Real-world evidence (RWE) and real-world data (RWD) can ‘generate insights about a medicine’s effectiveness, safety and associated costs,1 and due to the emergence of value-based payments (VBP), the relevance and importance of RWE is being further emphasized across the globe.
The number of real-world studies has increased and the approach to collecting, evaluating and using RWD around the world is inconsistent.2 This is no surprise given its broad potential and the complexity of healthcare ecosystems globally. Being able to collect RWD is a benefit to the health-care industry, as it allows providers to ‘form insights on how patients are responding to a drug in the real world’.1 As a result, stakeholders (regulators, biopharma industry, providers, payers and patients) have highlighted a need to systematize the use and impact of RWD. Here, we highlight how RWE and RWD are progressing on a global scale, and the benefits this trend could present.
RWE in Europe is largely used for accelerated access to medicines or drug safety review post launch. In Germany, the Federal Institute for Drugs and Medical Devices (BfArM) states that randomized control trial (RCT) data is the only drug-specific evidence appropriate prior to market authorization. However, in the UK, the Medicines & Healthcare products Regulatory Agency (MHRA) accepts RWE as supplementary to Phase II and Phase III data, as well as in cases of ongoing evidence collection.
Some challenges in Europe include registries that are not well connected or managed, restricted access to data and sub-optimal IT infrastructure.
There are several pan-European initiatives in motion with the aim to drive adoption of RWE. For example, in support of a smooth EU exit, the UK’s MHRA has plans to expand the use of RWD for accelerated access review and regulatory decision making across Europe. Different objectives for optimizing RWD use have been outlined by the agency, such as monitoring safety in real time through proactive regulatory surveillance.
RWE is already being used effectively in some European countries. In Sweden, The Swedeheart Study, a national registry of coronary artery disease care and valvular interventions, has been found to improve the quality of care, outcomes and costs (Jernberg et al.).3
Because the government is the largest financier in the U.S., the need for regulators and payers to align more closely is particularly acute. The Food and Drug Administration (FDA) has stated the need to ‘close the evidence gap between the information it uses to make decisions and the evidence increasingly used by payers and others charged with making healthcare decisions’.4
The 21st Century Cures Act (Section 3037) amended the U.S. FDA Modernization Act 11, which allows manufacturers to use RWE to support a new indication for an approved drug.5 By utilizing comparative Patient Reported Outcomes (PRO) data and Health Care Economic Information (HCEI), manufacturers can communicate a wider scope of a product’s value to payers and formulary decision-makers. This change has lowered the threshold required for proactive communication from ‘substantial evidence’ to ‘competent and reliable scientific evidence.’
Only last year, The Institute for Clinical and Economic Review (ICER), in collaboration with the Office of Health Economics (OHE), produced guidance to payers and manufacturers on the development and use of RWE for drug coverage and formulary decisions.6 It proposes the formulation of a potential protocol, requiring considerations to define the evidentiary assertion and associated evidence bar for RWE. The FDA aims to publish draft guidance for the use of RWE by October 2021.7 The FDA’s new strategic framework, released in December 2018, aims to advance use of RWE to support the development of drugs and biologics. Leveraging RWE & RWD to improve regulatory decisions is a top strategic priority for the FDA. The FDA is leading the way in terms of deploying cutting edge technology and analytics, including Natural Language Processing (NLP), machine learning (ML) and artificial intelligence (AI) for the collection and use RWD & RWE.8,9,10
The acceptance, use and knowledge of RWE, similar to Europe, is very diverse across Asia. Countries with advanced medical and health-related infrastructure, such as Japan, Singapore and Australia, are advanced in the development and adoption of RWE, whereas countries like India and China are less so. For example, in China, while there are registries for infectious diseases and rich hospital-level data, hospital information systems are not standardized and data is not consistently recorded. However, with the use of modern technology such as wearable devices, data could be easier to access and the value of RWD is likely to influence future healthcare improvement. Similarly, in India data sources are limited. The government does not currently finance healthcare in India, although it has launched ‘Modicare’ in 2018, a vast new health program to cover half a billion Indian citizens in what the Indian government says is the world’s biggest government-funded health scheme.11 However, databases, medical records and other sources of RWD have remained undeveloped. But the Indian Health Ministry plans to help move India towards the development and use of Electronic Health Records (EHRs) to improve the country’s ability to collect and store health data.
The development of RWE in Asia is evident in programs such as Japan’s “Rational Medicine” initiative launched in 2017, aiming to make the Japanese health care system more patient-centric and evidence-based. The Chief Executive of Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) stated the initiative would provide “better insight into the risk/benefit balance of drugs, medical devices, and regenerative medical products.” 12
Across all three regions there are countries where technological developments enable capturing RWD, but the systems, rules and safeguards are yet to catch up. When they do, accelerated market access is a real possibility. It is clear a multi-stakeholder approach, with international collaboration, is essential to ensuring robust RWE generation and utilization. Global pharmaceutical companies play a pivotal role in encouraging standardization of concepts, processes and approaches for RWE. A key imperative for organizations is to strategically utilize knowledge and technologies to aid expertise and help inform decisions on healthcare. Planning, protocol development, clinical study management, systematic review and reporting, are a few examples of activities that can be outsourced effectively. While it may not be possible to invest in all these areas, identifying those services that are key to your company will help ensure patient access and commercial success.
About the Author
Madhur Garg is Director,
Real-World Evidence and Market Access at Sciformix Corporation
About Sciformix, A Covance Company
Sciformix Corporation, a Covance Company, is a leading scientific knowledge-based organization that provides process, technology and consulting services to the life sciences industry. We employ best-in-class strategies, technologies and expertise that accelerates business, drives higher levels of performance and fosters innovation. What differentiates Sciformix is our ability to integrate scientific and technology expertise with quality driven processes to provide value to our clients throughout the entire drug development cycle. Our areas of specialization include Safety & Risk Management, Clinical Research & Post-Approval Support Services, Regulatory Affairs & Regulatory Operations, and Technology Services. Corporate headquarters is located in Westborough, MA with operations in NA, Europe, India and the Philippines. For more information, please visit: https://www.sciformix.com/
2. Blonde, L., Khunti, K., Harris, S.B., et al. Interpretation and Impact of Real-World Clinical Data for the Practicing Clinician (2018) 35: 1763. https://doi.org/10.1007/s12325-018-0805-y
3. Jernberg T, Attebring MF, Hambraeus K, et al The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) Heart 2010;96:1617-1621.
6. ICER (2018). Real World Evidence for Coverage Decisions: Opportunities and Challenges / Understanding the Context, Selecting the Standards: A Framework to Guide the Optimal Development and Use of Real World