Replies to post #502088 on NorthWest Biotherapeutics Inc (NWBO)

[hoffmann6383]

False narratives are not evidence

[CherryTree1]

I sent this to you yesterday. Here it is again.
Here is the 10k for financial year ending December 31, 2020
https://www.sec.gov/ix?doc=/Archives/edgar/data/1072379/000110465921044832/nwbo-20201231x10k.htm
They clearly state the submitted the SAP for the DCVAX-L Phase-3 to regulators with the modified endpoints and they well know this has to be done before unblinding.
GLTU

Our products and our ongoing development activities are subject to regulation by regulatory authorities in the countries in which we and our collaborators and distributors wish to test, manufacture or market our products. For instance, the FDA will regulate our product in the U.S. and equivalent authorities, such as the MHRA and EMA will regulate in Europe and other jurisdictions. Regulatory approval by these authorities will be subject to the evaluation of data relating to the quality, efficacy and safety of the product for its proposed use, and there can be no assurance that the regulatory authorities will find our data sufficient to support product approval of DCVax-L or DCVax-Direct. In addition, the endpoint against which the data is measured must be acceptable to the regulatory authorities, and the statistical analysis plan for how the data will be evaluated must also be acceptable to the regulatory authorities. The statistical analysis plan that we submitted to regulators for the Phase III trial embodies a different primary endpoint and secondary endpoint than did the original Protocol for the trial. Under the Protocol the primary endpoint was progression free survival, or PFS, and the secondary endpoint was overall survival, or OS. Both of these endpoints were confounded: the PFS endpoint by pseudo-progression, and the OS endpoint by the “crossover” provision in the trial design, which allowed all of the patients in the trial to cross over to DCVax-L treatment after tumor recurrence (while remaining blinded as to which treatment they received before tumor recurrence). The statistical analysis plan uses external control patients rather than within-study controls. There can be no assurance that regulatory authorities will allow a product approval to be based upon this approach.

The time period required to obtain regulatory approval varies between countries. In the U.S., for products without “Fast Track” status, it can take up to 18 months after submission of an application for product approval to receive the FDA’s decision. Even with Fast Track status, FDA review and decision can take up to 12 months. At present, we do not have Fast Track status for our lead product, DCVax-L for GBM. We plan to apply for Fast Track status, but there can be no assurance that FDA will grant us such status for DCVax-L.

Different regulators may impose their own requirements and may refuse to grant, or may require additional data before granting, an approval, notwithstanding that regulatory approval may have been granted by other regulators. Regulatory approval may be delayed, limited or denied for a number of reasons, including clinical data, the product not meeting safety or efficacy requirements or any relevant manufacturing processes or facilities not meeting applicable requirements as well as case load at the regulatory agency at the time.

Just stating the original protocol had NO recurrent GBM arm, it was only for naïve GBM patients is not evidence that it was submitted later. What is stated in the SEC I reference it evidence it was supported before unblinding.

You also state:

The rGBM arm could not have been considered until they had unblinded data as they had no knowledge of the sample was placebo controlled until they had unblinded the dataset.

Yes that is the whole point. You want to pick the criteria before unblinding else it is not statistically valid. The p-values are meaningless. I posted an article on this too on Data Dredging you may want to read.