The latest Investing Matters Podcast episode featuring Jeremy Skillington, CEO of Poolbeg Pharma has just been released. Listen here.
Many thanks for the CSP Alpha, it looks like they are genotyping...
Exploratory objective: Phases II and III: To explore the association between viral genotypes and
phenotypes, and clinical outcomes and response to agents......
It will be important if, as reported, omicron is causing more mild disease overall, otherwise, the results could be confounded quite heavily given the duration of the study and time course of predominating strains, and then confusion will reign again.
Alpha - I haven't been able to follow things closely on this for a while, do you know if the virus samples undergo genotyping in ACTIV-2, (all samples or a sub study). I'm thinking it will be important if, as is now purported, omicron is causing milder illness overall.
Do you think they have planned an interim? I suspect so, safety should not be an issue but I would imagine there is an independent safety review board involved and there may be interim markers of a strong efficacy signal? However, having an interim with two co-primary's could pose an issue, even if the efficacy signal turns out to be a strong one.
Does anyone know if further details of the Phase III study have been released and when the co-primary endpoints will be measured, will it mirror the Phase II i.e. at 14 days post initial dosing?
The drip fed updates to the AZ/Oxford interim trial results may well support a case for a ‘companion diagnostic’ in the elderly at least, but much still to be confirmed if the rumours are to be believed.
The better efficacy was shown in the low dose group, the low dose was given to the under 55’s. If the best efficacy seen in the high dose group is 62%, efficacy in the older and more vulnerable population has yet to be reported but likely to be lower than 62%. Then, a confirmatory or companion diagnostic in this group may be required. Lots of if/buts/maybes, including not knowing if a rapid IgG test would sufficiently act as the confirmatory diagnostic. I’m still not convinced the rumour is true, but based on what’s emerging I can see a potential case now, where I didn’t see one before. I still don’t see a confirmatory diagnostic required for the other vaccines. Be interesting to see how this one develops.
@regulator - understood and yes there will be yellow card reporting in the UK at least. Even if one were to think there will be additional risk management measures with any conditional licence, from the safety profile reported so far, which looks good, it's tough to see what the focus will be.
@regulator, your point about the trials not assessing safety is what I disagreed with, namely "You wouldn't test for safety reasons during a vaccination programme. "
Do you not agree that the trials are in fact designed to assess safety as well as efficacy? It will be a short discussion for the vaccine manufacturers with the country drug regulators if you disagree?
" The trials are robust in assessing safety, over 30000 and 45000 participants in the mRNA studies, picking up solicited and unsolicited events over 2 years. "
That's simply not true. The trials haven't been running for 2 years.
Yes, they haven't but the 2 year trial assessing safety through solicited and unsolicited reports in these large controlled cohorts is robust and does test for safety, which was the point I disagreed with in your earlier post.
@bakedbean - agree with the other posters - herd immunity rules and then with the odd case you may get that requires hospital intervention is easily absorbed in the current healthcare set up without the need for all these NPIs.
@ExXoc, you could make a case for countries with a larger population where it will take time for the population to be vaccinated. This is where I thought there might be a case to use the antibody tests, largely in the unvaccinated, rather than vaccinated. But, unfortunately, these countries will not major from a dollar perspective, and any manufacturer can enter these markets, see the problems Genedrive have had with their test, as a use case.
@russky - this was released by Roche before anyone knew about the efficacy profile of any of the vaccines. With 95% efficacy, there is no need to test for antibody response. BTW, the Elecsys platform is only available in labs, it is not point of care.
You wouldn't test for safety reasons during a vaccination programme. You'd be testing to see whether or not the vaccine has invoked a response. Safety concerns, including reported adverse reactions, would be reported through the Yellow Card system.
We have to bear in mind that these are new vaccines, two of which (Pfizer and Moderna) are of a type that have never been licensed for use in humans before. They have been developed in a fraction of the time normally taken and not subject to the longitudinal tests that would normally be carried out.
Even if every person who gets the vaccine is not tested, there will be a significant level of testing, over a long period of time, to measure efficacy in invoking a response and to ascertain longevity of cover.
