The original clinical trials are essentially irrelevant now for the vaccines, we have a lot more data from using the vaccines in the real world now. Of course that data is not randomized and double-blind, but because of the sheer numbers you can still do very good science on this. The original trials are also simply outdated because the virus changed, we're several big variants later now.

There are also more agencies than just the FDA that approved these vaccines, if you don't trust them specifically.

Publication bias is a real issue, and I'm annoyed that all efforts to reduce it seem to be rather ineffective. The ideas behind requiring registration of trials is good, but it doesn't do much if you don't actually police the rules. But the COVID vaccines got such enormous amounts of attention that it really doesn't matter in this specific case.

> Of course that data is not randomized and double-blind, but because of the sheer numbers you can still do very good science on this

But is the science being done "good" considering that the political and social pressures around reporting of negative results/adverse effects still exists? How do you get good data on adverse events if vaccine recipients don't even think to correlate strange symptoms x weeks or months post vaccination with the vaccine? How would you detect an autoimmune disorder with vague and nonspecific symptoms, for example, when doctors also are unwilling or unable to collect relevant data out of a combination of bias and ignorance?

It's a double whammy, because of the novelty we don't know exactly what we're looking for, and because of stigma/political pressure we are arguably not looking hard enough. Being labeled an anti-vaxxer is effectively career and social suicide, how many researchers are willing to stick out their necks, especially when rigorous proof would take years of research and funding to aggregate?

There was a very rare side effect in the Astra Zeneca vaccine that was discovered quite quickly. Not in the original trials as they are simply not powerful enough to detect side effects that rare, but in later observations. We also pretty quickly figured out that the risk is age-related, and many regulating authorities reacted based on that and adjusted the recommendations.

To me this is pretty good evidence that the existing mechanisms for detecting rare side effects work in general. One can argue about the details in this case on how exactly the authorities responded, and I think also reasonably disagree on how to weigh the risk/benefit in this particular case for specific age groups. But those are much more difficult questions based on inherently fuzzy data due to the low frequency of this serious side effect. But the detection itself worked well, and also produced very quick reactions.

There are lots of papers from researchers looking for possible side effects and then looking at population data to see if there was any change in the baseline rate that corresponded to it. It seems a pretty good way to get a publication out there to me, since it is both novel and relevant.

What? There was lots of work looking at side effects of the vaccines. The AZ vaccine was paused in several places whilst rare and unexplained blood clots were better understood. It was only because the huge numbers of recipients that such information was available. What point are you trying make? That somehow scientists are not willing to raise problems with the vaccines? That's demonstrably not true.

What is also demonstrably true is that the death rate from COVID is now negligible for those vaccinated. Might there be some super rare interaction we don't know about? For sure, but there's also as likely to be super rare interactions with COVID itself, or whatever crank treatment of choice replaces a vaccine.

>and the extreme rarity of adverse affects, I don't think it's reasonable anymore

There's a major caveat here, sudden and obvious adverse effects are rare. The subtle and possibly long term ones are still unknown. It took some 5-10 years before Thalidomide was found to cause severe birth defects, for example.

It took 4 years for thalidomide until it was removed from the market. And this is the text book case that triggered more stringent regulation for drugs.

Thalidomide isn’t a vaccine so that hardly seems relevant. We have extensive experience with many vaccines across huge populations and no reason to expect these ones to be any more dangerous than the others. Also it seems somewhat unlikely that any possible side effects, if they were to manifest, could possibly be as bad as millions of deaths and tens of millions with long term complications .

The vast majority of people objecting to covid vaccines have no history of vaccine denial, and no good reason to suspect the covid vaccines are particularly dangerous compared to the many vaccines they have accepted previously without a thought or any interest in their history, testing or method of action. It’s politically motivated from start to finish and has nothing to do with the medical facts.

The problem with this line of reasoning is that there is a huge difference between controlled trials (which are obviously imperfect themselves) and post-hoc analyses of uncontrolled real-world outcomes. There's a big leap of faith in trusting our public health authorities' ability to accurately measure and faithfully represent the real situation.

Just to name one small issue, our only measurements of vaccine efficacy are case counts, covid hospitalizations and covid deaths. Each one of these measurements is confounded by population-level differences in testing rate, testing polices (ie routine testing on entrance to hospital), PCR cycle count, and many other factors. There is no longer a monitored control group, so we can't ever account for any group-level differences or confounds. I've seen no attempt to address these issues.

We also have no access to reliable data about confirmed adverse effects. A year later, it is still very hard for a person to quantitatively assess his/her own age-stratified risk/benefit tradeoff, even with the confounded efficacy measures.

So, given all that, why isn't skepticism reasonable anymore?

I really don’t see why there is a huge leap of faith with coronavirus vaccines, but not with the many safe, effective vaccines and medications we all benefit from throughout our lives.

Have you always felt this way about the medical profession? Have you any specific reasons to doubt the medical profession and it’s institutions, across many nations and accreditation agencies, now in particular?

>but not with the many safe, effective vaccines and medications we all benefit from throughout our lives.

Because mRNA is a novel technology and that people obliviously make this argument is a testament to the effectiveness of the "safe and effective" propaganda.

>Have you always felt this way about the medical profession? Have you any specific reasons to doubt the medical profession and it’s institutions, across many nations and accreditation agencies, now in particular?

