[Please consider the following with an open mind]

Just because a study doesn't replicate, doesn't make it false. This is especially true in medicine where the potential global subjects/population are very diverse. You can do a small study that suggests further research based on a small sample size, or even a case study. The next study might have a conflicting finding, but that doesn't make the first one false - rather a step in the overall process of gaining new information.

I think it's much, much more powerful to think of "failure to replicate" as "failure to generalize."

In lieu of actual fraud or a methodological mistake that wasn't represented/caught in peer review, it's still extremely difficult to control for all possible sources of variation. That's especially true as you go further "up the stack" from math -> physics -> chem -> bio -> psych -> social. It is absolutely possible to honestly conduct a very high quality experiment with a real finding, but fail to account for something like "on the way here, 80% of participants encountered a frustrating traffic jam."

Their finding could be true for people who just encountered a traffic jam, and lack of replication would be due to an unsuccessful generalization from what they found.

Dislike being a pedant but the stack was missing math up front

Haha, math strikes me as a bit different from the others... but I'll add it just for you ;)

Dislike being a pedant but the stack is missing philosophy up front.

Math isn't a science, it is a tool we can use to construct coherent arguments. We can do this about our world, which science aims to do, but we can do this about many worlds. We can consider correct deductions within a mathematical system as fact, but they do not represent facts in the "real" world.

Elegant explanation of why I felt it didn’t belong! Thanks for writing :)

> but they do not represent facts in the "real" world.

In what sense do they not? On the assumption that there can be other "worlds" for which math, but not physics, holds?

One I always go back to: You can represent a perfect impulse (think electrical signals, a switch from 0 (low voltage) to 1 (high voltage)) mathematically, but it's impossible to physically create.

In our universe there are some number of physical constants that cannot be determined from maths alone, but only measured. If you go about changing these physical constants then we don't have physics as we know it (change 1/137 to 1/140 and electromagnetics no longer works). You get some totally different physics of which there may be nothing more complicated than hydrogen, or maybe hydrogen doesn't even exist at all.

https://en.wikipedia.org/wiki/Fine-structure_constant

Yes, you can make perfectly valid mathematical systems that have zero anchoring to any physical reality we experience (such as, trivially, n-dimensional geometries).

A geology that isn't anchored to our physical reality seems intrinsically invalid.

> Just because a study doesn't replicate, doesn't make it false.

But it also doesn’t make it not false. It makes the null hypothesis more likely to be true.

That is certainly one possible interpretation.

The other is the introduction or loss of critical cofactors or confounders that radically change environment and context.

Think of experiments of certain types before and after COVID-19.

"Just because a study doesn't replicate, doesn't make it false."

This is a subtle point, but truth or falsity isn't really the issue. The problem with a non-replicable study is that the rest of science can't build on it. You can't build your PhD on top of a handful of studies that turn out to be non-replicable, and so on. It is true you can't build science on outright false statements, either, but true statements that aren't adequately reproducible are also not a solid enough foundation. That may seem counterintuitive, but it comes down to this truth not being binary; even if a study comes to a nominally true conclusion it still matters if it didn't do it via the correct method, or is somehow otherwise deficient in the path it took to get there. Studies are more than just the headline result in the abstract.

But the whole process of science right now is based on building up over time. How could it not be? It has to be, of course. But non-replicable studies mean that the things you're trying to build on them are non-replicable too. It doesn't take all that much before you're just operating in a realm of flights of fancy where you may "feel" like you're on solid ground because of all the Science you're sitting on top of, but it's all just so much air.

However, it is also true that non-replicability is a signal of falsity, and that is simply due to the fact that the vast, vast, vast, exponential majority of all possible hypotheses are false. As is another subtle point, a scientist engaging in science properly should probably not come to that conclusion and may not want to change their priors about something because of a non-reproducible study very much, but externally, from the generalized perspective of "what is true and is not true" where science is merely one particularly useful tool and not the final arbiter, I may be justified in taking non-replicable studies and updating my priors to increase the odds of the hypothesis being false. After all, at the very least, a non-replicable study tends to put an upper bound on the ability of the hypothesis to be true (e.g., if someone studies whether or not substance X kills bacteria Y, and it turns out not to reproduce very well, the lack of reproducibility does fairly strongly establish it can't be that lethal).

"The problem with a non-replicable study is that the rest of science can't build on it."

This isn't true at all. You could have future experiments set out to prove the opposite, or to dig into what novel and confounding variables are at play causing conflicting results. The fact that you have studies that inconsistently replicate is actually a sign of possible new knowledge if you can find out which undiscovered variable is causing the conflicts. Especially in medicine, you can have a case study that leads to future studies even though that specific case may not be able to be consistently replicated in other n=1 populations.

"e.g., if someone studies whether or not substance X kills bacteria Y, and it turns out not to reproduce very well, the lack of reproducibility does fairly strongly establish it can't be that lethal"

Or there's another factor that hasn't been discovered, such as back in the day before understanding gram positive and negative bacteria was even a thing. If you don't know the subtypes exist, you would see inconsistent results as that is an undiscovered variable that you can't possible account for until it's discovered. Once discovered and controlled for, the substance could be very lethal.

Outright research fraud is probably very rare; the cases we've heard about stick out, but people outside of academia usually don't have a good intuition for just how vast the annual output of the sciences are. Remember the famous PhD comic, showing how your thesis is going to be an infinitesimal fraction of the work of your field.

