Multiple Real-World Data Sources in a Bayesian Framework to Inform Long-Term Survival Estimates of Mosunetuzumab in Patients with Follicular Lymphoma.

INTRODUCTION: Patients with follicular lymphoma (FL) receiving third-line or later (3L +) therapy have long survival, which can make estimating long-term overall survival (OS) from trial data challenging. The objective of this study was to estimate long-term OS for mosunetuzumab from the GO29781 trial (NCT02500407) using multiple real-world databases (RWDs) in a Bayesian framework. METHODS: Seven RWD sources for patients with FL receiving 3L + therapy and the expansion cohort in the GO29781 trial for mosunetuzumab were used. Hazard trends from the RWD sources were analyzed, and disease-wide pointwise OS and its corresponding uncertainty were estimated using Bayesian random-effects meta-analysis from the RWD sources. Pointwise OS obtained was used as an informative prior in Bayesian survival extrapolations to data from patients receiving mosunetuzumab. Results after adjusting for background mortality were compared to equivalent frequentist extrapolations using trial data only. RESULTS: Hazard patterns from RWD sources supported a constant or linearly decreasing hazard. Mean pointwise OS for patients with FL receiving 3L + therapy was estimated at 0.52 (95% credible interval, 0.29-0.85) at 8 years. Bayesian extrapolations for mosunetuzumab produced median survival estimates of 11.6 (6.7-20.7) years to 17.0 (6.4-22.7) years depending on the distribution used, reducing uncertainty by 20% to 46% relative to the frequentist estimation. CONCLUSION: Multiple RWD sources can be synthesized to augment the credibility of data with short follow-up, long patient survival, and few events to effectively estimate long-term survival and reduce estimated uncertainty. This method can be applied to other indications with similar characteristics. CLINICAL TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT02500407, July 16, 2015.

Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis.

BACKGROUND: Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment. SUMMARY: We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizu-mab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39-1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41-1.14]; 94%), sorafenib (0.59 [95% CrI 0.39-0.87]; 99%), SIRT (0.51 [95% CrI 0.32-0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25-0.64]; 100%). KEY MESSAGES: Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.

Evaluación multicéntrica del nuevo sistema analítico BioSystems BA 400 ® y comparación de procedimientos de medida / Multicentre evaluation of the new analytical system BioSystems BA 400 ® and comparison of measurement procedures

Objetivo. El objetivo de este trabajo fué evaluar, mediante un estudio multicéntrico, la imprecisión y la veracidad de un elevado número de procedimientos de medida en el nuevo sistema analítico BioSystems BA 400(R). Material y método. El estudio de la imprecisión se llevó a cabo siguiendo recomendaciones establecidas y utilizando sueros control con 2 concentraciones distintas. El estudio de la veracidad se ha realizado mediante la comparación de los procedimientos de medida del nuevo sistema con los utilizados habitualmente en los centros evaluadores. Resultados. Los resultados obtenidos para la imprecisión interdiaria con el nuevo analizador han sido en general excelentes en relación a los errores máximos permitidos. Se han encontrado algunas diferencias no despreciables y estadísticamente significativas entre los distintos procedimientos de medida, que son debidas a diferencias en el mensurando en algunos casos (transaminasas, inmunoanálisis) y a diferencias en los calibradores en otros. Conclusiones. La evaluación ha demostrado las excelentes prestaciones de precisión y veracidad del sistema. El nuevo analizador proporciona resultados en muestras de pacientes que son equivalentes a los obtenidos con otros analizadores (Olympus AU5400 y AU2700, Roche Cobas C711 y Siemens ADVIA 2400, 1800 y BNII) (AU)

Background. The purpose of the study was a multicentre evaluation of the imprecision and of the trueness of a wide variety of measurement procedures with the new analytical system BioSystems BA 400(R). Methods. The imprecision study was performed following established recommendations and using control sera with two different concentrations. The trueness was studied by means of a comparison of the measurement procedures of the new analyser with those of routine use in the evaluating centres. Results. The results obtained for the between-day imprecision with the new analyser have been in general excellent in relation to the maximum allowed errors. Several differences that are not worthless and that are statistically significant have been found between the measurement procedures. The differences are due to measurand differences in some cases (transaminases, immunoanalysis), and to the calibration in other. Conclusion. The evaluation study has demonstrated the excellent performance of the system regarding precision and trueness. The results obtained for patient samples with the new analyzer are equivalent to those obtained with other analyzers (Olympus AU5400 y AU2700, Roche Cobas C711 y Siemens ADVIA 2400, 1800 y BNII) (AU)

Proposed criteria for sorting examined properties in clinical laboratory reports.

