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Large effect size drugs like penicillin and insulin were not discovered via double-blind randomized controlled trials.

They were found via an iterative process. Call it results-based medicine.

Penicillin: acs.org/content/acs/en…

Insulin: medicalnewstoday.com/articles/323774
Now, to be clear, I do think well designed RCTs are a powerful statistical tool.

They can show that drugs with relatively small effect sizes are indeed effective.

So a key question is: are larger effect size treatments out there? And could iterative medicine help discover them?
Also, I respect the work of both @zachweinberg and @rabois and think this is an important discussion, especially given the urgency of the pandemic. Would be great to have it without vitriol if possible.
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Balaji S. Srinivasan
@balajis
The system of checkpoints between states has now arisen. Hawaii, Alaska, Rhode Island, Florida all require out-of-state visitors to quarantine.

States are limiting travelers from red zones/hotspots while they try to turn their own states into green zones.
npr.org/sections/coron…
Temporary bureaucratic things have a way of becoming permanent. This could be similar to the sudden breakup of the USSR and Eastern Bloc.

From one USA to 50 states, from one EU to 27 member states?
All through the 1980s the USSR & Eastern Bloc tottered, and then suddenly fell from 1989-1991. Just broke up into member states.

All through the 2010s the USA & EU tottered. And the EU is now arguably de facto broken up. Will the USA follow?
Read 10 tweets
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Balaji S. Srinivasan
@balajis
I think both/and. Also, many countries already ask for vaccination certs before crossing borders.

So the next TSA could be CT scans & point-of-care tests. Maybe with “airlocks” on both sides for 14 day quarantines. Much more friction for travel. Not done casually.
How “airlock” system could work: on each side of trip, a new kind of hotel connected to airport. You pass point-of-care tests and then quarantine for (say) 14 days before you fly.

The country taking you doesn’t take any chances. Administer test & monitor quarantine themselves.
I do think we get a vaccine eventually for COVID19 (see @PeterKolchinsky thread) but I also think the virus may mutate like the flu.

That will keep nations on guard against new strains, until wholly new kinds of biomedical tech can be developed.
Read 3 tweets
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Balaji S. Srinivasan
@balajis
There was a period from 1991-2020 where you could easily travel to any country. We took that for granted, we’ll miss it now that it’s gone.

But the second era of globalization is now over. The viral curtain has descended around the world.
Borders have returned on a level beyond what even the most ardent nationalist ever advocated.

Borders so strong they end casual tourism, bankrupt hotels & airlines, and prevent citizens from leaving quarantine. Borders that inhibit not just entrance, but exit.
There’s one silver lining though: we still have the internet. So all the cosmopolitan, international energy goes to the cloud.

Nationalist socialists control the land, internationalist capitalists still have the cloud.
Read 3 tweets

Related threads

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Jason Crawford
@jasoncrawford
Fascinating story I ran across reading the history of polio:

In 1954, when it was time for large-scale human trials of the vaccine, some researchers were *against* the idea of doing a properly randomized, double-blind, placebo-controlled clinical trial—including Salk himself
What did they want to do instead? An “observed control” trial. They would ask for volunteers (children) to get the vaccine, and then compare the rate of polio in the volunteers to the rate in their schoolmates who weren't vaccinated.

No placebo. No randomization. Not blind.
Of course, this was hopelessly confounded. In that era, the families most likely to volunteer were the more educated and affluent families (and those were actually the ones *most* at risk for the disease).

So why did Salk and others oppose proper randomized blind controls?
Read 35 tweets
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Dan Freedman
@dfreedman7
#funvaxfact placebo thread: I wanted to only focus on childhood vaccine trials with "inert"/saline placebos in kids since AVers love the "no true Scotsman" fallacy (h/t @handmadekathy). In the process, I found some great historical vaccine trials. Enjoy. #vaccinehistory
Disclaimer: saline is not the only choice of placebo & there are ethical considerations as to why placebos are not always used in vaccine trials but I wanted to show just how many saline studies there are. #VaccinesAreSafe

Thorough review of the topic:
ncbi.nlm.nih.gov/pmc/articles/P…
First, there is the largest randomized placebo controlled trial ever conducted: the 1954 polio field trials. 1.8 million children were enrolled with 200,000 receiving saline placebo. The vaccine was an enormous success and now polio is on the brink of eradication #VaccinesWork
Read 10 tweets
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Sam Westwood
@westwoodsam1
I am embarking on my own #PaperPerDayChallenge where I read at least one paper, well, per day for a whole year. To kick start, nature.com/articles/43573… inspired by @ukrepro Reproducibility Workshop @CumberlandLodge and a talk by @MarcusMunafo
Paper #2: Hard not be cynical about advocates of reproducibile science given most have careers built on the very questionable practices they wish to stamp out, so great to see @russpoldrack tackling this head on and offering great advice along the way 👍 ac.els-cdn.com/S0896627318310…
Paper #3 - false positives from multiple testing in anovas and importance of distinguishing exploratory and confirmatory hypotheses — also I thought anovas corrected for Multiple testing and this paper shows so too do many others, I’m not the only idiot! link.springer.com/content/pdf/10…
Read 245 tweets
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Maarten van Smeden
@MaartenvSmeden
Let's try something new: *7 days, 7 statistical misconceptions*.
Over the next 7 days I'll post about 1 statistical misconception a day. Curious to hear your favorite #statsmisconceptions, so feel free to add you own to this thread
Day 1: "Sample size has nothing to do with bias"
👆 is something I still hear regularly. This misconception seems to be based on the oversimplified idea that sample size only affects precision - something I was told repeatedly in the first years of my studies
Read 93 tweets
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Nathalie Martinek PhD
@NatsforDocs
Some thoughts: There seems to be an assumption in #medicine that patients receive the best care based on best evidence, where evidence usually means quantitative research (my assumption). Yet quality of care is dependent on personal characteristics of each health professional 1/
Knowledge derived from evidence is insufficient to translate into behavioural changes that support the 'best care' intention. Science-based evidence must be channeled through unquantifiable characteristics expressed by each individual health professional to provide best care 2/
These characteristics include: empathy, kindness, unconditional positive regard, non-judgemental attitude, empathic listening, intuition, warmth, encouragement, hope and so on. If we're touting science-based medicine, it must also include practice-based evidence 3/
Read 11 tweets

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