Here is why we don’t have more cures.

1. The science is lacking. Contrary to the article— this remains an issue. It isn’t honest to pretend we have the science to “cure” every disease. Some diseases are caused by genes so large, and so broken, that we do not yet have a way to correct or insert or remedy the problem. Some diseases have targets, but our therapeutics cannot reach the target. Some diseases have targets that are shared by healthy tissue, and our therapies need more effort to be gated solely at the abnormality (LOH HLA CAR-T is trying to do this). Some diseases accumulate damage throughout a lifetime, so fixing the root cause might be too little too late. Some diseases are completely ill-understood. If I were to quantify the sources of not having more cures, I would say the number one problem remains: the science is lacking.

2. The science is misleading. Yes, we have science on a topic, and wow, it really looks like it has found the underlying error, but it is irreproducible, flawed, broken or worse. This matters because it is hard to train AI on these data and expect insights rather than confusion.

3. Early clinical trial regulations is broken in the USA. The central thesis of the author’s is definitely a factor. I am not sure adaptive trials are the answer. I think platform approaches can be better. I think some investigators, with proven track records, should be credentialled and be able to skip some FDA oversight. There are many efforts in this space, which we began at FDA.

4. Separate IRB boards. The author faults separate IRB boards as being redundant, but one irony she misses is often, despite several boards, none do a good job and unethical trials still happen. I would favor a single ethics clearance, but done competently.

5. Manufacturing standards are too onerous. I agree, and drafted many CMC flexibilities at FDA. It is a pity small companies do not often read and take advantage of them fully.

6. China is beating us. This is a double edged sword. Yes, you can try more things in China, and that means you can innovate faster, but also kill people in novel ways with failed drugs. China, spoiler alert, has a bit of a fraud problem. Hard to know what to trust with purely Chinese data, and that is why FDA has moved to reject 100% China registration studies.

7. Too many trials which actually don’t provide useful information. Not all trials give information. If I do a trial of 5 cancer patients, and I give each patient a different combination of drugs, and one has tumors shrink— have I proven anything? Maybe the other combinations would work in other people— I only tested in 1. Maybe the responder, responded because of one drug or a couple or all of them. One of the examples in the article- of a child with cancer who gets a bespoke MRNA vaccine in Germany- struck me as unpersuasive because I am unsure if the child was helped or hurt by the shot. More informative trials would be a boon, just giving things haphazardly is not science, it is Brian Johnson.

8. The bar for FDA approval is too high. I don’t think I would say it is "too high,” but, I would say in many cases it is irrational. As I explained, asking for 2 clinical trials, when one or both have an incorrect control arm, crossover, blinding, concealment, power, etc. is likely worse than the default we set at FDA of 1 clinical trial— which actually answers a scientific question.

9. When we do have advances, these have poor market diffusion because they are unaffordable. A cure that no one can afford helps no one.

10. When we have duds, these often steal considerable money because of rhetoric, advertising or worse. The amount of money you can make from a drug that doesn’t work is so astounding, it is hard to work up the energy to make a drug that does work.

We showed several things. The price of an anti-cancer drug exceeded $100,000 per year of therapy. This represented a relentless increase since the 1990s. The price of a cancer drug had nothing to do with its mechanism of action-- whether new or next in class— it was not related to how much longer it helped you live, and ironically drugs that had merely been proven to shrink tumors cost more than drugs that extended survival.

We wrote review articles which were highly read and cited. A few years ago I gave a lecture summarizing some of our findings. Here's the link.

https://youtu.be/wJJzZaZzgSc?is=HDrUxS06o1YFddIO

Now it's 2026 and the only thing that's changed is the price of drugs. It's a lot higher now. Just like a decade ago, some drugs extend survival quite a bit, but others are much more marginal. Some may not work at all.

There's a new crop of researchers and they're studying the same things. Is the price linked to novelty? Is the price linked to the regulatory pathway? Is the price justified by R&D outlays? Their papers look very similar to our papers just with a slightly different y-axis.

What lessons have been learned?

In the last decade there have been a number of policy movements to shift the burden of payment from the patient to the payer. This is resulted in fewer stories of a desperate patient who cannot afford a drug. Ironically, this has largely eliminated the public outrage over this issue, allowing the prices to soar ever higher.

Many argue that the high prices drive innovation, and surely they have a point. The more incentive there is in a space, the more companies will be in that space. What remains totally not understood is the relationship between spending and innovation. I've seen no well done study on this topic. Is the relationship linear? Is there diminishing returns?

It is clear to me that continuing to study and publish on this topic— rerunning old analyses—is unlikely to achieve any policy goal. 15 years ago I felt like some of our findings and methods were novel, yet there are only so many arguments one can make and the last 5 years or so have seen intense rehashing to smaller audiences.

The politics of this issue are bipartisan. Both political parties are unwilling to challenge the status quo. Ironically, the single best thing that could happen to this issue is to somehow transform it into a partisan issue. Turning this into a populist partisan issue would open up opportunities politically that do not exist currently. My advice would be for the political right to take this issue, which I believe is broadly popular to the base.

I find it difficult to be sympathetic with physicians who complain about high drug prices while simultaneously promoting or running randomized studies that generate tremendous market share for marginal products, or generate tremendous market share for products tested against unethical control arms. Yet, sadly this is the norm.

All of the efforts to mandate payment and shift the burden have backfired tremendously, as this removed the last downward pressure that existed 10 years ago which was public shame and outrage. It's hard to have a 60-minute special on the topic when insurance picks up the tab in full, and the only person who feels the price is all of us when more of our paycheck is swallowed up by premiums.

The Atlantic has interviewed the baby’s father and mother (a nasty bit of journalism imo), and seemed to argue that measles is the cause of death— but notably what a parent was told/ believes is not the same as an independent medical appraisal. Parents can be misled. The other is age unknown, co-morbidities unknown. The CDC meanwhile has not counted those deaths. What is going on?

Another issue has entered the political fray. Whether these 2 deaths are possibly, probably, likely or certainly due to measles is now hotly debated, and it joins a growing number of medical issues with different opinions by political party.

Gender medicine: Democrats are pro-youth gender transition and Republicans are against it. Masking: A poorly fitting surgical mask is the MAGA hat for Dems, most Republicans avoid it. SSRIs: Dems happy to take it while pregnant; Republicans are extremely cautious about pregnancy and giving it to kids. ADHD: most boys under-diagnosed according to Dems; we are medicalizing being a normal boy, according to Republicans.

Generally on all these issues— I think the Republicans are closer to reality.

On the 2 measles deaths— it is amazing that Josh Shapiro did a press conference, proudly announced the deaths were in the unvaccinated, but completely abdicated giving any additional information. I suspect history will view his actions as reckless and ultimately contributing to vaccine hesitancy— conspiracies love a data vacuum. Also, FWIW, no matter how influential you think Bobby Kennedy is, I can assure you he did not convince the Amish to avoid vaccines. They reached that conclusion before he was born.

