New Guidance on the Use of Real-World Evidence

Pharmaceutical Technology, Pharmaceutical Technology, August 2022, Volume 46, Issue 8

Pharma’s leveraging real-world evidence to drive product approval, reimbursement, and market access.

While randomized controlled trials (RCTs) remain the gold standard for evidence-based medicines to achieve regulatory approval, interest in the use of real-world evidence (RWE) to support regulatory decision-making is growing (1). RWE provides additional insights pre- and post-marketing regarding the risk-benefit of a medical product in the real-world setting, and the analysis of real-world data (RWD) contained in electronic health records (EHRs), health claims, patient registries, and from patient-generated data can be leveraged by the pharma industry to drive healthcare decisions and support health technology assessment (HTA) decisions (2).

Pharma increases collation of RWE

Over the past decade, pharma has increased their level of activity and planning around the use of RWE and have gradually expanded their collection of RWE (Figure 1) (3). To date, most of the RWD in regulatory submissions have been limited to post-marketing safety data or confined to a limited number of orphan or rare disease products, where RCTs are more challenging to conduct (4). However, moving forward it is likely that the regulators will request RWE to support regulatory files for non-specialty and specialty drugs.

EMA increasingly assessing RWE

A retrospective analysis of clinical trials submissions to the EMA during 2018 and 2019 revealed that RWE was included in two-fifths of initial marketing authorizations applications and one-fifth of indication extension applications (5). A more recent analysis by Eskola et al. (2022) revealed that nearly all European Public Assessment Reports (EPARs) include RWE in drug discovery (98%) and life-cycle management (100%) and nearly half included it in the development phase (49%) or to support regulatory decisions at registration (47%) (6).

EMA and FDA increase guidance on RWE

In 2018, EMA and the US Food and Drug Administration (FDA) reinforced their collaboration on medicines including the use of RWE to support regulatory decisions (7). In November 2021, EMA outlined its vision for the use of RWE in European Union (EU) medicines regulations (8), and this vision is one of the pillars of the European Medicines Regulatory Network (EMRN) strategy to 2025, which aims to establish the use and value of RWE across a spectrum of regulatory use cases (9). During 2022, EU partners will gain access to the Data Analytics and Real-World Interrogation Network (DARWIN EU), allowing them to conduct studies and to access and analyze healthcare data from across the EU (10).

The DARWIN EU will deliver RWE from across Europe on diseases, populations, and the uses and performance of medicines. It will enable EMA and national competent authorities in the EMA network to use these data whenever needed throughout the lifecycle of a medicinal product. DARWIN EU will support regulatory decision-making by:

  • Establishing and expanding a catalogue of observational data sources for use in medicines regulation
  • Providing a source of high-quality, validated real-world data on the uses, safety, and efficacy of medicines
  • Addressing specific questions by conducting high-quality, non-interventional studies, including developing scientific protocols, interrogating relevant data sources, and interpreting and reporting study results (10).

In July 2022, the DARWIN EU advisory board met and is in the process of increasing the number of RWD sources that can be analyzed and to improve the efficiency of performing RWE studies (11). A technical workshop is planned for later this year to identify common “use cases” for real-world evidence that are important to the EMA, HTA bodies, and payers (12).

UK MHRA guidance on RWE

In December 2021, the United Kingdom’s Medicine and Healthcare products Regulatory Agency (MHRA) published consultation guidance on RCTs generating RWE to support regulatory decisions (13). The guidance covers simple trials and hybrid trials and sets out the factors that need to be considered when collecting RWD as part of a clinical trial. According to MHRA, there is no barrier to using RWE to gain an initial approval or approval of a new indication providing 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” (4). The guidance is part of MHRA’s mission to ensure the UK remains an attractive country in which to conduct clinical research in the post-Brexit era.

NICE’s new framework on RWE

Meanwhile, the UK’s HTA appraisal body, the National Institute for Health and Care Excellence (NICE), are reviewing the methods and processes for health technology evaluation programmes and published a framework regarding the use of RWE that will help reduce uncertainties in NICE guidance, fill in evidence gaps, and improve HTA evaluation.

The framework provides in-depth guidance and tools to support the implementation of these core principles across different uses of RWE. It is structured as follows:

  • It provides a background on RWD and RWE, discusses its strengths and weaknesses, and summarizes current and potential uses within NICE guidance.
  • It describes NICE’s expectations for planning, conducting, and reporting RWE studies, recognizing that acceptability of evidence will depend on the type of evidence, and other contextual factors.
  • It assesses data suitability describes the information needed to assess data provenance and its quality and relevance for addressing specific research questions.
  • It provides more specific recommendations for conducting non-randomized studies. These include traditional observational studies as well as clinical trials that use RWD to form an external control (14).

Future role of RWE

RWE presents pharma with new opportunities to complement RCTs and inform regulatory and HTA decisions. Given the fluid situation, it is essential for the industry to keep abreast of the regulatory environment and adapt and optimize their RWE strategies in Europe and the UK. Careful attention should be paid to the variations in the definition, scope, and application of RWE across continents to ensure that healthcare data are effectively leveraged to drive product approval and increase patient access to innovative medicines that improve clinical outcomes (15).


1. J. Comcato et al., Pharmacoepidemiol Drug Saf., 29, 1514–1517 (2020).
2. P. Arlett et al., Clin. Pharm. Therap., 111 (1) 21–23 (2022).
3. EMA, HMA-EMA Joint Big Data Taskforce Phase II report: ‘Evolving Data-Driven Regulation, Report, (2019).
4. J. Mulryne and E. Whiu, “UK MHRA Consultation on Real-World Evidence,” BioSlice Blog, Arnold&Porter, 3 Dec. 2020.
5. R. Flynn et al., Clin. Pharm. Therap., 111 (1) 90–97 (2022).
6. S.M. Eskola, et al., Clin. Pharm. Therap., 111 (1) 310–320 (2022)
7. EMA, “Reinforced EU/US Collaboration on Medicines,” News Release,, 22 June 2018.
8. EMA, “A Vision for Use of Real-World Evidence in EU Medicines Regulation,” News Release,, 24 Nov. 2021.
9. EMA, European Medicines Agencies Network Strategy to 2025, Strategy Report, (2020).
10. EMA, Data Analysis and Real World Interrogation Network (DARWIN EU) available from [Accessed 13 July 2022].
11. I. Scholfield, “EU DARWIN Project To Catalog Real-World Data Sources,” Pink Sheet (12 July 2022).
12. V. Sharma, “EMA, HTA Bodies & Payers Explore Common Ground On Use Of RWE,” Pink Sheet (28 June 2022).
13. UK MHRA, Consultation Document: MHRA Draft Guidance on Randomised Controlled Trials Generating Real-World Evidence to Support Regulatory Decisions, Guidance Document, (Updated 16 Dec. 2021).
14. NICE, NICE Real-World Evidence Framework, Corporate Document [ECD9],, 23 June 2022.
15. M. Li et al., Front. Med. (Lausanne), 8, 669509 (2021).

About the author

Cheryl Barton is director of PharmaVision,

Article details

Pharmaceutical Technology Europe
Vol. 34, No. 8
August 2022
Pages: 7–8


When referring to this article, please cite it as C. Barton, “New Guidance on the Use of Real-World Evidence,” Pharmaceutical Technology Europe 34 (8) 2022.