Two important points:
a) Trials pause. All the time. It’s a normal part of good science. It may be nothing. But…
b) Trials fail. All the time. It’s a normal part of good science.
And that’s why no treatment should be overly hyped or promised before making it through trials. https://t.co/lR3FygfjTE
— Daniel Liebman MD MBA (@D_Liebman) October 13, 2020
There are (to use a technical term) a bunch of COVID-19 vaccines and therapeutics working their way through clinical trials. Over the past week, several notable trials have been paused as there have been significant adverse
reactions events that need to be investigated.
THIS IS NORMAL!
We know historically, the funnel from a good idea to promising molecular results to mammalian trials to small scale human trials, to large scale human trials to Phase 3 trials to determine safety and efficacy to final approval has tremendous attrition. Things fail at every point in the process. Things get paused at every stage as weird things happen and need to be investigated to see if these are commonly weird things happening or one in a million events.
And that is okay.
Hell, I would be far more suspicious of the trials pipeline if there have not been stops and restarts. Given the number of vaccine candidates that are past Phase 1, I would, just based on historical record, be shocked if there was not a failure at both Phase 2 and Phase 3. Big failures and little failures are to be expected. Pauses are part of the process.
If Trump were conducting the trials, there’d be no announced failures or setbacks.
In terms of science and making sure that things work, obviously yes.
In terms of this ever ending and me getting to do something other than work, cardio, and going to the grocery store, AAAAAAAAAAAAAAAAH!
@Baud: A trump trial would be him looking at the size of his kickback and saying Yea or Nay based on it’s reflection of his self importance.
I have some confidence relief is on the way simply because of the number of vaccines. One or more of them should work out. The whole world is working on the problem. Everybody wants a solution.
My BIL was a researcher both in big pharma and venture capital startups, and the typical course was promising, promising, promising, promising, shit, not better than placebo. Lots of heartache thinking he had something that would make a real difference that, at the penultimate point after years of effort, didn’t.
Trump would assign the trials to Prince Jared, who would make a dog’s breakfast of the whole business. Then “your favourite President” would announce a bigly, powerful success, the best Covid-19 vaccine in the world. Which would turn out to be ineffective.
This situation is tailor-made for stock manipulation.
Safe bet he’ll do that yet, except instead of being ineffective it’ll just be inexistent.
This isn’t the real issue by a long shot; the real issue is effectiveness and what level of protection occurs. If it is 30% or lower that will cause major problems. Worse, if all the various vaccines that are produced next year offer varing levels of protection and none are anywhere near 100% people will be confused and less likely to try a vaccine. Hopefully, the virus drifts slow enough that the vaccines are good for at least a year. These are the real issue and why it always takes years to get a vaccine – takes time to get real results that are well understood as well as safe.
Gin & Tonic
@Amir Khalid: Having just fed the dog her breakfast, I’m not sure why “dog’s breakfast” is a pejorative.
Snarki, child of Loki
“inexistant” is better than “Lysol+Bleach+TRUMP brand licensing”, which is what’s more likely.
@Gin & Tonic: it goes with demonizing dogs, which seems to go hand in glove with denying humanity to various people.
Never trust someone who thinks “dog” is an insult.
Yesterday BigMediaMatt was chastising surveyed people for not being willing to try a virus if one were available right now, with no concept of what facts necessarily would be embedded in that hypothetical.
anyone following Putin’s vaccine trials? More info on that could be useful as an educational tool to inform the American people what happens when you don’t follow protocol. Sucks for the Russian people to be sure. But also an example for the Trumpsters of what happens when you politicize science and capitalize medicine. Dolt thinks he’s cured but that’s probably only the steroids masking the worst of his symptoms. He’s gonna keep getting his fix from his fake doctors and end up like Elvis and Michael Jackson sooner or later. He’s also probably still infectious. Sucks for the American people too.
In my time working at various biotechs, tracking adverse events seems weird but is super important. Every bad thing that happens to a person in a trial has to be tracked. Say you’re doing a clinical trial on a promising new cancer treatment and one of your subjects gets hit by bus. You have to enter that as an adverse event. But, TheOtherHank, what does getting hit by a bus have to do with a compound that treats cancer? Nothing, probably. But by definition this compound has not been put into people before. What if it has some unanticipated activity that makes people like to step into traffic (or to be less snotty, interferes with their ability to assess risk). You have to track everything so if strange things happen that can’t be explained by chance you notice it before you’re selling it to people.
