scholarly journals Effect Estimates in Randomized Trials and Observational Studies: Comparing Apples With Apples

2019 ◽  
Vol 188 (8) ◽  
pp. 1569-1577 ◽  
Author(s):  
Sara Lodi ◽  
Andrew Phillips ◽  
Jens Lundgren ◽  
Roger Logan ◽  
Shweta Sharma ◽  
...  
Keyword(s):  
Data Analysis ◽  
Antiretroviral Therapy ◽  
Observational Studies ◽  
Randomized Trials ◽  
Causal Effect ◽  
Treatment Strategies ◽  
Sensitivity Analyses ◽  
Eligibility Criteria ◽  
Study Protocols ◽  
The Impact

Abstract Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

Incidence of neurotoxicity and ototoxicity with cisplatin vs. non-cisplatin regimens: A meta-analysis with subgroup analyses based on renal eligibility criteria.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15555-e15555
Author(s):  
Brandon Kyle Bellows ◽  
Arati Dahal ◽  
Matt D. Galsky ◽  
Guru Sonpavde ◽  
Neeraj Agarwal
Keyword(s):  
Observational Studies ◽  
Literature Search ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Phase 1 ◽  
Exclusion Criteria ◽  
Eligibility Criteria ◽  
Subgroup Analyses ◽  
Grade 3 ◽  
The Impact

e15555 Background: Using glomerular filtration rate (GFR) to screen patients for trial eligibility may reduce the risk of cisplatin (CIS) associated nephrotoxicity compared to serum creatinine (SCr). The impact of using GFR or SCr on incidence of neurotoxicity and ototoxicity remains unknown. This meta-analysis compared incidence of neurotoxicity and ototoxicity among trials of solid tumors treated with CIS reporting nephrotoxicity when renal function was assessed using SCr or GFR. Methods: A PubMed literature search identified randomized trials comparing CIS to non-CIS containing chemotherapy regimens. Studies were included if performed from 1990-2010, used SCr or GFR as eligibility criteria, and reported incidence of WHO or NCI grade ≥3 nephrotoxic events. Separate analyses were performed on studies reporting grade ≥3 neurotoxic or ototoxic events. For neurotoxicity, studies comparing CIS to other neurotoxic drugs were excluded. Review articles, observational studies, phase 1 studies, non-randomized trials, studies without a comparator group, or studies not reported in English were excluded. Relative risk (RR) associated with CIS vs. non-CIS regimens was calculated and subgroup analyses were performed for studies using SCr, GFR, and either SCr or GFR for screening. Results: The literature search identified 2359 studies with 18 studies meeting all inclusion and exclusion criteria for neurotoxicity (N=3441 patients) and 9 for ototoxicity (N=2947). The RR for developing neurotoxicity was 1.27 (p=0.50) and ototoxicity was 2.32 (p=0.10) for CIS vs. non-CIS regimens. For neurotoxicity, the RR when SCr was used as eligibility criteria was 2.31 (p=0.11), 0.71 (p=0.54) when GFR was used, and 1.01 (p=0.99) when either was used. For ototoxicity, the RR for SCr was 2.33 (p=0.21) and 3.47 (p=0.20) for either. Studies using GFR reported zero ototoxic events. Conclusions: The risk of neurotoxicity and ototoxicity did not significantly change when SCr or GFR was used to screen patients. However, these analyses were performed on a subgroup of studies reporting nephrotoxicity and further research on all studies of neurotoxicity and ototoxicity is warranted.

