NorthWest Biotherapeutics Inc (NWBO)

[SkyLimit2022]

Thanks for asking.

There is new guidance involving RWE including ECAs, but since you prefer not to consider draft documents, I have included only the existing final guidance below. The full-context FDA source link is provided followed by two paragraphs excerpted in full mentioning crossover and ECAs.

While historical ECAs are recognized by the FDA as valid where appropriate, it is noteworthy that the murcidencel P3 utilized contemporaneous or concurrent studies. The studies were matched by an independent expert firm. Some studies ended far earlier than the murcidencel study, but began in the same cohort timeframe.


https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=314.126#:~:text=314.126%20Adequate%20and%20well%2Dcontrolled,placebo%20effect%2C%20or%20biased%20observation


Skip to timestamp 12:55 to hear how the controls were selected.

Dr. Ashkan was the chief investigator of the murcidencel trial for patients in Europe. At King’s College in London, Ashkan is the lead clinician for neuro-oncology and the chair of the King’s Neurosciences Clinical Trial Unit. He is a world-renowned cancer trial expert. A few years ago, Professor Ashkan was named the UK Clinician of the Year by The Brain Tumour Charity. Additionally, Ashkan serves as an advisor to the U.K. government.

Here is Pazdur’s recent paper about external controls. Pazdur is the director of FDA’s OCE:
https://www.annalsofoncology.org/article/S0923-7534(22)00006-0/fulltext

Skip to timestamp 8:01. Dr. Liau again confirms that the crossover was mandated by the FDA.
https://edhub.ama-assn.org/jn-learning/audio-player/18738384

Aside from the well-established existing FDA guidance, Real-World Evidence is a vastly significant topic to research and explore. The FDA’s shift toward RWE includes a renewed and enlightened position on ECAs which were and are already recognized as valid in settings where ECAs are the most feasible and ethical option. I hope we will bring further light to this topic in our discussions on iHub.

https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847

https://www.kcl.ac.uk/people/keyoumars-ashkan