The European Medicines Agency (EMA) has created a sustainable network called DARWIN EU, which aims to generate real-world evidence to support regulatory decision-making in the European Union. This coordination centre network uses data analysis techniques and real-world interrogation methods to extract information and insights from various data sources, including structured and unstructured sources. Its main objective is to provide timely and reliable evidence on the use, safety, and effectiveness of medicines for human use, including vaccines, from real-world healthcare databases across the European Union.
A “major enabler” of the EU’s DARWIN network has been a common data structure, which has sped up the completion of real-world evidence (RWE) investigations. This has made it easier to collect data at an enormous scale and boosted the ability of these research to produce solid proof.
Data Analysis and Real-World Interrogation Network, has completed its first year of establishment. It has on-boarded ten data partners and initiated four studies using real-world data (RWD) from Europe to better understand diseases, populations, and the uses and effects of medicines. In 2023, DARWIN EU intends to launch about 16 research and sign up ten more data partners.
The advantages of DARWIN EU, such as quicker study performance, greater capacity, and reduced expenses, have been made clear in the first four investigations. These study protocols and outcomes are openly accessible. The DARWIN EU intends to be fully functional by 2025, delivering about 150 RWE studies annually, contributing to the EU’s vision of enabling and establishing the value of RWE across regulatory use cases. It will continue to work with stakeholders and take part in pilots for the European Health Data Space (EHDS) [1].
What is the AIM behind DARWIN EU?
DARWIN EU was established last year with the intention of giving EMA, the European Commission, and national competent authorities in all 27 EU member states access to the findings of real-world healthcare database analysis. DARWIN EU has concluded its preliminary research and EMA has declared its intention to seek out new data partners. The main goal of DARWIN EU is to produce real-world evidence (RWE) to assist EMA and National Competent Authorities in making decisions regarding regulatory procedures. EMRN, European Medicines Regulatory Network is working with various stakeholders to facilitate the use of RWE and validate its effectiveness for regulatory decision-making by 2025.
What is RWE and its Importance?
Real-world data (RWD) is collected from ‘real-time’ sources beyond traditional clinical trials and is analysed to produce real-world evidence (RWE), which provides insights into the safety, effectiveness, and value of medical products and treatments in actual clinical settings. RWD and RWE are already utilised in the European Union for disease epidemiology and safety surveillance. During the COVID-19 pandemic, they provided significant evidence of drug and vaccine safety and effectiveness.
RWD’s and RWE’s significance is their ability to provide a more comprehensive understanding of how medical products and treatments perform in actual clinical settings. Clinical trials, while valuable, are typically carried out in controlled environments and may not fully reflect the diversity of patient populations, comorbidities, and treatment patterns seen in actual clinical practice. RWD and RWE can complement the evidence obtained from clinical trials and offer insights into how medical products and treatments are performed in relation to everyday clinical care.
Furthermore, RWD and RWE can be utilised to inform regulatory decision-making, healthcare policies, and clinical practice guidelines.
Drug authorisation for rare diseases done using RWE includes –
- In Phase 3 research without a control, RWE from a registry was utilized to evaluate Zolgensma for spinal muscular atrophy.
- Phelinun from Adienne Pharma & Biotech is used to treat a variety of blood malignancies, and its effectiveness is fully supported by published research, including clinical trials and observational studies [2].
Note: Although RCTs, or Randomized Controlled Trials, are still recognized as the gold standard for assessing the effectiveness of novel therapies, RWE can provide valuable insights to supplement RCTs in assessing their safety and effectiveness. However, for common diseases, RCTs are preferred due to their logistical advantages and their capability of using randomization to handle confounding bias.
What are the Insights Gained from the Pilot Phase of DARWIN?
The DARWIN EU project has conducted four studies that show the benefits of using a standard data model, agile processes, and standardized analytics, which have led to faster study performance, lower costs, and increased capacity. The studies have publicly available protocols and results in the EU PAS Register, covering topics such as rare blood cancers, the use of valproate-containing medications and alternative therapies in women, prescription patterns for antibiotics, and severe asthma. The results have been provided to relevant EMA committees to support future work.
The four studies of the Pilot Phase are:
- The frequency of uncommon blood cancers across five European nations. [3]
- The usage of valproate among females between the ages of 12 and 55 and its possible fetal risks. [4]
- The analysis of prescribing patterns for 141 antibiotics listed on the World Health Organization Watch List, with respect to antimicrobial resistance and guidelines. [5]
- An evaluation of the safety of all authorized or in-progress treatments for severe asthma in adolescents and adults. [6]
The project also emphasizes the importance of going step by step and bringing stakeholders along, both internal and external, in order to construct the network and increase trust in real-world evidence.
What is the Effect of Data Analysis and Real-World Interrogation Networks (DARWIN) on Regulatory Affairs?
DARWIN can help regulatory agencies make more informed decisions about the efficacy and safety of regulated products by leveraging large amounts of data from multiple sources, identifying potential safety issues earlier, providing valuable insights into product use in real-world settings, and streamlining the regulatory approval process. Ultimately, this can lead to faster and more efficient product approvals, benefiting both patients and companies developing these products.
Summary
DARWIN EU is a sustainable network established by the European Medicines Agency (EMA) that aims to generate real-world evidence (RWE) to support regulatory decision-making in the European Union. It uses data analysis techniques and real-world interrogation methods to extract information and insights from various data sources to provide timely and reliable evidence on the use, safety, and effectiveness of medicines for human use. RWE complements the evidence obtained from clinical trials and offers insights into how medical products and treatments are performed in relation to routine clinical care. DARWIN EU has conducted four studies that demonstrate the benefits of using a standard data model, agile processes, and standardized analytics, which have led to faster study performance, lower costs, and increased capacity. The project emphasizes the importance of going step by step and bringing stakeholders along, both internal and external, in order to develop a network and increase trust in real-world evidence. DARWIN EU aims to launch about 16 research and sign up ten more data partners in 2023 and be fully operational by 2025, delivering about 150 RWE studies annually, contributing to the EU’s vision of enabling and establishing the value of RWE across regulatory use cases.
References and Further Reading:
- EMA. DARWIN EU® has completed its first studies and is calling for new data partners European Medicines Agency. 2023
- RAPS Interview: EMA’s Peter Arlett reflects on RWE approvals, early learnings from DARWIN. Regulatory Affairs Professional Society. 2023
- ENCPP. DARWIN EU® – Prevalence of rare blood cancers in Europe. European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. 2023
- DARWIN EU® – Drug utilisation of valproate-containing medicinal products in women of childbearing potential. European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. 2023
- DARWIN EU® – DUS of Antibiotics in the ‘Watch’ category of the WHO AWaRe classification of antibiotics for evaluation and monitoring of use. European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. 2023
ENCPP. DARWIN EU® – Background rates of serious adverse events to contextualise safety assessments in clinical trials and non-interventional studies in adolescent and adult patients with severe asthma. European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. 2023