Importance of assessing and adjusting for cross-study heterogeneity in network meta-analysis: a case study of psoriasis

Abstract

Aim: The importance of adjusting for cross-study heterogeneity when conducting network meta-analyses (NMAs) was demonstrated using a case study of biologic therapies for moderate-to-severe plaque psoriasis. Methods: Bayesian NMAs were conducted for Psoriasis Area and Severity Index 90 response. Several covariates were considered to account for cross-trial differences: baseline risk (i.e., placebo response), prior biologic use, body weight, psoriasis duration, age, race and baseline Psoriasis Area and Severity Index score. Model fit was evaluated. Results: The baseline risk-adjusted NMA, which adjusts for multiple observed and unobserved effect modifiers, was associated with the best model fit. Lack of adjustment for cross-trial differences led to different clinical interpretations of findings. Conclusion: Failure to adjust for cross-trial differences in NMA can have important implications for clinical interpretations when studying the comparative efficacy of healthcare interventions.

Análise de custo por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe para tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro

“…Uma limitação desse estudo é que os dados de razão de risco utilizados para calcular o desfecho foram obtidos em metanálise em rede que considera dados de PASI 90 do período de indução, que vão no máximo até a semana 16, e o presente estudo considerou esses valores como aproximação para o desfecho na semana 52 (Cameron et al, 2018). Por se tratar de uma doença crônica, a persistência é um fator importante, porém não foi possível ser melhor explorada por essa metodologia.…”

“…O desfecho clínico avaliado foi a taxa de resposta PASI 90. Devido à ausência de um estudo head-to-head que compare esses tratamentos, utilizaram-se dados de razão de risco de metanálise em rede para comparação indireta com guselcumabe (Tabela 1), cujo dado foi obtido no estudo VOYAGE 1, referente ao desfecho de PASI 90 em 48 semanas, o que corresponde a uma taxa de resposta de 0,76 (Cameron et al, 2018;Blauvelt et al, 2017).…”

Combining threshold analysis and GRADE to assess sensitivity to bias in antidepressant treatment recommendations adjusted for depression severity

“…Covariate adjustment is important because antidepressant treatment effects as well as their relative rankings may differ in dependence on covariate values. 6 As a motivating example, the recent NMA by Cipriani et al 7 was used, which provided treatment recommendations on the use of 21 antidepressants in major depressive disorder (MDD). The treatment rankings provided by Cipriani et al 7 suggested amitriptyline (odds ratio [OR] 2.13, 95% credible interval [CrI] 1.89-2.41) as the most efficacious and reboxetine (OR 1.37, 95%.…”

“…Here, we aimed to show an application of the combined approach based on threshold analysis and GRADE, with an extension to covariate‐adjusted treatment recommendations. Covariate adjustment is important because antidepressant treatment effects as well as their relative rankings may differ in dependence on covariate values . As a motivating example, the recent NMA by Cipriani et al was used, which provided treatment recommendations on the use of 21 antidepressants in major depressive disorder (MDD).…”

The importance of considering differences in study and patient characteristics before undertaking indirect treatment comparisons: a case study of siponimod for secondary progressive multiple sclerosis

“…However, before undertaking ITCs, it is essential to assess the degree of heterogeneity among the studies regarding patient characteristics and study design to determine the suitability of synthesizing the results in a unified analysis [3][4][5][6] . ITCs can often be used to inform decision-making in situations where headto-head clinical trials do not exist; however, decision-makers need to be aware of the potential limitations that can arise if ITCs are conducted that do not adequately adjust for crosstrial heterogeneity 7 .…”