•Hit-And-Run enables efficient sampling of weights with linear inequality constraints.•A generalized change-of-basis can extend the method to handling equality constraints.•A flawed seedpoint ...generating method should be replaced by a linear program.
In our previous work published in this journal, we showed how the Hit-And-Run (HAR) procedure enables efficient sampling of criteria weights from a space formed by restricting a simplex with arbitrary linear inequality constraints. In this short communication, we note that the method for generating a basis of the sampling space can be generalized to also handle arbitrary linear equality constraints. This enables the application of HAR to sampling spaces that do not coincide with the simplex, thereby allowing the combined use of imprecise and precise preference statements. In addition, it has come to our attention that one of the methods we proposed for generating a starting point for the Markov chain was flawed. To correct this, we provide an alternative method that is guaranteed to produce a starting point that lies within the interior of the sampling space.
► Hit-And-Run enables efficient uniform sampling from convex polytopes. ► Imprecise preference information in MCDA can be expressed as linear weight constraints. ► We show Hit-And-Run can be used to ...sample weights with arbitrary linear constraints. ► Computational tests show the sampler is fast enough for interactive decision analysis.
Models for Multiple Criteria Decision Analysis (MCDA) often separate per-criterion attractiveness evaluation from weighted aggregation of these evaluations across the different criteria. In simulation-based MCDA methods, such as Stochastic Multicriteria Acceptability Analysis, uncertainty in the weights is modeled through a uniform distribution on the feasible weight space defined by a set of linear constraints. Efficient sampling methods have been proposed for special cases, such as the unconstrained weight space or complete ordering of the weights. However, no efficient methods are available for other constraints such as imprecise trade-off ratios, and specialized sampling methods do not allow for flexibility in combining the different constraint types. In this paper, we explore how the Hit-And-Run sampler can be applied as a general approach for sampling from the convex weight space that results from an arbitrary combination of linear weight constraints. We present a technique for transforming the weight space to enable application of Hit-And-Run, and evaluate the sampler’s efficiency through computational tests. Our results show that the thinning factor required to obtain uniform samples can be expressed as a function of the number of criteria n as φ(n)=(n−1)3. We also find that the technique is reasonably fast with problem sizes encountered in practice and that autocorrelation is an appropriate convergence metric.
The purposes of this study were to investigate whether, in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), percutaneous coronary intervention (PCI) ...should be confined to the culprit or also nonculprit vessels and, when performing PCI for nonculprit vessels, whether it should take place during primary PCI or staged procedures.
A significant percentage of STEMI patients have MVD. However, the best PCI strategy for nonculprit vessel lesions is unknown.
Pairwise and network meta-analyses were performed on 3 PCI strategies for MVD in STEMI patients: 1) culprit vessel only PCI strategy (culprit PCI), defined as PCI confined to culprit vessel lesions only; 2) multivessel PCI strategy (MV-PCI), defined as PCI of culprit vessel as well as ≥1 nonculprit vessel lesions; and 3) staged PCI strategy (staged PCI), defined as PCI confined to culprit vessel, after which ≥1 nonculprit vessel lesions are treated during staged procedures. Prospective and retrospective studies were included when research subjects were patients with STEMI and MVD undergoing PCI. The primary endpoint was short-term mortality.
Four prospective and 14 retrospective studies involving 40,280 patients were included. Pairwise meta-analyses demonstrated that staged PCI was associated with lower short- and long-term mortality as compared with culprit PCI and MV-PCI and that MV-PCI was associated with highest mortality rates at both short- and long-term follow-up. In network analyses, staged PCI was also consistently associated with lower mortality.
This meta-analysis supports current guidelines discouraging performance of multivessel primary PCI for STEMI. When significant nonculprit vessel lesions are suitable for PCI, they should only be treated during staged procedures.
