Here we have come to the end of the road where you and I have fenced so many times and I bet you $2000 I will win.
You think its great and wonderful to let control patients die against treatment in a GBM trial I have always said that that kind of medical unethical behaviour is NOT what the MHRA will accept and here we are. The ethical-regulatory trap that the MHRA — and frankly all regulators — face when it comes to GBM and similar terminal illnesses. proper randomized trial in GBM (e.g. DCVax-L vs. placebo) is widely considered unethical
Patients in the control arm die quickly.
There’s no cure and almost no meaningful SOC options.
No one — not patients, doctors, or ethics boards — wants to randomize patients to a known fast-death pathway.
This has become doctrine in neuro-oncology.
So: RCT is off the table.
If RCT is unethical, the only option left is an external control arm (ECA)
That’s what NWBO used: historical trial data + real-world patient datasets from GBM studies.
But: in GBM, the quality and granularity of RWD is poor.
No standardized collection of methylation status, MGMT, etc.
Different imaging protocols.
Incomplete survival data.
Limited matched comorbidity controls.
So: ECA is necessary, but weak. But there is NO other choice
They don't want to reject a potentially lifesaving treatment over trial design limitations that were ethically mandated. But they also can’t create a precedent that says “single-arm trials with loosely matched historical ECAs are fine. Hence: endless inspection cycles, request for manufacturing readiness, and now, public consultation on how to formalize RWD/ECA use.
No individual patient-level ECA data = no perfect statistical control
That’s why the draft guidance also says: "If those data are sufficiently convincing, then a positive decision can be reached, even if alternative approaches may have ideally been preferred." That line is tailor-made for DCVax.
The MHRA has been delaying because:
RCTs are unethical in GBM.
ECAs are methodologically weak but ethically necessary.
The DCVax-L case sits in a gray zone, and approval sets a precedent.
The recent Procurement license and MHRA consultation on ECA suggest we are finally near the end of this holding pattern — assuming NWBO did its part on documentation and manufacturing readiness.
MHRA wants to approve DCVax-L, but is buying time to:
Cover itself procedurally (“we followed due process”)
Set expectations for future sponsors (hence the consultation)
Ensure there is zero risk of regulatory criticism (i.e., they didn't “lower standards”)
In this light, the current situation isn't a “problem” with DCVax — it’s a precedent-setting decision, and MHRA knows it.
Conclusion: approval is NEAR...!
AI