I used to think it was bad that medical issues became polarized, but now I think the only thing worse is when we are not allowed to debate the issues. Consider if COVID was allowed to be openly debated. What if kids deaths were analyzed this way.

How many healthy kids died of COVID?

A German study shows COVID doesn’t kill healthy kids, and yet US totals reach a different conclusion.

What is likely happening is that the US figure is likely wrong— inflated— to suit political purposes. The US government routinely counted kids who were hospitalized with a broken arm who were incidentally found to have covid on PCR (universal testing). At other times, the US government deliberately refused to separate the risk of death in healthy vs kids with comorbidities. All deaths are tragic, but knowing the risk to your kid is critical for informed vaccine decisions. If a parent knew their healthy kid had a ~0% risk of dying of covid, and most covid in kids is like a cold, would they want a novel vaccine product?

Yet, at the time, this debate was entirely suppressed, and the difference in point of view by party was more narrow.

When it comes to measles, ironically, whether they were 2 deaths or 0 deaths— is largely a political talking point. The reality is the benefit-risk calculus to MMR is far more favorable to kids than COVID vaccines. It is a pity that public health has conflated the two, leading many people to choose neither.

Ultimately, I expect more medical issues will take on left-right valence. Cancer screening tests don’t improve all cause mortality— I can imagine one side being more skeptical. Statins in the elderly. A recent trial in NEJM shows a reduction in MI, no all cause mortality benefit, and a wide confidence interval for dementia that cannot rule out a meaningful increase— again, I suspect political polarization will soon happen. (I can understand skipping it in these situations).

What will be the next medical issue to undergo right/left politics? I am unsure, but there will certainly be something.

The problem is often is not good enough. A coin can give you 50%— you need ~100% agreement before you can trust an observational study design. In an effort to achieve this concordance, many modifications have been tried. Propensity score matching, inverse probability weighting, and dubious natural experiments have all been attempted. These efforts have yielded concordance of 60-80%, which frankly isn’t good enough— because you don’t know the 20-40% of the time you are wrong. If you are willing to accept 20-40% discordance— then let’s celebrate p values of 0.05-0.4 in randomized studies.

Enter Target trials. Surely they will solve the problem. Here it the latest installment in the saga.

A target trial to assess if statins reduce or increase dementia; The only thing more exciting than a target trial of vitamin D.

Achieves a huge win.

What’s the problem? A 9000 person randomized trial appearing literally days after this paper in the NEJM completely contradicts it.

(I discuss this paper on sensible medicine this week).

I love how the target trial authors end with a call for an RCT, and a pertinent one appears 2 days later. They could have taken the semester off.

What is the lesson?

I think it is time to recognize that target trials are looking like they are merely observational studies rebranded. These studies needed to have extremely high predictive value to succeed, and already have fallen short. They have fallen short on very important questions like multi-billion dollar drugs given to millions. They are unlikely to supplant RCTs.

With advances with AI, I suspect it won’t be long before AI itself recommends randomization over target trial emulation— that’s when I know for sure, it will have surpassed most researchers.

I just watched Josh Shapiro try to evade these questions (watch for yourself)

Josh Shapiro is in trouble. Today in the Free Press (link here), I discuss the measles outbreak, but since writing, it looks like there may be some uncertainty and factual errors at play. Allow me to give some free advice to all politicians as they consider matters of public health in the years to come.

The Free Press

Vinay Prasad: Understanding the Measles Deaths in Pennsylvania

Two deaths this week in Pennsylvania’s Lancaster County have reinvigorated the growing partisan debate about how best to promote measles, mumps, and rubella vaccination, as has President Donald Trump’s August 10 executive order recommending that the vaccine be divided into three separate shots, one for each disease. On the one hand, the mainstream media position appears to be that all leaders should shout louder that the MMR shot is lifesaving, the childhood immunization schedule is perfect and cannot be improved, and that we need more mandates and coercion to vaccinate, not less. On the other, you have conservative voices stressing the need for autonomy and empowering parents to make the right choice for their kid…

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11 days ago · 60 likes · 114 comments · Vinay Prasad, MD MPH

1. You need to assemble a team of advisors with diverse perspectives. If you go to the local university and ask for the best public health or ID professors to advise you— you are toast. You are asking for help from an activist group of experts with contempt for common sense and evidence. These people will hear a “baby died, measles test positive” and leap to the conclusion that a baby died of measles, and then tell you “now is a great opportunity to strike against RFK (particularly if you have presidential ambitions” But, because these people are not good thinkers— the same folks who told us to lockdown, mask our toddlers, and close schools— they haven’t thought things through. What test precisely was positive? Is it clear the death was attributable to measles? What is the clinical scenario exactly? What would a skeptical person say? These questions do not enter their mind.

2. Make the case for a medical intervention without relying on any one anecdote. Anecdotes can bite us in the ass— yet, the broader claim remains true. Measles does kill some kids (1/1000)— the chance a healthy vaccinated kid dies of measles is essentially zero. You don’t need to hang your hat on a single anecdote, and unless it is airtight, should refrain from doing so.

3. Once you messed up— come clean immediately. Toss your experts under the bus, and release all the information. Sacrificing the people who advised you to go on TV and say 2 measles deaths is preferable to continuing to evade questions. Just apologize— say you will hire better medical experts— move on.

4. Claiming this is about privacy is clearly false. It is being reported that the child died in a community of 1100 on Aug 14. Privacy is over. This is entirely identifying information.

   

   Governor, don’t double down. It is wise to immediate release the entire stories of both cases, and if one or both are incorrect to admit the error. Governor if your goal is not to be dragged down by the extreme wing of your party— remember that also applies to public health, which is one and the same.

They are back with a new paper on the Shingles vaccine making yet more magical claims. Shall we examine the work?

The premise is that this trial is a ‘natural experiment’

The idea is simple: compare the period of time in the first gray box to the second, where the type of vaccine used was dramatically different. Natural experiment means the people in the first and second gray box are otherwise comparable— they both got a shingles shot— the only difference is they are staggered 12 months or so in time.

To assess for the quality of a natural experiment, look at table 1. The two groups should be similar…

Holy cow, that’s not the case.

More women, younger age, more blacks, less asians, more married people— these are totally different groups of people.

This is not a natural experiment.

So, to fix this little screw up, the authors have to do propensity score matching. But that just makes this all a propensity score matched observational study with one problem— there is a temporal covariate imbalance! You might as well have just run a clean PS observational study.

Here is the main result

The authors spin this to mean the new vaccine lowers the event rate, but the alternative explanation was the old vaccine raised the event rate, or that ***MOST LIKELY** there is residual confounding because these are different groups of people.

