Abstract
BackgroundThis study aimed at applying the restricted mean survival time difference (rmstD) as an absolute outcome measure in a network meta-analysis and comparing the results with those obtained using hazard ratios (HR) from the individual patient data (IPD) network meta-analysis (NMA) on the role of chemotherapy for nasopharyngeal carcinoma (NPC) recently published by the MAC-NPC collaborative group (Meta-Analysis of Chemotherapy [CT] in NPC).Patients and methodsTwenty trials (5144 patients) comparing radiotherapy (RT) with or without CT in non-metastatic NPC were included. Treatments were grouped in seven categories: RT alone (RT), induction CT followed by RT (IC-RT), RT followed by adjuvant CT (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival and locoregional control. The rmstD was estimated at t* = 10 years in each trial. Random-effect frequentist NMA models were applied. P score was used to rank treatments. Heterogeneity and inconsistency were evaluated.ResultsThe three treatments that had the highest effect on OS with rmstD were CRT-AC, IC-CRT, and CRT (respective P scores of 92%, 72%, and 64%) compared to CRT-AC, CRT, and IC-CRT when using HR (respective P scores of 96%, 71%, and 63%). Of the 32 HR and rmstD analyzed, 5 had a different interpretation, 3 with a direction change (different direction of treatment effect) and 2 with a change in significance (same direction but a change in statistical significance). Results for secondary endpoints were overall in agreement.ConclusionThe use of either HR or rmstD impacts the results of NMA. Given the sensitivity of HR to non-proportional hazards, this finding could have implications in terms of meta-analysis methodology.
Highlights
Network meta-analysis (NMA), known as mixed treatment comparisons, is a statistical method that deals with conditions where multiple treatments have been investigated that have not all been compared pairwise [1]
The three treatments that had the highest effect on overall survival (OS) with restricted mean survival time difference (rmstD) were CRT-adjuvant chemotherapy (AC), induction chemotherapy (IC)-CRT, and CRT compared to CRT followed by AC (CRT-AC), CRT, and IC followed by CRT (IC-CRT) when using hazard ratios (HR)
There were seven different treatments: radiotherapy (RT) alone, which was used as the reference category; induction chemotherapy (IC) followed by RT (IC-RT); RT followed by adjuvant chemotherapy (AC) (RT-AC); IC followed by RT followed by AC (IC-RT followed by adjuvant CT (RT-AC)); concomitant chemoradiotherapy (CRT); IC followed by CRT (IC-CRT); and CRT followed by AC (CRT-AC)
Summary
Network meta-analysis (NMA), known as mixed treatment comparisons, is a statistical method that deals with conditions where multiple treatments have been investigated that have not all been compared pairwise [1]. To pairwise meta-analysis, NMA uses logarithms (log) of hazard ratios (HR) as input data and outcome measure for survival analysis. Restricted mean survival time (RMST) is an alternative outcome measure that is increasingly used [3,4,5]. The difference of RMST is used (rmstD); it can be expressed as the number of life years gained with the treatment. This study aimed at applying the restricted mean survival time difference (rmstD) as an absolute outcome measure in a network meta-analysis and comparing the results with those obtained using hazard ratios (HR) from the individual patient data (IPD) network meta-analysis (NMA) on the role of chemotherapy for nasopharyngeal carcinoma (NPC) recently published by the MAC-NPC collaborative group (Meta-Analysis of Chemotherapy [CT] in NPC)
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