Replies to post #773306 on NorthWest Biotherapeutics Inc (NWBO)

[dennisdave]

from the MHRA website

Consultation description
A real-world data (RWD) external control arm (ECA) comprises patient level data collected outside of a clinical study which will be used as a control or part of a control arm to estimate the comparative efficacy and safety of an intervention being studied in a clinical trial. As part of our ongoing series of guidelines on using RWD to support regulatory decisions, the MHRA, with independent scientific advice from the Commission on Human Medicines RWD ad hoc group, has drafted a new guideline.

This draft guideline provides clinical trial sponsors with points to consider and key principles that should be taken into account when planning a clinical trial which will include a RWD ECA and which will require regulatory approval. While the guideline is specifically aimed at sponsors planning to use RWD ECAs, many of the general principles would be relevant for external controls drawn from other sources, such as previously completed clinical trials.

The 6-week consultation aims to get feedback from relevant stakeholders regarding the clarity and wording of this guideline, including any perceived contradictions or omissions.

Following the consultation, the MHRA will amend and publish the guideline document as well as publishing an anonymised summary of the public feedback.

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

Let’s Put the “No RWD” Argument to Bed
From the official UK government consultation page on the MHRA draft guideline:

“While the guideline is specifically aimed at sponsors planning to use RWD ECAs, many of the general principles would be relevant for external controls drawn from other sources, such as previously completed clinical trials.”

Translation:
Even if NWBO used pooled control arms from prior RCTs (not EHRs or insurance data),
The same regulatory framework still applies — and MHRA explicitly acknowledges that.

This completely kills the lazy argument that “DCVax-L doesn’t qualify because it didn’t use real RWD.”
The guidance is written to include this kind of external control structure.

What About IPD? Yes, the MHRA draft says:

“A real-world data (RWD) external control arm (ECA) comprises patient-level data collected outside of a clinical study...”

So ideally, the external dataset should contain individual characteristics, outcomes, timelines — not just summary stats or K-M curves. That’s the preferred standard for a full RWD ECA.

But here’s the nuance:

“Many of the general principles would be relevant for external controls drawn from other sources...”

So: If a sponsor (like NWBO) builds an external control arm from published RCTs without full IPD...
Then the MHRA won’t reject it outright — it simply applies slightly different evaluation standards, focused on:
Bias mitigation
Estimand alignment

Pre-specification
Justification of data use
In other words: it’s still valid, just not “plug and play.”


This guidance isn’t just a playbook for the future. It’s regulatory cover — designed to justify approval decisions right now, in cases like DCVax-L, where:
The disease is rare and fatal
Traditional RCTs are unethical or infeasible
And the control data available isn’t perfect, but still meaningful
They’re not asking whether this type of approach is acceptable. They’re just asking for feedback on how to word the policy before finalizing it.

The public consultation closes July 14. Thats still 2 weeks out
After that, the MHRA either acts or stalls further, and really starts damaging its own credibility.