The drug isn't just an inert sugar pill. Placebo's don't cause bleeding in more then 10% of the patients. Additionally it does change a metric in the right direction. It's just not a metric that's clinically beneficial.
That suggests that other drugs that also target metrics that aren't clinically benefitial might get approved.
I doubt that many people will be satisfied enough with this drug to deter signups for new trials.
It results in trials being more work because they now have to make an argument about how their treatment relates to the "state of the art". That might mean having a control group that takes expensive aducanumab.
This decision made it harder to bring new Alzheimer drugs to market as one of the people who resigned from the FDA's advisory panel explains on CNN.
Companies already knew beforehand that Alzheimer drugs are a multi-billion dollar market.
The fact that the FDA approved the drug based on reducing amyloid beta plaques, suggest that other companies are incentivied to develop drugs that target amyloid beta plaques as well instead of going for something that's actually promising.
Previous discussion of why targeting amyloid beta plaques likely isn't a good idea can be found at the recent LessWrong post Core Pathways of Aging.
The approval and explanation riled advisory committee member Aaron Kesselheim, a professor at Harvard Medical School who is also director of the Program on Regulation, Therapeutics, and Law at Brigham and Women's Hospital. In a searing resignation letter sent to acting FDA Commissioner Janet Woodcock on Thursday, Kesselheim called the FDA’s decision "probably the worst drug approval decision in recent US history."
In resigning, he joins neurologists David Knopman of the Mayo Clinic in Minnesota and Joel Perlmutter of Washington University in St. Louis, both of whom also announced resignations this week.
If you want to go deeper into the topic, learn what the things in the pathway happen to be and what we already know about how the related genes are regulated. You can search through existing papers for everything involved.
If some of the involved parts of the pathway don't have Wikipedia pages, the task of writing a Wikipedia page about them to explain what information there is about them is a useful way to study them.
There are a lot of different genes and there's more reserach interest in some of them then others. If you can summarize on Wikipedia what a gene does for which there currently isn't that much research interest you might produce an article that's useful for anyone who cares in the future about knowing what the gene is about.
The patient's body is made of atoms that move according to physical laws.
Yes, but making treatment decisions based pathophysiological theories goes counter to what evidence-based medicine is about. The idea of this method is that it's going to be used by doctors practicing evidence-based medicine.
You can argue that evidence-based medicine is a flawed paradigm and doctors should instead practice physical-law-based medicine (or whatever you want to call it) but that's a more general discussion then the one about this particular heuristic.
Assume the doctor is rushed, and can't do a proper job (or perhaps lacks a relevant rapid test kit and/or lacks the ability to construct tests from first principles because of a brutally restrictive regulatory environment in medicine) and so can only go off of subpopulation data without measuring the patient for direct mechanistic pre-disposing allergy factors
Even if the doctor could run all the tests they desire on the patient, the orginal study that said 1% of the control group and 2% on the real drug does not contain information about what pre-disposing allergy factors the patients in the trial had.
Blood clots are not independent from VEARS reports. VEARS reports are how the FDA gets the data about the Blood clots.
The VEARS reports give them reports about many different kinds of issues and if there are many issues to look into and they are understaffed it's reasonable to put more attention on the blood clots issue then other issues given that blood clots in the brain are a serious issue.
Even so, I'm concerned about the reputational and public-safety consequences of not simultaneously gathering "no side-effect" reports
If you look at this thread there are plenty of people who do post "no side-effect" reports. When people send me those reports privately, I do post them here even when it's not the information that's valuable to me.
Doing anything that would effectively stop those reports from happening would be bad.
The question is whether to do this as a poll or not and not stopping the gathering of "no side-effect" reports.
Even so, I'm concerned about the reputational and public-safety consequences
Optimizing for reputation instead focusing on truth seeking is dangerous. This kind of reasoning killed a lot of people in the last year.
It's not easy to choose truth seeking but in the end that's what the rationalist project is about. It's not like I don't have impulses in the other direction as well, but then I go back and optimize for truth seeking even when it's an effort and comes with risk.
