The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published draft guidance on randomised controlled trials (RCT) generating real-world evidence (RWE) to support regulatory decisions.
RWE may help investigators understand how a treatment will really work when it is in community use as opposed to data generated by a conventional clinical trial. The main difference in RWE trial is that they are conducted completely in the real-world setting with no additional data, therefore do not involve patient blinding to treatment allocation.
These trials are likely to be classed as “Type A trials”. The MHRA states that these would be equally acceptable as a conventional open-label RCT if designed well. It must be noted that a trial may need to be blinded in certain situations, such as when comparative safety criteria are an important aspect of the trial.
Hybrid trials, where patients and healthcare professionals (HCP) provide data such as as patient-reported outcomes or clinical assessments in addition to the incorporation of RWE, are also a possibility.
This guidance focuses only on clinical trials of investigational medicinal products (CTIMPS). When planning prospective clinical trials that will incorporate RWE, sponsors should use protocols that incorporate all the elements of a conventional RCT, such as pre-specification of the objectives, patient consent, data to be collected, primary and secondary endpoints and analysis methods.
The draft guidance also reviews authorisation considerations for CTIMPs that involve RWE generation, including adverse event reporting requirements. It also provides an outline of what data characteristics are required for a trial database of sufficient quality. The guidance included examples of RWE study types and a discussion of various differences in these studies, such as endpoints derived from electronic health records and digital health technologies.
The draft guidance remains open for consultation for 6 weeks from its publication date and is aimed at sponsors planning clinical research in support of regulatory decisions.