Replies to post #773298 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

You're full of crap. The actual guidance from the MHRA says:

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. MHRA is also interested in engaging with sponsors who have proposals for using such data sources.

Why “other-trial controls” still fit the draft MHRA playbook

1. The draft explicitly says its principles also cover datasets drawn from previously completed clinical trials.
Paragraph 8 notes that although the focus is on real-world data (EHRs, registries, etc.), “many of the general principles would be relevant for external controls drawn from other sources, such as previously completed clinical trials” and even invites sponsors with such proposals to engage with the Agency.

2. Historical RCT controls are listed as an acceptable fallback when a fit-for-purpose registry doesn’t exist.
In the bias-mitigation section the guideline states: “If a registry with sufficient concurrent controls is not available, historical controls could be used as an alternative” (para 55). That is exactly the glioblastoma situation.

3. Data quality often trumps data provenance.
The same paragraph 55 warns that historical controls increase comparability issues—but the entire next section (paras 30-52) explains how to solve that through tight matching, pre-specification, and layered sensitivity analyses. NWBO’s Phase 3 programme did just that: reconstructed individual-patient data, MAIC weighting, six leave-study-out analyses, and “validator-switch” tests showing the method doesn’t create false positives. That package squarely targets the draft guideline’s bias-control expectations.

4. “Collected outside this clinical study” is what matters.
The draft defines RWD as data “collected outside of a clinical study” (para 14)—i.e., outside the investigational trial under review. An RCT finished years ago is indeed “external” to NWBO’s single-arm survivors, so it meets the spirit (and, by para 8, the letter) of the guidance.

5. High-fidelity trial data are often more reliable than routine-care databases.
Completed GBM RCTs come with adjudicated endpoints, uniform imaging schedules, and granular baseline variables—qualities registries rarely match. The guideline repeatedly stresses “quality and fitness-for-purpose” over source type (para 16); NWBO leveraged that higher-quality substrate, then applied every bias-reduction tool the MHRA recommends.

Conclusion: The draft document is flexible by design. It prefers concurrent registry data, but it also carves out a clear path for rigorously matched historical RCT controls when no suitable registry exists—precisely the route NWBO took for a rare, lethal disease where randomisation to placebo is neither ethical nor feasible.

[biosectinvestor]

No, it is NOT inaccurate. It is IN THE MHRA guidance. You did not read it apparently.

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