Abstract Objective To enable multicriteria benefit–risk (BR) assessment of any number of alternative treatments using all available evidence from a network of clinical trials. Study Design and ...Setting We design a general method for multicriteria decision aiding with criteria measurements from Mixed Treatment Comparison (MTC) analyses. To evaluate the method, we apply it to BR assessment of four second-generation antidepressants and placebo in the setting of a published peer-reviewed systematic review. Results The analysis without preference information shows that placebo is supported by a wide range of possible preferences. Preference information provided by a clinical expert showed that although treatment with antidepressants is warranted for severely depressed patients, for mildly depressed patients placebo is likely to be the best option. It is difficult to choose between the four antidepressants, and the results of the model indicate a high degree of uncertainty. Conclusions The designed method enables quantitative BR analysis of alternative treatments using all available evidence from a network of clinical trials. The preference-free analysis can be useful in presenting the results of an MTC considering multiple outcomes.
As evidence is inconsistent and based on either isolated Asian or Western studies, we conducted a network meta-analysis (NMA) to examine efficacy and safety of 5-FU (5-fluorouracil), capecitabine and ...S-1-based first-line treatment of advanced esophagogastric cancer in Asian and Western patients. Medline, EMBASE, CENTRAL and conferences ASCO and ESMO were searched up to January 2016 for randomized-controlled-trials comparing 5-FU, capecitabine or S-1-based regimens with equal chemotherapy backbones. Direct and indirect data for overall survival (OS) and progression-free-survival (PFS) were combined on the Hazard Ratio (HR)-scale using random-effects NMA and calculated as combined HRs and 95%credible intervals (95%CrI). Grade 1-2 and grade 3-4 adverse events were compared with pair-wise meta-analysis. Fifteen studies were identified including capecitabine (n = 945), 5-FU (n = 2,132) or S-1 (n = 1,636). No differences were found in respectively OS and PFS for capecitabine-based versus 5-FU-based regimens (HR = 0.89, 95%CrI = 0.76-1.04 and HR = 0.98, 95%CrI = 0.75-1.32), S-1-based versus 5-FU-based regimens (HR = 0.92, 95%CrI = 0.82-1.04 and HR = 0.88, 95%CrI = 0.70-1.11) and S-1-based versus capecitabine-based regimens (HR = 1.03, 95%CrI = 0.87-1.22 and HR = 0.89, 95%CrI = 0.65-1.20). Effects were similar in Asian and Western subgroups. Toxicity profiles were different but a lower frequency of relevant adverse events was observed with S-1 In conclusion, as efficacy was similar, choosing fluoropyrimidines should be based on their individual toxicity profiles.
ABSTRACT
Next‐generation sequencing in clinical diagnostics is providing valuable genomic variant data, which can be used to support healthcare decisions. In silico tools to predict pathogenicity are ...crucial to assess such variants and we have evaluated a new tool, Combined Annotation Dependent Depletion (CADD), and its classification of gene variants in Lynch syndrome by using a set of 2,210 DNA mismatch repair gene variants. These had already been classified by experts from InSiGHT's Variant Interpretation Committee. Overall, we found CADD scores do predict pathogenicity (Spearman's ρ = 0.595, P < 0.001). However, we discovered 31 major discrepancies between the InSiGHT classification and the CADD scores; these were explained in favor of the expert classification using population allele frequencies, cosegregation analyses, disease association studies, or a second‐tier test. Of 751 variants that could not be clinically classified by InSiGHT, CADD indicated that 47 variants were worth further study to confirm their putative pathogenicity. We demonstrate CADD is valuable in prioritizing variants in clinically relevant genes for further assessment by expert classification teams.
In silico estimation of pathogenicity is becoming a necessity to interpret the amount of variants produced by current high‐throughput DNA sequencing. Here we benchmark the promising new CADD method against a gold standard set of curated mismatch repair gene variants classified by the InSiGHT consortium and investigate any discrepancies we find.
A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and ...safety of first-line chemotherapy using Network meta-analysis (NMA).
Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin C and oxaliplatin Ox), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs).
The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx.
Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.
PDF
