A LIVING NETWORK META-ANALYSIS (NMA) FRAMEWORK INCORPORATING REAL-WORLD EVIDENCE (RWE) IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) USING THE ONCOSCOPE REAL-TIME AI-ASSISTED SYSTEMATIC LITERATURE REVIEW (REAL-SLR)
Author(s)
Andrew Briggs, DPhil1, Anna Forsythe, MBA, MSc, PharmD2, Saro Sarkisian, MD, MHA3, Mihaela Musat, PhD2.
1London School of Hygiene & Tropical Medicine, London, United Kingdom, 2Oncoscope, Miami, FL, USA, 3Frederick Health, Frederick, MD, USA.
1London School of Hygiene & Tropical Medicine, London, United Kingdom, 2Oncoscope, Miami, FL, USA, 3Frederick Health, Frederick, MD, USA.
OBJECTIVES: The optimal choice of a specific therapy in first-line (1L) and relapsed/refractory (R/R) CLL remains uncertain as randomized-controlled trials (RCTs) and anchored indirect comparisons do not cover all relevant treatment options. Evolving evidence requirements under EU-JCA increasingly require timely comparative effectiveness evidence. We propose a living RWE-informed NMA framework using Oncoscope REAL-SLR database to integrate RCT and comparative RWE to address evidence gaps in CLL.
METHODS: A living NMA framework was developed using the PRISMA-compliant Oncoscope REAL-SLR Database. RCTs and comparative RWE studies reporting adjusted relative effect on overall and progression-free survival (OS/PFS) are identified within 1L and R/R CLL populations. Relevant effect modifiers identified through REAL-SLR are documented in a living catalogue. After assembling of RCT-only network, comparative RWE data is evaluated for bridging any of the identified gaps. RWE integration uses bias-adjusted informative prior or three-level hierarchical/bias-adjustment.
RESULTS: The living NMA supports inclusion of new RCTs and/or comparative RWE studies as they are identified in the daily-updated REAL-SLR. As of June 15th 2026, REAL-SLR database included 81 RCTs and 72 comparative RWE studies. In 1L and R/R CLL, respectively, 32 studies (31 RCTs) and 15 studies (13 RCTs) informed PFS analyses, while 21 studies (10 RCTs) and 12 studies (8 RCTs) informed OS analyses. The treatment-naïve PFS network was the most complete; comparative RWE could bridge evidence gaps between acalabrutinib and ibrutinib. For OS, RWE data could potentially connect venetoclax+obinutuzumab, ibrutinib, acalabrutinib, and zanubrutinib. In previously treated population, RWE data could provide additional OS comparison between venetoclax-monotherapy and venetoclax+rituximab/obinutuzumab-combinations.
CONCLUSIONS: The Oncoscope REAL-SLR Database enables a living NMA framework that incorporates emerging trial and real-world evidence to address evidence gaps in CLL This approach provides a decision-relevant assessment of comparative effectiveness and a complete mapping of the multi-PICO evidence for JCA in rapidly evolving oncology landscapes.
METHODS: A living NMA framework was developed using the PRISMA-compliant Oncoscope REAL-SLR Database. RCTs and comparative RWE studies reporting adjusted relative effect on overall and progression-free survival (OS/PFS) are identified within 1L and R/R CLL populations. Relevant effect modifiers identified through REAL-SLR are documented in a living catalogue. After assembling of RCT-only network, comparative RWE data is evaluated for bridging any of the identified gaps. RWE integration uses bias-adjusted informative prior or three-level hierarchical/bias-adjustment.
RESULTS: The living NMA supports inclusion of new RCTs and/or comparative RWE studies as they are identified in the daily-updated REAL-SLR. As of June 15th 2026, REAL-SLR database included 81 RCTs and 72 comparative RWE studies. In 1L and R/R CLL, respectively, 32 studies (31 RCTs) and 15 studies (13 RCTs) informed PFS analyses, while 21 studies (10 RCTs) and 12 studies (8 RCTs) informed OS analyses. The treatment-naïve PFS network was the most complete; comparative RWE could bridge evidence gaps between acalabrutinib and ibrutinib. For OS, RWE data could potentially connect venetoclax+obinutuzumab, ibrutinib, acalabrutinib, and zanubrutinib. In previously treated population, RWE data could provide additional OS comparison between venetoclax-monotherapy and venetoclax+rituximab/obinutuzumab-combinations.
CONCLUSIONS: The Oncoscope REAL-SLR Database enables a living NMA framework that incorporates emerging trial and real-world evidence to address evidence gaps in CLL This approach provides a decision-relevant assessment of comparative effectiveness and a complete mapping of the multi-PICO evidence for JCA in rapidly evolving oncology landscapes.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
P25
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology