An assessment of the methodological quality of published network meta-analyses: a systematic review

Objective To assess the methodological quality of published network meta-analysis. Design Systematic review. Methods We searched the medical literature for network meta-analyses of pharmaceuticals. We assessed general study characteristics, study transparency and reproducibility, methodological approach, and reporting of findings. We compared studies published in journals with lower impact factors with those published in journals with higher impact factors, studies published prior to January 1st, 2013 with those published after that date, and studies supported financially by industry with those supported by non-profit institutions or that received no support. Results The systematic literature search identified 854 citations. Three hundred and eighteen studies met our inclusion criteria. The number of network meta-analyses has grown rapidly, with 48% of studies published since January 2013. The majority of network meta-analyses were supported by a non-profit institution or received no support (68%). We found considerable inconsistencies among reviewed studies. Eighty percent reported search terms, 61% a network diagram, 65% sufficient data to replicate the analysis, and 90% the characteristics of included trials. Seventy percent performed a risk of bias assessment of included trials, 40% an assessment of model fit, and 56% a sensitivity analysis. Among studies with a closed loop, 69% examined the consistency of direct and indirect evidence. Sixty-four percent of studies presented the full matrix of head-to-head treatment comparisons. For Bayesian studies, 41% reported the probability that each treatment was best, 31% reported treatment ranking, and 16% included the model code or referenced publicly-available code. Network meta-analyses published in higher impact factors journals and those that did not receive industry support performed better across the assessment criteria. We found few differences between older and newer studies. Conclusions There is substantial variation in the network meta-analysis literature. Consensus among guidelines is needed improve the methodological quality, transparency, and consistency of study conduct and reporting

Healthcare Utilization and Costs associated with Sickle-cell disease in the United States: A Retrospective Claims Analysis

Thesis (Master's)--University of Washington, 2019Introduction: Sickle cell disease (SCD) is a group of hereditary hematological disorders that are associated with high rate of medical resource utilization and medical costs. In the past few decades, improvement in medical care has contributed to increased survival in individuals with SCD resulting in a growing aging population which will consequently place a huge economic burden on health care resources in upcoming years. Past studies in SCD are either outdated, or focused on individual U.S. states, or focused on specific utilization categories, or had small sample size, or focused primarily on pediatric populations. An updated estimation of healthcare utilization and costs associated with sickle cell disease remedying the aforementioned shortcomings would be important to guide medical resource allocation and would be useful for various payers to anticipate and better plan for the needs of their patients along with appraising value of upcoming novel treatment options. The objective of this study was to measure the economic and healthcare resource burden associated with SCD in the United States. Methods: A retrospective cross-sectional study using matched cohorts of SCD cases and population controls was conducted using IBM® MarketScan® Commercial Claims and Encounters database. Eligible patients of all ages within both SCD and control cohorts were included if they had at least 24 months of continuous enrollment within the patient identification period from 1 January 2012 to 31 December 2017. Patients were identified as having SCD if they had at least 3 paid SCD-related claims in a given year. Control patients were obtained from the general population and were required to have no SCD diagnosis or claims during the patient identification period and were matched with SCD cases on age, sex, type of benefit plan, geographic location (state) of residence of the enrollee, and calendar year of eligibility. All-cause health care resource utilization and costs were measured during the 24-months continuous enrollment period for SCD cases and controls. Associations of SCD with cost and utilization were evaluated after adjustment of matching covariates and Charlson comorbidity index through generalized estimating equations using gamma and negative binomial distribution, respectively. Statistical analyses were conducted using SAS version 9.3 (SAS Institute, Cary, NC), STATA SE version 14.2 (StataCorp, College Station, TX) and R version 3.4.3. Results: A total of 7,446 patients with SCD and an equal number of matched population controls were identified. Nearly, half (44.7%) of the sample comprised of pediatric and adolescent patients aged 0-19. Majority of the patients were female (57.1%), from the southern region of the United States (52.7%), and covered under a Preferred Provider Organization (PPO) health plan (56.7%). SCD patients had significantly more health care resource utilization and incurred higher medical costs than controls across all service categories. After adjusting for age, sex, type of benefit plan, geographic location (state) of the enrollee, calendar year of eligibility, and Charlson Comorbidity Index, SCD patients on average had 83.20 (95%CI: 79.84–86.55), 1.18 (95%CI: 1.14–1.22), and 9.87 (95%CI: 9.08–10.67) greater outpatient visits, inpatient hospitalizations, and prescription drug dispensed than matched controls, respectively. Similarly, after adjusting for the aforementioned set of covariates, we found that SCD patients, on average had $40,657 (95$37,994 - $43,321) higher total medical costs than matched controls. Conclusion: We used real-world administrative claims data to measure the burden of SCD in a commercially insured population and found that SCD is associated with high health care resource utilization along with significant direct medical costs. Increased life expectancy among SCD patients in recent decades along with advent of new expensive treatment options like gene therapy will consequently add to the economic burden of SCD

Effects of Second-Generation Antidepressants on Cognitive Functions: A Systematic Review and Meta-Analysis

