UK MHRA Consultation On Real-world Evidence – Food, Drugs, Healthcare, Life Sciences

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The UK MHRA has issued draft
on randomised controlled trials generating real-world
evidence (RWE) that are used to support regulatory decisions. It is
intended to be the first in a series of guidance documents
addressing RWE. The guidance is part of the MHRA’s push to
reinforce the view of the MHRA as a pro-innovative regulatory
authority, and that the UK is a leading country in which to conduct
clinical research, post-Brexit.

Real World Evidence

Real world data (RWD) is broadly defined as routinely collected
health data. Sources of RWD include electronic healthcare records,
disease registries and observational studies, and data collected
via wearable devices. This data, when analysed to make inferences
about treatments, produces real world evidence (RWE).

Interest in RWE has increased, with the view that generating
such data can be a cheaper alternative to costly randomised
controlled trials. RWD is also regarded as more representative of
the population as a whole and of the real life use of a product,
compared to data produced in a conventional, and somewhat
sanitised, clinical trial. Indeed, it was said at the “Global
on COVID-19 real-world evidence and observational
studies” in July 2020 that “Evidence generated by
high-quality observational research is fundamental to understanding
the safety and effectiveness of medicines in everyday use by
patients and doctors

However, up to now, the use of such data in regulatory
submissions has been largely limited to safety data, for
post-marketing follow-up to explore areas where there is
insufficient evidence pre-authorisation, or to support pricing and
reimbursement approval. The use of RWE in regulatory submission for
new products or indications has been confined to a limited number
products, where randomised controlled trials are more
difficult to conduct. Regulatory authorities maintain some caution
about relying on RWE, given the wider range of ways in which it is
collected and the questions over the quality of the data.

Increasingly, companies are exploring RWE for a wider range of
products and to support a broader set of regulatory submissions.
While there have been lots of discussion and pilot schemes about
using RWE, the call from industry has been for concrete guidance
about how and when such data will be accepted by authorities. The
EMA has acknowledged in the HMA-EMA Joint Big Data Taskforce Phase
: “Evolving Data-Driven Regulation”, that
It is clear that the data landscape is evolving and that
the regulatory system needs to evolve as well.”
is seeking to answer that call.

MHRA consultation

The current draft guidance document sets out points to be
considered when planning a randomised clinical trial using RWD
sources, and where the sponsor intends to submit this trial for
regulatory approval.

The guidance covers simple trials and hybrid trials:

  • Simple trials are trials that are set
    up to generate RWE. An example may be a randomised, controlled
    trial involving patients in a database that are randomised to one
    of a choice of interventions, and are then followed-up as is
    routine practice for the database concerned.

  • Hybrid trials are trials where some
    of the data collected is RWD, and some is collected for the trial
    outside of the RWD source. As example may be where patients and/or
    healthcare professionals provide trial specific data such as
    patient reported outcomes or additional clinical assessments, as
    well as the routinely collected data that may be entered into the

As patients are randomised into cohorts in these trials, they
will be classed as interventional trials. However, they will likely
be low interventional trials, where the potential risk associated
with the investigational medicinal product is considered no higher
than that of standard medical care. The guidance categorises these
trials as “Type A trials”.

The guidance sets out the factors that need to be considered
when collected RWD as part of a clinical trial. In terms of safety,
monitoring and reporting requirements will vary depending on the
proposed population and adverse event profile. The fact the trial
is set up to collect RWE does not change the legal requirement to
report serious adverse events as set out in the legislation.

In terms of using RWE for regulatory submissions, the MHRA says
there is nothing barring the use of RWE to gain an initial approval
or approval of a new indication – it is not the source of the
data that is the critical question, but whether the data quality is
“robust” and the trial is “designed in a way
which allows it to provide the evidence required to answer the
regulatory question
“. For Type A trials, or low
interventional trials, the MHRA will accept the data for regulatory
purposes “if the key endpoints necessary to make the
regulatory decision are routinely collected in the database and are
sufficiently objective such that they would not be subject to
meaningful bias from the knowledge of treatment allocation in an
open-label setting
“. Notwithstanding this, the
consultation states that a RWE approach is likely to be most suited
to decisions regarding labelling changes and adding a new

The MHRA is consulting on this draft until 11 December 2020 to
get feedback from relevant stakeholders regarding the clarity and
wording of this first piece of guidance; you can provide comments
on this

EMA consultation

The EMA s also running a
on RWE, this time on the use of registry-based
studies as a source of RWE. The guidance aims to optimise the use
of registry-based studies as a source of RWE that can be used in
the context of benefit-risk evaluation of medicinal products.
Stakeholders are invited to send their comments via an online
by 31 December 2020.

Originally Published by Arnold & Porter, December

The content of this article is intended to provide a general
guide to the subject matter. Specialist advice should be sought
about your specific circumstances.

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