Replies to post #608624 on NorthWest Biotherapeutics Inc (NWBO)

[iclight]

The SAP is a moot point because the trial design is bullshit.

This is from a huge law firm that assists companies with clinical trial issues.

King & Spalding

Consistent with FDA’s prior guidance on the use of RWD to develop RWE for regulatory decision-making5, the External Controls Draft Guidance clarifies that multiple sources of patient-level data could potentially serve as the control arm data in an externally controlled clinical trial, including but not limited to data from other clinical trials, registries, natural history studies, electronic health records (“EHR”), and medical claims data. The External Controls Draft Guidance emphasizes that summary-level data will not suffice for use in an externally controlled trial.

And here's confirmation that the trial is shitty when one actually reads the FDA document on external controls:

IV. CONSIDERATIONS TO SUPPORT REGULATORY REVIEW

Sponsors must include in their marketing applications relevant patient-level data (i.e., data on each participant and patient in the externally controlled trial), as required under FDA regulations, 33 for both the treatment and external control arms. If sponsors do not own the data used for the external control arm, they should structure their agreements with the data owners to ensure that patient-level data can be provided to FDA in support of the marketing application.

[HyGro]

NWBO's SEC filings confirm that the FDA has not approved the P3 revised protocol. FDA Guidance requires the changed protocol be filed, but does not make any approval or rejection decision.

Management, under penalty of perjury has said:
"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."

FDA is clear they only "comment" on protocol changes IF the sponsor requests one. The approval requirement is from the trial IRB that is independent from the FDA.

From FDA Guidance:
:Once an IND application is in effect, the sponsor of the application may amend the application as needed to ensure that the clinical investigations are conducted according to protocols included in the IND application. Sponsors are expected to submit protocol amendments for new protocols or changes to existing protocols before implementation of the respective changes. New studies may begin when the sponsor has submitted the change to FDA for its review and the new protocol or changes to the existing protocol have been approved by the Institutional Review Board (IRB) with the responsibility for review and approval of the studies. If the IND application sponsor desires FDA to comment on a submission, they should submit a request for such comment and the specific questions that FDA's response should address."

Nowhere does the FDA state that an FDA approval is required.