Interest in real-world evidence (RWE) in the pharmaceutical industry continues to increase due to regulatory opportunities and payer demands.
Sources of real-word data are numerous and include electronic health records (EHRs), medical- or pharmacy-claims data, product and disease registries, and patient-generated data from wearable devices. EHRs present a viable source of clinical information and, when data is analysed appropriately, the resulting RWE yields insights that can improve both the overall standard of care and health outcomes for individual patients.
However, data collected for clinical rather than research purposes requires strict protocols to ensure data validity. This limits one’s ability to develop RWE-based insights that are reliable and clinically accurate enough to inform regulatory, payer and clinical decision-making.
Fortunately, ongoing improvements in compute power and data-analytics – including but not limited to natural language processing and other artificial-intelligence based machine-learning and modelling techniques – are allowing stakeholders to gain accurate and reliable insights from EHR data, in ways that were not possible even a few years ago.
When these efforts are successful, observational studies based on RWE are often able to demonstrate specific advantages for a given therapy, especially in patient sub-groups that may not have been studied in the underlying clinical trials. This provides direct impact for several stakeholder groups:
- Providers – Compelling RWE-derived findings related to a given therapy option help physicians to make well-informed, data-driven improvements to the standard of care that benefit patients and are supported by value-based payment models.
- Payers – When reliable RWE can demonstrate specific clinical and economic advantages for a given therapy, payers are able to justify broader reimbursement and more favourable formulary placement, increasing patient access to therapies
- Regulators – Regulatory-grade RWE can provide essential insights to verify and expand the findings of the randomised clinical trials (RCT), supporting label expansions and post-marketing commitments, which has direct benefits for physicians, patients and the pharma brand teams.
So what can we expect to see in 2020 and beyond?
1. Life science companies will focus more on the accuracy of the underlying data sources, by establishing minimum requirements related to accuracy measurement within the study protocol. This is imperative as studies increasingly make clinical assertions and have the potential to change the standard of care.
As studies increasingly show that accuracy levels in terms of sensitivity and specificity for EHR data can be as low as 30% and as high as 90%, high-quality studies can no longer afford to ignore accuracy if study authors hope to be taken seriously. This will lead to an increase in the number of RWE protocols that specifically require a gold standard and accuracy measurement for a sampling of cases, and require minimum thresholds for study validity. Where data is insufficiently accurate, unstructured data, artificial intelligence, and data enrichment will increasingly be required.
2. Sponsors will express greater interest in collaborating with academic research centres and health systems to carry out observational studies following robust RWE protocols.
Academic medical centres and community health systems represent important sources of data directly related to real-world patient care and prescribing practices. Yet such healthcare systems are often under-appreciated by stakeholders in the pharmaceutical industry looking to access large data sets. When pharmaceutical companies and other stakeholders work in close collaboration with such health systems, the resulting RWE-derived insights have the potential to change the standard of care via a tight feedback loop, enabling improved patient care and clinical outcomes. This data, in turn, can help to inform clinical studies.
3. US regulators will provide further clarity on the appropriate regulatory use of RWE, with formal guidance anticipated in 2021. By contrast, the situation in the EU is less formalised to date.
Today, many stakeholders throughout the healthcare and pharmaceutical sectors in the US have embraced RWE as they search for deeper understanding of how today’s high-cost life saving therapies work in patient populations that are considerably more diverse compared to patients who were enrolled in formal clinical trials according to strict inclusion and exclusion criteria. The regulatory approval that extended the label for the Pfizer oncology therapy Ibrance (palbociclib) in 2019 – based solely on RWE – was a watershed event and provides a clear bellwether that this trend will continue in 2020 and beyond.
In the EU efforts to generate RWE for therapies are less formalised. While the European Medicines Agency already uses RWE sources in its evaluations, it does so when there is a specific need for it. It is expected that European agencies will develop a more formal approach to RWE over time.
4. The healthcare industry will increase privacy and security scrutiny for secondary use of data (marketing and research) versus primary use (care delivery).
As today’s advanced modelling and data-analytics techniques allow for broader analysis of EHR data, the need to ensure the security and privacy of such data will continue to grow in importance. Patient-advocacy groups will focus on ways to enforce these objectives. Some sponsors and health systems will work to get ahead of this curve, developing strategies to balance privacy with patient benefit. The best organisations will make their approaches transparent, thereby staying on the right side of history and protecting against costly bad press.
5. Pharmaceutical companies will continue to explore ways to integrate multiple types of data associated with real-world patient experiences into observational studies.
The full value of the patient data that can be found in EHR systems is only beginning to be fully understood and explored. Going forward, stakeholders in the pharmaceutical and healthcare arenas will develop even stronger data-driven scientific arguments when they pursue observational studies that integrate multiple data sources, including phenotype from EHRs, exposures from pharmacy and device data, outcomes from claims data, value-based programs, sensors, and other sources.
6. Pharmaceutical companies will continue to pursue novel use cases that demonstrate the full potential of RWE.
In addition to using RWE to demonstrate effectiveness of a given therapeutic option, pharmaceutical companies will continue to explore other objectives. These may include designing observational studies to bolster an efficacy argument. Augmenting an RCT based on a precise RWE cohort will increase power for endpoint analysis.
Together, the trends toward developing clinically accurate and reliable RWE and using it to support regulatory, reimbursement, and clinical decision-making provides a significant opportunity to refine the standard of care. Moving from generalised RCTs to tailored therapy enabled by added RWE represents a sea change in healthcare. There is no other way to form precise care with sub-groups who were not analysed or included in the original clinical trials due to strict inclusion and exclusion criteria.
As we move forward in the 2020s, it is no longer sufficient for healthcare stakeholders to rely on generalities. It is our obligation to use the data we have available to benefit patients. We cannot leave it in silos and ignore it. A holy grail in healthcare is to match unique patient characteristics to the unique therapeutic offerings. Thoughtful use of RWE is a critical pathway to achieve this goal.
Dan Riskin MD is founder and chief executive of Verantos