Nemesis18,
Regulators basically already agreed that early treatment is better for patients than late treatment because some early patients would have no chance to receive benefit if not treated early enough. Why do I suspect this so strongly?; ). Well maybe interference by regulators into this trial tells the story that couldn’t be told outright while additional data was being collected. Regulators interfere for safety issues or efficacy ie Fraunhofer stating that enrollment occurred to the point statistically necessary. No safety issues were found with regard to treatment but Germany does not allow experimentation on patients with known lesser treatments and regulators are responsible for making determinations along the way if issues arise. The DSMB is in charge of investigating safety issues and that includes looking through data that allows comparative eventing by one group or another if eventing appears to be more rapid than expected ie treatment induced
pseudoprogreession. The DSMB is allowed to unblind data to the point needed to make their safety determination which is why NWBO would not confirm or deny that an interim analysis had been done because they knew the DSMB had done one although the one NWBO saw was based on blinded data. What they saw led to the screening hold which led to all treatment patients being enrolled and 17 remaining SOC/placebo patients being left out. This is consistent with Germany’s laws about experimentation and Fraunhofer’s claim that the trial was enrolled to the point statistically necessary.
The issue has always been since then about manufacturing, adjustments needed to properly measure treatment effect, data analysis to determine the method of action by the treatment, identification of targets ie proteomics and long term data that creates a better picture of effect. The wealth of data and fitting out of novel manufacturing processes being developed and validated for mass commercial scale manufacturing pave the way for a highly detailed presentation of complex issues overcome by sufficient measures of treatment effect, manufacturing, handling and product release breakthroughs all described in the marketing application. You can’t stop that validation process from happening now but you can try to stop enthusiasm for what has already basically been initially but not finally affirmed by both regulators and JAMA Oncology. Best wishes.
