A national framework for real-world evidence: Insights from the Philippine Guidance Document Development Process
18 Dec 2025
By Dr Michelle Yap Siao
Real-world evidence (RWE) complements the findings from controlled clinical trials by showing how a treatment performs in a diverse patient population in a real-world setting. Health technology assessment (HTA) provides evidence-based evaluation of new technologies, guiding decisions on their integration into clinical practice, and promoting cost-effectiveness and equity. It helps ensure that innovations, such as digital health tools and new medical devices, effectively improve patient outcomes, reduce mortality and morbidity, and support public health goals in a financially sustainable way. The process considers clinical, cost, and ethical factors to make informed decisions about which technologies to adopt.
Tan-Lim and colleagues from the University of the Philippines Manila outlined a systematic process undertaken to create a national framework for incorporating RWE into HTA in the Philippines. The work was produced to address a gap in the existing Philippine HTA Methods Guide, which lacked detailed recommendations on using RWE for clinical evaluations. According to the authors, this guidance was developed as a response to the growing importance of RWE in decision-making, especially under the mandate of the Universal Health Care Act, which requires all health technologies procured or reimbursed by the government to undergo HTA. [Int J Technol Assess Health Care. 2025;41(1):e72. doi:10.1017/S0266462325100512]
The study was conducted in two phases: a systematic review and the creation of a draft guidance document, followed by expert validation through consultation with key informant interviews (KII) and pilot testing. Phase 1 involved extensive searching of biomedical databases and HTA organization websites. The researchers retrieved 79 journal articles and nine guidance documents, which were screened, appraised, and synthesized. They extracted definitions, methodological approaches, and recommendations regarding the use of RWE in clinical evaluations. The authors said that the literature review revealed considerable global variation in how RWE is applied, but it also identified shared principles, such as the importance of transparency, methodological rigor, and careful appraisal of observational studies.
The extracted information was organized into six thematic areas: defining RWD and RWE; determining when RWE is appropriate for clinical evaluation of health technologies; methods for the search and selection of RWE for clinical evaluation of health technologies; methods for the critical appraisal of RWE; methods for data extraction of RWE for clinical evaluation of health technologies; and methods for data analysis and synthesis of RWE for clinical evaluation of health technologies. Based on these synthesized themes, the first draft of the Philippine RWE guidance document was produced. Reportedly, this initial draft closely followed the Preferred Reporting Items for Systematic Reviews and Meta-Analayses (PRISMA) standards for systematic reporting and attempted to balance global best practices with contextual realities in the Philippines, such as limited resources and variable data infrastructure.
Phase 2 focused on validation. According to the Tan-Lim et at., three international methodological experts from Singapore, Thailand, and Australia were invited for key informant interviews (KIIs). They evaluated the clarity, comprehensiveness, and relevance of the draft guidance. Among the major issues raised were the need for stronger appraisal strategies for secondary data, more clarity about qualitative research, the ambiguous status of N-of-1 trials, and the proper use of target trial emulation (TTE). One expert said that transparency and reproducibility should be emphasized when using routinely collected data such as electronic medical records and administrative claims. The authors stated that these comments were integrated into the revised guidance document, with adjustments outlining the benefits and limitations of each data source as well as the appropriate use of complementary designs like TTE.
The experts also highlighted that RWE should not be used to replace randomized controlled trials (RCTs) when RCTs are feasible. Instead, RWE should complement or extend traditional clinical trials, especially in scenarios involving rare diseases, long-term outcomes, or ethical constraints. This aligned with the overall theme of the guidance: while RCTs remain the gold standard, RWE can fill evidence gaps when trials are not feasible or ethical, incomplete, or insufficiently powered. The authors said that expert feedback on reporting standards, comparators, bias, and hierarchy of observational evidence further helped refine the guidance document.
Following expert consultation, a pilot assessment was conducted. Five assessors—experienced evidence reviewers—tested the revised guidance document using diverse health technologies, including cancer therapies (pazopanib, sunitinib and pembrolizumab + axitinib for renal cell carcinoma; trastuzumab emtansine for breast cancer; palbociclib and ribociclib for breast cancer), antibiotics (ceftaroline fosamil for community acquired pneumonia), diabetes treatments (biphasic insulin aspart 30), and immunotherapies (atezolizumab and pembrolizumab for nonsmall cell lung cancer). Their comments focused on clarity, applicability, and ease of use. They agreed that the manual was clear and logically organized, although they suggested refinements in terminology, such as replacing “noninterventional” with “nonexperimental” in the definition of RWD. They also recommended additional clarification on surrogate outcomes, selection bias, adjusted effect estimates, and network meta-analysis. The guidance document was revised accordingly.