Objectives: Second-generation antidepressants are currently the first-line of treatment for depression and are widely used. The aim of this study was to determine the effects on cognition by second-generation antidepressants through a systematic review and meta-analysis of recent scientific literature. Methods: Electronic search in Medline, PubMed, PsycINFO, CINAHL, and Embase for English-language abstracts from 1980 through May 2014, supplemented with a manual search from reference lists of relevant review articles was carried out to identify eligible studies. Studies were included if they met the following selection criteria: Population: adults (age≥18) with diagnosis of depression; Intervention: second-generation antidepressants (SGAD) marketed in the United States based on the American Hospital Formulary Service (AHFS) 2014 drug classification; Comparator: placebo or second-generation antidepressants; Outcomes: attention, processing speed, executive function and memory; and Study Design: Randomized Controlled Trials (RCTs) and observational studies. Data management and screening procedures were carried out by using RefWorks (ProQuest) and Microsoft Excel workbook. Data extraction and synthesis was conducted by the primary author using a data extraction form specially designed for this study. Studies were sorted according to type of neurocognitive test used and a minimum of 3 studies per test per study design type was required in order to conduct further systematic review and meta-analysis. The methodological quality of the included studies was assessed by Cochrane risk of bias tool. A random effects model was used to estimate the pooled effects of antidepressant use on cognitive functioning. Heterogeneity was assessed by I2 testing. Egger's regression test and Trim and Fill method were used to examine for the presence of potential publication bias along with analysis of funnel plots. All analyses were performed using Comprehensive Meta-Analysis, v2.2 (Biostat, Englewood, NJ) Results: A total of 4,274 abstracts were screened; 342 were retrieved for a full-text review. Of the reviewed full text articles, 17 (13 RCTs and 4 Observational) studies involving a total of 2,437 depressed patients) met the inclusion criteria. Studies were of optimum quality as assessed by the Risk of bias tool. Out of the 43 unique neurocognitive test; Mini-Mental State Exam (MMSE), Stroop Color Word test (SCWT), Choice Reaction Time Task (CRT) and Digit Symbol Substitution Test (DSST) were the most common tests used across the studies which fulfilled the selection criteria (minimum of 3 studies per test per study design type) for further systematic review and meta-analysis. Six studies were found eligible for inclusion into the meta-analysis for MMSE and the results were not significant with (SMD=0.126; 95%CI -0.046, 0.298; p > 0.05). There was no heterogeneity (I2=0%, p= 0.975) and publication bias (Egger’s regression intercept (B0= 0.29359; 95%CI -1.04627, 1.63344; p > 0.05). Insufficient and inconsistent reporting of results involving SCWT, CRT and DSST prevented meta-analysis of study findings; hence, a systematic review was performed. Four studies were found eligible for SCWT out of which two studies with positive findings which had a combined sample size of almost 13 times that of the non-significant study, which suggests improvement in executive function with second-generation antidepressants compared to placebo. The systematic review conducted on four studies which had used CRT suggests positive results with one study with sample size 30 times that of the non-significant study showing improvements in attention and processing speed in depressed patients treated with low dose second-generation antidepressants. The systematic review conducted on three studies which had used Digit Symbol Substitution Test suggested mixed evidence with two studies showing significant improvement in attention and processing speed with SMs compared to placebo while one study suggesting otherwise with SNRIs. Conclusions: Meta-analysis of studies using MMSE suggests that SGADs do not affect global cognition but might affect other specific domains. Systematic reviews on studies involving SCWT, CRT and DSST suggest variable evidence regarding the effects of second-generation antidepressants on specific domains of cognition. However, there were indications of possible improvements in executive function, attention and processing speed with SGADs compared with placebo. Further studies involving reliable and widely used neurocognitive tests reporting necessary statistical detail for computing effect sizes are needed to estimate and quantify the effects of second-generation antidepressants on cognition.Pharmacological and Pharmaceutical Sciences, Department o

Correction: An Assessment of the Methodological Quality of Published Network Meta-Analyses: A Systematic Review.

[This corrects the article DOI: 10.1371/journal.pone.0121715.]

Identification of network meta-analyses included in review.

<p>Identification of network meta-analyses included in review.</p

Assessment of network meta-analysis study characteristics.

<p>^† Regions in which submissions to HTA agencies generally require a NMA;</p><p>* 17 studies published in journals with no associated impact factor;</p><p>** 3 studies for which source of study support was unclear;</p><p>*** 77 studies reported both fixed and random effects models, 38 studies did not report models used;</p><p>**** Consistency only reported for studies with a closed loop</p><p>Assessment of network meta-analysis study characteristics.</p

Frequency of network meta-analyses (n = 210) by year, indication, and country.

<p>^† We limited our literature search to studies published in the medical literature. We did not include NMAs submitted to national health technology assessment agencies unless also published in the Ovid-MEDLINE database.</p><p>* ‘Other countries’ includes Greece, Ireland, Singapore, Australia, Cameroon, Denmark, Finland, Hong Kong, Korea, Norway, Poland, and Portugal.</p><p>Frequency of network meta-analyses (n = 210) by year, indication, and country.</p