Just taking a quick peek. WOW!…sure is a coincidence that Raga’s buddy would pen a butt licking piece over a holiday weekend when the actual real news was just released by LC2020 to near silence by the disciples. Perfect change of subject timing. Nicely done.
>>Euro Roundup: MHRA seeks feedback on using external control arms based on RWD
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| 22 May 2025 |
Nick Paul Taylor
Euro Roundup: MHRA seeks feedback on using external control arms based on RWD
The UK Medicines and Healthcare products Regulatory Agency (MHRA) is holding a consultation into the use of external control arms based on real-world data (RWD) to support regulatory decisions.
Using patient-level data collected outside of a clinical study for all or part of a control arm to estimate the comparative efficacy of an intervention frees sponsors from enrolling patients to receive placebo or standard of care. MHRA wants sponsors to continue running randomized controlled trials, when possible, but the draft guideline opens the door to submissions based on external control arms made from RWD.
“Any regulatory decision is based upon the data presented in the submission, and if those data are sufficiently convincing then a positive decision can be reached, even if alternative approaches may have ideally been preferred,” MHRA said in the draft guideline. “Therefore, there is no general scenario where the use of RWD external controls is explicitly ruled out.”
External control arms are more likely to be acceptable in “situations where conducting an adequately powered randomized trial is not ethical or feasible, would result in a significant delay or where the effect of the intervention is expected to be large enough to allow interpretation of the study results despite potential bias,” MHRA said.
The agency would prefer sponsors that face such challenges to run a randomized controlled trial with an internal control arm that is augmented with external controls. That design allows for better control of potential biases than single arm trials that rely solely on external controls. MHRA’s guidance covers both single arm trials with external control arms and randomized trials with RWD-augmented control arms.
The draft provides points to consider about the protocol, pre-specification and addressing bias that apply to both trial designs, although the focus is on fully external control arms. MHRA expects the protocols for the trials to “be of the same standard, style and level of detail” as for traditional randomized trials. The protocols should pre-specify the objectives, data to be collected, endpoints and analysis methods.
Adding an external control arm after the analysis of a single-arm trial “may inflate type I error if it is not clear which was the primary analysis,” MHRA said, but the agency is open to incorporating RWD after pre-specification in some cases. If an appropriate external dataset was not available when the trial was designed, a sponsor can amend the protocol, justify the switch and note the change in regulatory filings.
MHRA began the consultation on International Clinical Trials Day. The agency and UK government used the day to highlight work to create a faster, more effective clinical trials system, notably the move to a new regulatory framework that began last month.
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