Replies to post #328042 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

I don’t think it works as you suggest. I think they likely stopped submitting questions or comments at some point, which is how the FDA “approves” NDA’s and updated SAP’s.

But, if they decide in the process of approval that they preferred something else, the company is in a difficult spot having said “they approved the update”. It is not in their interest to communicate that info given the litigious nature of things in the US market.

Where the regulator communicates that approval, it’s not the company’s fault if the regulator changes its mind later. The FDA’s job is to keep for itself a maximal range of options in terms of its assessment, and they do not really care what that might mean for the companies. They are focused on efficacy and safety, period.

[ATLnsider]

I disagree, the FDA & all 4 RAs are on board. There is buy-in by the UK, Germany, US & Canada. Please read this message post:

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=159361738

[anders2211]

On what do you or anyone else base your assumption then? I really honestly don't get it why the FDA would deny NWBO's SAP.
For the FDA changing endpoints is the same as submitting a SAP when asking permission to start phase 3. The only problem that the FDA has when changing endpoints is bias.

https://www.fda.gov/media/87621/download

8.1.2 Reviewing Changes to the Statistical Analysis Plan
Changes to critical elements of the analysis (e.g., the primary endpoint, handling of dropouts) during a trial can raise concerns regarding bias, specifically whether the changes could reflect knowledge of unblinded data. Concerns are inevitably greatest when the change is made late and has an important effect on outcome. In theory, if such changes are unequivocally made blindly (e.g., because of data from other trials or careful reconsideration) they should not pose problems, but the assurance of blinding can be hard to provide. For obvious reasons, changes made with data in hand (but purportedly still blinded) pose the greatest difficulties and are hard to support. When changes to the original SAP are proposed during the course of conducting the trial, it is critical to determine exactly what information, if any, regarding trial outcomes was available to those involved in proposing the change. Changes made with knowledge of results can introduce bias that can be substantial and impossible to measure. Note that such biases can occur subtly (e.g., the likelihood of adoption of a proposal made by an individual with no knowledge of data can be influenced by the comments or nonverbal communication of an individual who does have such knowledge). Therefore, major protocol changes are not credible if knowledge of interim outcome data is available to any individual who is involved with those planning the change. If there is any potential for such changes, sponsors should be encouraged to describe fully who has had access to data and how the firewalls were maintained, among other information.

If there is any revision with the FDA and perhaps, therefore, delay it over this

After trial data collection is completed, and before unblinding, there is often a blinded data cleanup phase. During that phase, previously unaddressed specific concerns about the data may be identified (e.g., types and amounts of missing data, concomitant therapies), and decisions are often made by the sponsor as to how to address those concerns. Typically, any changes made during this data cleanup phase should be minor clarifications of the SAP. If more than minor clarifications are made to the SAP, sponsors should be encouraged to submit these changes to the FDA for review as protocol amendments.

Also, the FDA itself described that changes and revision SAP are made FIRST and THEN trial data collection.