Replies to post #683647 on NorthWest Biotherapeutics Inc (NWBO)

[User-840664]

“A Phase 3 Prospective Externally Controlled Cohort Trial”.

This is a remarkable title, as the investigators have re-analyzed the OS data of the study against published external controls and present this as a prospective trial. It is obvious, however, that this is not a prospective analysis but a post hoc retrospective analysis: the investigators had seen the data, both of their own study and of the cohorts taken for comparison and then decided to go ahead with cross-trial comparisons.'

[learningcurve2020]

L's Plll rGBM didn't even divide up into two groups.

>>This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan–Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group.

https://www.nature.com/articles/s41598-023-36290-2

[exwannabe]

The trial remained blinded prior to the protocol change. This happens quite often in trials. Not “Ex post facto.”

The key to protocol changes is that they not be based on information from the trial itself. If they are, then it is post hoc.

Being formally blinded to the patient level data does not mean they do not know per arm data from the trial. You will often see PR's by BPs announcing primary results and saying the trial will continue blinded to evaluate secondary results.

We know as a fact there was an efficacy IA in 2015 that would have most certainly provided information about the designed primary endpoint. Does anybody in their right mind think that if this IA had said the primary was a solid win NWBO would have changed endpoints? Further, it is obvious to anybody with a brain that the IA reported the trial as designed was toast. And knowing that NWBO changed the trial. And that is post hoc.
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Further, on OS they outright said they changed the endpoint based on what happened in the trial.

Outside of that they knew the trial data they were selecting and the blended data from the -L trial.

Clearly post host.