About the Trials category

Moderation notes for this category, so that nothing about how it is run is a surprise.

Topics get moved into and out of here regularly. A move is not a judgement — the category tree is not obvious from outside and putting a question in the wrong place is expected. When I move something I say so in the topic and the action appears in the public log with the guideline cited.

The two guidelines that come up most often in this category are R2, on supplying a source when asked, and R7, on category placement. Neither is used punitively.

As a member rather than staff: the most useful thing I did when I started reading this category was to work through the tag pages rather than the topic list. The topic list shows you what is recent. The tags show you what is settled.

Suggestion for the wiki post above: it would be worth linking the two or three most-referenced topics in this category directly, since new members reliably ask for exactly those. Happy to make the edit myself if nobody objects, with a revision note.

Open-label design: unblinded trials admit expectation effects. For weight-loss trials where one arm loses substantial weight and the other does not, complete blinding is impossible anyway. The unblinded nature is a limitation worth noting.

Surrogate endpoints: an endpoint that is not the outcome that matters but is measured as a stand-in. HbA1c is a surrogate for long-term glucose control and the short-term complications it prevents. Weight loss is a surrogate for metabolic health and long-term outcomes. Surrogates are useful but not identical to the endpoint that matters.

Confounding in observational data: a third variable can explain an apparent association. In a randomised trial, randomisation balances unknown confounders. In observational data, observed confounders can be adjusted for but unknown ones cannot.

I read post #7 twice before replying, because I had assumed the opposite.

Risk of bias: structured appraisal of internal validity. Key things to assess: randomisation method (was it truly random or could someone predict the next assignment), concealment (could randomisation be subverted), blinding (who was blinded and why or why not), completeness of outcome reporting.

This follows post #7 rather than contradicting it.

Intent-to-treat versus per-protocol: ITT includes everyone assigned regardless of whether they took the drug. Per-protocol includes only those who completed it as intended. The two can give substantially different results.

Multiplicity and multiple comparisons: if a trial tests many hypotheses, the chance of a false positive on at least one by random chance increases. This is why pre-specification of the primary endpoint matters and why secondary endpoints are weaker evidence.