NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

what is or has happened?

If you were waiting on an update to the FDA Industry Guidance to "Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products" (linked below):
https://www.fda.gov/media/133660/download

... some might suggest that the "European" Annals of Oncology journal article written by 13 "United States" FDA authors entitled "External Control Arms in Oncology: Current Use and Future Directions" dated January 9, 2022 "happened."
https://www.annalsofoncology.org/article/S0923-7534(22)00006-0/fulltext

Some will remember that Larry Smith of Smith on Stocks called attention to this article on January 21, 2022.
https://smithonstocks.com/northwest-biotherapeutics-fda-statement-regarding-use-of-external-controls-in-clinical-trials-is-a-huge-positive/

Below are just a few of the relevant call outs from this new, some might consider, "guidance" article. Anyone interested in the science here, and what the FDA would be looking for would be well advised to read through this, IMO.

As discussed earlier, external control data has previously been used in oncology marketing applications reviewed by the FDA to establish natural history of disease, with or without an established standard of care, provide descriptive information regarding the treatment effects of individual components of a combination treatment effect, or to provide supportive analyses of direct comparison to an experimental arm [23, 24, 25, 26, 27, 28, 29]. To date, no primary efficacy analysis of a study used to support approval of a marketing application in oncology has included a formal comparison to an external control arm.

If the appropriateness and feasibility of the clinical study question of interest is suitable for utilizing an external control arm, careful attention should be paid to determining if the proposed data are fit-for purpose, developing a detailed study protocol, and the pre-specification of a comprehensive statistical analysis plan. Figure 2 depicts some of the key elements can be considered when determining whether a proposed external control data source is fit-for-purpose. Precisely defining the patient population, through eligibility criteria that can be applied to both the investigational arm of interest as well as the external control arm, can reduce subjectivity of the comparison.

A pre-specified statistical analysis plan for any study that incorporates external control data increases the integrity of the data analysis and results. The analysis plan should include statistical methods to account for various types of potential bias, including major threats from lack of randomization (e.g., selection bias) and confounding amongst others. An assessment of the similarity of the patient populations in each arm using pre-specified criteria to measure balance [16, 17], before and after any statistical procedures or adjustments could further minimize the concern of bias. These comparisons of the populations of interest before and after analytical adjustments to account for bias and confounding are ideally conducted prior to the analysis of any outcome data.

Please note: the SAP was formulated prior to data lock, analysis and results.

Is it possible that the company chose to incorporate a few or some of the considerations noted in this very recently published FDA journal article into their own perhaps completed and perhaps even peer reviewed journal article of the P3 DCVax-L data? And if assembling the BLAs and the MAAs are following on parallel paths, and simultaneously, if this article is being addressed, would longs who have had patience beaten into them consider this to be a bad thing, or a good thing?