Research fraud is likely very rare but it's not about a few stories that show up about unreplicable studies that stick out. There was a study a few years where they tried to replicate a bunch of top cited psychology papers and the majority of the experiments were not replicated. Then people did the same for other disciplines afterwards and, while it wasn't as bad as psychology, there were plenty of papers they couldn't replicate.

Every time this topic comes up I'm reminded of what Stefan Savage, a hero of mine, said about academic papers ("studies", in the sense we're discussing here): they are the beginnings of conversations, not the end. It shouldn't shock people that results in papers might not replicate; papers aren't infallible, which makes sense when you consider the process that produces them.

That is a generous interpretation. But in many cases we try our best to dress up studies and tell good stories—-preferably stories with compelling positive statistics and with slick figures. The story telling often obscures the key data.

No, "Science" "Journalists" who have zero scientific training will take an extremely limited study and completely miss the point and make wild claims that the general population becomes convinced the "science" said.

Scientists do not consider a study to be more than an observation. What matters to scientists is the totality of the evidence.

There are several chemistry youtubers who have failed to "reproduce" papers they are working from. Does that mean chemistry is a farce and doesn't work? No, it means some chemist at some point in history failed to write something down, mostly because they didn't even know or realize it mattered. Science is incredibly difficult and we can only hope to be okay at it.

Both ways. I have published several hundred peer-reviewed papers in biomedical research over 40 years. My experience is that almost all papers are written to maximize impact on the minds of readers—-ideally hewing to the data and limits of the design. But often the story telling aspects of a paper and the data snd design do not see eye-to-eye.

Just keep in mind while we're scare-quoting "journalists" that the scientists on HN also seem to think a failure of replication in a paper is a devastating indictment of whole scientific fields. It's not like we're that much better.

Yes, papers start conversations, not end them. Replication issues are part of the academic process.

Is incompetence fraud? Or just incompetence? I'm asking because a fair number of the molecular biologists who get caught by Elizabeth Bik for copy/pasting images of gels insist they just made honest mistakes (with some commentary about the atrocious nature of record-keeping in modern biology).

I alter Ionnides's conclusion to be instead: "Roughly 50% of papers in quantitative biological sciences contain at least one error serious enough to invalidate the conclusion" and "Roughly 75% of really interesting papers are missing at least one load-bearing method detail that reproducers must figure out on their own" (my own personal observations of the literature are consistent with these rates; I was always flabbergasted at people who just took Figure 3 as correct).

There is no one hovering over scientists all the time ready to stick a hot poker in them when they make a mistake or get careless. I was in academia and my impression is there is a reluctance to double and triple check results to make sure they are right as long as the results match your instincts, whether it's time pressure, laziness, bias, or just being human.

At least in my own mental model of publishing a paper (I've published only a few), I'd want my coauthors to stick hot pokers in my if I made a mistake or got careless. But then, my entire thesis was driven by a reproducible Makefile that downloaded the latest results from a supercomputer, re-ran the whole analysis, and wrote the latex necessary (at least partly to avoid making trivial mistakes). It was clear everything I was doing was just getting in the way of publishing high prestige papers.

All too easy to understand your situation. NIH is finally but slowly waking up and is imposing more “onerous” (aka: essential and correct) data management and sharing (DMS) document. Every grant applicant now submits following these guidelines:

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-24-1...

Unfortunately, not all NIH institutes understand how to evaluate and moderate this key new policy. Oddly enough the peer reviewers do NOT have access to DMS plans as of this year.

Is this a process whereby the researcher is forced to submit the thesis (null, etc) of the research, ahead of the study and its findings?

I think you are referring to clinical trial registration. Different idea and process (a QA-like step).

The NIH DMS mandates are about the data generated by an award.

> I'm asking because a fair number of the molecular biologists who get caught by Elizabeth Bik for copy/pasting images of gels insist they just made honest mistakes

You're talking about (almost certainly) fraudsters denying they committed fraud. The vast majority of non-replicable results have nothing to do with these types of errors, purposeful or not.

> Is incompetence fraud? Or just incompetence?

Fraud requires intent; it's a word that describes what happened, but also the motivations of the people involved. Incompetence doesn't assume any intent at all; it's merely a description of the (lack of) ability of the people involved.

Incompetent people can certainly commit fraud (perhaps to try to cover up their incompetence), but that's by no means required.

> ...insist they just made honest mistakes

If they're lying about that, it's fraud; they're either covering up their unrealized incompetence with fraud, or trying to cover up their intended fraud with protestations of mere incompetence. If they really did make honest mistakes, then it's just garden-variety incompetence. (Or just... mistakes. To me, incompetence is when someone consistently makes mistakes often. One-time or few-time mistakes are just things that happen to people, no matter how good the are at what they do.)

The legal phrase I like is "knew or should have known". If there is a situation where you should have known something was wrong, it's as bad as if you really knew it was wrong. To hold otherwise incentivizes willful blindness and plausible deniability.

I don't think the fact that the law (rightly, I will grant) unified two things when determining whether to punish means that we should always unify those things in our reasoning in other contexts.

People often use incompetence as an excuse for what were actually intentional bad decisions. Never attribute to malice that which is adequately explained by stupidity.

Maybe someone was incompetent but also knew they were cutting corners. Should they get a pass because they claim they didn't mean to do it? We should hold people accountable regardless of intent.

People should be held accountable for the impact of their decisions

> Outright research fraud is probably very rare

Not sure what rare means in this context. The more important research is, the more likely there is fraud involved. So in terms of size of impact, it's probably very common.

And then if you combine this with poorly done, non repeatable, or inconclusive research being parroted as a discovery...You end up with quite a bit of BS research.