[bryan0]

> When the investigators compared just the 42% of participants in the invited group who actually showed up for a colonoscopy to the control group, they saw about a 30% reduction in colon cancer risk and a 50% reduction in colon cancer death.

I’m really confused by this data. First of all, are they testing the efficacy of colonoscopy or the efficacy of inviting people to colonoscopy?

And then how is the former group’s reduction in deaths 50% and the latter group’s is about 0%?

[JamesBarney]

The gold standard is the invitation. Imagine a study where you try to get one group of people to exercise, and you leave the other alone as a control group. Imagine you find that everyone who actually does the exercise lives much longer. This might be due to the exercise, or it could be that exercise doesn't work but healthier more responsible people followed through with the exercise. And the being healthier and more responsible causes you to live longer not the exercise.

This could also be true for the colonoscopy, that the more responsible/healthier people in the treatment group are more likely to get the colonoscopy and it's very possible responsibility/healthiness are driving the difference in health outcomes instead of the colonoscopy.

[pbourke]

In this case they are examining colon cancer and deaths from it, and the colonoscopy is a diagnostic test for colon cancer. I feel that the results are being presented to the public in a very misleading way. People will read this headline and conclude that they don’t need to get a colonoscopy which I don’t think follows from this study at all.

[gwd]

> People will read this headline and conclude that they don’t need to get a colonoscopy which I don’t think follows from this study at all.

What this appears to show is that you need to get a colonoscopy to avoid colon cancer; but that you don't need to get a colonoscopy to avoid death. I'd much rather avoid colon cancer entirely than have colon cancer and survive.

But as GP pointed out, maybe you need something else to avoid death: something that is correlated with responding to the invitation to get a colonoscopy. Maybe if you're willing and able to get a colonoscopy when invited, you're willing and able to more pro-actively go to the doctor when you notice other issues that are indicative of colon cancer, allowing you to get early treatment. And conversely, maybe if you're not willing or able to get a colonoscopy when invited, you're more likely to ignore symptoms until it's too late.

Again, avoiding colon cancer in the first place is better than successfully treating it; but it does point to the fact that other interventions might be more helpful in actually preventing deaths.

[kashunstva]

> And conversely, maybe if you're not willing or able to get a colonoscopy when invited, you're more likely to ignore symptoms until it's too late.

Yes. This is the argument against relying on the secondary analysis in this study. Although the invited and standard care groups were randomized such that differences in putative confounders were adjusted for, the rejection of the intervention itself may have reintroduced systematic differences that reduce the reliability of the hypothesis that intention to screen for colon cancer reduces mortality. Possibly those who accepted screening colonoscopy are more attentive to other health and lifestyle practices that reduce colon cancer mortality.

[divbzero]

I agree. Even if intention-to-treat is the gold standard endpoint for trials, a more accurate and nuanced headline for the general public would be:

Inviting patients to undergo screening colonoscopy fails to reduce rate of cancer deaths

[pessimizer]

Or: If you compare a group of people who never get colonoscopies with a group of people containing many who do get colonoscopies, the same number of people die.

Imagine two cages filled with identical mice. One you drop some food into, and the other you don't. They starve to death at the same rate. Surprised?

[JamesBarney]

The study results are "colonoscopies do not lead to a reduction in colon cancer mortality". Reporting that isn't misleading that's what the study says.

Basically in the treated group of 1103 of every 10,000 people died. And in the control group 1104 of every 10,000 people died.

So to summarize the study. Inviting someone to a colonoscopy reduces their risk of getting colon cancer by 22 basis points. Their risk of dying from colon cancer by 3 basis points, and their risk of dying of any cause by 1 basis point.

With the actual risk reduction being up to 5x this assuming it's a 20% difference in the rate of getting colonoscopies which is driving the difference.

But this makes metformin look good because it drives a much larger overall reduction in risk.

[pbourke]

> The study results are "colonoscopies do not lead to a reduction in colon cancer mortality". Reporting that isn't misleading that's what the study says.

The measured intervention was not the colonoscopy, it was the invitation to screen. Only 42% of invited patients actually got a colonoscopy. This is far more persuasive to me:

> "When the investigators compared just the 42% of participants in the invited group who actually showed up for a colonoscopy to the control group, they saw about a 30% reduction in colon cancer risk and a 50% reduction in colon cancer death. “That adds to a bunch of observational study data that suggests exposing people to colonoscopy can reduce risk of developing and dying of colon cancer,” Gupta said."

As a member of the public, I don't really care about invitation to screen, but do care about the efficacy of colonoscopy. I can see invitation to screen being an important concern from a public health standpoint.

[JamesBarney]

The problem is whether or not they chose to get a colonoscopy is a confounding variable which inflates the value of the colonoscopy when some of the results are driven by other attributes.

[driggs]

Thank you for pointing out that insightful detail!

The control group was 50% of the population who didn't get an invitation.

The experimental group was 50% of the population who got an invitation for colonoscopy, but turned out to be subdivided into ~40% "health conscious" who actually followed up on the procedure, and ~60% who ignored it.

