Eighteen of the 20 (90%) TransCelerate member companies responded to the 30-questions’ form, though not all companies answered each question. Of the 18 respondents, 16 (89%) indicated that they were actively leveraging RWD specifically for signal assessment, regardless of whether the approach was considered rapid or not. Some companies also specified using RWD in other areas of the signal management process, with 8/18 (44%) using RWD for signal detection and 7/18 (39%) for signal validation. When asked to provide acceptable time frames to fulfill company needs for the delivery of rapid RWD analysis for signal assessment, half (9/18) of the respondents specified 2 weeks or less (Fig. 1). Several companies indicated more than one time frame, with responses ranging from less than 1 week to more than 90 days.

Acceptable time frame for delivery of rapid real-world data analysis in signal assessment reported by TransCelerate member companies (N = 18). Companies could select more than one response.

Out of 18 respondent companies, 8 (44%) reported routinely using a rapid approach to RWD analysis during safety signal assessment, 7 (39%) reported use of rapid RWD analysis, though not routinely, 2 (11%) indicated rapid RWD analysis as under consideration, and 1 (6%) reported no current plan to incorporate rapid RWD analysis. Most companies (14/18; 78%) reported that they plan to increase the use of rapid RWD analysis in signal assessment over the next 3 years.

Regarding the value of rapid RWD analysis, most companies indicated that RWD adds context to safety signal assessment (17/18; 94%) and enables decision-making (12/18; 67%). Companies also indicated that using rapid RWD analysis in signal assessment improves confidence in (16/17; 94%) and quality of the assessment (12/17; 71%) and reduces time to decision-making (12/17; 71%). Among companies currently using rapid RWD analyses, 7/8 (88%) routine users versus 5/9 (56%) non-routine users reported reduced decision-making time.

When asked how rapid RWD analyses are or will be performed, nearly all respondent companies (16/17; 94%) reported conducting such analyses within their company using internal and/or in-licensed data. Nearly half of the companies (8/17; 47%) reported using external third-party analyses, and 3/17 (18%) reported leveraging data networks.

Companies reported using or planning to use rapid RWD analysis across a variety of signal assessments, including for specific adverse events or outcomes, therapeutic areas or indications, populations, geographic regions, and signal priorities. The types of rapid RWD analyses planned or performed include both descriptive (characterizations of adverse events, disease, or drug utilization) and comparative analyses (population estimation, product event pair characterization, patient level prediction) (Fig. 2). Stratification by usage revealed no notable differences in the types of analyses planned or performed between the routine and non-routine users (data not shown).

Types of planned and performed rapid real-world data analyses for signal assessment reported by TransCelerate member companies (N = 17). Companies could select more than one response.

Of 17 respondent companies, all use or are considering use of electronic health records and claims databases as sources for RWD (Fig. 3). Most routine users of rapid RWD analysis also indicated using or considering using claims databases, surveys, registries, or genetic and genomics data as RWD sources.

Real-world data (RWD) sources used or considered for use among routine (n = 8) and non-routine users (n = 9) of rapid RWD analyses in signal assessment. Companies could select more than one response.

To implement rapid RWD analysis in signal assessment, 8/17 (47%) companies indicated using or planning to use a full protocol and statistical analysis plan, as with a formal observational study. Of 17 respondents, 14 (82%) reported use of a minimal protocol specifically focused on signal assessment, 4 (24%) specified other options, and 2 (12%) chose a non-protocolized approach, suggesting that protocol types are situational, with a minimal approach being preferred. Stratification by rapid RWD analysis usage revealed that 6/8 (75%) routine users versus 2/9 (22%) non-routine users considered a full protocol, and all 8 (100%) routine users versus 6/9 (67%) of the non-routine users considered a minimal protocol (data not shown). The follow-up questionnaire indicated that responding companies that use rapid RWD analyses (N = 12) tend to use a minimal protocol for analyses of background rates, disease and adverse events characterization, and population estimation. A full protocol is more often used for drug utilization, patient-level prediction, and product event characterization types of analyses.

To rapidly deliver RWD analysis, companies primarily streamlined or standardized efforts in execution and planning rather than protocol development and result documentation. Streamlined activities include analysis execution (13/17; 76%), acquiring access to relevant data sources (12/17; 71%), data source selection and feasibility (12/17; 71%), analysis parameterization (11/17; 65%), output development and visualizations (11/17; 65%), and establishment of relevant phenotype/code lists (9/17; 53%).

Among 17 respondents, 14 (82%) submitted results of rapid RWD analyses for signal assessment to a health authority. All 14 (100%) of these companies submitted to the European Medicines Agency (EMA) and 10/14 (71%) submitted to the United States Food and Drug Administration (FDA). Some companies indicated receiving methodological questions from health authorities regarding their rapid RWD analysis.

Routine users estimate that half (median 50%) of signal assessments at their company use rapid RWD analysis, compared to a median 4% of assessments at companies with non-routine use (Table 1). Companies with routine use of rapid RWD analyses estimated a median 80% of signals assessed per year could benefit from such analyses, compared to a median 40% of signals at companies with non-routine use. The company-level gap between the frequency of actual and potentially valuable rapid RWD analyses for signal assessment was lower for routine users (median 10%) versus non-routine users (median 35%).

Respondents were asked to identify the top three challenges to performing rapid RWD analysis in signal assessment. The most frequently reported challenge, identified by 8/18 (44%) companies, was time required for analysis execution. Two challenges were each ranked by 4 companies as their top challenge: availability or access to relevant RWD sources and uncertainty around acceptance of non-protocolized or minimally protocolized approaches by health authorities. Other reported challenges included establishing relevant phenotypes or code lists, establishing a protocol, and timeliness of available RWD data sources.

Though some companies indicated that these challenges have not yet been resolved, several specified various potential solutions. Notably, having analytical preparedness allowed companies to overcome many of the barriers to rapid RWD analysis. In addition, to address the time required for analysis execution, companies reported allocating appropriate resources, piloting, learning while growing, and developing internal expertise. Non-access to or unavailability of relevant RWD sources was addressed by active collaboration with data partners and investment in new data sources. To establish relevant phenotypes or code lists, companies required internal company collaboration, internal expertise, and process standardization. To address uncertainties around acceptance of the protocol approach by health authorities, some companies specified seeking feedback from the respective health authority. Process standardization was one approach to reducing time required for documentation.