[phkahler]

I'm also confused about the "invited" group. Not all of them had the procedure and there is a part talking about lower cancer rates among the subset that actually accepted the invite. It sounds like there is still confusion about how to interpret it.

[timr]

There's not confusion. The study did an intention-to-treat analysis, which failed to find a significant result.

"Intention to treat" here means that you count everyone in the group that got an invitation to get a colonoscopy, regardless of whether or not they actually did it. Though this sounds counterintuitive, it's the "gold standard" because, if you don't do this, you leave yourself open to bias -- maybe the people who seek out colonoscopy have some symptom, family history or other reason that leads them to seek out treatment. Maybe the people who get a test get more treatment, and that treatment is harmful in the marginal case. Or just as importantly: maybe the people who don't have the time/inclination to do one would be better served by an alternative test.

Everyone (including GP) is fixating on the magnitude of the primary outcome and squabbling about whether or not colonoscopies help people. But I think the more interesting aspect of this study is that it shows that the genetic tests probably aren't inferior to the invasive, painful, time-consuming rectal exam. If that's true, it's great news!

[dahart]

> Though this sounds counterintuitive, it’s the “gold standard” because, if you don’t do this, you leave yourself open to bias

Isn’t there just as much chance for bias if the treatment is voluntary? Maybe the people who are more likely to have health issues are less likely to treat them.

I think there is a valid question about how effective a colonoscopy is given that you get one, and a separate valid question about how effective telling people to get colonoscopies is. According to the article, this paper answer the second question strongly via “gold standard”, and the first question less strongly via secondary analysis.

Part of the reason it’s counterintuitive here is the title of the article is “effect of colonoscopy screening”, not “effect of a doctor’s invitation to have a colonoscopy screening”. The title more than suggests that we’re comparing the outcomes of actually having the screening to not having one.

> maybe the people who don’t have the time/inclination to do one would be better served by an alternative test.

I see what you’re saying - the overall effectiveness of our current system may be low because of a low rate of voluntary adoption of the colonoscopy is low, and even a lower accuracy screen could be more effective if more people opt in.

One problem with drawing a conclusion this way is it ignores the possibility for dramatic changes in either opinion or in procedure of colonoscopies. What if we had the tech to do the colonoscopy at home in private? Would that change the voluntary rate of testing dramatically?

[timr]

> Isn’t there just as much chance for bias if the treatment is voluntary?

I'm not quite sure what you're asking here. If you're wondering if voluntary opt-out of colonoscopy carries risk of bias, then I'll say the following: it's an intervention that is painful, intrusive and time consuming. No reasonable person would get one absent demonstrated benefit.

Pick a thing where people are reasonably likely to do it as default behavior (eating chocolate, say), and the intervention is to abstain from doing the thing, then you'd be right to ask that question. I imagine people who voluntarily abstain from chocolate are pretty different in substantial ways than people who have to be coerced to do so. But people who don't get a colonoscopy when not pestered to do so are just...normal.

> I see what you’re saying - the overall effectiveness of our current system may be low because of a low rate of voluntary adoption of the colonoscopy is low, and even a lower accuracy screen could be more effective if more people opt in.

Not quite. I'm saying that this study did the fairest possible test for effectiveness of colonoscopies, and the effect sizes they found were on par with the genetic tests (to be clear: they didn't actually make this comparison in the RCT; I'm extrapolating from other studies.)

The evidence presented here is not that the genetic tests are a "lower accuracy screen", it's that colonoscopies are likely not better than genetic tests. That's very different.

[dahart]

> No reasonable person would get one absent demonstrated benefit.

But if we insist on measuring demonstrated benefit by factoring in participation rates, then it’s a catch-22. What if given a prior distribution of 100% opt-in, colonoscopies are effective? And you ignored my question about what if we made colonoscopies more convenient, less intrusive and time consuming, which is becoming possible with new tech. These things can change the participation rate, which in turn can flip the outcome from little demonstrated benefit to high and conclusive demonstrated benefit.

> this study did the fairest possible test for effectiveness of colonoscopies

“Fair” is a subjective term, and it depends on what question you’re asking. I agree with your statement if the question is how effective is the current system of recommending colonoscopies. It’s not the fairest test of how effective a colonoscopy screen could be if everyone shows up for the screen. Colonoscopies might be not better than genetic tests because participation rates for genetic tests are higher, as opposed to colonoscopy screening being less effective on their own.