Also look how fast the effect is. Take heart failure. How does a vaccine reduce cumulative heart failure 100 days after receipt? Heart failure is the destination of a longstanding maladaptive process, it doesn’t happen in an instant— its not twisting your ankle, it is getting a hip replacement.

This study is as low quality as all other shingles literature, which I have detailed here:

Final thought, I don’t understand why vaccine researchers are competing with fringe groups in the battle of who can produce the most misinformation.

If I were trying to get people to believe vaccine science, I would stop publishing false, misleading or low quality work, making outrageous claims. If someone wants to get or not get a Shingles shot— that decision should be based on…. spoiler alert… Shingles. Why do you need to produce false research trying to show dementia reductions or cardiovascular event reductions? I don’t understand why the push for clearly implausible findings—

Are you trying to get a job in the Cambridge sociology department or as President of Stanford or something?

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Today for Reason

Yesterday for Get the Check

For background, Nathan Cofnas was the post-doc at Ghent university who first reported that Jason Arday had plagarized parts of his scholarly writing, and his biography contained impossible claims. After Arday resigned, and tragically committed suicide, Ghent university suspended Nathan Cofnas. In a coincidental act that in no way was naked retaliation *wink wink he has been suspended. definitely not retaliation.

Hundreds of Academics have signed a letter opposing this suspension. I signed, and you can too here. But I have 3 problems with the letter

1. In order to sign this letter, you have to log in with your ORCID id. That’s 5 minutes down the drain, trying to look up my password.

2. At this point, it is inadequate to not punish Nathan Cofnas. Petra De SUTTER— the signatory of his suspension letter must resign. I want the letter to call for her immediate resignation. Here is why.

In the dumpster fire of this story, there have been many errors. Jason Arday shouldn’t have lied and plagiarized. Cambridge should have detected those obvious falsehoods, and not heralded him as the greatest professor. But the single biggest failure is that a Rector of university should not engage in naked retribution against the whistleblower. The Rector should be held to the highest standard in this whole fiasco— the rector has clearly abandoned academic freedom, and disgraced the university. The Rector did this in cold blood— after days to think and a legal team — and still screwed up— The Rector has to resign.

Being a Rector is one of those jobs where the bar is abysmally low. You just have to shake hands, smile, make empty statements (the more empty the better), and not screw up by abandoning the core values of the institution. This Rector could not even do that. No action was literally all that needed to happen. Rector has to go.

3. Finally, I have mixed feelings about signing, because I would advise Nathan Cofnas to no longer be a post-doc at Ghent. The university system is failing before our eyes. The Harvard president was a plagiarist. Cambridge celebrated a serial fabulist. Universities are woke indoctrination camps on the express train to being defunded. Nathan Cofnas will probably be much better off joining a think tank, or even going all in on Substack or moving on in life.

   Signing the letter feels like asking a kidnapper to keep your child safe. I guess, yes, sure, but what about letting them go? and can we arrest the kidnapper?

Someone please create a letter asking for the Rector’s resignation. Feel free to add my signature, don’t ORCID me.

Suspension Letter

225KB ∙ PDF file

Download

Download

I share the sentiment, and have been making a similar argument for 10+ years. One of my early papers showed that medical school and early residency publications have no predictive value over who will have a research career (i.e. continue publishing in fellowship). Since then, others have confirmed and extended this finding.

Of course, you can’t criminalize research, but the feeling is right. The bulk of this research is slop. It has no scientific value. It is not the best use of a student’s time. It is all part of the modern “arms race” to pick students— but it is unclear these capricious metrics means we get better candidates.

The reason students jump through the ‘useless research’ hoop is because the people on the committees that select them value the commodity. That’s the real failure— the leadership of admissions committees for medical school and residency programs.

Our paper from a decade ago showed that doing research in the past was not able to predict future research— meaning it was all for show and didn’t tell you who the budding scientists were. I assumed (naively) that it would lead programs to stop valuing these projects. I didn’t count on the fact that program leadership is numerically illiterate.

I joke— but it is also not a joke— it is amazing how little medical school and residency admissions folks know about the science of prediction. In fact, the Venn diagram of people interested in medical education and people who understand medical research has slim overlap— which is why medical admission decisions often appear closer to pseudoscience or the selection criteria for the Cambridge sociology department.

Some argue that doing bad research is the best way to understand how to read and critically appraise bad research. Nothing can be further from the truth. Cooking poorly does not help you become a restaurant reviewer. Killing houseplants does not teach you how to manage a farm. Watching a video lecture series on critical appraisal is a much better way to train students to understand and dissect research. If only we had one for free…. oh you are in luck.

Sensible Medicine

How Not To Get Fooled by the Medical Literature

Earlier this month, Adam, John and I met in San Francisco and recorded 10 installments of How Not to Get Fooled by the Medical Literature. This brings us to 19 episodes, spanning 2 seasons. We cover everything from randomized trials to decision analysis, case control studies to target trials, back pain to the Watchman device…

Read more

a month ago · 212 likes · 18 comments · Vinay Prasad MD MPH

Forgotten in all this debate is one unspoken assumption: the goal of medical school is to train doctors to take care of patients. If that remains the core goal— and I still think it is (for the time-being)— we have to prioritize that.

Of course, folks running labs will be disappointed to have fewer hands to help. Don’t worry about that— with the next batch of cuts to science funding, you won’t have reagents for the students to work with anyway.

Folks running retrospective chart review will be disappointed to have to pay for Claude subscription.

Folks doing qualitative research will have to fall back to just making things up.

(Ok, these are jokes, don’t @ me)

Jokes aside, I have been lucky to have worked with amazing pre-med and med students. Because my research has been challenging of conventional, entrenched interests, I have almost always gotten students and residents who had read and processed a lot and wanted to do the work for the sake of the work.

One student—Ben Knudsen—comes to mind. He, like me, was frustrated by COVID-19 policy that was deranged, illogical, and unscientific. He read voraciously and found me. Together we published research that challenged the CDC and “the science” himself— Dr Fauci. Ben was (and is) brilliant, and he did this work not to check a box, and probably at great career risk— because it was the right thing to do and he believed in it. In many ways, he inspired me to be braver and more outspoken— because he had much more to lose than I did, and yet he felt compelled to do the right thing.

I know it is possible for students to do work that actually matters, and for the right reasons. I just think the majority of medical student research is not this. If we deprioritized it in admissions— I am not worried about folks like Ben— They would still do it— because they were never checking a box.

The same is true for all types of research. There are some people who work in lab who actually want to do that. There are some people who actually do good chart review work. By removing the incentive, you will retain the folks who do it because they aren’t do it for points.

