OT:AstraZeneca Phase III Vaccine Trial Put on Hold
...due to an "adverse reaction" by a participant in the UK. As the article states, it could be nothing and things could proceed quickly after a brief pause. Apparently a non-life-threatening reaction, and the subject will recover. But given that it is the vaccine furthest along in trials and, by many accounts, the most promising candidate, it's still troubling.
September 8th, 2020 at 9:31 PM ^
It's actually a promising sign that AZ is exercising abundant caution. If the trial continues with a thorough explanation, then that will add to confidence that the pharma companies and regulators aren't rushing things.
September 8th, 2020 at 9:34 PM ^
On the one hand, this is a great, accurate take. On the other hand, a huge segment of Americans believe COVD-19 is a plot by Bill Gates, the Chinese and 5G network providers to control Americans' brains and somehow has something to do with a global, elite-run child trafficking ring. So I am not sure this signal of "abundant caution" will move the needle for many folks...
September 8th, 2020 at 9:50 PM ^
I’m not sure much of anything will move the needle for those folks. However there is a pretty large group that has concerns about how the approval process may be run. This is the exact type of thing to give those people a little more confidence.
September 8th, 2020 at 10:43 PM ^
I thought the global, elite-run child trafficking ring ended with the "suicide" of Jeffrey Epstein.
September 8th, 2020 at 11:10 PM ^
No, Tom Hanks is still on the loose...
September 8th, 2020 at 11:55 PM ^
Whoa there, let's leave Otm Shank out of this!
September 9th, 2020 at 12:08 AM ^
Let's be honest - the typewriter fetish is definitely weird
September 9th, 2020 at 9:19 AM ^
Tom Hanks has sex with typewriters? Poor Rita Wilson. “God dammit Tom, the E, R, and T buttons are all stuck together again!”
September 8th, 2020 at 9:35 PM ^
Was about to say something similar. May be not great news for an arbitrary late October deadline for availability of the vaccine, but exactly the type of news that should give us more comfort in any vaccine that is ultimately approved.
September 9th, 2020 at 11:13 AM ^
The October deadline exists only in Trump’s fetid mind.
September 8th, 2020 at 9:49 PM ^
Unless this whole incident was staged in order to make it look that way ?
September 8th, 2020 at 10:00 PM ^
That is likely giving the people who might want to stage such a thing much more credit for their abilities at staging such a thing than history has shown us they deserve.
September 8th, 2020 at 11:51 PM ^
AZ’s vaccine technology is a new one, unproven. They basically use a harmless virus as a vector to carry a DNA to your body and ask your body to produce a fake COVID-19 virus protein so that your body startS to intiate self defense system (like a practice in football) be4 the real one hits you. Interesting to see what they find out.
September 9th, 2020 at 6:49 AM ^
It's not AZ's tech, it's Oxford University's. AZ is the manufacturing partner. The technology is new-ish, but is also being used by J&J in its candidate vaccine and one Chinese pharma, as well. The mRNA vaccine tech being used by Moderna and Pfizer in their candidates are even newer platforms.
September 9th, 2020 at 9:20 AM ^
Hi I'm here for the nuanced and knowledgeable discussion about how the medication approval process actually works. It's such a breath of fresh air compared to what I normally see.
September 9th, 2020 at 8:45 AM ^
Will we be able to ”hear football” if we take it?
September 9th, 2020 at 9:45 AM ^
Not the intent. The developers are trying to make sure that you are getting "all the feels."
September 9th, 2020 at 8:48 AM ^
I understand the sentiment, but the trial sponsor is required by law to report serious adverse reactions to the regulatory agency (I haven't looked up which one it is for this trial, but likely at least the EMA and probably the FDA, it depends on which world region they are running the trial in). So don't give them too much credit.
Further, the doctors (investigators) who are actually administering the trial are not AZ employees and are required to be independent. The investigators report to their hospital's institutional review board (IRB) which oversees the trials in cooperation with the sponsor (AZ). So someone would be announcing this if AZ didn't.
September 8th, 2020 at 9:37 PM ^
Me, Shea, and Sparty all run our own pony ranch. It’s in South America (Bolivia specifically).
We are (the ranch) is fully funded by the US federal government.
September 8th, 2020 at 9:41 PM ^
Obviously hope this turns out to be a non-blocking reaction to the trial, but this also highlights have dangerous some of the political pressures to get a vaccine out by some date can be. This might just be an isolated, unrelated incident, but if not you'd want to catch it early and deal with it if possible instead of exposing it to lots of people and causing more damage and, likely, diminishing trust in the current and future vaccines.
