Replies to post #323831 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Thanks. I had not read this before.

[exwannabe]

Yes, but that is published papers vs protocol. For changing the endpoint proper, consider this from the paper you linked:

Guiding Principles

The principle consideration when evaluating whether to modify an endpoint is whether the decision is independent of the data obtained from the trial to date. If the decision to revise endpoints is independent of the data from the trial, then such revisions may have merit. In fact, Wittes [8] encourages consideration of changes in long-term trials, as medical knowledge evolves or when assumptions made in design of the trial appear questionable. Wittes further argues that researchers “may consider changes to the primary endpoint when the trial has airtight procedures to guarantee separation of the people involved in making such changes from data that could provide insight into treatment effect” [8].

Some trials have successfully changed endpoints after the trials began by maintaining independence between the decision and the trial data. For example, the randomized Post-CABG (Post Coronary Artery Bypass Graft) trial [9] compared two lipid-lowering regimens in patients who had coronary artery bypass surgery. The investigators explicitly did not identify a primary endpoint when they designed the trial. An angiogram to assess lipid deposition in the coronary arteries was conducted at entry and then again five years later. The researchers planned to compare changes in lipid deposition over the five-year interval between the two regimens. Because by design no endpoint would be available for five years after randomizing the first participant, the protocol team used this period to define the endpoint and to develop methods for analyses. Although the endpoint was not prespecified in the design phase, a practice that is not generally recommended, trial leadership ensured that the selection of the endpoint was independent of data from the trial.