For these reasons, I am supportive of the fact that we should not value these metrics early in one’s career. For Cambridge professors of sociology— however— I do think research matters.

PS: I picked Ben, but this applies to probably all of the people who are my co-authors— you know who you are— I am fully aware that given the nature of the topics we discussed and papers we wrote, you weren’t checking boxes.

Pinker believes the answer is:

Although the arts and humanities have been captured, the sciences remain grounded in rationality. We have the occasional e.g. outside of this, but largely we remain intact.

I believe Pinker underestimates the extent to which woke ideology has rotted out medicine and science, likely because he isn’t knee deep in it, instead here are 20 points for consideration:

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1. During COVID-19 public health experts said George Floyd protests were OK to have, while Trump rallies were not. The truth is all outdoor events were totally fine, and this distinction only reflects public health being hopelessly captured by the woke to the point they would say obviously ludicrous things, expecting the public to believe it. (a Jason Arday-esque claim)

2. Modern universities have performed gender transition surgeries and given puberty blocking hormones to many minors. Claims are made about rates of suicide, but medical science has not performed a single well controlled experiment to demonstrate if people are happy or saddened by this choice; if suicide is up are down— all comparisons are biased. Common sense and conservatives are rightly critical of these practices in the absence of good data.

3. Universities do not have a coherent position on race and genetics. Is race a purely social construct or is it linked to genetic differences? On the one hand medicine says it’s “purely social”, on the other hand, medicine says broad genome sequencing efforts need to recruit people of diverse race. Which is it: you need diverse races for genetic datasets because they are different or there are no genetic differences by race? This hypocrisy is not discussed.

4. Science and medical departments are consumed with DEI hiring and promotion and tenure decisions. Universities continue to defy the Supreme Court and use race as an independent consideration for recruitment and admission. Trump’s DOJ has issued many warnings— I discuss that here. Universities think the Supreme Court is just optional.

5. Medical researchers routinely produce false reports on issues of race. Claiming that black babies had twice the death rate when cared for by white providers instead of black providers. This paper was obviously false— you may recall, I said so at the time— now, it has been debunked (the authors didn’t adjust for birth weight, and white docs took care of sicker (lighter) babies), it remains un-retracted. You could never write a paper that reached the opposite conclusion and publish it. If a paper reaching the opposite conclusion was proven wrong, it would be retracted. The authors might be fired.

6. Cloth masks never worked. Community masking never worked. Mask mandates don’t work. Masks are the MAGA hat of the woke movement— a visible symbol to show allegiance. Now woke doctors continue to force the rest of us to wear a cheap surgical mask in the hospital during “respiratory virus season”— something with as much evidence as slaughtering a goat to ward off infection.

7. Woke medicine attacks proposals that have little downside and are preference sensitive merely because the political right favors autonomy. Raw milk— not my cup of tea, but fine if others want to do it. The societal impact is negligible, and many European countries allow it. Shifting hep B shots in neonates from day 0 to day 60, if mom tests negative with ultra-sensitive assay, and is low risk for hep B— again, societal impact is negligible. Totally fine to delay it in an effort to show the public that vaccine recommendations can be open to different views. Woke experts routinely lie and fear-mongered about topics important to the political right to extinguish discussion. You would think these decisions are like an asteroid striking earth given how media experts screech about it.

8. Monkeypox largely affected men who had sex with a lot of men. Not even gay men who had sex with few gay men were at high risk— but rather men with extreme numbers of sex partners. Spread was from sexual activity and use of spit as lubricant. Yet, woke medical experts promoted the use of masks in school, or vaccines to all college kids and other deranged views. This coincided with masks coming off because covid was over, ergo, woke experts repurposed monkeypox to promote a policy goal they had already reached for false reasons.

9. Every single public health issue is filtered through the irrational woke lens in 2026. Hantavirus was a nothing burger. Check out my piece

   Sensible Medicine

   Hantavirus, What You Need to Know

   Public health messaging around the hantavirus cruise ship outbreak has been, ‘there is an extremely low risk to the general public,’ but this is suboptimal. Instead, messaging should be, ‘there is no chance this will become a pandemic. You have no risk…

   Read more

   4 months ago · 346 likes · 37 comments · Vinay Prasad MD MPH

   Cyclospora outbreak on produce does not mean you should give up eating vegetables. Each of these issues meets a hysterical woke medical expert response. Public health is the gender studies of medicine— first to be rotted out fully.

10. Medical experts speculate wildly about Trump’s health— when he is clearly the same— while missing the obvious signs of Biden’s dementia— as he clearly deteriorates. For the latter they put “stutter” and “cold medicine” on their differential diagnosis. No greater double standard exists than the health of politicians by political party. Check out this gem we got for SM:

    Sensible Medicine

    I was Cheney's Radiologist. Trump Doesn't Look Good. We Deserve to Know Why

    The New York Times was able to get an op-ed by Dick Cheney’s Cardiologist asking about Trump’s health. At Sensible Medicine, we are honored to get a piece on this same topic from his radiologist…

    Read more

    23 days ago · 228 likes · 137 comments · Sensible Medicine

11. Many science commenters criticize Robert Kennedy's decision to cut mRNA vaccine funding. They mislead the public into thinking he cut all mRNA vaccine funding, but he merely cut infectious disease and not cancer indications. Second, they deceive the public into thinking that taxpayer money is needed for mRNA technology— after products become commercially lucrative. Taxpayer money subsidizes research in a commercially unfavorable time, but is not needed when companies have made $100 billion or more. It would be like subsidizing Apple to make new iphones. Ending mRNA vaccine subsidies is in the public interest.

12. Medical researchers perform thousands of low quality observational studies to further justify the woke agenda on countless topics including race, vaccines, and why Republicans are bad, etc. Our criticism of one E.g..

    

13. David Sabatini was forced out at MIT (and blocked from employment by NYU) because of woke ideas about workplace power dynamics. His consensual 30 year old partner and later jilted lover worked in a different lab. I think most sensible people think he should be allowed to run a lab.

14. Nature and NEJM endorsed Joe Biden for president— as all politically neutral medical journals do.

    

15. The irony about woke medicine is that if you're poor, if you're Black, if you are from a rural area, if you are native America—-all the rhetoric, all the bluster, all the DEI seminars, retrospective observational studies, disparities research, and universities are actually doing nothing to help you. Instead, woke medicine uses these groups to justify a bizarre scheme that largely rewards upper middle class, overeducated, professionals. Universities are as much help to the downtrodden as the Detroit Tigers are to tigers.

16. Scott Atlas was right about COVID but remains censured by Stanford Faculty Senate. In general, every single faculty member who made truthful points about COVID has faced retaliation from their university. (I will note that my disagreement with the political right about covid remains they promoted useless drugs and supplements. The left promoted unnecessary vaccines in kids, vax mandates, lied about origins, natural immunity, closed schools, masked us, etc etc. Probably the best response would have focused on nursing homes, the elderly, and left the rest of us alone. Most of us needed little more than orange juice and rest. Some of us said so at the time).