There were numerous reasons to be skeptical before covid - regulatory capture and the replication crisis in particular. Suddenly bringing these up gets you branded an anti-vaxxer. Wr shouldn't be blindly trusting our modern institution, it has strayed increasingly far from clean science over the years, now you have influences from industry and unrelated politics, in addition to the pressures that come with sticking close enough to orthodoxy to maintain a career and receive funding for grants.

When I was younger I also had much more trust in our institutions, but with age and experience I have grown to recognize how imperfect they are, and none of those imperfections disappeared when the president decided he wanted a new vaccine yesterday; in fact many of those problems were enormously amplified.

Novel medical technologies are developed all the time. Every year new life saving treatments and drugs come out that transform the lives of people all over the world. Medical technology is still very much on the vertical part of the technological development S-curve, and development and testing methodologies have been improved and refined over many decades of experience, in many countries around the world working together to develop best practices and cross-check each other's work.

Why are you particularly concerned about these ones? Are there any others of the many, many new medical technologies coming out for which you have the same concern, or is it all of them?

>Why are you particularly concerned about these ones?

I'm particularly concerned about this one because the critical safety evaluation process was accelerated by a factor of 5-10 and the clinical safety data is not available for third party review, however it was used to justify propaganda that has influenced (biased) all subsequent research. Just like software, the marginal gains of throwing money at a problem eventually approach zero, some things just take time, especially when you're evaluating biological side effects which may develop slowly.

I'm particularly concerned about this one because it hijacks your cellular machinery to manufacture a sudden megadose of an inflammatory protein (not a complete virus) which results in short term (at least) autoimmune behavior.

I'm particularly concerned about this one because it was effectively mandated for hundreds of millions of people with an obviously incomplete cost/benefit analysis and anyone who asks if maybe the benefit is overestimated and the cost is underestimated is immediately branded an anti-vaxxer/right wing conspiracy nut.

>Novel medical technologies are developed all the time. Every year new life saving treatments and drugs come out that transform the lives of people all over the world.

And how many of the candidates that make it to clinical trials never make it to market, or worse, are withdrawn after measurable harm? Now throw in the accelerated (rushed) safety analysis and systemic pro covid vaccine bias and it would be foolish not to be at least a little skeptical.

>and development and testing methodologies have been improved and refined over many decades of experience, in many countries around the world working together to develop best practices and cross-check each other's work.

And those testing methodologies still take time because of the nature of biology, you can't just snap your fingers and make adverse events happen more quickly. All those best practices and cross checking go out the window once a rigid sociopolitical orthodoxy solidifies around certain subjects, and suddenly few researchers are willing to risk careers for simply asking the wrong questions.

Nothing about the mRNA vaccine development process has been "normal", and these are emphatically not typical vaccines, this technology is unprecedented and its effects on the body are complex and difficult to study.

> the clinical safety data is not available for third party review

That’s best practice, due to the problem that access to data from past trials can bias the planning and design of new trials. It’s SOP from hard win practical experience over many decades.

I would trust sound data and transparent analyses showing age-stratified risk analyses if they existed. With all respect, what you just wrote is essentially hand-waving and talking past what I wrote. High effectiveness for elderly people (which I find plausible but also still deeply confounded by testing rate differences) in no way justifies mandates for people in their early 20s.

In some proportion of hospitals, when someone who is not vaccinated goes to hospital for any reason, they are tested for COVID-19. If found positive this is counted as a COVID-19 hospitalization. We have no access to the precise rate of these incidental hospitalizations. In some of these hospitals, it is the policy that vaccinated people who go to the hospital are NOT routinely tested unless they have symptoms. If this is the policy at a substantial number of hospitals, it could dramatically change the "effect size" of the measurements that we are talking about. The same issues essentially applies to COVID-19 deaths and cases.

Large effect size alone generally isn't convincing when you're using such fundamentally confounded sampling procedures, merged age-groups with wildly different risk profiles, and data aggregated across long time-windows with different population sizes.

These confounders are everywhere. Sort of in the way that only the dumb criminals get caught, we're probably missing many more confounding factors because our statistical analyses have limitations. Now add the stigma around questioning the vaccines political/financial pressures and you have a recipe for poor quality science.

It's not a conspiracy, people just tend to look away from things that could endanger their livelihoods. An emergent property of socioeconomic systems. A failure mode, so to speak.

Even if this particular vaccine was ok (and I still feel fine after the booster), the process seems shady if results are kept secret (having good processes is very important. remember "checks and balances")

Trial data is kept confidential due to the risk that access to the data or information about it by research teams could influence or bias the design or conduct of further trials. This is routine in medical trials based on hard won lessons from previous problems due to biased trials and conflicts of interest.

It might seem shady if you don’t know the reasons for it (what are they hiding?). I understand that, but the fact is this is standard practice and releasing the raw data would be reckless and irresponsible.

as chistians say, "turn the other cheek". (labeling did not made much harm, dont get too ivested in that)

reality is, that we can't have policy/public sentiment that is nuanced. (I heard it breaks the timecontinuum)

Find the silver lining and move on. I'm just glad that, a lot of people are in pro-vaccine side overall. While in your case it is a bit of mob mentality (mostly appeal to authority + optimism + jugde_dissagreeing_side), in the long run "pro vaccines" is (even if only on average) leaps and bounds and couple of parsecs better than "no vaccines".