• Chinese (Simplified, PRC)

Payers are facing a challenge. They have to balance the need to improve outcomes for patients, and the opportunities provided by innovative new drugs and technologies, with the requirement to stay within increasingly straightened budgets. Randomized clinical controlled trials (RCTs) may not provide enough information to resolve payer uncertainty around the drug’s benefit in real life. Because of this, the requirement for real-world evidence (RWE) to support healthcare decision making has been growing.

The importance of RWE

While RCTs remain the gold standard for collecting the data required to obtain marketing authorization, the importance of RWE is increasing in terms of positioning a drug for optimal pricing and reimbursement; providing validated long-term insights for health care providers; showing value for money for payers; and enabling best care for patients. RWE can answer questions RCTs cannot address and, depending on the stakeholder’s perspective, can allow for a more holistic assessment of a drug in a real world context.


Generating the right quality evidence in the right time at the right cost is an important part of the route to patient access for a new drug. RWE can be collected from a variety of sources, including:

  • Pragmatic trials
  • Prospective observational cohort studies and patient registries
  • Hybrid designs
  • Distributed data networks
  • Chart reviews
  • EMR data analysis
  • Claims data analysis

These data helps companies to:

  • Understand the current treatment pathway
  • Explore heterogeneity and natural history of the disease
  • Map between outcomes
  • Measure patient-reported outcomes (PROs) including quality of life
  • Assess adherence
  • Estimate relative effectiveness of the drug
  • Estimate the effectiveness in subpopulations
  • Understand the burden of illness, resource use and cost

Many of these aspects of RWE will also be useful as part of the HTA process, allowing payers to understand how the drug actually works in a real life clinical setting, including the balance of patient outcomes and healthcare system cost.

RWE in the real world of the HTAs

While the regulatory authorities often require collection of RWE post-authorization to monitor safety and effectiveness, payers across Europe have different views on the use of RWE. For example:

  • France – request registry data regarding tolerance be provided if available; occasionally requests RWE
  • UK – RWE is an advantage but isn’t mandated
  • Italy – highly decentralized with limited guidance
  • Germany – RWE only taken into account if there is no alternative study design other than the RCT

“The differences in how HTA bodies use real world evidence today and the breadth of research approaches available is driving the need for an insight and science-driven approach to real world evidence planning. This will ensure that the right evidence is available at the right time for decision makers,” says Louise Parmenter, global head of Operations, Epidemiology & Outcomes Research, Quintiles Real World & Late Phase Research.

To understand more about the use of RWE by HTA bodies, Quintiles carried out a review of the use of RWE in HTA appraisals of multiple sclerosis (MS) drugs in the UK, France, Germany, and the Netherlands. Of 38 assessments published by HAS (France), G-BA (Germany), NICE (UK), SMC (Scotland) and ZIN (Netherlands) between 2011 and 2014, half (19) reported RWE. No German assessments included RWE, but most or all of the assessments in France and the UK included the data. In the UK, RWE was used in the initial submission. In the Netherlands it only played a part in two re-assessments, and in France it was used in both initial and re-assessments.

Overall, RWE was mostly used to support safety, but also had a role in modelling for cost-effectiveness analysis (e.g., modelling the natural history of the disease, and to provide information on health state utilities and costs). It seems to have only been used to support relative effectiveness of the drug in reassessments.

Challenges and solutions

RWE could play a significant role in supporting biopharma companies through the process of HTA submissions, particularly in understanding the treatment pathway, linking surrogate endpoints to patient-relevant outcomes, understanding heterogeneity and natural history of the disease, and looking at the burden of illness and medical resource utilization in a real life clinical setting. The use of real world data it faces a number of challenges, including timely collection, the investment required to collect the data, dealing with missing data, and any bias in the data.

Generating RWE can be carried out throughout the entire process of clinical development, and fill in any knowledge gaps for stakeholders. The ideal approach is keep all the stakeholders in mind from the beginning, in order to create evidence that can serve more than one purpose.

Solutions to these challenges need to understand the needs of the different stakeholders, evaluate the best ways to capture the data, and select the right methods for data generation and analysis, in terms of speed, cost and data quality. This could include using registry systems to help to standardize real world data and make it more rigorous and consistent.

As HTAs become more familiar with RWE and see its usefulness in confirming cost effectiveness, and as economic criteria play an even greater role in drug approval and recommendation, the acceptance is likely to become more widespread.


> To learn how real-world evidence is vital to support decision-making, please read our recent white paper, "HTA and market insights: Real-world evidence generation for evolving stakeholder needs"

Topics in this blog post: Biopharma, Evidence, EU, HTA, Registries