    Sensible Medicine

    Cornell's New Dean, Bob Harrington, Asked Jay Bhattacharya & Eran Bendavid to stop talking to the press about COVID policy, per B's account

    I released this on my own substack, but honestly think the readers of Sensible Medicine should know this. If your chair tells you to not talk to the press, the chair should be fired…

    Read more

    3 years ago · 287 likes · 21 comments · Vinay Prasad MD MPH

17. All training programs have been so invaded by woke ideas that work hours, educational rigor are all in decline. Mental health days are up, hard work is down. The university will pay for you to freeze your eggs, while they add an extra year of Lymphoma fellowship (rather than shorten training so you can have a family).

18. Medical universities have incessant lectures on climate change and other woke catnip that have little to do with daily medical care. In contrast, there are no lectures on conservative ideas with tangential medical relevance (e.g. the need to have more kids).

19. Some universities have floated preferential treatment by race, for e.g. heart failure, which would be illegal.

20. Some argue that they work at universities, disagree with the woke culture, and do good work that has nothing to do with this. Cutting science funding hurts them, and they are not to blame. This is true. And this is also true about sanctions. If the US sanctions a nation, there are some citizens in that country who aren’t part of the political regime who are hurt. But, just like nations, financial penalties are the only way to exert pressure on large institutions or nations to change their behavior. I am also unsympathetic because these jellyfish say nothing at work, and allow the culture to change before their eyes.

My prediction: Right now Trump is squeezing universities, but not hard enough. They still have enough lobbying clout on the right to continue the status quo largely. As such, they are unrepentant, and hiding the woke ideas from view, but largely continuing them. The are waiting Trump out. In the next one or two presidential cycles, we will get a Democrat president, and Congress, who will double down on subsidizing universities, which will lead to an expansion of this irrational woke world view. It will be woke like you have never seen before. Then, when more conservatives realize that Pinker is wrong, the backlash will come, a subsequent Republican congress and president will slash universities so badly, they may not fully recover. My guess is they will aim for revoking tax exempt status and giving them $0 in federal funds. This is my 12-15 year prediction.

If I were a university president, I would pull my head out of my ass, and realizing this, hire some conservative faculty and at least make an effort to show that we are running a balanced institution whose midpoint is the same as all of America. But you don’t get to the top of leadership by being a leader.

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Here is the New England Journal of Medicine Voices section (Note NEJM is, last I checked, a medical journal)

The article makes incredible statements. First, I see no evidence to support the claim that anyone was trying to “kill us” or Jason Arday. I think the rhetoric about federal agencies is irresponsible and wrong. It is tragic Arday’s life ended— in what is widely thought to be suicide— but ultimately that decision, like his fabrications and plagiarism, were a product of his own troubled mind.

How can you claim this is the message? The message to everyone is try to be truthful in what you say about yourself, and don’t plagiarize your academic work. The message to universities is please verify the scholarship of people you hire.

Ironically, I could imagine these lines being said about Roland Fryer rather than Jason Arday. Fryer does stellar work, and was disciplined largely for reaching conclusions that contradicted the liberal narrative. Even this headline misrepresents the allegations, and the role politics and Claudine Gay played.

This NEJM line astounded me:

He was cleared of “deliberate” plagiarism? Plagiarism has no distinctions. The intent may determine the punishment, but plagiarism is plagiarism. And the other allegations— that Arday told grand, fabulous, impossible lies are precisely why his plagiarism was put under the spotlight. If one read his work and claims, and saw the plagiarism and falsehoods— how did he get a Cambridge professorship? Unless the university is deeply broken, and missed the obvious. That’s the story in a nutshell.

This was also incredible:

Three things. First, I agree that all of academia is rife with bad work. I write that essay every month (link below)

Second, that said, comparing MTL (discussed below) to Jason Arday is ridiculous. I was critical of MTL, but his failure was pushing his teams so hard that they felt they had to make things ups (at times). Other papers were true, and led to FDA approved drugs. MTL never plagiarized. MTL probably didn’t make up data himself (he just failed to catch it). MTL’s work is broadly hard science (and not sociology). MTL also didn’t say he ran 600 miles in 6 days, or that he couldn’t talk till he was 11, or any other ludicrous and obviously false personal claims. They are not comparable.

Third, as I alluded to yesterday with James Frei— had Jason Arday not ended so tragically, he probably could have, like Frei, made a fortune writing books, or perhaps like Frei, embracing his imagination, and turned to fiction writing (AI assisted). MTL is not the Stanford president, but he too has moved on to something different.

Here is the biggest take away. This essay is in… the New England Journal of Medicine.

The mere fact the essay appears in NEJM validates the central problem of the Jason Arday story, which is that institutions which are supposed to be ideologically balanced and adhere to some basic standards of logic and merit, are saying Jason Arday is the most brilliant scholar, and, if you disagree, that “they are trying to kill us.”

This is really wild stuff. We have to celebrate someone who makes things up, and if we don’t it’s on par with trying to kill someone— and this isn’t the deranged view of some rando on the internet— it is the sanctioned view of Cambridge and the New England Journal. This is genuinely concerning.

Additionally, I also found the attached letter ridiculous. Nathan Cofras is the postdoc at Ghent who raised the Arday story— now suspended. The attached letter notes his crimes:

I have never seen a university police how an academic defines the scope of their work— I don’t even know if the above terms fall under ‘future of liberalism’ (vague) or not.

I also was not aware that a postdoc was prohibited from working on things outside of their contract (they all do). In fact, I haven’t read an employment contract spell out the scope of acceptable topics to study. Instead the letter writers are conflating the post to which he applied with what he is allowed to study. It is dangerous to confuse the two.

The letter adds this:

But the “disabled” language is how his supporters refer to him

As for “worthless scholar” — that’s harsh no doubt, but universities are full of people who say that about their colleagues every day. I’ve been told that a few times about my own work, and that was just from Adam Cifu.

One grand irony is that if an US university postdoc did exactly what Nathan Cofras did, and their university ejected them, Trump’s DOJ— particularly Harmeet Dhillon— would go after that university, and it may even end in a congressional hearing, etc.

It would probably be an 80:20 issue for the Republicans, i.e. most Americans would think it is clearly absurd that a professor at a top university told so many tall tales, and the post doc who targeted them was clearly the victim of liberal retribution for saying the Emperor had no clothes.

Imagine if that story ended with the boy saying “you have no clothes!” and then the rector of Ghent had the boy arrested; his child ticket clearly says no outbursts besides on the topic of the future of liberalism.

