Real-world evidence (RWE) is increasingly important both for regulatory agencies and reimbursement authorities, providing a way to monitor efficacy, safety, and cost-effectiveness post-launch. The FDA approval of palbociclib in combination with endocrine therapy for male breast cancer and the inclusion of RWE in paliperidone palmitate’s labeling for schizophrenia are two recent examples. For pharmaceutical companies, therefore, generating and accessing RWE is critically important as a means of achieving their goals.
Increasingly, randomized controlled data (RCT) is being augmented with RWE from electronic health records, patient-generated data from in-home medical devices, wearables and mobile devices, healthcare claims and billings activities, and product and disease registries.
In 2020 Deloitte highlighted the strategic importance of RWE for pharmaceutical companies, particularly as a means to enhance the R&D process. In the near future, pharma executives envision RWE, “supporting regulatory filings and augmenting clinical trials, in contrast to the more traditional applications where they realize value today.”
Incorporating RWE into clinical and regulatory decisions is challenging. There are three dominant issues:
- The disparity of data.
- The lack of standardization among studies.
- The significant time lag between the time the evidence is gathered and the time it is published.
Frameworks developed by the Institute for Clinical and Economic Review (ICER) and the U.S. Food & Drug Administration (FDA) to guide the use of RWE in drug and biological development and in clinical trials, address the issues of data disparity and standardization.
Key Benefits
By considering efficacy, safety and therapeutic implications in the lives of people outside of RCTs, pharmaceutical developers may gain deep insights into actual treatment patterns, including dosing, compliance, adherence, off-label use, efficacy, and safety, and may detect any emerging safety issues.
Additional benefits, listed in the Deloitte study, include:
- Better decision-making regarding target product profiles or early development strategy.
- Faster to-market time.
- Reduced costs of post-marketing regulatory commitments.
- Fewer trial failures.
- Easier label expansion for marketed products.
Main Drawbacks
RWE, despite its benefits, also has well-recognized limitations. The lack of research-grade data is foremost, followed by the need for more transparent standard for RWE curation, and regulatory guidance regarding its use. Biases, the lack of patient stratification and misinterpretation of results are additional challenges.
The FDA guidances regarding RWE are overcoming many of the issues, but RWE is not yet perfect. Pharmaceutical executives, therefore, are forming strategic alliances to access new data sources, and are investing in internal talent and technologies to make better use of RWE.
Fulfilling the Promise of RWE
RWE has caught the attention of healthcare players across the continuum from scientists and researchers, to drug and device developers, payers, clinicians, regulators – and patients.
For example, Milind Kamkolkar, the first enterprise chief data officer in a major pharmaceutical company, Sanofi, told PharmaTimes: “We’re moving into an era of real-world evidence, and it’s going to be very interesting when we start moving from clinical endpoints to physiological endpoints to behavioural endpoints. All of those are an aggregation of different data that come from all sorts of things. You can literally store anything now.”
Mary Jo Lamberti, Ph.D., senior research fellow at Tufts CSDD and lead investigator on a study conducted by Tufts about the promise of RWE, also is optimistic: “While the cost and effort to integrate data sources, and then convincing regulators and payers of the validity of that evidence, pose hurdles to expanded use of real-world evidence, developers are confident that emerging technologies will help them address those issues.”
RWE is here to stay, and with the development of standards, it will gain in importance.
In Understanding the Context, Electing the Standards: A Framework for RWE, a companion paper to its report, ICER concludes: “Guided by a shared understanding of the contextual considerations, and supported by process principles of transparency, collaboration, and communication, RWE can be developed and applied as a vital complement to other evidence in improving the care for patients in the US healthcare system.”
The number of studies mentioning RWE is growing steadily. Pharmaspectra data indicates that nearly 200,800 publications and presentations mentioned RWE in 2019. Although that number declined in 2020 because of pauses during the COVID-19 pandemic, the number (184,066) was still significant. Notably, Pharmaspectra revealed 50% more scientific abstracts than PubMed, and found them well in advance of publication. Consequently, customers can access the most up-to-date data and make informed decisions as soon as new abstracts become available.
For RWE to be most useful, it must be timely. Yet, publication in peer-reviewed journals typically comes months after submission. Review times for PLoS journals, which are open access and have shorter publication times, vary from 150 to 250 days, with another 50 days added for production. A review of papers published before 2015 and appearing in PubMed showed an average of approximately 100 days elapsed between the time a paper was submitted and the time it was accepted. Another analysis reviewed median publication times for 3,482 journals with time stamps between January 2014 and June 2015. It found that Nature had a 173-day delay between submission and acceptance with publication 45 days later, while Developmental Cell had a 194-day delay, with publication 41 days afterward. Evidence-based studies have ever longer delays that stretch as long as two years.
Researchers concerned with protecting intellectual property for their organizations continue to turn to traditional journals, often exchanging timeliness for prestige. But, particularly for critical topics (like COVID-19 research), such lags may be unacceptable.
Pharmaspectra Provides Comprehensive Access to RWE
Comprehensive, timely and easy access to RWE is vitally important to pharmaceutical and medical device companies. Yet, an article in The Cochrane Database of Systematic Reviews noted that only 37.3% of all abstracts were fully published within 10 years. For randomized and controlled trials, the study estimated the figure at 68.7%.
Conference data and abstracts – even those that do not become full publications – can provide quick access despite publication lead times of up to 12 to 18 months. RWE abstracts also may be drawn from real world data that was generated without a company’s knowledge. Therefore, having access to the most complete data set is key not only for a company’s own products but also for monitoring those of competitors. To remain cognizant of the rapidly increasing numbers of papers and presentations and the immediate needs of fast-moving science, pharma professionals, from research to market access need a fast, accurate strategy to access the world’s scientific literature.
Pharmaspectra has the world’s largest scientific data lake of ‘traditional’ (including abstracts, publications and clinical trials) and digital sources (owned and earned content from social media and digital news). Pharma professionals, therefore, can access evidence as soon as they are publicly available – even if they don’t appear in PubMed.
With RWE now frequently required by regulatory and reimbursement authorities worldwide, it has become increasingly important to several functions across the pharmaceutical industry. Having a database that includes the most comprehensive set ofscientific disseminations is key to deliver and monitor complete analyses and, therefore, to success.
Authors:
Christian Schweiger MD, PhD. VP, Medical Affairs Strategy
Gail Dutton