September 8th, 2020 at 10:01 PM ^
Has nothing to do with political pressure.
Drug companies want to bring life saving medications to patients as quickly and efficiently as possible. It is in their best interest, not to mention it is required by law, to make sure the product is safe and effective.
there is also a huge financial incentive to being first. It’s a race, yes, but a measured one. Whomever is first cant afford to screw it up. The consequences would be no less than catastrophic.
I will add that trials exist for exactly this reason. Finding out it’s an issue in trials isn’t necessarily the result of rushing anything. Thousands of products fizzle out in trials because, no matter what paper data tells you, there is just no substitute for administration to actual patients.
September 8th, 2020 at 10:12 PM ^
Agreed. There is way more to lose by getting in wrong and being first than there is to being second and getting it right.
September 8th, 2020 at 11:14 PM ^
I'm in agreement with you; I probably didn't word my response in the best terms.
I don't believe that there is any rush for results; in fact I think the reason they were able to identify this particular negative reaction (and possibly other ones in other studies) was because they are being diligent and not bending to pressure. But since the various drug companies stated they would be pushing back against perceived political pressure from the FDA to fast-track a vaccine, I was just noting that this particular outcome is exactly why you take your time with these trials and hopefully proves the efficacy of those practices.
September 8th, 2020 at 9:46 PM ^
Are we sure it was due to the vaccine and not the food they serve there?
September 8th, 2020 at 10:00 PM ^
Aren't Pfizer and Moderna actually the furthest along in trials? I thought they started Phase 3 in July, while AZ started in August?
I'm honestly not too troubled by this. Holds aren't rare events during Phase 3 of the process. They're more frequent in that Phase versus anywhere else.
September 8th, 2020 at 10:18 PM ^
Sorta. Moderna was also delayed because of a manufacturing issue (IIRC) which is a bigger deal more likely (see my comment below). Further, there’s no way that one company will be able to make enough for the US and EU so you can expect that at least 3 will be widely marketed to meet demand regardless of when the first approval occurs.
September 8th, 2020 at 10:33 PM ^
Cool, thanks for the response.
A tangential question, which perhaps you know. I appreciate your posts about the vaccine science.
I wasn't paying too much attention to CNBC this AM, but it was on in the background and one of their guests mentioned a reason why a vaccine may not be approved --- because active CoronaVirus cases would be so low that we wouldn't have statistical proof as to the vaccine's efficacy.
Is that really a potential risk? I understand the statistical idea (measuring the response between the test and the control group). But that seems intuitively highly improbable. I'd think our test numbers are so high (N > 30,000) and there still are enough background cases for us to reach statistical significance.
September 9th, 2020 at 12:14 AM ^
I can’t imagine they would have a problem getting enough positive results if they have a reasonably good sample. About 1 in 8000 are being diagnosed positive every day in this country. So for a study population of 30k, that’s about 4 per day. If they need 150 positive cases, it’s roughly 40 days to get a sufficient sample.
The most difficult part is getting a good sample.
September 9th, 2020 at 9:12 AM ^
This feels very low risk. It's not really my area of expertise (I'm in program management and regulatory strategy not trial design). There is someone on that team (like myself) that is asking that question of the trial design team and assessing the risk and making a mitigation plan if needed.
September 9th, 2020 at 8:50 AM ^
Moderna seems to be mostly hype. Their insiders in the last 3 months have cashed out over $226 million and the majority of their ownership! MRNA insiders now care more about where to invest their money next, not if their company is profitable, a huge red flag. Insider ownership of MRNA is 2.6% and just 3 months ago was 30%, another red flag. Those aren't things you do when you're on the verge of having a successful product.
September 9th, 2020 at 10:47 AM ^
I figure about 3/4 of he vaccine news is just exactly this. A few vaccine hype millionaires will be put to the torch in courtrooms, to make people feel like the government is doing something. Meanwhile half our Congressman and Senators quietly cashed out themselves.
September 9th, 2020 at 11:27 AM ^
Lot's of Enron vibes from Moderna. Not sure how they're not under investigation by the SEC.
September 8th, 2020 at 10:03 PM ^
Buy the dip people.
