NorthWest Biotherapeutics Inc (NWBO)

[abeta]

History of Stat Sig

A very long read

Snip -flies in the ointment .....

Uniprost

The importance of this standard became clear very quickly, in an FDA decision on United Therapeutics’
application for the drug Uniprost (later renamed Remodulin).

Submitted in October 2000, the NDA specified an alpha level of 0.049 (“the traditional standard for
two confirmatory studies with an adjustment” for one subgroup test).161

The statistical reviewer found this standard reasonable, and when the p-values for the two studies
came in at 0.0607 and 0.0550 the reviewer found “no justification for stretching beyond what was
specified in the protocol” and was additionally unpersuaded by a p-value derived from pooling those
studies that was above the threshold for a single study.162

This review led to a letter by the Director of the Division of Cardio-Renal Drug Products
urging the non-approval of Uniprost.163 In the end, a re-submission focusing on the results
of a surrogate endpoint in the studies was approved,
conditional upon beginning an additional postmarketing ...

Portola Therapeutics

In 2017, Portola Therapeutics decided to test the willingness of the new presidential administration and its FDA leadership to be flexible with statistical cutoffs. The drug in question, betrixaban, showed promise in early-stage trials in preventing blood clots after an illness.
In its pivotal phase 3 trial, however, betrixaban failed to meet the pre-specified 0.05 alpha level for the primary endpoint, showing a p-value of 0.054.261 Portola pointed FDA towards an alternative
interpretation of the results, however, and won approval in late June.262

Opinions

V. Statistics at FDA: Contemporary Challenges and Future Directions
Ever since the initial disagreements between Neyman and Pearson and Fisher, the p-value and the 0.05 alpha level standard have caused controversy.
Statisticians have debated the proper use and interpretation of the p-value, to the point of questioning whether it belongs in statistical reasoning at all.
Policymakers and FDA stakeholders have questioned whether the roles of the p-value and the 0.05 standard in drug approvals have been appropriate. And there has been
no shortage of alternatives presented. Even as the field of statistics has changed and FDA’s standards have adjusted to new trial designs and statistical analysis plans, the p-value has not lost its influence, or controversy, at the agency.

My Favorite

Avastin

Avastin

There was not a significant increase in OS with the addition of Avastin. However, adding Avastin to lomustine resulted in a median PFS of 4.2 months versus 1.5 months with lomustine alone

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