Primary endpoint hierarchies and why order matters

Primary endpoint hierarchies and why order matters Writing it up because I had to work it out twice and would rather nobody else did.

I was wrong about primary endpoint hierarchies in a thread last spring and I would like to correct it publicly rather than quietly.

The error was in the units, which changed the conclusion by an order of magnitude. Setting out the corrected version, and the way I now check for that class of mistake.

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.

The opening post and I disagree about the size of the effect, not about the direction.

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.

Adding a source would improve this post and I do not have one to hand.

Taking the opening post at face value and following it one step further.

Pre-specification is the property that makes a primary endpoint trustworthy. An endpoint chosen after seeing the data can be the best endpoint in the world and it no longer carries the same guarantee.

Not disagreeing with anyone above, just adding the bit I keep having to look up.

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

Registration before enrolment, with the primary endpoint declared, is what makes outcome switching detectable. Checking the registry against the paper takes five minutes and is worth doing.

It is worth checking rather than assuming, which costs nothing.