Gastrostomy Tubes Placed in Children With Neurologic Impairment: Associated Morbidity and Mortality

2021 ◽  
pp. 088307382110001
Author(s):  
Jody L. Lin ◽  
Joseph Rigdon ◽  
Keith Van Haren ◽  
MyMy Buu ◽  
Olga Saynina ◽  
...  
Keyword(s):  
Severe Pneumonia ◽  
Sensitivity Analyses ◽  
Tube Placement ◽  
Composite Outcome ◽  
Eligibility Criteria ◽  
Risk Of Death ◽  
Cox Proportional Hazard ◽  
Neurologic Impairment ◽  
Increased Risk ◽  
The Impact

Background: Gastrostomy tube (G-tube) placement for children with neurologic impairment with dysphagia has been suggested for pneumonia prevention. However, prior studies demonstrated an association between G-tube placement and increased risk of pneumonia. We evaluate the association between timing of G-tube placement and death or severe pneumonia in children with neurologic impairment. Methods: We included all children enrolled in California Children’s Services between July 1, 2009, and June 30, 2014, with neurologic impairment and 1 pneumonia hospitalization. Prior to analysis, children with new G-tubes and those without were 1:2 propensity score matched on sociodemographics, medical complexity, and severity of index hospitalization. We used a time-varying Cox proportional hazard model for subsequent death or composite outcome of death or severe pneumonia to compare those with new G-tubes vs those without, adjusting for covariates described above. Results: A total of 2490 children met eligibility criteria, of whom 219 (9%) died and 789 (32%) had severe pneumonia. Compared to children without G-tubes, children with new G-tubes had decreased risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.39-0.55) but increased risk of the composite outcome (HR 1.21, CI 1.14-1.27). Sensitivity analyses using varied time criteria for definitions of G-tube and outcome found that more recent G-tube placement had greater associated risk reduction for death but increased risk of severe pneumonia. Conclusion: Recent G-tube placement is associated with reduced risk of death but increased risk of severe pneumonia. Decisions to place G-tubes for pulmonary indications in children with neurologic impairment should weigh the impact of severe pneumonia on quality of life.

scholarly journals Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

2021 ◽  
Vol 17 (6) ◽  
pp. e1009686
Author(s):  
Taina T. Immonen ◽  
Christine M. Fennessey ◽  
Leslie Lipkey ◽  
Abigail Thorpe ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Rhesus Macaques ◽  
Treatment Strategies ◽  
Viral Reservoir ◽  
Virus Population ◽  
Analytical Treatment ◽  
Treatment Interruptions ◽  
The Impact ◽  
Hiv 1

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.

Endogenous democracy: causal evidence from the potato productivity shock in the old world

2020 ◽  
pp. 1-8
Author(s):  
Joan Barceló ◽  
Guillermo Rosas
Keyword(s):  
Economic Development ◽  
Causal Effect ◽  
Transition To Democracy ◽  
Sensitivity Analyses ◽  
Old World ◽  
Omitted Variable Bias ◽  
Productivity Shock ◽  
Variable Bias ◽  
The Impact ◽  
New Evidence

Abstract Despite a high cross-country correlation between development and democracy, it is difficult to gauge the impact of economic development on the probability that autocracies will transition to democracy because of endogeneity, especially due to reverse causation and omitted variable bias. Hence, whether development causes democracy remains a contested issue. We exploit exogeneity in the regional variation of potato cultivation along with the timing of the introduction of potatoes to the Old World (i.e., a potato productivity shock) to identify a causal effect of urbanization, a proxy for economic development, on democratization. Our results, which hold under sensitivity analyses that question the validity of the exclusion restriction, present new evidence of the existence of a causal effect of economic development on democracy.

scholarly journals Estimating the Impact and Cost of the WHO 2010 Recommendations for Antiretroviral Therapy

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
John Stover ◽  
Lori Bollinger ◽  
Carlos Avila
Keyword(s):  
Antiretroviral Therapy ◽  
Cd4 Count ◽  
Eligibility Criterion ◽  
Eligibility Criteria ◽  
Art Programs ◽  
Middle Income ◽  
Middle Income Countries ◽  
Country Level ◽  
Potential Impact ◽  
The Impact

