indirect comparison
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Richard T Maziarz ◽  
Jie Zhang ◽  
Hongbo Yang ◽  
Xinglei Chai ◽  
Chengbo Yuan ◽  

No head-to-head trials have compared the efficacy of tisagenlecleucel versus historical treatments for adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study indirectly compared the overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel, using data from the JULIET study (NCT02445248), versus historical treatments assessed in the CORAL study follow-up population. To assess treatment effects in the treated (full analysis set [FAS]) and enrolled (intent-to-treat [ITT]) study populations, the JULIET FAS vs. the CORAL follow-up FAS and JULIET ITT vs. CORAL follow-up ITT populations were separately compared. Propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW) was used to compare OS and ORR, adjusting for baseline confounders. The results indicated that tisagenlecleucel was associated with a lower hazard of death among the FAS (adjusted hazard ratio [95% CI], both FSW and SMRW: 0.44 [0.32, 0.59]) and ITT populations (FSW: 0.60 [0.44, 0.77], SMRW: 0.57 [0.44, 0.73]; all p<0.001). Median OS was 12.48 months (JULIET) vs. 4.34-4.40 months (CORAL) for the FAS, and 8.25 (JULIET) vs. 4.04-4.86 (CORAL) for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared to historical treatments among the FAS (adjusted response rate difference [95% CI], both FSW and SMRW: 36% [22%, 0.48%]; p<0.001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; p=0.043). This analysis supports that improved response and OS are achieved in r/r DLBCL patients treated with tisagenlecleucel when compared to those treated with alternative historical treatments.

Children ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 28
Roberto Walter Dal Negro ◽  
Massimiliano Povero

The useability of DPIs (dry powder inhalers) depends on several factors that are influenced by the patients’ subjectivity and objectivity. The short-form global usability score (S-GUS), a specific tool for the quick ranking and comparison in real life of an inhaler’s usability, was used to investigate six of the most prescribed DPIs (Breezhaler, Diskus, Ellipta, Nexthaler, Spiromax, and Turbohaler) in consecutive asthma patients aged <18 years. A Bayesian indirect comparison (IC) was carried out to merge all pairwise comparisons between the six DPIs. Thirty-three subjects participated: eighteen tested Breezhaler, Spiromax, Nexthaler, and Ellipta simultaneously, while fifteen tested Breezhaler, Spiromax, Diskus, and Turbohaler. The estimates of the S-GUS, by the IC model, allowed us to rank the DPIs by their degree of usability: Ellipta, Diskus, and Spiromax were classified as “good to pretty good” (S-GUS > 15), while Spiromax, Turbohaler, and Breezhaler were classified as “insufficient” (S-GUS < 15). The multidomain assessment is recommended in asthma adolescents in order to approximate the effective usability of different DPIs as best as possible. The S-GUS proves particularly suitable in current clinical practice because of the short time required for its use in adolescents.