To get back to the poll question, there are two choices:
Have an anonymous poll. This opens us up to outsiders coming and creating a lot of false votes.
Have a named poll, this discourages people who might say something inconvient from participating.
Having cost/benefit in mind is not enough. If you don't use a heuristic like the one Anders writes about, you need either causal models or something like prediction-based medicine which gives you a way to decide which of two algorithms for decision making is better by looking at the Briers score (or a similar statistic).
The bed market is similar to a prediction market but less efficient then a good prediction market. If people buy hotel beds and then resell them that adds a lot of overhead that you don't have if that market function is done through a good prediction market.
From another member that's also in the 25-100 karma range:
A family member of mine works in health care and has seen a representative sample of more than a thousand vaccinations and the side effects. Their impression is that the side effects are the strongest after Sputnik V, the weakest after Sinopharm, with mRNA-based vaccines being somewhere between the two. They reported no obvious cases of serious long-lasting side effects, only anecdotes of e.g. lasting loss of sense of smell that may or may not be linked to the vaccine. They has no experience in rationality.
Let’s say you are extremely confident that the Tokyo Olympics will take place this summer. You could place a wager on the Yes outcome by buying Yes shares at $0.91 per share (Total cost, ~$0.93 per share, as there is a 2% Liquidity Provider fee for market makers).
Previous suggestion on LessWrong suggests that savy uses of PolyMarket don't do that. They would create a Yes/No share pair and then sell the No for a few of 2% of $0.09.
While arriving at an accurate probability that a sporting event will take place is perhaps not as useful to society, when it comes to markets in health, economics, and politics, there is utility to forecasting an accurate probability of an outcome.
I don't think that's the case. Having access to an accurate probability about whether the Olympics will tell local hotels about how important it is to have a lot of beds available. It will tell AirBnB whether it makes sense to run ad campaings to get people to rent out their homes for hosting tourists that come for the Olympics.
It would be great if we would have a bunch of physicians that practice prediction-based medicine and could run a trial whether physicians that use the status quo method are better or worse then those that use your method to predict side effects for their patients.
While I do appreciate the theoretical argument it feels like our medical system is deeply flawed when it doesn't provide an easy way to run a practical way to run experiments whether the technique you propose is helpful for practicing physicians.
Is there a pithy summary which explains the basic object level idea in a sentence of four? Like when "Mindel C. Sheps proposed a principled solution", what was it? Is her solution the same as yours, or not?
Have you watched the video? To me it seems like a clear presentation of the basic idea.
It kinda seems like the idea is "use causal graphs to formally reason about diagnosis and treatment decisions" but I don't think causal graphs were common in 1958.
No, the causal graphs are used to justify that the heuristic proposed in the video is better then the status quo.
At the least, I would have expected this to be a poll, so as to get a denominator.
A denominator doesn't help with falsifing the thesis. If we do get a bunch of reports of significant side effects and a bunch of reports of no side effects, the conclusion wouldn't be that the thesis is correct but that it deserves more expensive attempts at verification.
I don't see anything significant to be gained by having a dominator.
My thought process was:
I could run a mechancial turk experiment to get a representative sample and get representative numbers from that.
That would cost money and I haven't done it before, so is there an experiment that would falsify the thesis that's cheaper to run?
If the situations looks like what Kirsch is describing, we there are likely rationalist with signficant side effects. This not being the case, would suggest that the thesis of Kirsch is wrong.
Let's write question to get to know whether there are rationalists with significant side-effects.
If there are I might even get someone else to run the mechanical turk experiment ;)
The fact that we have a lot of autoimmune disorders suggests that the negative selection step isn't perfect.
If you want to vaccinate I think you would start with a peptide that's not identical to a transporase subjection but similar and first give a vaccination dose against that. Then you vaccinate again with a peptide that's more similar and work your way towards transpoase.
Reading more it's likely that PGBD5 actually gets used productive in the brain to increase cell diversity and thus isn't as good of a target.
