NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

We will see how the final reads. The draft had:

25. Appropriate study design and analysis methods must be pre-specified in the protocol (see next section). Potential sources of bias should be identified and discussed in the protocol, along with details of how these will be explored and addressed.

26. It is important that the protocol is finalised before enrolment begins e.g. the design and analysis methods should be sufficiently specified in the protocol and there should be no amendments planned to fill in important missing details. Ideally the protocol should encompass all plans for the trial including the use of a pre-specified RWD ECA.

And on other issues:

. A RWD ECA comprises patient level data collected outside of a clinical study which will be used as a control or part of a control arm to estimate the comparative efficacy and safety of an intervention being studied in a clinical trial.

Yes, patient level data, not summary data. There is a sound reason why everything we have seen on the subject from any RA says this.

A trial with an ECA is not the preferred clinical trial design as a fully powered randomised controlled trial (RCT) should be used if possible.

Obvuiously it is possible as they completed an RCT, they just did not like the results.

27. Without sufficient pre-specification there could be issues related to multiplicity. For example, if a trial is analysed without an external control, and after the analysis an external control is added, this may inflate type I error if it is not clear which was the primary analysis. Therefore, it must be clear what the pre-specified primary analysis for the trial is.

I guess performing an efficacy IA then changing to an ECA would be a concern.