1,720,962 research outputs found
Acoramidis in Transthyretin Amyloid Cardiomyopathy
No full textTo the Editor: In a phase 3 trial of acoramidis for transthyretin amyloid cardiomyopathy, Gillmore et al. (Jan. 11 issue)(1) used the Finkelstein-Schoenfeld test to assess the hierarchical composite primary outcome. They expressed the treatment effect as a win ratio, thereby following the initial presentation of the analysis of a prioritized outcome.(2) However, the generalized pairwise comparison method, to which the Finkelstein-Schoenfeld test and the win ratio belong, has evolved substantially since this first application.(3) To aid the interpretation of the results, it is now recommended that the proportions of wins and losses for each outcome are reported to understand the . .
From non-inferiority to superiority: the shift towards patient-centric outcomes
No full textThe recently published REC-CAGEFREEI trial 1 provides an interesting example of non-inferiority vs. superiority design of clinical trials. The trial failed to show non-inferiority (P = 0.65) of drug-coated balloon angioplasty (with the option of rescue stenting) to the intended deployment of drug-eluting stents on the primary composite endpoint of car-diovascular death, target vessel myocardial infarction, and target lesion revascularization. However, not the result, but the motivation and reporting on the trial draw our attention (Figure 1). Non-inferiority designs aim to show that a novel therapy is not worse than a standard of care by more than a pre-specified non-inferiority margin on an efficacy outcome. This margin represents an acceptable loss on efficacy, which is justified by a putative advantage of the novel therapy on patient outcomes other than efficacy, such as improved safety, better quality of life, more convenient administration, or lower cost. A non-inferiority design should thus be motivated by a clear advantage. In stent trials, for example, a short-term reduction i
Generalized pairwise comparisons of prioritized outcomes are a powerful and patient-centric analysis of multi-domain scores
No full textBackgroundGeneralized pairwise comparisons (GPC) can be used to assess the net benefit of new treatments for rare diseases. We show the potential of GPC through simulations based on data from a natural history study in mucopolysaccharidosis type IIIA (MPS IIIA).MethodsUsing data from a historical series of untreated children with MPS IIIA aged 2 to 9 years at the time of enrolment and followed for 2 years, we performed simulations to assess the operating characteristics of GPC to detect potential (simulated) treatment effects on a multi-domain symptom assessment. Two approaches were used for GPC: one in which the various domains were prioritized, the other with all domains weighted equally. The net benefit was used as a measure of treatment effect. We used increasing thresholds of clinical relevance to reflect the magnitude of the desired treatment effects, relative to the standard deviation of the measurements in each domain.ResultsGPC were shown to have adequate statistical power (80% or more), even with small sample sizes, to detect treatment effects considered to be clinically worthwhile on a symptom assessment covering five domains (expressive language, daily living skills, and gross-motor, sleep and pain). The prioritized approach generally led to higher power as compared with the non-prioritized approach.ConclusionsGPC of prioritized outcomes is a statistically powerful as well as a patient-centric approach for the analysis of multi-domain scores in MPS IIIA and could be applied to other heterogeneous rare diseases.Vaiva Deltuvaite-Thomas, Mickaël De Backer, Samuel Salvaggio and Marc Buyse are members of the BENEFIT research consortium, which was partially funded by the region of Wallonia (BioWin Consortium Agreement No 7979).
The authors gratefully acknowledge comments received from Dr. Julie Eisen‑ gart, of the Department of Pediatrics, University of Minnesota, Minneapolis, MN
On the use of extreme value tail modeling for generalized pairwise comparisons with censored outcomes
No full textIn randomized clinical trials, methods of pairwise comparisons such as the 'Net Benefit' or the 'win ratio' have recently gained much attention when interests lies in assessing the effect of a treatment as compared to a standard of care. Among other advantages, these methods are usually praised for delivering a treatment measure that can easily handle multiple outcomes of different nature, while keeping a meaningful interpretation for patients and clinicians. For time-to-event outcomes, a recent suggestion emerged in the literature for estimating these treatment measures by providing a natural handling of censored outcomes. However, this estimation procedure may lead to biased estimates when tails of survival functions cannot be reliably estimated using Kaplan-Meier estimators. The problem then extrapolates to the other outcomes incorporated in the pairwise comparison construction. In this work, we suggest to extend the procedure by the consideration of a hybrid survival function estimator that relies on an extreme value tail model through the Generalized Pareto distribution. We provide an estimator of treatment effect measures that notably improves on bias and remains easily apprehended for practical implementation. This is illustrated in an extensive simulation study as well as in an actual trial of a new cancer immunotherapy.This research was partially funded by the regions of Wallonia (BioWin Consortium Agreement No 7979
Generalized Pairwise Comparisons to Support Shared Decision-Making in the CODA Trial
No full textImportance Shared decision-making (SDM) can be made difficult by the multifaceted nature of outcome assessment. A rigorous method for analyzing results from multiple outcomes is called generalized pairwise comparisons (GPC), which could assist in SDM. Objective To examine whether GPC can be useful in SDM by using individual-patient data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants This comparative effectiveness study used data from participants in the multicenter US CODA trial (conducted between May 2016 and March 2020). All possible pairs of patients (one from each arm) were formed to analyze each of 7 outcomes of interest sequentially. Data were analyzed between February 2020 and early 2024. Exposures Three scenarios of priorities related to a different order of outcomes were considered. The first scenario came from a consensus exercise with patients that favored antibiotics, whereas the other 2 were arbitrarily chosen to illustrate the range of possible outcomes depending on prioritizations. Scenario 2 favored neither treatment, and scenario 3 favored appendectomy. Main Outcomes and Measures The primary outcome was the net treatment benefit (NTB), a formal measure of benefit-risk, which is the net probability that a randomly selected patient from the antibiotic-assigned arm would have a more favorable outcome than a randomly selected patient from the appendectomy-assigned arm. Results A total of 1552 patients were included in the CODA trial, with 776 (mean [SD] age, 38.3 [13.4] years; 286 [37%] female) in the antibiotic arm and 776 (mean [SD] age, 37.8 [13.7] years; 290 [37%] female) in the appendectomy arm. The NTB of antibiotic treatment was 12.8% (95% CI, 7.1% to 18.3%; P < .001) for the first scenario, 3.2% (95% CI -2.4% to 8.7%; P = .27) for the second, and -14.5% (95% CI. -20.2% to -8.8%; P < .001) for the third. These results respectively favored antibiotics, neither treatment, or appendectomy, thus illustrating that benefit-risk varies considerably according to individual priorities. Conclusions and Relevance This comparative effectiveness study of antibiotics and appendectomy illustrates that the GPC method is a flexible yet mathematically rigorous quantitative analysis of benefit-risk balance. This method provides a more exhaustive and nuanced quantitative assessment of the differences between 2 treatment modalities in terms of prioritized outcomes. Furthermore, GPC could support SDM by considering individual prioritizations of the multiple outcomes.This comparative effectiveness study used patient-level data from a randomized clinical trial comparing the outcomes of antibiotics vs appendectomy. Using generalized
pairwise comparison, the net treatment benefit significantly favored antibiotics, was neutral, or significantly favored appendectomy, depending on the patient’s order of priority.
This work was supported in part by the Government ofWallonia, Belgium (BioWin Consortium Agreement No. 7979). The CODA Trial was funded by a PCORI Award (No. 1409-240099)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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