PGBD5 being upregulated in Alzheimers and in brain tumors makes the PGBD5 Alzheimers link interesting. If PGBD5 gets constantly expressed in train cells and creates a lot of DNA damage, it's plausible that this leads down the line to enough mutations to be a problem and Alzheimers appearing.
Edit: somehow I mistook the link to be about Alzheimers because that's what a googled for. It's instead about sporadic Creutzfeldt-Jakob disease. I however have found another study that does make the link https://doi.org/10.1371%2Fjournal.pmed.1002487
Having been able to predict that link between Alzheimers and PGBD5 ahead of time seems interesting.
California in particular will be a region to watch for new cults - our data clearly support the popular notion that California is the cult capital of the world, however only two cults have formed in California since 1990.
Raising real estage prices might be one of the key reasons why less cults formed in California. Getting a boulding to host a lot of cult members together just got a lot harder then it was in the past.
Seems like you’re looking for anecdotes rather than data which strikes me as strange for a purported rationalist.
There's a hypothesis in my post and I'm running a cheap experiment to disprove it. Absences of anecdotes would falsify the hypothesis.
If the hypothesis isn't falsified that would justify running more expensive experiments. Having detailed accounts of side effects in turn allows setting up expensive experiments in a more targeted way.
"Anecodates are not evidence" is a slogan that's quite fundamentally opposed to what this community that founded on ideas like everything is Bayesian evidence is about.
If it helps,
It doesn't help for the experiment that I care about, but I'm not going to do anything to supress any data reporting.
The French government has an official designation for cults. While I might argue that some groups are on the list that shouldn't be there and political pressures might also have changed over time to change the borders of the definition, I would expect them to be one of the best sources for looking at the changing number of cults over time.
Universally, accepted medical ethics according to which our system runs suggests that biases in the direction of finding side-effects of medications is generally good. Doctors don't report about every patient to VAERS but about those that are worth reporting about.
I do think that for people with signifanct side-effects describing them is no unnecessary burden and those descriptions is what I'm looking for.
A pure poll would better be done on mechanical turk, survey monkey a similar service that actually give you a representative sample. If someone wants to run such a poll I'm would be happy to see the results.
A general LessWrong survey in the form of our previous survey that includes the standard questions of previous surveys while also including questions both about COVID-19 infection and side-effects while also including questions about vaccine's and side-effects would be another worthwhile project. It's a while since we had a survey and a survey that includes risks of both COVID-19 infection while also includes possible risks of vaccine would be very helpful for making useful decisions.
Note that answers here, on their own, will give a one-sided view of the side-effect situation which may mislead everyone's Systems 1.
If you believe that we should expect a certain number of side-effect reports even if there's no issue with the vaccine (and reacting it would mislead System 1), how reports of significant side-effects do you think we should expect?
Anonymous post from a user with between 25 and 100 karma (range wide enough to be anonymizing):
"A few COVID vaccine data points for you, from the people in my close circle that I know about.
Me, M, early 40s. One dose of Pfizer. No side effects. Mother, late 60s, F. Two doses of Pfizer. No side effects. Father, early 70s, M. Two doses Astrazeneca. No side effects. Brother, early 40s, M. One dose Astrazeneca. Reported side effects. Thinks it may have made him react to a spice in a meal he made. Colleague, mid 40s, F. One dose Astrazeneca (I'm unsure on that). No major sure effects. Reported feeling grotty / wiped out for a day or two.
There are several other people in my circle who have had vaccine doses by now where I think it's quite likely I'd have heard of they'd had adverse reactions, but I've not had specific conversations with them about it. So I'd assume most of them have had no significant reactions."
It's worth noting that inventing good ways of measuring issues is as important for developing the field as developing interventions.
I'd love to see posts on LessWrong that purely focus on the way to measure a particular issue inside of rationality. We had some of that in the past with credence calibration but it would be great if talking about how to measure what we care about would a larger part of the rationalist discourse.
More concretely, if my proposed model is accurate, then one explanation of why this issue is not more central to the modern left is that the transactional costs of entering the left's zeitgeist have so far not been paid.
