NorthWest Biotherapeutics Inc (NWBO)

[Galzus Research]

I don't feel defensive about the 73 authors. I'm just pointing out that having more authors of a high pedigree doesn't make the study unimpeachable.

Clearly, the results were good enough to get the study published. The data are the data. But if you haven't seen NEJM papers that have questionable methods and conclusions that don't quite fit, then it would be valuable to start paying attention. It's why I've cited the POLO study, and could continue on.

For example, a program I ran with a lung cancer KOL openly, publicly criticized AstraZeneca, who happened to be funding that program, for the design and conduct of the ADAURA trial. There were issues with that study that I won't belabor here.

But that hasn't stopped adjuvant osimertinib from becoming standard of care in operable EGFRm NSCLC. POLO's controversy didn't stop olaparib from being approved in pancreatic cancer. Even after it didn't show OS, the approval has not been pulled.

And I can go on here. IMbrave150 showed a suspiciously poor outcome for the control arm compared with the SHARP trial on which the control was based, and that led to questions about the relevance of those results. IMbrave150 regimen is the standard of care for advanced HCC. Authors of that study I've seen in action and respect immensely. That doesn't make the study flawless.

I can go on and on with examples here. Your study doesn't have to be flawless to be good enough to change practice.

As for the checks and balances you cite re: peer review, the data from the study, as it was eventually designed, show what the authors claim it showed. It's not (or at the very least should not be) about the reviewers adjudicating what results make it out to the public. They're there to assess the rigor of the study and see if the data shown support the conclusions drawn from the authors.

I'm not arguing that what they're showing us is not real. I (and people smarter than me) do have questions about the real-world relevance of these data, considering the challenges faced in the trial. And I'm not accusing them of malfeasance and tampering. Clinical science is messy. Pivots happen. Just because this trial had a very strange conduct does not mean it shouldn't have been published in JAMA. And it feels like a lot of people on this board commenting on the matter feel that the 73 authors and the peer reviewers are anything more than a group of researchers who did the work and published their findings.