Real-World Data: Pioneering New Frontiers in Pharmaceutical Development

In the pharmaceutical development landscape, “Real-World Data (RWD)” and “Real-World Evidence (RWE)” are currently garnering significant attention. These innovative approaches are transforming healthcare for the better.

What is Real-World Data (RWD)?

Real-World Data refers to various medical data obtained from actual healthcare settings outside of clinical trials. It primarily includes the following data sources:

Patient symptoms and treatment progress recorded in electronic health records (EHRs), health examination results, prescription records from pharmacies, medical claims data (receipt data), Diagnosis Procedure Combination (DPC) data, disease registry data, and health data obtained from wearable devices such as smartwatches—all “real” data reflecting patients’ conditions in actual medical settings.

What is Real-World Evidence (RWE)?

“Real-World Evidence” refers to medical insights and evidence derived from analyzing RWD. Specifically, it provides clinical evidence about relationships between medication use and adverse events, actual effectiveness of treatments, impacts on patients’ quality of life (QOL), and effects on healthcare costs.

Why Are RWD and RWE Receiving Attention Now?

1. Limitations of Traditional Clinical Trials

Traditional clinical trials, particularly Randomized Controlled Trials (RCTs), have the following constraints:

Limited number of participants, strict eligibility criteria that may not adequately represent actual patient populations, high costs and extended timeframes, and difficulties conducting trials in specific patient populations such as rare diseases or pediatric cases.

2. Benefits of RWD and RWE

In contrast, RWD and RWE offer the following advantages:

Ability to utilize data from large patient populations, reflection of real-world medical practice conditions, collection of data from broader patient demographics (including elderly patients and those with comorbidities), relatively low-cost data collection through secondary use of existing data, and capability for long-term effectiveness and safety evaluation.

Specific Use Cases

Example 1: Safety Monitoring of New Drugs (Post-Marketing Surveillance)

After approval of a blood pressure medication, analysis of electronic health record data and databases such as MID-NET (Medical Information Database Network) enabled early detection of unexpected adverse events in elderly patients. This allows for assessment of incidence rates and causal relationships that would be difficult to capture through traditional spontaneous adverse event reporting systems.

Example 2: Indication Expansion Considerations

Analysis of real-world usage data for an existing anticancer drug suggested effectiveness in cancer types beyond its initially approved indication, leading to consideration of new indication additions. RWD is particularly facilitating the development of new treatment options in rare disease areas.

Example 3: Understanding Treatment Patterns and Improving Healthcare Quality

Analysis of diabetes patient medical data has enabled understanding of which treatments are selected for which patients and their trends. This contributes to personalized medicine and formulation of optimal treatment strategies.

Latest Regulatory Developments

International Harmonization Efforts

In May 2024, at the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), “ICH M14: General Principles on Planning, Design and Analysis of Pharmacoepidemiological Studies That Utilize Real-World Data for Safety Assessment of Medicines” reached Step 2, and following public comments, development as an international guideline is progressing. This guideline provides an important framework for ensuring the reliability of RWD-based studies.

Also in May 2024, the ICH Reflection Paper “Exploring Opportunities for Harmonisation on the Use of Real-World Data (RWD) to Generate Real-World Evidence (RWE) with a Focus on Effectiveness of Medicinal Products” was approved, initiating full-scale consideration of international harmonization of RWD use not only for safety evaluation but also for effectiveness evaluation.

Regulatory Environment Development in Japan

Japan has also made steady progress in regulations and infrastructure development to promote RWD utilization.

In April 2018, the Ministerial Ordinance on Good Post-Marketing Study Practice (GPSP) was revised, establishing post-marketing database studies within the ordinance framework.

In March 2021, the “Basic Principles for Use of Registry Data in Marketing Authorization Applications” was notified, providing specific guidelines for utilizing registry data in marketing authorization and re-examination applications.

In April 2024, the “Amended Act on Anonymized Medical Data to Contribute to Research and Development in the Medical Field” was enforced, newly establishing “pseudonymized processed medical information.” This enables research utilization of RWD including rare diseases and unusual test values that would be deleted in anonymized processing, with linkage analysis with the National Database (NDB) also coming into view.

