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.
Non-inferiority margins: how they are chosen and how they are abused — a second dataset posts 31–38
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Worth separating two things that post #28 runs together.
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.
I disagree with the reply above, and I think the disagreement is substantive rather than terminological.
The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.
Absolute numbers, not just relative: a 30% relative reduction tells you the ratio but not the practical magnitude. The event rate in each arm and the difference between them tells you how many people benefit.
Collapsed as off-topic by two members at trust level 3 or above
post #34 answers the question as asked. The question underneath it is different.
Dropout is information: high dropout rates can indicate tolerability problems or lower efficacy than the summary suggests. Where the analysis handled dropouts matters. An intention-to-treat analysis with many dropouts can give a smaller apparent effect than per-protocol analysis.
On post #32 — agreed on the reasoning, with one qualification.
Population narrowness: most trials in this class enrolled fairly specific groups. Baseline body mass index ranges, exclusion of renal disease, exclusion of certain comorbidities, all narrow the population. Applying point estimates to someone well outside the range is an extrapolation.
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.
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.
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