Relative effectiveness of sunitinib versus everolimus in advanced pancreatic neuroendocrine tumors: an updated matching-adjusted indirect comparison

Ishak, K. Jack; Rael, M; Hicks, Meagen; Mittal, Sangeeta; Eatock, Martin; Valle, Juan W.

doi:10.2217/cer-2018-0020

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…CDP outcomes were assessed by estimated hazard ratios (HRs) using digitized Kaplan-Meier curves and the Guyot algorithm to generate pseudo-IPD data from aggregate trials (Guyot et al, 2012;Ishak et al, 2018). Cox proportional hazards (PHs) were used to obtain HRs by: 2 Appending pseudo-IPD to individual weighted IPD trials, as if they were a single trial (pseudo-IPD are assigned a weight of 1, which is equivalent to "no weight") 3 Running the Cox PH model, using specified weights and step 2 data, between the treatments of interest (an HR is obtained for each IPD trial vs aggregate-level) 4 Performing a meta-analysis to obtain a final pooled HR of OZM 1 mg vs TERI 14 mg for the endpoint of interest (CDP at 3 months) using HRs from the step above…”

Section: Methodsmentioning

confidence: 99%

Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis

Cohan

Tencer

Arndorfer³

et al. 2021

Multiple Sclerosis and Related Disorders

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Background: A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS. Methods: A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. Results: After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI. Conclusion:In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

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Section: Methodsmentioning

confidence: 99%

Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis

Cohan

Tencer

Arndorfer³

et al. 2021

Multiple Sclerosis and Related Disorders

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“…CDP outcomes were assessed using hazard ratios (HRs) and RRs. The first approach was to estimate HRs using digitized Kaplan–Meier curves and the Guyot algorithm to generate pseudo-IPD data from APD trials [ 54 , 55 ]. Cox proportional hazards (PHs) were used to obtain HRs using the following four steps: Digitizing Kaplan–Meier curves for APD trials to generate pseudo-IPD via the Guyot algorithm [ 55 , 56 ].…”

Section: Methodsmentioning

confidence: 99%

Comparative Efficacy and Safety of Ozanimod and Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis Using Matching-Adjusted Indirect Comparison

Cohan

Kumar

Arndorfer³

et al. 2021

CNS Drugs

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Background Patients with multiple sclerosis (MS) experience relapses and sustained disability progression. Since 2004, the number of disease-modifying therapies (DMTs) for MS has grown substantially. As a result, patients, healthcare providers, and insurers are increasingly interested in comparative efficacy and safety evaluations to distinguish between treatment options, but head-to-head studies between DMTs are limited. Objective The aim of the current study was to compare efficacy and safety outcomes with the DMTs ozanimod and dimethyl fumarate (DMF) using a matching-adjusted indirect comparison (MAIC) to adjust for cross-trial differences in study design and population. Methods A systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod compared with DMF. Individual patient-level data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate-level patient data (APD) for DMF were obtained from CONFIRM and DEFINE. A MAIC is used to weight IPD to APD based on important baseline patient characteristics considered to be effect modifiers or prognostic factors in order to balance the covariate distribution to establish more homogenous trial populations. Once trial populations are determined to be sufficiently homogenous, outcomes of interest are estimated and used to generate treatment effects between the weighted IPD and APD. We used MAIC methodology to compare efficacy and safety outcomes of interest between ozanimod 1.0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. Results After matching patient data, baseline patient characteristics were balanced between patients receiving ozanimod and those receiving DMF. Compared with DMF, ozanimod demonstrated significantly improved CDP at 3 months (hazard ratio 0.67; 95% confidence interval [CI] 0.53–0.86), ARR (rate ratio [RR] 0.80; 95% CI 0.67–0.97), proportion of patients relapsed (odds ratio [OR] 0.66; 95% CI 0.52–0.83), overall AEs (OR 0.11; 95% CI 0.08–0.16), SAEs (OR 0.27; 95% CI 0.19–0.39), and discontinuations (OR 0.11; 95% CI 0.07–0.17). CDP at 6 months did not differ significantly between the two agents (RR 0.89; 95% CI 0.62–1.26). Conclusions After adjustment of baseline patient characteristics, the MAIC demonstrated that the efficacy and safety of ozanimod 1.0 mg OD was superior to that of DMF 240 mg BID. Although a MAIC is less likely to produce biased estimates than a naïve or a standard indirect treatment comparison via a common comparator, limitations include potential confounding due to unobserved and thus unaccounted for baseline differences.

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“…Previous discussion of and studies on the properties of MAIC have focused on anchored analyses of linear-scale outcomes [3][4][5][6]. The properties of unanchored MAIC in the context of time-to-event analysis have not been investigated so far yet the literature is gradually picking up the approach without appreciating the unique profiles of this estimator [11][12][13]. This represents a major methodological gap that needs to be filled.…”

Section: Introductionmentioning

confidence: 99%

Performance of unanchored matching-adjusted indirect comparison (MAIC) for the evidence synthesis of single-arm trials with time-to-event outcomes

Jiang

2020

BMC Med Res Methodol

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Background The objectives of the present study were to evaluate the performance of a time-to-event data reconstruction method, to assess the bias and efficiency of unanchored matching-adjusted indirect comparison (MAIC) methods for the analysis of time-to-event outcomes, and to propose an approach to adjust the bias of unanchored MAIC when omitted confounders across trials may exist. Methods To evaluate the methods using a Monte Carlo approach, a thousand repetitions of simulated data sets were generated for two single-arm trials. In each repetition, researchers were assumed to have access to individual-level patient data (IPD) for one of the trials and the published Kaplan-Meier curve of another. First, we compared the raw data and the reconstructed IPD using Cox regressions to determine the performance of the data reconstruction method. Then, we evaluated alternative unanchored MAIC strategies with varying completeness of covariates for matching in terms of bias, efficiency, and confidence interval coverage. Finally, we proposed a bias factor-adjusted approach to gauge the true effects when unanchored MAIC estimates might be biased due to omitted variables. Results Reconstructed data sufficiently represented raw data in the sense that the difference between the raw and reconstructed data was not statistically significant over the one thousand repetitions. Also, the bias of unanchored MAIC estimates ranged from minimal to substantial as the set of covariates became less complete. More, the confidence interval estimates of unanchored MAIC were suboptimal even using the complete set of covariates. Finally, the bias factor-adjusted method we proposed substantially reduced omitted variable bias. Conclusions Unanchored MAIC should be used to analyze time-to-event outcomes with caution. The bias factor may be used to gauge the true treatment effect.

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Relative effectiveness of sunitinib versus everolimus in advanced pancreatic neuroendocrine tumors: an updated matching-adjusted indirect comparison

Abstract: Findings indicate comparable PFS and OS with sunitinib and everolimus.

Cited by 5 publications

References 16 publications

Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis

Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis

Comparative Efficacy and Safety of Ozanimod and Dimethyl Fumarate for Relapsing-Remitting Multiple Sclerosis Using Matching-Adjusted Indirect Comparison

Performance of unanchored matching-adjusted indirect comparison (MAIC) for the evidence synthesis of single-arm trials with time-to-event outcomes

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