The Philippine HTA Council and HTA Division conducted a final review. They emphasized that pragmatic clinical trials—even though experimental—should still be considered as sources of RWE due to their real-life setting. They also recommended recognizing pandemics as emergency situations in which RWE plays a crucial role in fast decision-making pending RCT results. According to the authors, these revisions ensured the guidance remained practical during public health crises while still emphasizing the primacy of RCTs when available.
Tan-Lim et al. explained that this newly developed guidance document is aligned with international frameworks but tailored for local needs. For example, frameworks from the United States and France focus on regulatory decisions such as post-marketing surveillance, while the UK brief spans the entire life cycle of health technologies and includes evaluation of service delivery. Meanwhile, guidance from Canada (CADTH and INESS) emphasizes reimbursement decisions in public health programs and pre and postdrug marketing evaluations. In contrast, the REALISE guideline, which applies to health systems in Asia, provides practical recommendations for low- and middle-income countries with limited resources. The Philippine guidance document sought to integrate these approaches with local priorities—particularly the evaluation of technologies under resource constraints and fragmented health systems. It focuses on the application of RWE in HTA assessment to guide regulatory agencies in their decisions regarding the procurement and reimbursement of health technologies. According to the authors, achieving this balance ensures both methodological rigor and feasibility within the Philippine context.
Although their research did not focus on cardiovascular disease, the guidance has meaningful implications for cardiovascular health technologies. Real-world evidence is especially valuable in cardiology, where long-term outcomes such as major adverse cardiovascular events (MACE), hospitalization rates, and survival are critical but often extend beyond the duration of RCTs. According to the authors, RWE is particularly useful when trials cannot capture long-term or rare outcomes, which is often the case for chronic cardiovascular therapies that require years of follow-up.
In summary, Tan-Lim et al. provided a detailed account of the creation of the Philippine guidance document on RWE in HTA. They aimed to help ensure that RWE is used appropriately, transparently, and rigorously—always with the understanding that RCTs remain the gold standard. Still, RWE plays a crucial role when trials are insufficient or infeasible.
Their document is intended for researchers conducting HTA in the Philippines, but it also serves as a foundation for future expansions tailored to specific health technologies. It reflects an evolving global landscape of evidence generation and highlights the importance of adapting methodologies to national health system needs. The authors acknowledge limitations, including the small number of expert informants, but they emphasize that the guidance will continue to be updated as the field develops. Ultimately, the article underscores the critical role of high-quality RWE in supporting equitable, efficient, and evidence-based health decision-making in the Philippines.
Real-world evidence (RWE) complements the findings from controlled clinical trials by showing how a treatment performs in a diverse patient population in a real-world setting. Health technology assessment (HTA) provides evidence-based evaluation of new technologies, guiding decisions on their integration into clinical practice, and promoting cost-effectiveness and equity. It helps ensure that innovations, such as digital health tools and new medical devices, effectively improve patient outcomes, reduce mortality and morbidity, and support public health goals in a financially sustainable way. The process considers clinical, cost, and ethical factors to make informed decisions about which technologies to adopt.
Tan-Lim and colleagues from the University of the Philippines Manila outlined a systematic process undertaken to create a national framework for incorporating RWE into HTA in the Philippines. The work was produced to address a gap in the existing Philippine HTA Methods Guide, which lacked detailed recommendations on using RWE for clinical evaluations. According to the authors, this guidance was developed as a response to the growing importance of RWE in decision-making, especially under the mandate of the Universal Health Care Act, which requires all health technologies procured or reimbursed by the government to undergo HTA. [Int J Technol Assess Health Care. 2025;41(1):e72. doi:10.1017/S0266462325100512]
The study was conducted in two phases: a systematic review and the creation of a draft guidance document, followed by expert validation through consultation with key informant interviews (KII) and pilot testing. Phase 1 involved extensive searching of biomedical databases and HTA organization websites. The researchers retrieved 79 journal articles and nine guidance documents, which were screened, appraised, and synthesized. They extracted definitions, methodological approaches, and recommendations regarding the use of RWE in clinical evaluations. The authors said that the literature review revealed considerable global variation in how RWE is applied, but it also identified shared principles, such as the importance of transparency, methodological rigor, and careful appraisal of observational studies.
The extracted information was organized into six thematic areas: defining RWD and RWE; determining when RWE is appropriate for clinical evaluation of health technologies; methods for the search and selection of RWE for clinical evaluation of health technologies; methods for the critical appraisal of RWE; methods for data extraction of RWE for clinical evaluation of health technologies; and methods for data analysis and synthesis of RWE for clinical evaluation of health technologies. Based on these synthesized themes, the first draft of the Philippine RWE guidance document was produced. Reportedly, this initial draft closely followed the Preferred Reporting Items for Systematic Reviews and Meta-Analayses (PRISMA) standards for systematic reporting and attempted to balance global best practices with contextual realities in the Philippines, such as limited resources and variable data infrastructure.