Without having a good idea whether the costs are equivalent to ~10,000 dollars in effort or ~100,000,000 dollars I don't think that explanation contains much information.
There are some issues where it's very cheap to put them into public attention and others where it isn't.
If I would ask "Why don't have have interstellar travel?" answering "Because the costs of developing interstellar travel haven't been paid" might be a correct answer but at the same time completely useless for understaning the challenges of developing interstallar travel.
For example: If we can afford to give half a billion doses of COVID vaccine to poor countries, why can't I as an American Citizen in the Public System, get the type of mental health care I need? The money to buy those doses going to other countries could fund the type of therapy I need to heal my severe PTSD, but instead I don't receive appropriate care because the money isn't available.
Developed nations can't afford not to give a lot of COVID vaccine doses to poor countries. Not giving poor countries vaccines means giving COVID-19 more opportunity to mutate and cause a new wave in developed countries.
The cost of a new wave in a country like the US is so high that it makes a lot of sense to prevent it buy giving poor countries vaccines.
Why is it the needs of poor people in other countries are often times prioritized over the needs of poor Americans?
Americans whether poor or rich need poor people in developed countries to take vaccines. Pandemic prevention doesn't work if you don't think globally and fight viruses where ever they are. Fighting viruses while they are in foreign lands with vaccines is similar to send the military to foreign lands to prevent people from attacking your homeland and generally there's much more money wasted in military for preventing foreign threads then in public health.
In general the US spends a lot less on foreign aid that most people assume and a lot of the money it does spend gets spend for geopolitical aims such as paying off the Egyptian millitary for accepting Israel as a state.
Mask synthesis: Use elastomeric respirators. Elastomerics offer better fit and more protection (N100) than any disposable PPE. If necessary, develop respirators that fit even better with little to no fit testing (like PAPRs).
I think you get to that position by using first-principle thinking which is a different way to reason then the dialetic way. Practically, first-principle thinking is also seldomly done by those making health policy but we should keep different reasoning strategies apart as rationalists when we want to understand how to think about thinking.
As far as the substance matter goes:
"Use elastomeric respirators" is a decent personal decision if you are in a jurisdiction that doesn't require you to wear a FFP-2. It's not a general policy position.
"Require everyone to wear elastomeric respirators" would be a policy position but there are certainly contexts where those are unpractical.
One problem with elastomeric respirators is that they are generally designed for a use-case where filtering exhaled air isn't central for that use-case they often have ventils that allow exhaling unfiltered air. From the outside it's hard to know whether someone wearing a elastomeric respirators is filtering their exhaled air or isn't which makes it harder to enforce policies around them and many people won't understand that they should not use the exhaling vents. While it might be better policy it isn't a slam dunk.
How confident are you in this being the main reason and not other suggested reasons provided in this thread?
One type of person is going to see a bad seed when they see this story, another type of person is going to see a corrupt institution.
The fact that the story exists and there doesn't seem to be a follow up and some agency felt it's responsible for fixing the issue is part of the story.
You can argue that something is a bad apple when the bad apple gets removed by the owner when attention comes to it.
I remember when there was a lot of attention being given to Amanda Knox here on LW. Someone asked a similar question as you...something along the lines of "Why aren't more people up in arms about this?"
My question isn't about the number of people who are up in arms but about understanding the makeup of the modern left. In this thread you find people asserting that psychatristic patient are in a similar reference class as child abuse, animal suffering in factory farming and prisoners being mistreated. The fact that it gets a lot less attention then other topics in that reference class is what the question is about.
I would answer that systemic issues are more important then the fate of individual people. To the extend that the Amanda Knox case is about the Italian Justice system being bad and in need of reform, that's largely a topic for Italians.
Kirsch (blue shirt guy) seems less careful than the other two, and may or may not be a crackpot.
We should still try to verify their claims. Are these guys who they say they are? Do they have valid credentials?