2021 ◽  
Anna Ostropolets ◽  
George Hripcsak

Importance Randomized clinical trials and observational studies have demonstrated high overall effectiveness for the three US-authorized COVID-19 vaccines against symptomatic COVID-19 infection. Nevertheless, the challenges associated with the use of observational data can undermine the results of the studies. Objective To assess the feasibility of using observational data for vaccine effectiveness studies by examining granular weekly effectiveness. Design, Settings and Participants In this retrospective cohort study, we used Columbia University Medical Center data linked to State and City Immunization Registries to assess the weekly effectiveness of mRNA COVID-19 vaccines. We conducted manual chart review of cases in week one in both groups along with a set of sensitivity analyses for Pfizer- BioNTech, Moderna and Janssen vaccines. Main Outcomes and Measures We used propensity score matching with up to 54,987 covariates and fitted Cox proportional hazards models to estimate hazard ratios and constructed Kaplan-Meier plots for two main outcomes (COVID-19 infection and COVID-19-associated hospitalization). Results The study included 179,666 patients. We observed increasing effectiveness after the first dose of mRNA vaccines with week 6 effectiveness approximating 84% (95% CI 72-91%) for COVID-19 infection and 86% (95% CI 69-95) for COVID-19-associated hospitalization. When analyzing unexpectedly high effectiveness in week one, chart review revealed that vaccinated patients are less likely to seek care after vaccination and are more likely to be diagnosed with COVID-19 during the encounters for other conditions. Sensitivity analyses showed potential outcome misclassification for COVID-19 ICD10-CM diagnosis and the influence of excluding patients with prior COVID-19 infection and anchoring in the unexposed group. Overall vaccine effectiveness analysis in fully vaccinated patients matched the results of the randomized trials. Conclusions and Relevance Observational data can be used to ascertain vaccine effectiveness if potential biases are accounted for. The data need to be scrutinized to ensure that compared groups exhibit similar health seeking behavior and are equally likely to be captured in the data. Given the difference in temporal trends of vaccine exposure and baseline characteristics, indirect comparison of vaccines may produce biased results.

Metrologia ◽  
2021 ◽  
Vol 59 (1A) ◽  
pp. 06002
C Kessler ◽  
D Burns ◽  
B Downton ◽  
M McEwen ◽  
E Mainegra-Hing

Main text A new key comparison of the standards for air kerma of the National Research Council of Canada (NRC), Canada and the Bureau International des Poids et Mesures (BIPM) was carried out in the 60Co radiation beam of the BIPM in October 2020. The comparison result, based on the calibration coefficients for three transfer chambers and expressed as a ratio of the NRC and the BIPM standards for air kerma, is 1.0022 with a combined standard uncertainty of 2.2 parts in 103. The result agrees within the uncertainties with the indirect comparison carried out in 2009. The results are analysed and presented in terms of degrees of equivalence, suitable for entry in the BIPM key comparison database. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

2021 ◽  
Vol 37 (S1) ◽  
pp. 11-12
Véronique Raimond ◽  
Emmanuelle Kaltenbach ◽  
Christophe Adam ◽  
Sébastien Lazzarotto ◽  
Catherine Le Galès ◽  

IntroductionSince 2013, the coverage of innovative and expensive drugs by the French National Health Insurance considers cost-effectiveness and budget impact, as assessed by the National Authority for Health (HAS) on the basis of an evaluation submitted by the firm. First CAR-T cell therapies were subject to economic evaluation in 2019 in France. We aim at describing the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel and the challenges these evaluations raised.MethodsPrimary evaluations were submitted by the firms to be reviewed by HAS. The final analyses were submitted to the Committee of Economic Evaluation and Public Health (CEESP), composed of independent economists, clinicians and patients’ representatives. The CEESP issued Opinions related to i) the methodological quality of economic evidence and ii) the cost-effectiveness and budget impact of the drugs under review.ResultsThe estimated incremental cost-utility ratio (ICUR) of tisagenlecleucel were rejected, being based on insufficient clinical evidence to estimate and extrapolate the long-term progression and to compare tisagenlecleucel with alternatives. Thus, the CEESP concluded that tisagenlecleucel was not proved cost-effective. The estimated ICUR of axicabtagene ciloleucel at 114,509EUR/QALY vs. chemotherapies was associated with an acceptable level of evidence despite being based on a frail indirect comparison and limited data on quality of life. In a context where France has no official cost-effectiveness threshold, the CEESP considered axicabtagene ciloleucel ICUR to be “very high” and questioned the collective acceptability of the claimed price.The CEESP stressed that the main source of uncertainty surrounding the ICUR estimates of both drugs was related to the lack of hindsight on effectiveness, especially in terms of overall survival and safety.ConclusionsThe economic evaluation of CAR-T cell therapies highlights the sources of uncertainty underlying the decision and the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for the uncertainty, and effective collection of relevant post-marketing data.

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