In Praise of Observational Evidence

https://asteriskmag.com/issues/14/in-praise-of-observational-evidence

by fi-le • 21 days ago

78 52 21 days ago

khalic• 16 days ago

Damn fine article, lovely conclusion, a real pleasure to read

samuell• 16 days ago

Quite thought-provoking, and connecting it to a related field it seems the (relative) success of LLMs and the likes are indications that enough data can at least learn you something without always needing to interfere with the world first(?)

AnimalMuppet• 16 days ago

Let me restate that: Enough accurate data about the real world can let you learn something about the real world without having to yourself interface with the real world. So, for example, Kepler's Laws were based on Tycho Brahe's observations, not on Kepler's.

SomeHacker44• 16 days ago

They reference RCT without first defining it.

Vohlenzer• 16 days ago

https://en.wikipedia.org/wiki/Randomized_controlled_trial

I noticed that as well. My eyes feverishly scanning the previous paragraph for the definition.

qsera8• 16 days ago

The increasing availability of large datasets should make this an especially good time to reconsider observational evidence in many fields.

This is not happening.

I was surprised to find that they usually discard papers based on observational evidence wholesale.

He he...welcome to the real world!

A_D_E_P_T3• 16 days ago

In medicine, observational evidence is actually better and far more ethical than the RCT. (Which simply dooms the terminally ill to fake treatment.) You just need large datasets and an agile culture that's responsive to new input.

Don't forget that RCTs are very far from perfect and issues -- sometimes literally fatal issues -- have later turned up via observational evidence in large cohorts. Vioxx, for instance. Many others.

I believe, without the tiniest shred of doubt, that the only trials drugs need to go through are initial safety/toxicity trials (phases 0/1) and that everything else would be much better left to access+observation.

taeric2• 16 days ago

This feels off. In medicine, any evidence can also be blinded by confounding factors that are far easier to miss without adding specific controls. Really, in any field this will be the case.

Should we demand an RCT before we accept evidence? Of course not. At some point you do have to make a choice on things.

And it should be noted that most drugs do have early cutoff criteria if the evidence is strong enough that it is working. It isn't like people are wanting to withhold good treatments from the world. Adding controls and randomizing them, though, has proven to be highly effective at helping progress.

A_D_E_P_T3• 16 days ago

"This feels off. In medicine, any evidence can also be blinded by confounding factors that are far easier to miss without adding specific controls. Really, in any field this will be the case."

If you have enough data, you can smooth out individual fluctuations due to things like drug interactions, non-compliance, etc. (And indeed you might discover drug interactions!) Observational trials ultimately mirror how drugs are used in the real world.

"Adding controls and randomizing them, though, has proven to be highly effective at helping progress."

I would argue just the opposite. Demands for increasingly byzantine trials have ballooned the costs associated with drug development, and have slowed things to a crawl. There's a reason the field's golden age was in the 1940s and 1950s, and it's not just "low hanging fruit." Today nobody in their right mind wants to work in drug development when they could work in tech or even finance.

naasking• 16 days ago

Which simply dooms the terminally ill to fake treatment.

I wish people would stop saying this. First, controls aren't necessarily "fake treatment", they are often compared to other standard treatments.

Second, the treatment being tested can actually harm the patient more, therefore the people receiving your alleged "fake treatment" can actually come out better off. Which is the "fake treatment" now?

I don't disagree with your final point, but mainly with this increasingly pervasive and wrong framing of RCTs.

FeteCommuniste• 16 days ago

Yes. Potentially life-saving drugs in RCTs are usually compared to "standard of care," i.e. already-approved treatments, not to placebos.

timr2• 16 days ago

In medicine, observational evidence is actually better and far more ethical than the RCT. (Which simply dooms the terminally ill to fake treatment.)

This is just nonsense. First, everyone in a trial is informed of the situation. It's not "unethical" unless you lie about it. If you participate in a trial, you do so knowing that you might not get the experimental drug. It's a selfless, honorable thing to do, and we shouldn't be framing it as some kind of scam.

Second, we don't give terminally ill people "fake treatment" (placebo trials). We give them current standard of care. Giving someone a placebo trial doesn't prove anything that would change clinical practice, because you want to know if the drug works better than what is out there today. Rarely is that standard of care "nothing", and this (bad controls) is actually a primary reason that a lot of drug company trials are rejected by the FDA.

If I didn't see the Wall Street Journal editorial board repeating the same garbage in defense of patent medicines, I'd write you off as simply having a sophomoric understanding of how trials work. I'm convinced that someone is driving this absurd narrative.

doginasuit• 16 days ago

The reality that individuals and cultures create can be a dark and confining place. Empiricism is our only window to a universe full of possibility and light. Humanity is like a child, standing on our toes to peer through and wonder.

pinko• 16 days ago

Seth Roberts was arguing this ~20 years ago and would have loved the advent of LLMs...

derbOac• 16 days ago

Experimental designs are critical for obvious reasons but they have a few critical flaws, that mostly all reduce to the fact you can't randomize manipulations with everything. Whether it be due to ethics or practical constraints, you can't conduct a RCT all the time.

This can be more subtly critical than it might seem, in that even if you can manipulate some proxy, often that proxy is insufficient in actually representing the phenomenon of interest, or the conditions under which they actually occur.

I often use the example of videogames and aggression. There were plenty of experimental studies of this but it was always questionable whether lab-induced anger is the same thing as, say, the sort of violence we generally are concerned about societally.

I generally have tried to teach students that experimental designs when done right provide powerful causal evidence of something, but often with limited generalizability; observational designs in contrast provide powerful generalizable evidence of some kind of association, but often with limited certainty about the causal pathways involved.

I've been in a department that was rabidly experimental in its focus and it always seemed sort of short-sighted, because people were idolizing RCTs with proxy manipulations that had questionable generalizability to the real-world phenomena they were trying to model.

Ideally you'd bring both experimental and observational evidence to bear on a question. Your conclusions should be robust to different types of designs.

CGMthrowaway• 15 days ago

Yes. Even conceding every point made in this article, RCTs are still the gold standard. The article points out that RCTs are often impractical, expensive or ethically challenging. Well, so is the gold standard of anything.

OP suggests that alternative methods like target trial emulation, propensity scoring and double machine learning can be used to approximate the conditions of an RCT using existing data. In saying so he gives away the tell, which is that RCTs are the standard being aspired to.

Observational data may well be undervalued. But RCTs are still the gold standard.

1970-01-013• 16 days ago

RCT is Random Controlled Trial. Definitions are the very basics in writing, check them before you publish.

KempyKolibri4• 15 days ago

Where is it defined as "Random Controlled Trial"?

esafak• 15 days ago

Ignoring the typo above, it's mentioned in the text: https://en.wikipedia.org/wiki/Randomized_controlled_trial

1970-01-013• 15 days ago

In the author's mind

compiler-guy• 15 days ago

One classic paper for on this topic:

_Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials_

https://pmc.ncbi.nlm.nih.gov/articles/PMC300808/

"Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute."

timr2• 15 days ago

That's not a "classic". It's just a silly, overwrought straw-man [1] that gets passed around by people who think they're being clever, and/or don't understand the topic with any degree of nuance.

Nobody reasonable suggests that RCTs must be used for every problem. When the effect size is enormous, or there's obviously no alternative (as in the parachute example), it's silly to suggest the use of an experiment.

On the other hand, if you want to compare some subtle difference between two competing parachute designs, for example, then perhaps an RCT would actually be appropriate. This is much closer to what is actually being measured in real clinical trials.

[1] To be completely fair to the authors, it was intended as a joke, not an argument. The real joke ended up being that people took it seriously.

mchusma• 15 days ago

Good article. I will only add that I think the problems outlined in the article are exacerbated by the regulatory apparatus. If this were a debate related to truth seeking alone, it would be good. But trials drive banning/unbanning of treatments and medicines, as well as their mandated coverage by insurance.

We could be much more flexible in our approach to things if we would un-ban things. For example after phase 1 trial or based on sufficient observational evidence, things can no longer be banned but have a higher standard for "insurance is now required to cover it".

In Praise of Observational Evidence

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