Without having watched the video my prior before this conversation from what Steve Kirsch did before:
Steve Kirsch was listening to Corona virus experts (experts that studied Corona viruses before the pandemic) and organizing funding clinical trials for the drugs those experts considered promising (and invested significant personal money into it). He's one of the few people who scored A+ in 2020 at fighting COVID-19 by being sensible.
When we discuss whether he's a crackpot we should also discuss whether all those people in power who initially said masks don't work listening to think tanks instead of the most qualified experts should be considered crackpots. I think the case for Fauci being a crackpot is a lot better then for Kirsch.
Robert Malone wrote https://www.pnas.org/content/86/16/6077 which is a paper about using mRNA from 3 decades ago. When it comes to inventing mRNA vaccines there were a lot of steps on the way and it's unclear whether any single person should be considered "The Inventor" but he seemed to played part in it.
The procedures for these hospitals would be hard to change.
Hard in the sense that there's a lot of lobbying power behind the legacy system but that's not for lack of alternatives.
Prediction-based medicine where one doctor makes predictions about what's likely to happen when the patient doesn't get hospitalized and what happens with them when they are hospitalized and then letting another doctor make the decision to hospitalize or not hospitalize isn't very hard.
Then you fire those people who make bad predictions because they are unqualified to do their job.
I think it's perfectly fine to require the opinion of two doctors to take away the freedom as taking freedom away is a major move and I think it's reasonable to require the ability to make accurate predictions about harm to justify taking away someones freedom.
There's an enormous amount of work into fighting child-hood abuse in the last decades. We criminalized hitting children and have see-something-say-something as a paradigm for whole of of different policies. While those policies don't bring childhood abuse to zero society tries very hard. The LGBT community that used to ally with pedophiles stopped doing so and people who are advocating for the marginalized group of pedophiles are now clearly out of the coalition because caring about children not being abused is central to the modern left.
That's such a strange word. The word incurable is a license to avoid accountability for not curing illnesses. It's a class of illnesses for which psychiatric hospitals lack the skills to cure them at this point in time. It's a feature of the psychatristic community and not an inherent feature of the disease.
As the Schizophrenia Research Project suggests it's plausible that for a good portion of them the drugs that the psychologists give them inhibits the natural healing process.
I think "why doesn't it get more attention" is the wrong question to ask. "What's the better solution" and "what should I do to improve things" are likely to get more traction here.
This looks to me like it comes from a mindkilled point of view, that discount the value of knowledge.
"How should we solve X?" is a different question from "Why is the current political coalition the way it is?"
The first question is about solving a political cause. The second question is about understanding.
In the model that deluks917 proposes animal rights, prisoners and psychatric patients should have similar amount of backing for their cause. In our world that's not the case. There's something wrong in the model. The rational way to deal with unexplained derivations from models is to try to understand them to update the model.
The fact that people like shminux and deluks917 mistakenly put it in the same reference class as problems that the modern left cares about is interesting and suggest a broken model.
In some way we treat mental patients even worse then prisoners. Prisoners don't get medicated against there will.
Being inside the system I expect you to understand it well. Given the suggestion in other comments that the problem might be due to a lack of obvious policy proposals it would be valuable to have easy to understand proposals. Do you have one? I think it would be valuable to have it spelled out.
There are certainly other possible ways to make address the mask issue.
I can improve my decision making over that of people who simply follow the official recommendation a large percentage of the population likely won't be able. In a situation like a pandemic I'm very dependent on the actions of others around me.
There are some diverging interested between the population of Switzerland and the population of the whole world.
If you cooperate with either of the group agenda of the groups you belong to, that's not antisocial.
Systematically, I do believe that as an individual it's worth to cooperate with vaccination policy of the country in which you live and that the more people cooperate with the health policy of their home country the more effective the policy will be generally as there's less resources spent on internal friction.
If you live in Australia that has strong border I think you can argue that controlling Covid is more or less fine. In a country in Europe with relatively open border there's no control and the Delta varient multiplying in some corners.
Stamping out COVID-19 everywhere is a way to prevent further dangerous mutations and for that it's good for Western countries to go to herd immunity.