In order to clean up this mess, I offer a 5 point plan:

• Whoever at Ghent made the decision to suspend a lowly postdoc— fire that person (this is now the biggest error of the whole story; a vengeful retributive act defying academic freedom).

• Whoever hired this troubled man at Cambridge— and said he was the most brilliant scholar. Please demote that person (this person has no business hiring). Also, if you wouldn’t mind writing a review of my books on Amazon… “best book since the bible…” I would appreciate it!

• NEJM voices— hire a conservative or heterodox columnist/ and a conservative editor/ come up with policies about when it is appropriate to claim someone is being “killed”

• To parents: Send your kids to an SEC college

• To all readers: Please subscribe to this stack to support this work

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See attached letter

Suspension Letter

225KB ∙ PDF file

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1. It is tragic whenever anyone kills themselves. I feel bad for their family and friends. Suicide is never good.

2. Cambridge is the villain. The university picked a mentally-disturbed, serial fabulist, and told the world he was the most brilliant scholar. He did fabricate things which tricked Cambridge, yes, but they were outrageous and obvious lies. Cambridge was negligent in basic diligence. It would be like if I made up insane combine stats (I can bench 92 reps and run 40 yrds in 2 seconds), and the SF 49ers said that I am the greatest quarterback in human history, an unstoppable force, and then put me out on the field to watch me get obliterated on the first play. You should blame the coach, manager and team that didn’t catch the lie sooner. Yes, I would also deserve some blame, but not the lion-share.

3. Cambridge’s error reflects a broader obsession with DEI and woke politics at universities that has verged on madness. This madness began with the arts and humanities, and has extended to the sciences. In medicine, we now have annual lectures on climate change and health. Our gender medicine programs are politically, and not science based.

   Covid was an extension of woke politics. Hospitals worshipped lord Fauci— mandated shots against all logic or reason— forced unethical boosters— ignored natural immunity— and now have an annual “respiratory season” mask mandate (level of evidence: wishful thinking), and other constant non-evidence based nonsense. Did I mention all the woke training modules? Jason Arday being celebrated by Cambridge is the Emperor has no clothes. Universities are so woke— the only response from the political right should be defunding them. I suspect this is the future: more extreme swings in funding. Eventually there will be a US president who sets the NIH budget at $0— and I am not sure I would disagree. Universities are making no efforts to fix their naked partisan bias; they should not be surprised at future partisan punishment.

   Now that Covid is over, woke politics is spilling to other medical debates. Should a woman who is hep B negative have her baby get a hep B vaccine on day 0 vs day 60? A simple— honestly low stakes question— but since it is political, many have lost their minds. Should an extremely commercially lucrative medical product receive further tax subsidies? This would be an obvious no— the private sector can fund it, but because it is political many scream yes. Should doctors tell families to avoid American football? Many questions have ridiculous woke answers these days.

4. I was more sympathetic to Jason Arday as a troubled individual until I learned that he used the police and legal firm to attempt to silence his critics. That’s even worse than lying in the first place.

5. Nathan Cofras— I know nothing about this guy other than he broke this story. He holds a lowly appointment in a lowly university. The woke university ecosystem would never let a guy like him succeed. Then they announced he was suspended today. Unlike Jason Arday, no university said he was the most brilliant person on earth— I feel bad for him. It was punishment enough to remain a postdoc at Ghent.

6. I reviewed the examples of Jason Arday plagarizing, and I believe that yes, he did plagarize, but I think that misses the bigger issue: The work is total gibberish. It is unintelligible, unproven, empty rhetoric. It is hardly scholarship. What is going on? How could anyone think this is valuable intellectual discourse?

7. I do think demoting the person who hired him makes sense. That person is not fit to make hiring decisions. That would happen in a normal company.

8. Out of curiosity: I randomly picked 5 universities, and looked up their sociology department faculty. I randomly picked papers written by the faculty. Wow, my mind was blown. At least 60% was similar gibberish. Constant politically charged assertions— no underlying data. Anti-colonialism— everything is somehow a legacy of racial injustice and colonialism. Never mind— no actual data to support that claim. The climate catastrophe— Immigration injustice— the department looks like a Democrat think tank. I would even be ok with that, if it relied on good methods, or maybe even 10:1 included a scholar pushing Republican ideas— I mean even if just for funsies. I could find no example of a Republican idea from a sociologist department.

9. Another ending to the Jason Arday story might have been James Frey. James Frey was also a person whose memoir was riddled with fantastic stories. For Frey, Oprah was Cambridge. A 800 year old university and Oprah Winfrey— that is about right. After the hurricane of criticism, Frey just did his own thing. He wrote many more books, built his own publishing empire. I can’t say I read his work— it’s not my style— but at least he moved forward productively. Sadly that was the not the ending here.

10. Ultimately, I think this post by Dawkins is right.

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A new French study claims to provide information. 1100 75 yo + people on a statin, randomized to stop or not. The trial met non-inferiority. (the margin was insanely large) Some argue, these data mean it is ok to stop. Others say this study is useless.

Unfortunately, the entire field is poorly conceived. The last thing we need is another statins trial in the very elderly. Allow me to explain…

If you are 77, 82, or 90 and haven’t had a cardiovascular event, you are one of three people.

1. You don’t care about marginal differences, and will never take a statin.

2. You don’t mind taking meds, and will happily swallow for some possible marginal gain.

3. You are waiting for a new trial to inform your choice.

There is almost no one left in the third bucket. It is very likely that taking a statin has some small reduction in MI— as even this study also finds 2.1→1.4 %. At worst, the overall impact is really rather marginal.

You could run a 10,000,000 person randomized trial, and you will spend 10 billion dollars in taxpayer money, and you won’t change the mind of the first and second groups. Some people will tell you to go to hell, and some love taking medicine.

Randomized trials are great when the upside and downside are not well known, and the trial can provide estimates that change our minds. Oseltamivir in critically ill flu pts— great trial— increased mortality is a reason not to do it. Chemotherapy in an early stage cancer pt— great trial— a toxic drug which may or may not help.

Statins in a very old person. Not much benefit, not much harm. Preference sensitive. Do whatever you want.

But if you do run a randomized trial— please don’t make it non-inferiority and pick a margin like this

This margin is ludicrous. You could randomize 75 year olds to discontinue all medical care, and only pray to a god made from coconut shells and achieve this margin. Anyone who thinks this trial is a good use of money is mistaken.

My answer is: I won’t be taking a statin at 75 (if event free to that date). If you want to take one, do it. Just don’t waste time and money with uninformative trials. Better to make it over the counter.

Oh, too late….. 90 million

I have just 5 points to make:

1. The essay’s central claim is: AI will make some— perhaps many— medical decisions better than most doctors, and doctor+AI is actually (or will be) worse than AI alone. Is this possible? Or science fiction?

