Restricted mean survival time as outcome measure in advanced urothelial bladder cancer: analysis of 4 clinical studies

Immunotherapy ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 95-101
Author(s):  
Melania Rivano ◽  
Luca Cancanelli ◽  
Lorenzo Di Spazio ◽  
Marco Chiumente ◽  
Daniele Mengato ◽  
...  
Keyword(s):  
Survival Time ◽  
Standard Care ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Urothelial Bladder Cancer ◽  
Mean Survival Time ◽  
Restricted Mean Survival Time ◽  
Urothelial Bladder ◽  
Advanced Urothelial Carcinoma ◽  
Post Hoc

Background: The purpose of this study was to assess the effectiveness of immune checkpoint inhibitors (ICIs) in advanced urothelial carcinoma. Materials & methods: We selected seven cohorts of patients published in four clinical trials. The restricted mean survival time (RMST) was used to analyze survival curves, perform the comparisons and rank the treatments based on their effectiveness. The performance of RMST was compared with that of a network meta-analysis. Results: Three ICIs, vinflunine and best standard care, given as second line, were examined. ICIs significantly improved overall survival compared with best standard care. However, the survival gain was quite limited (up to 2.27 months). Post hoc pairwise comparisons were calculated. Conclusion: Our results summarized the efficacy of these treatments and confirmed the good methodological performance of RMST.

OP236 Evidence Synthesis Of Time-To-Event Outcomes In The Presence Of Non-Proportional Hazards

2021 ◽  
Vol 37 (S1) ◽  
pp. 8-8
Author(s):  
Suzanne Freeman ◽  
Nicola Cooper ◽  
Alex Sutton ◽  
Michael Crowther ◽  
James Carpenter ◽  
...  
Keyword(s):  
Survival Time ◽  
Simulation Study ◽  
Proportional Hazards ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Clinical Effectiveness ◽  
Time To Event ◽  
Mean Survival Time ◽  
Restricted Mean Survival Time

IntroductionSynthesis of clinical effectiveness is a well-established component of health technology assessment (HTA) combining data from multiple trials to obtain an overall pooled estimate of clinical effectiveness, which may inform an associated economic evaluation. Time-to-event outcomes are often synthesized using effect measures from Cox proportional hazards models assuming a constant hazard ratio over time. However, where treatment effects vary over time an assumption of proportional hazards is not always valid. Several methods have been proposed for synthesizing time-to-event outcomes in the presence of non-proportional hazards. However, guidance on choosing between these methods and the implications for HTA is lacking.MethodsWe applied five methods for estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption to a network of melanoma trials, reporting overall survival: restricted mean survival time, an accelerated failure time generalized gamma model, piecewise exponential, fractional polynomial and Royston-Parmar models. We conducted a simulation study to compare these five methods. Simulated individual patient data was generated from a mixture Weibull distribution assuming a treatment-time interaction. Each simulated meta-analysis consisted of five trials with varying numbers of patients and length of follow-up across trials. For each model fitted to each dataset, we calculated the restricted mean survival time at the end of observed follow-up and following extrapolation to a 20-year time horizon.ResultsAll models fitted the melanoma data reasonably well with some variation in the treatment rankings and differences in the survival curves. The simulation study demonstrated the potential for different conclusions from different modelling approaches.ConclusionsThe restricted mean survival time, generalized gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can all accommodate non-proportional hazards and differing lengths of trial follow-up within an evidence synthesis of time-to-event outcomes. Further work is needed in this area to extend the simulation study to the network meta-analysis setting and provide guidance on the key considerations for informing model choice for the purposes of HTA.

Effect of PARP Inhibitors as Maintenance Treatment on Restricted Mean Survival Time in Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic Review and Meta-analysis

2021 ◽  
pp. 106002802110134
Author(s):  
Masayuki Kaneko
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Alternative Measure ◽  
Brca Mutations ◽  
Mean Survival Time ◽  
Platinum Sensitive ◽  
Restricted Mean Survival Time ◽  
Efficacy Parameter

Background Earlier trials on the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors in platinum-sensitive relapsed ovarian cancer used the hazard ratio (HR) as an efficacy parameter. Objective The present meta-analysis was focused on improving the robustness and clinical interpretability of the efficacy evaluation of PARP inhibitors using the restricted mean survival time (RMST). Methods A search for relevant studies published up to July 31, 2020, was performed in electronic databases to identify eligible trials comparing PARP inhibitors with placebo. The difference in RMST was used as a PARP inhibitor efficacy parameter. Combined differences in RMST with 95% CIs across studies were calculated using a random-effects model. Results Four trials (6 articles) were assessed, including 1079 patients treated with PARP inhibitors and 598 with placebo. The combined RMST differences for up to 360 days (PARP inhibitors minus placebo: point estimate and 95% CI) among all patients and the patients of subgroups with BRCA mutations, homologous recombination-deficient (HRD) carcinoma, and BRCA wild-type carcinoma were 87 days (95% CI = 71, 102), 112 days (95% CI = 96, 129), 99 days (95% CI = 80, 119), and 69 days (95% CI = 47, 92), respectively. The combined RMST differences for up to 660 and 720 days were also larger among patients with BRCA mutations than among those with HRD carcinoma. Conclusion and Relevance Based on using the RMST difference as an alternative measure to the HR, this meta-analysis suggests that PARP inhibitors are the most effective for patients with BRCA mutations, followed by patients with HRD carcinoma.

Estimation on conditional restricted mean survival time with counting process

2020 ◽  
pp. 1-15
Author(s):  
Junshan Qiu ◽  
Dali Zhou ◽  
H.M. Jim Hung ◽  
John Lawrence ◽  
Steven Bai
Keyword(s):  
Survival Time ◽  
Counting Process ◽  
Mean Survival Time ◽  
Restricted Mean Survival Time
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