A Systematic Literature Review to Assess the Variability in Conducting and Reporting of Matching-Adjusted Indirect Comparisons in Chronic Lymphocytic Leukemia: Findings and Implications for EU HTA

OBJECTIVES: The objective of this study was to examine the variability in how Matching-Adjusted Indirect Comparisons (MAICs) are conducted in Chronic Lymphocytic Leukemia (CLL) through a systematic review of published MAICs, focusing on differences in methodology and reporting practices.

METHODS: A systematic literature review (SLR) was conducted using PubMed and Embase databases to identify published MAICs in CLL from the past 5 years (2019-2024), including those in peer-reviewed journals and conference abstracts. If an updated analysis was available, the older one was not considered. The review focused on treatment-naive and relapsed/refractory (RR) CLL populations. Data were extracted on the process of identifying prognostic variables and treatment effect modifiers, list of adjusted variables, effective sample size (ESS), outcomes analysed (efficacy, safety, or both), and the use of sensitivity analyses.

RESULTS: The search identified eight unique studies, with four studies each in the treatment-naive and RR populations. The ESS ranged from 35% to 86%. Five MAICs evaluated both efficacy and safety, while three focused solely on efficacy outcomes. Two studies used exploratory Cox regression analysis on trial data for selecting matching variables, four relied on published literature and expert clinician opinion, and the remaining two did not report their methodology. Sensitivity analyses were conducted in five of the MAICs.

CONCLUSIONS: The findings demonstrate substantial variability among published MAICs in CLL with respect to adherence to guidelines on analysis methodology and reporting. This inconsistency underscores the need for more standardized practices, particularly with the upcoming EU Health Technology Assessment (HTA) regulation, which will apply to oncology products from January 2025. Given the prevalence of single-arm trials in oncology, standardized MAIC practices will be crucial for ensuring robust and reliable comparative effectiveness research. Similar assessments should be conducted in other indications to evaluate consistency and the need for standardization.