   Of course, yes, this is absolutely possible. I am surprised anyone would disagree. AI is already solving mathematical proofs that no human has been able to. AI can run statistical simulations that used to take a good statistician a week. AI can do the work of 10 medical students in gathering research information. What would take 1 months, is done in 1 hour.

   And the corollary, it is possible that doctors override AI and worsen outcomes. Absolutely, this is possible. The authors give many examples. This is definitely a possible, plausible point of view. We can debate how fast and how extensive.

2. What about the human touch? Won’t patients always need a shoulder to cry on?

Of course this is also true, but we need to be honest: in the course of an oncologist’s week, what percentage of the time do you spend an hour talking about end of life care? 5%? And how much of that time does the person consoling the patient have to be a board certified oncologist vs. a palliative care doctor, or a general doctor, or an oncology nurse, or a medical student— my point is simply that they need to have a human touch in oncology does mean having oncologist exactly as they are today. I would imagine the JAMA authors saying AI + a local oncology nurse selected for best bedside manner visiting you at home is greater than going to see Jame in his cold Cleveland clinic office, waiting in the lobby, etc etc.

3. What about the author’s conflicts of interest? They profit from AI companies. Yes, I see that. I hate to break it to you, but the vast majority of essays in JAMA are written by people who profit from what they are recommending/ promoting. When drugs are recommended for on and off label uses, the doctors are often consultants. When devices are recommended, the doctors often make money by placing those devices. I have been a critic of much of this, but this is not unique to this piece. Also some of the disclosures are ridiculous. Zeke received an honoraria for speaking at UCSF grand rounds? Who cares? Disclosing everything means hiding what’s relevant. I am happy to have every conflicted article have a rebuttal written by someone with no conflict— but let us apply that everywhere in JAMA. (Good luck oncology).

4. Why are the authors writing in JAMA at all? AI is so wonderful, and modern communication is so amazing, and yet the authors are still writing about what AI will do in an old fashioned peer reviewed medical journal that mostly collects dust on coffee tables. And frankly a journal that is not fit for the times, and actually pretty boring. To be honest, this is the biggest mystery. I see no value to the authors for writing this article at all— they don’t need the line for the CV, they could publish this on a website and get more views, I see no reason for them to write this, which leads me to…

5. Why argue about what AI will do. Both the authors, and their critics are arguing about what AI might or might not do. This is in contrast with useful medical debates about what you should do in clinic tomorrow. Should you extend anticoagulation therapy? Give chemo and a TKI or TKI alone? Try a new pain pill? I get medical debates about decisions we make daily, but fighting over the future— I don’t get it.

6. I did find this one funny though. It’s tough to make predictions, especially about the future.

In short: Providers shouldn’t be upset at the idea that AI will steal some— perhaps all of their work. Ok, Doctors, I mean doctors. That was just to get your blood pressure up. How much work will AI take from me— I am curious to find out. Only way to do that is to stick around for a while. In the meantime, publishing viewpoints about the future in JAMA is about as valuable as reading and getting mad about it.

The company that makes the drug might say: it would have worked, if only…

If only… we used a lower dose

If only… we managed side effects earlier

If only… we gave it in the evening, not the morning

The problem with if only… medicine is that it can be said for anything. A drug can fail a hundred times, and you can think of 3 more ways to deliver it, and say if only …

This is why the burden of proof in medicine is to show your product works and not to keep making excuses why it didn't work, and say if only..

This lesson is not unique to drugs. It also applies to the topic of yesterday’s post: HEPA filters

A few readers wrote me saying

If only… they used more units

If only.. the increased the flow rate

Well, until your actually do that and prove it helps, it's just empty rhetoric. No different than the failed drug company.

Listening to proponents rationalize negative trials reminds me of interviews with losing sports teams.

If only.. we executed the defense

If only.. we didn't have so many injuries

If only.. we scored more points

Yes, sure but you didn't, so take the L and try again next time. The rest is just speculation.

HEPA filters have not shown they can improve any outcome in any setting in any population in all of human history. So run a positive trial, until then: if only…

I had my doubts. There are a million reasons why this hypothesis might not work. Most notably, that, in the course of our day-to-day lives, we eventually will go someplace that doesn't have filtration. Additionally, it might not work as well as you think. Some air, or pockets of air, will be unfiltered. Instead of spending millions, we should study these interventions in cluster randomized trials-- that was always my position.

Here are some receipts.

Well, it appears we have more evidence.

I was going to summarize the randomized trial, but my sensible medicine colleague John Mandrola did that superbly

https://www.sensible-med.com/p/lessons-from-the-hepa-filter-rct

The authors chose a nursing home population— I.e. if this intervention is going to work anywhere, it should work here. Here's what they found

Per Dr John

• There was no evidence of a difference in the number of respiratory infections per winter per intervention vs control bedroom residents (0.99 vs 1.04; adjusted incident rate ratio, 0.92; 95% CI, 0.64-1.33; P = .67).

To my knowledge, and a reader can correct me if I'm wrong, no one has shown a benefit to having these filtration systems on any clinical endpoint, in any setting, in cluster randomized or randomized fashion.

In my opinion this story illustrates the two most important lessons of modern medicine

1. The greatest source of misinformation— i.e. the most damaging and least likely to be questioned— comes from experts, frequently quoted in the mainstream media. These experts are far more dangerous than random people on the internet who also hold incorrect views precisely because the latter group is vigorously questioned and the former group is not.

2. I place zero trust in public health experts. There's no qualifications to that. I wouldn't trust a single thing they said if I cannot independently verify it. These days, the distorted claims are too many to count. Everyday I open the newspaper and I see every story is incorrect. Wild! I wrote about one recently for the Free press.

Cuts to science funding can be unwarranted, or they can be justified. Recently I saw New York times article complaining about a randomized control trial of the flu vaccine that was cut. It was a study across many hospital systems where pediatric patients received a vaccine before discharge versus usual care. On the face of it, it seems like a useful study.

Then I looked up the primary endpoint. I expected to see something like all cause mortality. Maybe influenza related mortality or influenza related ICU visits. Instead, I found the endpoint was:

Receipt of flu vaccine.

You mean to tell me we're spending millions of dollars on a randomized study comparing giving a flu vaccine before discharge versus usual care and the primary endpoint, the thing gets powered for, is receiving a flu vaccine?

What if I randomized people to getting a Big Mac, versus usual care, and the primary endpoint was how many people ate McDonald's?

Now the authors might say something like our secondary endpoints were to look at… but that's already misleading. If it's a secondary endpoint, the study is likely not designed or powered to evaluate it.

How much of science funding is wasted?

How much of our precious taxpayer money is thrown in the toilet?

Well obviously any basic science research that cannot be replicated is a waste of money.

