Evidence · Trials

Run-in periods and the population they select — the long version

Evidence › Trials randomised trial estimand intention to treat surrogate endpoints

a.lindqvistTL2 Moderator17 Oct 2025#1

Run-in periods and the population they select — the long version Writing it up because I had to work it out twice and would rather nobody else did.

Session topic: SUSTAIN 6 (N Engl J Med, 2016). Please read it before posting; the discussion is much better when everyone has.

The question I would like us to start with is what the trial set out to estimate, rather than what it found. Once that is on the table we can talk about whether the design could have answered it, and only then about the numbers.

Specific things I would like covered: the population and how far it generalises, how discontinuation was handled, whether the comparator was a fair one, and what the absolute rather than relative effect looks like.

I will summarise at the end and the summary will feed the relevant digest page.

55 likes 9mo

figure_reviewTL2Member18 Jan 2026#2

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.

15 likes 6mo

e.kuipersTL2 Moderator25 Mar 2026#3

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

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

3 likes 4mo

Promoted into the documentation commons. The content of this topic is maintained at STEP 3 — trial digest, with named maintainers and a review date. The promotion was discussed in doc review. Corrections are best raised against the document, which is the version that gets kept current.

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