Replies to post #773259 on NorthWest Biotherapeutics Inc (NWBO)

[skitahoe]

ATL, what you're saying is true. What's unknown is if the UK regulators after starting to work determined that they wanted RWD on everything that had been done with DCVax-L. That I believe would bring in information from all compassionate use done in the UK, and perhaps elsewhere. It might also bring in partially completed trials, like those being done at UCLA. In short it could bring the idea that this is a tumor agnostic vaccine into focus, whether NWBO initiated that kind of thinking, or not.

Gary

[dennisdave]

Huge pile of BS
You are just splitting hairs. Whether you call NWBO’s control data “RWD” or “historical ECA” is semantics.
What matters is that MHRA is preparing a formal framework to approve therapies based on external controls, and DCVax-L fits squarely within that scope

Yes, NWBO used pooled control arms from other GBM trials, not EHRs or insurance data. So? That still fits under MHRA’s broader definition of RWD, which includes data from registries, past studies, and external datasets. What matters isn’t what bucket you put it in it’s that the control arm was external. And that’s exactly what the MHRA draft guidance is about:
Approving drugs based on external control arms, especially when RCTs aren’t ethical or feasible.
DCVax-L fits that perfectly. Lethal disease? No standard-of-care control left? Big effect size? All boxes checked.

So stop claiming its this guidance isn’t about DCVax. It absolutely is.

Have you now become a bear and short? Interesting

[manibiotech]

As usual wrong again:

From chatGPT:

“Yes — under the MHRA’s recent guidance (May 2025), external control arms (ECAs) are explicitly considered a use of Real-World Data (RWD) and the evidence generated from them qualifies as Real-World Evidence (RWE).

?

📌 Key points from the MHRA guidelines:

✅ External control arms use RWD as a comparator group instead of a concurrent randomized control group.
✅ They can be constructed from:
• Historical clinical trial data
• Registries
• Electronic health records (EHRs)
• Administrative or insurance claims data
• Other observational datasets

✅ ECAs are a subtype of RWD study, where the control group comes from real-world sources instead of being randomized within the trial.
✅ When properly designed, ECA-based studies can support regulatory decisions — but the MHRA guidance emphasizes:
• Ensuring data quality (accuracy, completeness, traceability)
• Minimizing bias (e.g., through careful matching, statistical adjustment)
• Using pre-specified protocols reviewed by regulators.

✅ The MHRA draft guideline explicitly calls out ECAs as a legitimate approach in rare diseases, oncology, or settings where randomization is unethical or infeasible, provided the RWD source is robust.”

https://www.gov.uk/government/consultations/mhra-draft-guideline-on-the-use-of-external-control-arms-based-on-real-world-data-to-support-regulatory-decisions

https://assets.publishing.service.gov.uk/media/6825bab1a4c1a40fde4e63e5/Draft_MHRA_Guideline_on_Studies_with_RWD_ECA_May2025.pdf?utm_source=chatgpt.com

Only glitch is that they mention patient level data matching in their guidance .

[Baxers]

I thought I would help settle this argument once and for all. I wrote the following email to the MHRA back in May:

I have read your most recent draft guideline regarding the use of external control arms based on Real World Data (RWD) and have just noticed this week that you are holding a consultation into this subject is now underway to support regulatory decisions. I have two questions that I would like answered for better clarification and understanding please:

1. If the sponsor of a new biologic uses the pooled overall survival (OS) results of external control arms (ECAs) from several other contemporaneous randomised controlled trials (RCTs) as the control group for its clinical trial (where care has been taken to use RCTs with similar exclusion and inclusion criteria), would the use of this ECA be considered RWD or Real World Evidence (RWE) or something else?

2. Under the MHRAs existing regulatory framework, can an MAA (which is already under review and is based on the Phase 3 trial data that includes the sort of trial outlined in 1 above) be approved, or would it need to wait until the final guideline on the use of of external control arms based on RWD is published?

And I have just had a reply:


Simply leaving this here for others to hash out, but it seems pretty clear to me!