NorthWest Biotherapeutics Inc (NWBO)

[AVII77]

You raised the possibility that an interim analysis could have found futility and not be made public. Supposing that was true, wouldn't we expect a recommendation to stop the trial?

If "this stuff doesn't work" why is this trial allowed to continue to fruition?

Thanks for rewording your question.

Yes, you might expect a rec to stop the trial. That rec would come from the DSMB and be non-binding (a "recommendation"). If not just futility but evidence of harm then it is more clear cut.

ILT, this is the thing; futility does not mean the trial failed. It means if it continues it is likely to fail. If it continues, the chances of additional data swinging the data positive is very small.

It is unethical to tell a patient you want him to participate in a trial to determine that drug X improves PFS if you already know from an interim analysis that there is a very low chance of answering that question.

Enrollment should stop.

Consider, for example, Cel-Sci's partial clinical hold.

They disclosed the reason as:

In its partial clinical hold letter, FDA identified the following specific deficiencies: a) FDA stated that there is an unreasonable and significant risk of illness or injury to human subjects and cited among other things the absence of prompt reports by us to the FDA of IDMC recommendations to close the study entirely (made in spring of 2014) or at least to close it to accrual of new patients (made in spring of 2016); ........

https://www.sec.gov/Archives/edgar/data/725363/000165495416005085/cvm_8k.htm

We do not know precisely what the DSMB rec'd for Cel-Sci, but we do know that the FDA believed the trial was futile and enrollment should stop.

FDA stated that we did not provide the information identified as necessary to address FDA’s statement that continued enrollment of patients in the study exposes the patients to unreasonable risks and FDA furthermore stated that the study is unlikely to demonstrate that the addition of our investigational drug Multikine to the standard of care is superior to standard of care and thus should be terminated for futility

Your next question:

If "this stuff doesn't work" why is this trial allowed to continue to fruition?

Futility does not mean harm. If the treatment is reasonably safe, they sometimes let enrolled patients continue receiving the treatment.

Consider this ILT: at a late interim, the futility hurdle might be something like HR < 0.90. That means that if the interim data isn't showing at least a 10% RRR the trial is unlikely to be stat sig at the final analysis. A 10% relative risk reduction sure isn't harm, is it? It's something anyway. If a patient was exposed to an invasive procedure (like Leukapheresis) and the side effects of the treatment were modest, why not let those already enrolled continue to receive the treatment?

Now consider the same circumstance with an interim HR of 1.0 (Drug x does nothing good or bad). Do you think it would be unethical to allow patients to continue receiving Drug x? Do you think it would be ethical to allow patients to continue to enroll in that trial?

IMO, the answer to the first question is yes and the second is no.