I understand your point that the total probability is important. But so is understanding the Bayesian factors, it’s equally enlightening and important to separate and understand the effectiveness of the screen given participation, from the likelihood of participation. And you effectively cemented how important this point is by clarifying that people use knowledge of these outcomes in order to choose whether or not to participate, so framing them incorrectly can and likely does lead to unnecessary loss of life.

[timr]

> What if given a prior distribution of 100% opt-in, colonoscopies are effective?

That is what the "per-protocol" analysis in this RCT estimates. They considered only those people who had a colonoscopy. This completely breaks randomization and is subject to investigator bias, but at least it gives you an idea of the best you could possibly do if you lived in a world where everyone was forced to get one.

And that is: a drop of 0.15% in colo-rectal death. They then attempt to extrapolate this to estimate the effect on all-cause mortality if you somehow forced everyone to get a colonoscopy, and come up with a number of 10.88% (vs. a baseline of 11.03%). So, even if you forced everyone to get a test, you'd need to test 667 people to save one life.

That's a lot of pain for very little gain.

[dahart]

> a drop of 0.15% in colo-rectal death.

Where’s that coming from? I didn’t read the paper yet, but the article says: “A secondary analysis also offers another silver lining, Gupta said. 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.“

> This completely breaks randomization and is subject to investigator bias

Yes, true. I agree with you. This is important when asking the question “how effective is recommending screenings”. But, voluntary opt-in also breaks randomization, and is subject to patient bias.

> you’d need to test 667 people to save one life. That’s a lot of pain for very little gain

Assuming that’s accurate (the article appears to disagree), I’d still be very hard-pressed to agree with this conclusion. Why is a once or twice a decade doctor’s visit spread out over many people amounting to enough pain to let someone die? How much is a life worth? Is the colonoscopy really so bad that you’re willing to risk a greater than one in a thousand chance of dying? That risk is comparable to many extreme sports.

The problem with this kind of sum up the cost and make it look large is that you didn’t do this for anything else and compare it for reference, which makes this framing prone to cognitive bias. We spend billions and have laws for keeping drivers safe, for example. You could make it look insane by adding up the billions of dollars and people-years people spent bucking and unbuckling seatbelts, but the truth is that it’s a teeny inconvenience per person for a sizeable gain in safety and reduction in the accumulated secondary costs of accidental death.

[jdeibele]

My father died of colon cancer at age 67. I've been getting screened every 5 years, first by sigmoidoscopy and the last couple of times with the full colonoscopy.

With a sigmoidoscopy you're awake and the doctor will show you what they're looking at. I guess that's intrusive but it certainly wasn't painful.

With colonoscopy, you're under anesthesia. It was probably intrusive but since I wasn't conscious, I didn't care. There was no pain when I regained consciousness.

I'd rather do a stool sample by mail or dropping it off at the clinic if it has the same results as the colonoscopy. There's always a risk with general anesthesia.

I don't know if my case is the norm and yours is the exception. I tend to think it is. My dad missed spending time with his grandchildren and it's possible he'd still be around if he'd been examined. So get that colonoscopy.

[timr]

I grant you that I'm using an expansive definition of "pain" here...I'm including the day of diarrhea before the test, the stress and (yes, some) pain of the sedation itself, and the unpleasant recovery (nausea, fatigue, etc.) that follows. Maybe it isn't "pain", per se, but it's something we'd all rather avoid.

I should also say the following: if you've got a family history of colon cancer, active symptoms, or some other reason to believe that you're at risk, studies of statistical averages don't apply to you.

[JoeAltmaier]

I never have anaesthesia for colonoscopy. The post-procedure nausea etc are worse than the discomfort of being probed. I you're not squeamish (and I am not) then it's not a big deal to be awake for the procedure.

[SoftTalker]

There's not only a risk with the anesthesia but there's a risk of a perforated colon. It's not the routine risk-free procedure that the providers make it out to be.

[JoeAltmaier]

1 in 1000 have complications. Colon cancer attacks 1 in 25. So that math check out - have your colonoscopy

[2devnull]

The important part of your post, “If that’s true…”

Is it true, or not?

[timr]

To the extent that we can assess it by this single study, yes.

There is no answer to the question you're asking. You're seeking absolute certainty where none can be had. We only know what we know as far as we know it. Always and everywhere.