UK’s First Real-World Evidence Guideline Targets Randomized Trials
Executive Summary
The UK Medicines and Healthcare products Regulatory Agency is developing a series of guidance documents on general points to consider when planning a trial to generate real-world evidence. The first document in this series focuses on prospective randomized trials.
The UK medicines regulator is inviting stakeholder feedback on a draft guideline on the general factors that drug companies should consider when planning a prospective randomized trial using real-world data (RWD) sources.
The guideline on randomized control trials (RCTs) is the first in a series of guidance documents that the Medicines and Healthcare products Regulatory Agency intends to publish to address issues around using real-world evidence (RWE) in support of a regulatory submission. These guidelines will each be based on a different type of trial design which could be employed.
While randomized trials using an RWD source are most likely to be considered for label changes for already approved products, including drug repurposing, the draft RCT guideline says, “nothing is completely ruled out on principle, including the investigation of new products.”
The guideline covers different types of RCT trials that companies can undertake using RWD sources, such as simple and hybrid trials. It also discusses aspects relating to clinical trial authorization, trial design (including choice of endpoints and safety data requirements), and requirements in terms of database quality and inspections.
On the regulatory acceptability of RWD-based trials, the MHRA says it is important to ensure that the trial is designed in a way that allows it to provide the evidence required to answer the regulatory question. “The considerations regarding which endpoints are required, whether blinding is necessary, and any of the many other decisions made when designing, conducting and analysing a clinical trial depend upon the questions the trial seeks to answer and not upon the source of data,” it states.
On the quality of the database/data source being used, the MHRA expects sponsors to provide a description of the tools and methods for selection, extraction, transfer and handling of data and how they have been validated. “It is essential that processes are established to ensure the integrity of the data from acquisition through to archiving and sufficient detail captured to allow for the verification of these activities,” the guideline states.
Regarding inspections of RWD trials, the MHRA explains that the “systems and processes used for the oversight of RWD suppliers and the subsequent onward management of RWD data” may also be inspected, in addition to the inspections faced by the trial sponsor or the contract research organization. Areas of particular interest for review would include randomization methods, data management, investigational medicinal product management, safety reporting, sponsor oversight, and cases where externally provided databases are used to collect trial data.
Comments on the draft RCT guideline will be accepted until 11 December.