Many empirical studies suggest this is the majority of basic science research.

You take a post doc or a PhD student, you tell them that they will never have any career unless they generate results, then you leave them have access to equipment where the result can hinge on how the equipment is set or managed, and you wait. There's no question that in an environment like this fraudulent and reproducible results will run rampant.

Indeed that was the case with the former Stanford president. Wherever he went, questionable results would follow. Obviously it probably was the fault of the junior researchers doing the science, but also very likely he created a pressure cooker where they felt like they had no alternative.

One obvious thing is that the national institutes of health should sample experiments from major universities and labs and check if they can be replicated. People in the bottom quartile of replication scores should lose their funding. Ironically, some of the biggest labs may crumble.

The next sort of waste is asking questions for which there's a right answer. Who has better surgical outcomes, men or women? If you do this study, only one answer can be published. If you find the answer that pleases the political left, you can publish that, but if you find the opposite answer, you cannot.

There's so much of this sort of research. Does banning bump stocks reduce gun related death? They're only two acceptable answers: yes, and it does, but we were unable to demonstrate that in this study, because we didn't capture the necessary information.

Did the Dobbs decision hurt women? The only acceptable answers are yes, or it did and we are unable to measure it. Had we measured it correctly we would have found it did. Never mind that national evidence shows an increase in abortions since the decision.

What sense does it make to fund science that directly applies to ongoing political debates, when that science is preferentially done by liberal researchers, at liberal universities, with liberal peer review, with a clear agenda?

Instead, it makes complete sense to defund this research.

Racial disparities. Billions of dollars have been spent on racial disparities research and the net effect has largely been to enrich the wealthy, upper class, researchers who will conduct this work. The least effective way to help a racial minority is to give money to a university to study the problem.

Then there is just bad science. Each year millions of people who have never done science before start doing it. They make loads of mistakes. Methodological mistakes. Ignorance of history mistakes. Numerical mistakes. But the system is particularly ill-equipped to criticize these studies.

How much medical science is false or useless? Different empirical estimates exist but it's entirely plausible it's the majority. In fact, this was the conclusion of two famous papers by John Ioannidis.

So what does science funding mean in a world where so much of it is wasted?

It's a tax on all citizens of America to divert large amounts of money to wealthy well-educated people, in liberal universities, who are intolerant to individuals who disagree, to further weaponize science in political disputes. Given this, it is no surprise that it is being fiercely defunded.

I'm surprised that people are surprised. The cycles of boom and bust are just going to get worse. Universities have made no effort to actually cater to the median American or to actually have common sense, or follow science properly. As such, very likely, future Democratic administrations will give lots of funding to science, leading to massive hires, which will follow by future Republican administrations cutting it severely, leaving to massive layoffs.

What's the way to escape this cycle? Perhaps universities could consider doing what they're meant to do, which is actually have voices across the political spectrum, across ideological beliefs, including heterodox voices and actually enforcing the rules of methodology in science. I won't hold my breath. In the meantime, I'll read the next New England journal article telling pediatricians to advise their patients not to play American football. ;) a science-based position obviously.

They block research that needs to happen—- worse, that is unethical NOT to conduct

And they permit flawed, biased studies.

Consider the first case. Here is a recent example.

Brian Locke has picked a great example. Having read the evidence base for Tamiflu, I think the right number of people who should get it annually is 0. My conclusion is based on the totality of the randomized evidence. To reach this conclusion however, an astonishing number of people, perhaps hundreds of thousands, if not millions, over decades, were given the drug. At least 20 billion were made by the sponsor. And all of that was a waste. A few simple randomized trials before adoption could have saved society billions.

Modern medical ethics spends time wondering about whether or not it's ethical to deprive the control arm of a treatment that was adopted for unsound reasons. When, despite those concerns, trials are eventually done, and it's discovered the treatment is actually harmful, the ethicists shrug. They have no skin in the game and there are no repercussions for the error.

We see the same thing for interventions given to pregnant women. Instead of testing these extremely carefully— there's a growing view that we should deploy these therapies, and look to see if their problems after the fact.

Obviously such a system exposes pregnant women to significant risk, and the observational systems that exist to look after the fact are incredibly poor. You can miss huge differences. I discussed this in my recent free press article.

The Free Press

Vinay Prasad: Anthony Fauci’s Vaccine Deceptions

On Monday, Republican senators Rand Paul of Kentucky and Ron Johnson of Wisconsin—both fierce critics of Anthony Fauci—released a number of pandemic-era text messages from the former head of the National Institute of Allergy and Infectious Diseases (NIAID). One exchange in particular has raised the ire of his many critics…

Read more

a month ago · 166 likes · 336 comments · Vinay Prasad, MD MPH

The second error is everywhere. A novel therapy comes to market in a study that is unable to provide any useful information. Either there's no control arm. The novel drug is given in combination with another drug and there's no control arm. The control arm is something we no longer use. The control arm is not the way we use it in clinical practice.

A quick example is the Sprint trial. This is a trial that tried to test whether or not we should crank up blood pressure medicine in elderly people. Such a simple question. Somehow the researchers managed to bungle it.

Instead of having the control arm receive usual care, the researchers introduced a non-standard maneuver. Something that only is done in the clinical trial that is not done in the real world. In fact in the real world, if you did this, other doctors would think you lost it.

If a patient took a little bit of a blood pressure medicine and their blood pressure was too well controlled, the researchers forced the patient to dose reduce the medicine or to remove it. This happened even if they were asymptomatic.

Let me reiterate: In usual clinical practice you would never dose reduce someone who had achieved very good blood pressure targets with minimal effort and is asymptomatic. Yet, the Sprint investigators chose to do this. This could very well be harmful. This makes the entire trial useless. You can't draw any firm conclusions.

Aiming for a lower blood pressure target was superior to potentially harming people by playing around with medicines that don't need to be played around with-- That's the real takeaway of Sprint.

I won't bore you with the dozens of oncology examples that fit this model. I've written about them extensively. IRBs have never been able to fix this problem. Elsewhere I suggest that betting markets may do what IRBs cannot and have not done for decades.

https://www.sensible-med.com/p/betting-on-clinical-trials

Why does this happen? What can be done about it?

A number of hospitals offer medical ethics training but there's no evidence that completing this training improves your ability to think about any problem in medicine, let alone an ethical problem. I would encourage the groups that run these training programs to formally evaluate them. Evaluation would center on real clinical actions and not the results of some survey or test

The IRB industry is hopeless. If you want anything approved that can generate massive profits you can find a IRB to grant it. It's a race to the bottom. Meanwhile, if you want to do trials to steward medical interventions, or to potentially overturn dogma you are facing headwinds.

The only way to encourage the conduct of clinical trials that can save society billions is to introduce incentives to do so. Perhaps someday.