To date not much importance has been given to the sorting of examined properties ("tests") in clinical laboratory reports. The present article contains a proposal about sorting the examined properties of clinical laboratory reports, in order to facilitate their interpretation to the requesting physicians. This proposal is mainly based on clinical and patho-physiological criteria. A set of groups of properties has been established according to the main clinical indications of each property. Some of these properties have several clinical indications and, consequently, have been included in more than one group. Some of these groups have been associated to other groups, so that the properties conforming them will always appear consecutively, since they are patho-physiologically related. Finally, an association between each group with the different medical specialities or areas of knowledge has been made, according to the clinical indications of each property. The groups of properties proposed are in concordance with their main clinical indications and their patho-physiological relationship. This ordering system gives priority, first, to the alarm (critical) values and, second, to the medical speciality or knowledge area of the requesting physician. This proposal can help the requesting physician to see first of all the most relevant clinical laboratory information related to her/his patient.

Propuesta para mejorar la sensibilidad del algoritmo diagnóstico de evaluación de la función tiroidea / Proposal to improve the sensitivity of the diagnostic algorithm for thyroid function evaluation

La medida en suero de la concentración de tirotropina y tiroxina es la base para la evaluación bioquímica de la función tiroidea. Con frecuencia, el intervalo de referencia de la tirotropina sirve como cribado inicial para valorar la necesidad de añadir la medida de tiroxina. Este trabajo se ha realizado con el objetivo de mejorar la sensibilidad diagnóstica del cribado. Se seleccionaron todos los resultados de tirotropina y tiroxina solicitados de manera simultánea a pacientes de consultas externas: para la primera parte del estudio se usaron los del año 2008 (n=10.900) y para la segunda parte, los de pacientes del año 2009 sin seguimiento en el año previo (n=5.367). Se realizaron dos curvas ROC para delimitar el intervalo de decisión del algoritmo con una sensibilidad del 90% y se contabilizó el número de resultados falsos negativos obtenidos. Los intervalos de tirotropina obtenidos en el primer y segundo estudio fueron (2,11-3,50) mint.u./L y (2,04-3,41) mint.u/L respectivamente. En ambos estudios la sensibilidad aumentó aproximadamente de un 70% de media con el intervalo de referencia a un 90% con el intervalo del algoritmo. El número de falsos negativos se redujo de 75 a 30 en el primer caso, y de 37 a 13 en el segundo. La aplicación de un intervalo de tirotropina calculado para la evaluación de la función tiroidea, en pacientes ambulatorios con o sin seguimiento previo, supone un aumento en la sensibilidad diagnóstica, respecto al empleo del intervalo de referencia de tirotropina (AU)

The measurement of thyrotropin and thyroxine concentrations in serum is the basis of the biochemical evaluation of thyroid function. The reference interval of thyrotropin is frequently used as an initial screening to assess the need for thyroxine measurement. This study was carried out to obtain a different and more adjusted interval of thyrotropin, in order to improve the diagnostic sensitivity. All of the results of thyrotropin and thyroxine requested at the same time on outpatients were selected: for the first part of the study, those from year 2008 (n=10,900), and for the second part, those from 2009 with no follow-up in the previous year (n=5,367). Two ROC curves were used to define the algorithm decision interval with a sensitivity of 90% and the number of false negative results was calculated. The thyrotropin intervals obtained in the first and second studies were (2.11-3.50) mIU/L and (2.04-3.41) mIU/L, respectively. In both studies, the sensitivity increased approximately from an average of 70% to 90% of the confidence interval using the algorithm interval. The number of false negatives was reduced from 75 to 30 in the first case, and from 37 to 13 in the second case. The application of a calculated thyrotropin interval to assess thyroid function in outpatients with or without prior monitoring, leads to an increase of the diagnostic sensitivity with regard to the use of the thyrotropin reference interval (AU)