In July 2010, WHO published new recommendations on providing antiretroviral therapy to adults and adolescents, including starting ART earlier, usually at a CD4 count of 350 or lower, specific regimens for first- and second-line therapies, and other recommendations. This paper estimates the potential impact and cost of the revised guidelines by first, calculating the number of people that would be in need of antiretroviral therapy (ART) with different eligibility criteria, and second, calculating the costs associated with the potential impact. Results indicate that switching the eligibility criterion from CD4 count <200 to <350 increases the need for ART in low- and middle-income countries (country-level) by 50% (range 34% to 70%). The costs of ART programs only to increase coverage to 80% by 2015 would be 44% more (range 29% to 63%) when switching the eligibility criterion to CD4 count <350. When testing and outreach costs are included, total costs increase by 62%, from US$26.3 billion under the previous eligibility criterion of treating those with CD4 <200 to US$42.5 billion using the revised eligibility criterion of treating those with CD4 <350.

scholarly journals PD-L1 Test-Based Strategy With Nivolumab as the Second-Line Treatment in Advanced NSCLC： A Cost-Effectiveness Analysis in China

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiao Liu ◽  
Xia Luo ◽  
Zhen Zhou ◽  
Liubao Peng ◽  
Lidan Yi ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Treatment Strategies ◽  
Cost Effective ◽  
Price Reduction ◽  
Chinese Patients ◽  
Sensitivity Analyses ◽  
Line Treatment ◽  
Second Line ◽  
Life Years ◽  
The Impact

ObjectiveOur previous economic assessment found that nivolumab was not cost-effective for Chinese patients with advanced non-small cell lung cancer (NSCLC) and without EGFR mutations or ALK translocations, when compared with the standard second-line drug docetaxel. However, a greater survival benefit with nivolumab was observed for patients with 1% or greater tumor programmed death ligand 1 (PD-L1) expression. In view of this, we designed the present analysis to explore whether it is cost-effective to use the PD-L1 test to guide second-line nivolumab treatment in China.Material and MethodsA Markov model was established to project the lifetime costs and quality-adjusted life-years (QALYs) of three second-line treatment strategies: nivolumab and docetaxel (strategies without a PD-L1 test) and PD-L1 test-based strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of our results. Additional price reduction and willingness-to-pay (WTP) threshold scenario analyses were performed to explore the impact of economic and health policies with Chinese characteristics on our results.ResultsThe PD-L1 test-based strategy costs approximately CNY 194,607 (USD 28,210) or more and yielded an additional 0.27 QALYs compared to the docetaxel strategy without a PD-L1 test, equating an incremental cost-effectiveness ratio (ICER) of CNY 731,089 (USD 105,978)/QALY. Deterministic sensitivity analyses showed that the price of nivolumab was the strongest source of variation in the ICERs. Probability sensitivity analysis showed that the probability for the PD-L1 test-based strategy being cost-effective increases with the increase of WTP thresholds.ConclusionFrom the perspective of the Chinese healthcare system, using a PD-L1 test to guide second-line nivolumab treatment was not cost-effective. The National Healthcare Security Administration negotiation on the price reduction of nivolumab was found to be the most effective action to improve its cost-effectiveness in China.

scholarly journals Evaluating Causal Relationship Between Metabolites and Six Cardiovascular Diseases Based on GWAS Summary Statistics

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahao Qiao ◽  
Meng Zhang ◽  
Ting Wang ◽  
Shuiping Huang ◽  
Ping Zeng
Keyword(s):  
Cardiovascular Diseases ◽  
Causal Relationship ◽  
Metabolic Pathways ◽  
Causal Effect ◽  
Treatment Strategies ◽  
Sensitivity Analyses ◽  
Biological Processes ◽  
Summary Statistics ◽  
False Discovery ◽  
Pathological Mechanism

Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality worldwide. The pathological mechanism and underlying biological processes of these diseases with metabolites remain unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of metabolites on these diseases by making full use of the latest GWAS summary statistics for 486 metabolites and six major CVDs. Extensive sensitivity analyses were implemented to validate our MR results. We also conducted linkage disequilibrium score regression (LDSC) and colocalization analysis to investigate whether MR findings were driven by genetic similarity or hybridization between LD and disease-associated gene loci. We identified a total of 310 suggestive associations across all metabolites and CVDs, and finally obtained four significant associations, including bradykinin, des-arg(9) (odds ratio [OR] = 1.160, 95% confidence intervals [CIs]: 1.080–1.246, false discovery rate [FDR] = 0.022) on ischemic stroke, N-acetylglycine (OR = 0.946, 95%CIs: 0.920–0.973, FDR = 0.023), X-09026 (OR = 0.845, 95%CIs: 0.779–0.916, FDR = 0.021) and X-14473 (OR = 0.938, 95%CIs = 0.907–0.971, FDR = 0.040) on hypertension. Sensitivity analyses showed that these causal associations were robust, the LDSC and colocalization analyses demonstrated that the identified associations were unlikely confused by LD. Moreover, we identified 15 important metabolic pathways might be involved in the pathogenesis of CVDs. Overall, our work identifies several metabolites that have a causal relationship with CVDs, and improves our understanding of the pathogenesis and treatment strategies for these diseases.

scholarly journals Meta-Analysis of Standard Temozolomide versus Extended Adjuvant Temozolomide following concurrent Radiochemotherapy in newly-diagnosed Glioblastoma (MASTER-G)

2021 ◽  
Author(s):  
Tejpal Gupta ◽  
◽  
Riddhijyoti Talukdar ◽  
Sadhana Kannan ◽  
Archya Dasgupta ◽  
...  
Keyword(s):  
Observational Studies ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Newly Diagnosed ◽  
Individual Study ◽  
Eligibility Criteria ◽  
Concurrent Radiochemotherapy ◽  
Adjuvant Temozolomide ◽  
Newly Diagnosed Glioblastoma ◽  
Review Question

Review question / Objective: To assess the safety and efficacy of extended adjuvant temozolomide compared to standard adjuvant temozolomide after concurrent radiochemotherapy in patients with newly-diagnosed glioblastoma. Condition being studied: Newly-diagnosed glioblastoma. Eligibility criteria: Prospective clinical trials randomly assigning patients to extended (>6-cycles) adjuvant TMZ (experimental arm) or standard (6-cycles) adjuvant TMZ will be included. Randomization in an individual study may have been done upfront before concurrent phase (RT/TMZ), after completion of concurrent RT/TMZ and before starting adjuvant phase, or after completion of standard adjuvant TMZ (6-cycles). Emulated RCTs, quasi-randomized trials, propensity matched analyses, non-randomized comparative studies, or observational studies will not be considered in this review.

Methodological issues in the design and analysis of cluster randomized trials

2021 ◽  
pp. 113-128
Author(s):  
Kathy J. Baisley ◽  
Richard J. Hayes ◽  
Lawrence H. Moulton
Keyword(s):  
Gold Standard ◽  
Randomized Trials ◽  
Controlled Trials ◽  
Cluster Randomized Trials ◽  
Methodological Issues ◽  
Eligibility Criteria ◽  
Experimental Conditions ◽  
Cluster Randomized ◽  
And Control ◽  
The Impact

Randomized controlled trials are the accepted gold standard for evaluating the effects of interventions to improve health. In the majority of such trials, individuals are randomly allocated to the experimental conditions under study, for example, to treatment and control arms. However, in some situations it is more appropriate to randomly allocate groups of individuals to the treatment arms. These groups are referred to as clusters, and trials of this kind are known as cluster randomized trials (CRTs). Examples of clusters include schools, villages, workplaces, or health facilities, but there are many other possible choices. In some CRTs, all individuals within the selected clusters are automatically included. In others, there may be additional eligibility criteria. Similarly, the impact of the intervention may be measured in all individuals in the cluster, or in a random subsample. This chapter aims to discuss methodological issues that arise in the design and analysis of CRTs

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