Replies to post #57707 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

It is not important to get to 348 exactly, but one loses powering with a smaller trial (at least at that interim). That would make success at the first interim a higher hurdle, but the second interim might be fully enrolled and not suffer the same high hurdle.

Trials are often over enrolled as well. Larry Smith stated he speculates enrollment is about 320 (I'd guess higher, but Larry is the experienced veteran). That would be 28 patients shy of full enrollment.

In the Tariquidar case, they suspended enrollment BEFORE enrollment was complete, to conduct an efficacy analysis for the first interim. The reason they did this was as follows:

http://www.qltinc.com/newsCenter/2003/030221.htm

The DSMC has recommended that accrual to the trials be temporarily halted until all patients currently enrolled have been followed for a minimum of three months and that the patients should continue to be treated and followed according to the protocol. The committee also stated that all data should remain blinded and that the intention of this halt in accrual is to permit, for those patients already entered, acquisition and review of additional data on safety and efficacy. The DSMC concluded that the recommendations above “provided the best opportunity for these trials to remain intact and to serve, in their entirety as pivotal registration trials for regulatory purposes.”

One scenario

Basically, the general idea is that trials are very complicated, and because endpoints such as immune response to treatment can happen months after initial therapy, there needs to be a follow up period before any interim analysis. If you keep adding patients instead of temporarily halting screening, there will continue to be a segment of the enrollees who have not been followed for a long enough period of time before IA. LP once stated after enrollment is complete, there would be top line results within three to five months after full enrollment. She stated that at that time the trial would reach the finish line. The trial has not technically completed full enrollment, but it arguably might have sufficient enrollment.

Whatever analysis is occurring, it was not complete at the time of the Seattle conference.

Which analysis has not completed? It could be the blinded pre-interim analysis. Or, it could be the Interim Analysis itself. It sounded like the trial was still being analyzed at the time of the Seattle Conference, so under the Tarquidar type scenario, I'd assume the trial is still at the pre-interim analysis. JMHO

Many things might happen during that time period, and the FDA has the capacity to look under the hood without unblinding the sponsor. The things that might happen during the pre-interim analysis may also be attributed to the cause for the halt, but there are many moving parts, and one thing triggers another.

It could be 300 enrollment was agreed upon by regulators as a reason for temporarily halting screening, with the thought it mind that it might get them to full enrollment by November. Perhaps it did not get as close as I think, but the ability to assess at the first interim is not hindered if this generally followed the Tariquidar example. One difference is that the FDA is also reviewing the data in NWBO's case.

Under this possible scenario, I think reviewing/confirming the reliability of scans with the new standards might be one thing the FDA may wish to do during that time. It's the last chance to do so before an IA would make any protocol changes nearly impossible.

Anyway, it's all speculation at this point.