RWE 201 – UK – MHRA – Randomised Controlled Trials Using Real World Data


MHRA RWD Guidance:

The MHRA guideline focuses on sponsors planning to conduct randomised, controlled clinical trials (RCTs) primarily using Real-World Data (RWD) for regulatory decisions concerning medicinal products.


The guideline covers:

  1. Clinical trial authorisation in the UK.
  2. Trial design, including endpoint selection and safety requirements.

It excludes discussions on observational studies, and clinical trials using RWD as a control arm.

Definition and Types of RWD Trials

RWD is health data obtained outside clinical studies and can include electronic healthcare records, disease registries, and patient-reported outcomes. In a simple RWD-based RCT, patients are randomized to receive standard clinical care alone or an added intervention. Data quality and study design need to be as rigorous as traditional RCTs for the results to be valid for regulatory decisions.

Protocol Requirements

The protocol should pre-specify objectives, data collection methods, and primary and secondary endpoints. Consent is required before enrolment, and in most real-world settings, patients are not blinded to treatment allocation.

Regulatory Acceptability

From a regulatory standpoint, the source of the data (RWD, hybrid, or traditional) is irrelevant as long as the trial answers the necessary regulatory questions. The need for blinding should be considered, especially if the primary endpoints are not sufficiently objective.

Examples and Practical Considerations

The guideline suggests that RWD-based trials can be effective when dealing with an established EHR database and objective endpoints like all-cause mortality. Scenarios where the intervention is an existing licensed product with a well-known safety profile are particularly suited for RWD trials. It’s critical not to assume the completeness of potential endpoints in EHRs. Sponsors are advised to conduct a feasibility study to assess the reliability of the data capture methods.

Data Gaps and Hybrid Trials

If the RWD source does not cover all required endpoints, a hybrid trial can supplement RWD with specific additional data. These could be additional clinical assessments, which might even be carried out remotely.

In summary, the MHRA guideline serves as a comprehensive framework for sponsors interested in leveraging RWD for RCTs aimed at supporting regulatory decisions for medicinal products. While RWD-based trials offer advantages in reducing patient and healthcare burdens, they must be designed and executed with rigor comparable to traditional RCTs to be deemed acceptable for regulatory purposes.

Share this story...