websites as possessing good vaccine information. That’s the MVEC website and also the National Centre for Immunisation Research and Surveillance website. And so both of those are good places to get up to date accurate information. We do do some immunisation education through TikTok together with other child health information and it can be extremely effective. But as with any social media, you have to be very careful about where you’re accessing that information.  

25:20 Prof Nigel Crawford 

And maybe just one last site is the raisingchildren.net site as well has obviously lots of information both for parenting and both education and health related issues again supported here through the Murdoch Children’s Research Institute and lots of paediatricians, other colleagues help write some of those resources and we have worked with them through MVEC. That’s another resource to utilise. 

25:40 Rachael 

Great. Always good to give everyone a plug. Alright, thank you both for taking the time to sit down and share your experience with us. It’s been a great chat and hopefully we’ve shared some information or provided some clarity on the process for recommending vaccines here in Australia. So thanks Jim. Thanks Nigel.  

25:55 Prof Jim Buttery 

Thanks very much, Rachael.  

25:55 Prof Nigel Crawford 

Thanks, Rachael.  

25:57 MVEC credits 

This podcast was produced with the assistance of Podcast Recording Services. MVEC is a part of the World Health Organization’s Vaccine Safety Net. All members are verified by the World Health Organization as a source of reliable and credible vaccine safety information. MVEC provides vaccine education and news on our website, mvec.mcri.edu.au and through our newsletter and social media profiles. You’ll find links to subscribe to the newsletter and our social media profiles in the notes of this episode. MVEC also offers professional development opportunities for healthcare providers through our online education portal and our events.