@Gin & Tonic:
I suppose it depends on what one gives a dog for breakfast. I could have said “pig’s breakfast” instead, but I’m not sure if that’s halal.
No, I think it just reflects that dogs tend not to be fussy about culinary presentation.
TS (the original)
From the article linked in the tweet
This news casts doubt as to the wisdom and safety of the approach used by President Trump’s medical team. Trump, who became infected with SARS-CoV-2 sometime in late September, received a combination of medications, including a cocktail of monoclonal antibody for which there is scant clinical and safety data.
Whether this current setback will turn out to be a small safety problem or a large one remains to be seen. Either way, this episode highlights the perils of proceeding with giving patients unvetted treatments on the basis of the fool-hardy premise that says, “what’s the harm?”
@Gin & Tonic: Anyone who has ever seen their dog snacking on Crunchy Clusters out of the cat’s litter tray might have other opinions.
You know that thing when your dog licks your face to demonstrate showing its affection? Actually it’s saying “C’mon Mom, regurgitate some warm partially-digested food for me, will ya?” in puppy-talk. They are Very Disappointed in you when you don’t oblige but they love you just the same.
Anonymous At Work
People in glass houses shouldn’t make sausage, especially with “natural casings.”
This is just science on display and paid attention to by journalists and editors who, in bygone years, would routinely produce pieces overhyping Phase I results without understanding how much was left to do.
Given the current situation (second wave hitting everywhere, Northern Hemisphere going into winter, hygiene compliance fatigue etc.) a COVID-19 vaccine which passes safety protocols and has 30% effectiveness and provides a year’s protection is going to be welcomed because there isn’t anything else right now. There will be better vaccines in the future with higher efficacy providing a longer-lasting immunity for the recipients but until they arrive the not-very-good first-generation vaccines will be manufactured and deployed to at least blunt the spread of this disease a little.
Much later, the ads for the medication will show smiling people doing fun things with their friends and family on a sunny day, while the fast-talking announcer says “Common side effects include being hit by a bus.”
@Zzyzx: Try working on a clinical trial. :) I was once running a Phase 1 trial for what’s called a first-in-class drug. That’s where a drug of that type or that mechanism of action had never been put into humans before. I spent months waking up at 4 am hyperventilating, wondering if we had missed something in the animal tox data, or if we had picked the right dose escalation for the trial, or any number of other things. When you get right down to it, there’s no way to know how something will work (or not work) in people until you do it.
@TheOtherHank: Isn’t that one side effect of owning (I use that term loosely) a cat? The reduction in fear response by people due to Toxoplasmosis?
To be pedantic, those trials have encountered adverse events, not necessarily adverse reactions. Part of what needs to be investigated is whether they really are adverse reactions to the treatment. After all, the people in a clinical trial generally have an underlying condition that can cause all kinds of problems. Even in a vaccine trial, it’s possible one of the healthy subjects had a previously unknown problem that’s not related to the vaccine.
@Gin & Tonic: I always assumed it was about the marked tendency of dogs (as much as I love them) to eat vomit or poop. Or about the dog’s breakfast after it came back up again. Or just about the habit of some people of feeding dogs a mess of table scraps.
@Robert Sneddon: I agree absoultly that even 30 or just 20% protection is vastly better than no vaccine; however, that might destroy trust in future vaccines when so many people still get ill with the vaccine resulting in far more deaths overall when a far better vaccine is produced. That was the concern I was getting at very poorly.
@Cermet: Supposedly. There’s this one guy who keeps putting out papers about the psychological effects of toxoplasmosis infection in cat owners and every time he does, it makes the papers, but the whole business always sounded shady to me, though maybe that is just the brain parasites from kitty talking.
I recall one of them claimed that toxoplasmosis made people act more like their national stereotypes: it was something like, Americans become more violent, French become louche and horny, Russians get more drunken and maudlin, etc. The whole thing smelled fishy as hell.
@Roger Moore: Updated and thank you!
@Cermet: I think the FDA standards for mass distribution require at least a 50% reduction in infection. Don’t know how they decided that–maybe it’s weighing the benefit vs. the behavioral danger of people thinking they’re immune because they got vaccinated.
This is also why, you know, there are ~29 vaccines under development, rather than the second or third team/company that started working on a vaccine saying “you know, that first team probably has this, there’s no reason for us to waste our time duplicating their work”.
We have ~29 vaccines under development. If 1 or 2 of them prove safe and effective, that’s all the success we need, and it will have been worth it to the global community to have spent the time developing so many failed attempts in parallel to get to one or two successes that much quicker.