Edit: not financial advice. A musing on a sports blog
September 8th, 2020 at 10:04 PM ^
This exactly why there are phased trials. It’s being used on more people and this is where we would expect to see issues if there are some. There will be a thorough investigation into what caused it: whether it was a drug interaction, if the patient had some type of unknown condition that created an issue, or something else will determine whether it’s a pause or a showstopper.
September 8th, 2020 at 10:23 PM ^
Well phase three is really to iron out manufacturing issues in my opinion. It’s basically the Wild West until then for money reasons (at least in the US. EU is a different but still not heavily regulated until late phase/post approval).
In my experience you don’t usually run into patient specific SAEs in phase three.
September 8th, 2020 at 10:12 PM ^
It happens. I usually work on cancer so I’m not sure if it is as common in vaccine development. Regardless, It doesn’t mean much right now other than the trial is on hold and it’s unlikely this will be the first to market.
There will be an investigation into what caused the SAR (this is standard language in clinical trials. There are usually criteria in the trial protocol for what makes something a SAR (SAE in the US) and multiple levels with serious being the highest). Keep an eye out for the results of the investigation, but with it only being one person it’s not likely a manufacturing issue and more likely something specific to that patient.
September 8th, 2020 at 10:16 PM ^
Is it normal and routine to stop a drug trial because of an adverse but not-life threatening reaction in just one individual?
September 8th, 2020 at 10:34 PM ^
What I read in one article about this topic is that the patient was probably admitted to a hospital, which is why the study paused.
September 8th, 2020 at 10:48 PM ^
Yes. Completely normal. They aren’t stopping the trial. They are pausing it just to investigate. If it turns out not to be anything with the vaccine, the trial could resume in a matter of days. This actually happens a fair amount in many clinical trials. Also, note that pausing the trial just means that they are not going to inject new people during the pause. They continue to track those that have already been injected. So the trial is still progressing with those people.
September 8th, 2020 at 11:18 PM ^
I have zero knowledge about trial regimens so my curiosity was about pausing the trial because of just a single negative event.
There are 62 trial sites in the US and an unnamed number of sites in the UK, Brazil, and South Africa, but I have no idea how many total test subjects there are—could be several dozens or several hundreds. I can easily envision pausing a trial if there were numerous negative reactions, but I admit I'm somewhat surprised at one negative resulting in a pause. It seems like a good thing from a safety standpoint, certainly.
September 8th, 2020 at 11:57 PM ^
I’m not in the medical field but I a knowledgeable about clinical trials because I invest somewhat actively and have, over the years, invested heavily in pharmaceutical companies. I don’t invest unless I know a shit ton about what I am investing in, so I’ve read up a lot on the processes. If there are those closer to the process please feel free to correct me.
That disclaimer aside, pausing trials for every negative reaction is the standard, but only if the reaction is somewhat significant. For example, a rash will usually not pause a trial, nor will injection soreness or flulike symptoms. Keep in mind, though, that many of these pauses last for only a few days while the trial vaccine is ruled out as the cause of a major reaction. We never think about this because there has never been a rush to get a vaccine or this much day to day coverage in the past.
September 9th, 2020 at 8:05 AM ^
I am in the field, specifically clinical drug development for novel technologies like these. You always stop a trial in the case of a Serious Adverse Event (SAE). There are other level of adverse events which dont require a hold.
September 9th, 2020 at 12:05 AM ^
The case is said to be transverse myelitis. This condition might be on their watch list.
September 9th, 2020 at 12:36 AM ^
The number of test subjects for each Phase 3 trial is on the order of 30,000.
Now, about 30% of them receive placebos. They're important as a control group. But it also means only 20,000 have the chance of having an adverse reaction.
September 9th, 2020 at 4:01 AM ^
Yep. On something like this, particularly. Someone mentioned this above, but I interpret the abundance of caution as a good sign, not a setback.
September 8th, 2020 at 10:44 PM ^
I read that it was a case of transverse myelitis which may or my not be related to the vaccine. The anti-vaxxers will have a field day with this. I talk to parents in my practice on a daily basis and at least 80% are not eager to be immunized by any product that results from Operation Warp Speed. We’re in for a long struggle.
September 8th, 2020 at 10:54 PM ^
In truth, we don’t need a lot of kids or even healthy tough adults to take the vaccine in order for it to be effective. We need the vaccine to be taken by the elderly, front-line workers, those with compromised immune systems and those with other identified conditions.
September 8th, 2020 at 11:46 PM ^
I suspect you’ve just identified well more than 50% of the US population.