Phase 2 focused on validation. According to the Tan-Lim et at., three international methodological experts from Singapore, Thailand, and Australia were invited for key informant interviews (KIIs). They evaluated the clarity, comprehensiveness, and relevance of the draft guidance. Among the major issues raised were the need for stronger appraisal strategies for secondary data, more clarity about qualitative research, the ambiguous status of N-of-1 trials, and the proper use of target trial emulation (TTE). One expert said that transparency and reproducibility should be emphasized when using routinely collected data such as electronic medical records and administrative claims. The authors stated that these comments were integrated into the revised guidance document, with adjustments outlining the benefits and limitations of each data source as well as the appropriate use of complementary designs like TTE.
The experts also highlighted that RWE should not be used to replace randomized controlled trials (RCTs) when RCTs are feasible. Instead, RWE should complement or extend traditional clinical trials, especially in scenarios involving rare diseases, long-term outcomes, or ethical constraints. This aligned with the overall theme of the guidance: while RCTs remain the gold standard, RWE can fill evidence gaps when trials are not feasible or ethical, incomplete, or insufficiently powered. The authors said that expert feedback on reporting standards, comparators, bias, and hierarchy of observational evidence further helped refine the guidance document.
Following expert consultation, a pilot assessment was conducted. Five assessors—experienced evidence reviewers—tested the revised guidance document using diverse health technologies, including cancer therapies (pazopanib, sunitinib and pembrolizumab + axitinib for renal cell carcinoma; trastuzumab emtansine for breast cancer; palbociclib and ribociclib for breast cancer), antibiotics (ceftaroline fosamil for community acquired pneumonia), diabetes treatments (biphasic insulin aspart 30), and immunotherapies (atezolizumab and pembrolizumab for nonsmall cell lung cancer). Their comments focused on clarity, applicability, and ease of use. They agreed that the manual was clear and logically organized, although they suggested refinements in terminology, such as replacing “noninterventional” with “nonexperimental” in the definition of RWD. They also recommended additional clarification on surrogate outcomes, selection bias, adjusted effect estimates, and network meta-analysis. The guidance document was revised accordingly.
The Philippine HTA Council and HTA Division conducted a final review. They emphasized that pragmatic clinical trials—even though experimental—should still be considered as sources of RWE due to their real-life setting. They also recommended recognizing pandemics as emergency situations in which RWE plays a crucial role in fast decision-making pending RCT results. According to the authors, these revisions ensured the guidance remained practical during public health crises while still emphasizing the primacy of RCTs when available.
Tan-Lim et al. explained that this newly developed guidance document is aligned with international frameworks but tailored for local needs. For example, frameworks from the United States and France focus on regulatory decisions such as post-marketing surveillance, while the UK brief spans the entire life cycle of health technologies and includes evaluation of service delivery. Meanwhile, guidance from Canada (CADTH and INESS) emphasizes reimbursement decisions in public health programs and pre and postdrug marketing evaluations. In contrast, the REALISE guideline, which applies to health systems in Asia, provides practical recommendations for low- and middle-income countries with limited resources. The Philippine guidance document sought to integrate these approaches with local priorities—particularly the evaluation of technologies under resource constraints and fragmented health systems. It focuses on the application of RWE in HTA assessment to guide regulatory agencies in their decisions regarding the procurement and reimbursement of health technologies. According to the authors, achieving this balance ensures both methodological rigor and feasibility within the Philippine context.
Although their research did not focus on cardiovascular disease, the guidance has meaningful implications for cardiovascular health technologies. Real-world evidence is especially valuable in cardiology, where long-term outcomes such as major adverse cardiovascular events (MACE), hospitalization rates, and survival are critical but often extend beyond the duration of RCTs. According to the authors, RWE is particularly useful when trials cannot capture long-term or rare outcomes, which is often the case for chronic cardiovascular therapies that require years of follow-up.
In summary, Tan-Lim et al. provided a detailed account of the creation of the Philippine guidance document on RWE in HTA. They aimed to help ensure that RWE is used appropriately, transparently, and rigorously—always with the understanding that RCTs remain the gold standard. Still, RWE plays a crucial role when trials are insufficient or infeasible.
Their document is intended for researchers conducting HTA in the Philippines, but it also serves as a foundation for future expansions tailored to specific health technologies. It reflects an evolving global landscape of evidence generation and highlights the importance of adapting methodologies to national health system needs. The authors acknowledge limitations, including the small number of expert informants, but they emphasize that the guidance will continue to be updated as the field develops. Ultimately, the article underscores the critical role of high-quality RWE in supporting equitable, efficient, and evidence-based health decision-making in the Philippines.