Presumably there's a corresponding ~40% "health conscious" component of the control group, but this experiment had no method for identifying them.

If the study only looked at that ~40% subset of the experimental group, as opposed to the entire group who received invitations, then they could no longer compare them to the control group.

[rob74]

Or it could be that the people that are not necessarily healthier, but have a history of cancer in their family, may be more likely to respond to a colonoscopy invitation? One way or the other, this is all just guesswork...

[kmonsen]

I feel this is a really reasonable take. This study doesn’t say anything bad about colonoscopy, it says that it is possible the effects are not only due to the colonoscopy so it is probably between 0 and claimed effect effective. Can’t really say where in the range from the study.

[em500]

Yup.

The study answers a question from health policy makers: Should we invite everyone (in some age group) for a colonoscopy? Based on this study, probably not.

It does not answer questions from individuals: Should I get a colonoscopy? If you have some good reason (symptoms, doctor advice, family history), probably yes (based on other studies, not this one).

[sokoloff]

To the extent that there’s a spread in those answers, a third possibility emerges: how can we, as health policy makers, find a way to make the invitations more effective at converting to administered colonoscopies?

[thaumasiotes]

Why would that be a goal? First you'd need to show that colonoscopies were helpful in general, or that invitations were going to a subpopulation in which colonoscopies were helpful.

[Supermancho]

> The gold standard is the invitation.

I'm not sure what gold standard you are referring to (or the article or the paper - https://www.nejm.org/doi/full/10.1056/NEJMoa2208375).

Double blind studies require there to be data. An invitation doesn't speak to the effects of Colonoscopy screening at all, while simultaneously adding a confounding variable about participation. The data is about the effects of offering screenings, not the effect of those screenings, per se.

Lifelong data is the gold standard for questions about mortality and most Colonoscopy randomized trials started around 2010 (hence this very early 10-year study, which I would say is premature).

[uslic001]

They used intention to treat in the analysis so it included everyone invited to get a colonoscopy but only 42% got the exam. So 58% did not even get the colonoscopy. It is impossible to say what colonoscopy does or does not prevent when the majority of people in the intervention arm of the study did not get the intervention.

[JamesBarney]

Participation is a confounding variable if you compare the subset of invitation group that participated with the control group instead of the invitation to the control group. That's the whole reason they use intent to treat.

Lifelong correlational data is not the gold standard for questions about mortality. It's intent to treat RCTs.

[Supermancho]

> Participation is a confounding variable if you compare the subset of invitation group that participated with the control group instead of the invitation to the control group.

I believe that's what I said. That's certainly what was used. You can't compare the group subset that didn't participate, so it's a confounding variable.

> Lifelong correlational data is not the gold standard for questions about mortality.

AFAIK it is and has been over the last century. If you aren't tracking lifelong data, your mortality data is always skewed against hidden results because you didn't want to wait. When making a paper that isn't qualified (decade long effects vs effects), it's not expected to have short time-boxed data.

[paul_f]

Seems the only way to prove the test itself reduces deaths is to force unhealthy/irrresponsible people to get colonoscopies. Is there another approach?

[hannob]

They're doing an intention to treat analysis, which can be a bit confusing, but statistically makes sense and is the gold standard for clinical trials.

You're basicall saying "our randomization at the beginning of the trial is key to avoid biases, so we can't reassign people from the treatment group to the other group, even if they practically don't get the treatment". The reason is if you allow people to switch, your assignment is no longer random. People who avoid the treatment may have different health properties than the ones who don't.

In essence, you need your trial to be robust and large enough that a few people not getting the treatment don't matter.

[hef19898]

Then the title is wrong, since colonoscopies actually do increase survival rates (everything would have surprised me a lot as someone who was saved by one), but rather that invitations for colonoscopies don't work. No idea why, but maybe people willing to do one go anyway while those unwilling are very unlikely to follow an invitation. Either way, the title is wrong, misleading and very clickbaity.

[elcomet]

What you're saying is not totally correct. If you look only at patients that did get a colonoscopy, you cannot be sure that it is the colonoscopy that helps, or another variable (those people might monitor their health closer). Your assignment is not random any more so you cannot make any causal statement.

[bryan0]

Thanks. That explanation on avoiding selection bias makes sense, but it seems like the study is saying those who choose to get a colonoscopy (whether invited or not) are 50% less likely to die of colon cancer.

Also I’m not sure if the article mentioned this, but the data seems to imply that the % of people who opted to get a colonoscopy was similar in the invited and control group.

[akvadrako]

That suggests something strange though – that those who were invited but non-tested were more likely to die of colon cancer than non-invitie non-testers.

[zerocrates]

I suppose that by refusing to get a colonoscopy even when specifically prompted to do so, you're maybe sorting yourself into a more "unhealthy" group than the general population of non-colonoscopy-havers.

[robertlagrant]

That would make the outcome less surprising.

[bluGill]

It would be unethical to refuse to invite someone with a family history of colon cancer. Thus I think it is perfectly reasonable to assume there is something different.