Did you see this nice critique from @pwgtennant.bsky.social?

DAN ZOSTER trial has completed enrollment, so we should have a definitive answer soon!

Further evidence that being rich is one of the best things you can do for your health

Thanks - the RCT has completed enrollement already, so we'll have the answer soon enough!

I'd like to see some methods work looking at how reassured we should be by negative control outcomes

I think the DAN ZOSTER study has already completed recruitment

I wouldn't fund a stand alone RCT but I could perhaps support a Vit D randomisation in a TB prevention platform trial

I can see where you are coming from, but the Vit D - TB trials were small compared with other prevention trials

Big savings can be made elsewhere, e.g. trial regulation, affordable placebos, trials embedded in routine care, platform designs, fewer observational cohorts on questions amenable to RCT

At NNT 1000, you could prevent 60,000 cases of TB per year in South Africa ~ 720,000 DALYs

South Africa is willing to pay USD 3200 per DALY, so USD 2.3bn approx threshold for this intervention

I suspect you could fortify commonly eaten foods in South Africa for much less than that?

The Mongolian trial was wildly underpowered for disease outcomes

What happens if you use the results of the Tanzanian trial as your prior?

For individual patient treatment, I would offer something low risk with NNT of 100, perhaps 200, to prevent a case of TB

For mass supplementation, I would be interested in smaller effects

The 1.1 is for an infection endpoint, and the negative South African trial also had an infection endpoint

There is no good reason to think Vit D would reduce Mtb exposure

Primary disease endpoints were 0.87 (0.49-1.55) in Mongolia and 0·78 (0·54-1·13) in Tanzania

I'm not convinced that the TB trial is negative, I think they chose the wrong primary outcome

I think the big scandal here is how much it costs to run RCTs of low risk interventions