My point is that even if durability of response is variable, for argument's sake, say variability lasts from 6-12 months. With the current known safety profile, a booster dose would be recommended at 6 rather than 12 months. As an option, it's far easier and less costly than asking everyone to test themselves every few months or even monthly from 6 months onwards. I also disagree with the safety comment you made. The trials are robust in assessing safety, over 30000 and 45000 participants in the mRNA studies, picking up solicited and unsolicited events over 2 years. This will give far more robust safety data than the yellow card reporting. The yellow card reporting will only add value in this instance for rare and ultra rare events and is subject to the usual reporting bias.
Again, this is all speculation and a tweet from an academic confirming the same antibody is in play is not evidence that a test is required.
As I was not getting answers, I managed to find a paper that gave me some hope that rising IgG levels confers some degree of immunity to the infection. However, to assess vaccine effectiveness in the short and long term, there is no data. We need to know if this data will be available from the vaccine trials.
On long term effectiveness, unless the variation in durability to response is wild, there is no need to test in the general sense. The schedule (every 6/12/18 months) will dictate when the boosters are required. The safety of the vaccine is, as we currently know, good, so no need to test. I'm playing devil's advocate because I want to believe this test will be used, but apart from vanity reasons, can't see the need in the vaccine setting.
I bet that Ciga removed the tweet because they were forced to by AZ/Oxford. I've asked the question before and no-one was able to answer it, so I'll ask again. What is the evidence to support the UK RTC rapid test being used as a de facto confirmatory diagnostic with the AZ vaccine?
There is no data to date to support this position.
Why would AZ/Oxford not want a 'companion diagnostic'? Because the competitors have 95% efficacy, who wants to take the vaccine that needs a 'crutch' to confirm whether it has worked. And if you're going to the regulators with data on only 2000 people supporting your argument for 90% efficacy, you don't want to market yourself as the vaccine for the world that's cheap, convenient and efficient and....oh yes, you have to buy another test to show it works too.
The part mentioned earlier about detecting neurtralising antibodies worries me too, the rapid test developed by ODX is for the detection of IgG, it is not a plaque reduction neutralising assay.
I'd love to see the data which supports the position of vaccine= this test, but i don't see it. I'm still holding but now it's really to see if the antigen test is near completion. The case for the antibody test is wearing thinner by the day. All my opinion, DYOR and good luck.
Thanks Regulator for the comment - Although not all vaccines are rolled out with confirmatory testing, the early indications are that these vaccines will be.
Do you have any insight here? Have there been any indications that antibody testing will be required to accompany vaccinations? I've not seen anything to suggest it is. I've seen a number of exploratory endpoints and sub-studies reported for the Phase III's and that's it.
Thanks for the explanation. Agree that controlled studies and real world usage can differ, however, such a strong efficacy signal is not going to change to 50% in a real world setting, where a confirmatory test would be useful. I agree with the WHO on test, test, test. I'm invested in a number of the diagnostics stock still, even after the heavy losses the past couple of weeks.
The Phase III vaccine publications will be more informative, we still don't know if antibodies are the biomarker of choice and how well they correlate to immunity and protection, nor do we know of the variability of response. But I suspect in a large trial with 30000 to 45000 subjects, the data will be very informative and we can have a good degree of confidence in the results. Compare flu trials, where millions are vaccinated based on trials of 5000 people!
EkXoc - I don't understand your rationale. These studies will not detect the ultra rare adverse events, sure, you'll see more in real world usage. But the use of a test will not tell you anything about side effects. If you've been given something that's 95% effective, would you really need a test to show you've responded?
TWatcher, I agree and posed the same question earlier. Apart from the speculative tweets, I don't see the rationale in using antibody tests of any sort when vaccine effectiveness is 95%, the clinical and health economic arguments are week.
If one of the vaccines demonstrates poor(er) efficacy and requires, what is effectively a companion biomarker, then I can see the use case for this.
Or, if durability of response is highly variable in a population setting, again I can see another use case.
In both cases, you'd need substantial evidence to demonstrate the biomarker is validated and is the indicator to inform clinical decision making.
All that being said, it will take a while for populations to be vaccinated and so in the meantime, this test is still useful to inform people whether they have antibodies to Sars-Cov-2