Furthermore, in the revision of the Pharmaceuticals and Medical Devices Act (PMD Act) promulgated in May 2024, utilization of Real-World Data for regulatory submissions and safety measures was clarified. Requirements for submission documents were revised to facilitate drug development environments aimed at resolving drug lag and drug loss. However, operations that consider the importance of rigorous evidence from randomized controlled trials are premised.

RWD Infrastructure Development in Japan

MID-NET (Medical Information Database Network), managed and operated by the Pharmaceuticals and Medical Devices Agency (PMDA), began full operation in fiscal year 2018 and currently serves as a large-scale medical information database covering over 8.3 million people (as of December 2024), collecting and storing electronic health record data, receipt data, DPC data, and laboratory test results. It is utilized for post-marketing surveillance by pharmaceutical companies, academic research, and safety measures by PMDA.

Additionally, diverse database development is progressing, including the National Database (NDB), the Rare Disease Platform, and disease-specific registries, with construction of the “National Medical Information Platform” also underway.

International Trends

U.S. FDA

The FDA is actively promoting the RWE Program based on the 21st Century Cures Act. In March 2024, it published a draft guidance on non-interventional studies (observational studies), presenting important considerations such as data reliability, appropriateness of study design (relevance), and regulatory suitability.

European EMA

The EMA is advancing infrastructure development for integrated RWD utilization across Europe through the DARWIN EU (Data Analysis and Real World Interrogation Network) project. From 2023 to 2024, dozens of studies have been conducted, accumulating experience in utilizing RWE for regulatory decision-making.

Ensuring Data Quality and Reliability

One of the most important challenges in RWD utilization is ensuring data quality and reliability. The International Medical Device Regulators Forum (IMDRF) presents “six perspectives” for data quality assurance: representativeness, completeness, accuracy, consistency, credibility, and reliability.

In Japan as well, PMDA has established consultation services for registries and databases, supporting quality improvement of data suitable for regulatory submissions through database reliability assessment consultations and registry reliability assessment consultations.

Future Prospects

RWD and RWE utilization is expected to contribute to medical advancement in the following ways:

1. Pharmaceutical Development Efficiency

Expected benefits include reduced development costs, shortened development timelines, more accurate clinical trial planning, and reduction in the number of trial participants through RWD use as external control groups. Promotion of drug development particularly in rare diseases and pediatric areas is anticipated.

2. Healthcare Quality Improvement

This will enable selection of appropriate treatments for individual patients (personalized medicine), early detection and countermeasures for adverse events, improved health economics, and evaluation of long-term effectiveness and safety in real clinical practice.

3. Enhanced Patient Benefits

Expected outcomes include provision of more treatment options, realization of safer healthcare, more effective treatments, and improved access to medicines (resolution of drug lag/loss).

4. Advancement of Regulatory Science

Through RWD utilization, scientific evidence for regulatory decisions will be strengthened, with further advancement of regulatory science expected. Global harmonization is also progressing through development of international guidelines such as ICH M14.

Challenges and Future Initiatives

RWD and RWE utilization is still a developing field. Current major challenges include ensuring data standardization and interoperability, balancing personal information protection with data utilization, continuous improvement of data quality, cultivation of specialized personnel in RWD utilization, and accumulation of cases through continuous dialogue with regulatory authorities.

However, with the advancement of digital technology, development of AI and machine learning technologies, and progress in international regulatory harmonization, the possibilities are steadily expanding. Future healthcare will aim to realize better medical care by combining traditional clinical trial data with RWD and RWE.

Conclusion

Healthcare professionals are called upon to pay attention to these new trends and examine the possibilities of RWD and RWE utilization from their respective positions. For pharmaceutical companies, it serves as a means for efficient drug development; for healthcare institutions, as a tool for improving healthcare quality; for regulatory authorities, as a basis for scientific regulatory decisions; and for patients, as an opportunity for improved access to better treatments—RWD and RWE utilization holds significant meaning.

This transformation is considered an important step toward realizing better healthcare. With advancing international harmonization and domestic regulatory environment development, innovation in drug development and benefit delivery to patients through appropriate RWD and RWE utilization are expected to be realized.