[CrazyStat]

I'm going to strongly push back on both (1) the notion that overall survival is the wrong metric and (2) that I'm misinterpreting something, given that I didn't really offer any interpretation at all. I just cited a paper.

> What you want to do is

No, what I want to do is assess whether broad screening programs actually make people live longer. Overall survival is the correct metric. Evidence in favor of the claim is lacking.

> none of the studies are sufficiently powered for OS.

"Sufficiently powered" is relative to what size of effect you want to detect--which you haven't specified, so I'm not sure how you can make the assertion that none of the studies are sufficiently powered.

> The available evidence behind currently recommended screening programs unequivocally shows improved cancer-specific survival and earlier stage at diagnosis.

These outcomes ignore negative effects of screening on people who don't have cancer, which is why I'm not interested in them. And yes, there are negative effects, and no, they are not negligible.

[haldujai]

> No, what I want to do is assess whether broad screening programs actually make people live longer. Overall survival is the correct metric. Evidence in favor of the claim is lacking.

Correct according to whom? If you want to choose only one metric quality adjusted life years is likely the best one.

While OS may be your goal that's not the primary endpoint of screening programs.

Some examples of why OS is limited: breast lumpectomy vs mastectomy and systemic therapy or polypectomy vs neoadjuvant therapy and colonic resection are both associated with very high morbidity that is very important to patients. The vast majority of patients care about quality of life.

> "Sufficiently powered" is relative to what size of effect you want to detect--which you haven't specified, so I'm not sure how you can make the assertion that none of the studies are sufficiently powered.

We do not expect any one screening program to have a large change on overall survival because there are many ways to die, very few studies are powered to detect the small differences expected. The reference below does some modeling and discusses cancer-specific vs all-cause mortality for your perusal.

https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.2476

> These outcomes ignore negative effects of screening on people who don't have cancer, which is why I'm not interested in them.

See morbidity discussion around delayed diagnosis above.

> And yes, there are negative effects, and no, they are not negligible.

As you're choosing to limit the discussion to overall survival, do you have any data to support the claim that screening has more than a negligible negative effect?

There is a better argument to be made for other harms of screening like cost and stress but if we want to discuss these negative effects of screening we also have to step back from overall survival and discuss morbidity benefits.

ETA:

> 2) that I'm misinterpreting something, given that I didn't really offer any interpretation at all.

This is your interpretation, and is an incorrect one:

> The evidence in favor of mass screening programs in the hope of early detection is actually weak to non-existent [1].

The evidence you cite says nothing about early detection and treatment paradigms.

[CrazyStat]

> Correct according to whom? If you want to choose only one metric quality adjusted life years is likely the best one

By all means, if you have studies showing that broad screening programs are beneficial in terms of overall (not cancer-case only) QALY then please share them. I'm guessing you don't.

> As you're choosing to limit the discussion to overall survival, do you have any data to support the claim that screening has more than a negligible negative effect?

Do you have any data to support the claim that screening has more than a negligible positive effect on overall survival? (No).

Stop trying to put the burden of proving a negative on me. If you want to advocate for spending ten of billions of dollars annually (not to mention time and stress) on broad screening programs you bear the burden of demonstrating that's useful.

If we can afford to spend the money on screening everyone certainly we can afford to spend less money to run a large randomized trial screening only some people, but advocates of the screening programs won't stand for it because they are convinced of their own righteousness and refuse to admit uncertainty about whether the screening programs are actually doing more good than harm.

[haldujai]

> By all means, if you have studies showing that broad screening programs are beneficial in terms of overall (not cancer-case only) QALY then please share them. I'm guessing you don't.

I gave you one.

> Stop trying to put the burden of proving a negative on me.

You're making the claim there's more than a negligible negative effect not me.

> Do you have any data to support the claim that screening has more than a negligible positive effect on overall survival? (No).

Did I say there is a sizable positive effect on overall survival? I said it's irrelevant.

[CrazyStat]

> I gave you one.

No you didn't, you gave me a simulation study that discussed what kind of sample size might be necessary to find statistically significant effects in all-cause mortality. There's not a single mention of QALY in there. Please stop misrepresenting things.

> You're making the claim there's more than a negligible negative effect not me.

The cost itself is a nonnegligible negative effect.

> Did I say there is a sizable positive effect on overall survival? I said it's irrelevant.

You're wrong.

It's borderline fraud, in my humble opinion, to go around suggesting that massive interventions should be evaluated based on their effects only on the people who benefit most, ignoring the negative effects on the other 98% of the population. Which is exactly what you did in your first reply to me:

> What you want to do is look at stage at presentation, treatment costs by stage, and screening costs. These were done for nearly every recommended screening program.

> The available evidence behind currently recommended screening programs unequivocally shows improved cancer-specific survival and earlier stage at diagnosis.

This approach to evaluating an intervention is intellectually dishonest and emotionally manipulative. Any evaluation that does not take into account the other 98% of the population--through overall survival or QALY or some other metric--is giving an extremely biased picture of what the intervention is actually doing to the population as a whole.

[haldujai]

What are the downsides? You're speaking nebulously about negative effects on 98% of the population without mentioning them.

Several screening programs like breast have been rigorously evaluated from costs, benefits and harms. I know very well what the negative effects are, do you? You haven't mentioned anything specific or provided estimates of harms yet you're the one making the assertion.

> You're wrong.

So if we're all wrong, what's the argument and where's the evidence without resorting to no OS benefit ignoring that this is again not the point of screening.

> It's borderline fraud, in my humble opinion

Your humble opinion disagrees with the entire medical community, including the study you initially cited. So we're all fraudulently screening for what purpose? You know that physicians don't collect billings or work fee for service in academic medicine correct?

> Which is exactly what you did in your first reply to me:

Did I say that was the only reason to screen and ignore the harms? I used that as an example of why overall survival is not useful as an isolated statistic.

You're the one who wanted to limit the discussion to one measure, I was pointing out the flaws.