@Matt McIrvin: Derek Lowe’s “In the Pipeline” blog had a post on the 50% rate. I don’t think he got into why the FDA set that as the minimum acceptable limit. He did discuss how they go about verifying the number in this case, since they’re not doing challenge trials (pesky medical ethics).
One interesting thing is that the better the vaccine is, the sooner they can statistically detect that, and the higher the confidence in the result.
@Cermet: Well, COVID is near the upper limit for a RNA virus with 10,000 pairs. So it’s VERY sophisticated, BUT it mutates very slowly.
I notice that at least one of the paused trials involves a modified adenovirus. Are they easier to engineer, because they do seem a bit dangerous.
@Cermet: Not only this, but we as a nation have bought into the notion that every medical problem is a nail and that drugs are the most suitable hammer. Part of this comes from the disproportionate level of research funding that now comes from pharmaceutical manufacturers. Don’t get me wrong, a vaccine with at least 50% efficacy would be a great thing, but the reality is that we could obtain a lot of the benefits of so-called herd immunity simply by engaging in more effective testing, tracing and social distancing. They understand this in most African countries because they know that they will inevitably face profound financial and logistical hurdles to relying on vaccines or drugs or hospital resources to treat diseases.
@artem1s: Trump is a good candidate for re-infection. It might be useful to science if he does get the bug twice. Maybe the only “positive” in his miserable existence.
The root cause is income inequality. Like so much in our society, our pharmaceutical industry targets things that benefit rich people because that’s where the profits are. Something that benefits all of society but has a limited profit margin isn’t very interesting to big business.
Somewhat off topic but pertinent to current events:
Who exactly benefits from a repeal of the ACA?
Insurance companies value stability and seem to have adjusted to the ACA environment. The recipients certainly don’t benefit from having their insurance ripped away. Even those not covered by the ACA benefit from mandated coverages, like keeping “kids” on their parents’ policies. Hospitals and doctors don’t seem to oppose it. And the health insurance industry isn’t that large in the grander scheme of things to have much effect on the economy.
I spent most of my working career with crappy self-employed-person health insurance. Unfortunately I was in the 60+ pre-Medicare age group and am relatively healthy, so the ACA didn’t really help me personally, but I certainly see the value from a public policy standpoint.
So who benefits from the chaos caused by torching the ACA? I don’t get it.
I don’t know that anyone really benefits from repealing ACA, but some people may want to repeal it out of ideological motives. I also think there’s some truth to the idea that the Republicans, as the small government party, want to make sure there are no essential government programs because that would encourage people to see the government as important and necessary.
@Neophema: It’s totally ideological. Republican agenda now seems to revolve exclusively around maintaining the fiction that yes, we can resurrect the 1950s. This hasn’t yet morphed into a determination to repeal Medicare or Social Security but it wouldn’t surprise me if that’s next.
@Roger Moore: It’s more subtle than that. Pharma manufacturers have for the last 30 years concentrated their resources on chronic conditions with a view towards marketing products that will generate revenue over the life of an individual taking them. It’s not that they would not follow up on a dramatic cure if they had good enough clinical research (Gleevec and the Hep C drugs are proof of this) but it’s not where their resources have been directed. They deflect cost concerns by supporting (generally) policies that expand insurance coverage. They oppose only those elements that tie their hands when it comes to pricing. Indigent people benefit from those policies, of course, but they would benefit more if those programs did more to reduce the cost of drugs.
I don’t blame manufacturers for pursuing their own interests. I blame public policy for not funding public health, or more research into non-pharmaceutical treatments or even cures, and for not being stronger in limiting the freedom of manufacturers to establish prices, which does not happen for any other kind of service reimbursed by a federal program.
Now, if you are talking more generally about health care and medical procedures overall, there is no question that hospitals and all kinds of other entities are focused on doing those things that pay well, even if they don’t create any particular boost in public welfare. I am not sure many people understand how much our response to the pandemic should be viewed as a crash course in how disconnected American medicine is from public health.
In semi-related news, Elizabeth Holmes’ motion to dismiss the indictment has been denied. Trial is tentatively set for next March.
‘Maybe she and Ivanka can be cell mates.
@burnspbesq: Holmes is a sociopath. It’s impossible to see her in any other light.
I just love how this blog has authors that will strike out “reactions” and replace it with “events” (because we don’t know if it was a reaction, yet).
And damn it all, I can’t think of anything to say in an Agent Smith voice that would be funny, and complimentary to a “Mr. Anderson”. Sigh.