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Applications of the Wei-Lachin multivariate one-sided test for multiple outcomes on possibly different scales.

ABSTRACT: Many studies aim to assess whether a therapy has a beneficial effect on multiple outcomes simultaneously relative to a control. Often the joint null hypothesis of no difference for the set of outcomes is tested using separate tests with a correction for multiple tests, or using a multivariate T2-like MANOVA or global test. However, a more powerful test in this case is a multivariate one-sided or one-directional test directed at detecting a simultaneous beneficial treatment effect on each outcome, though not necessarily of the same magnitude. The Wei-Lachin test is a simple 1 df test obtained from a simple sum of the component statistics that was originally described in the context of a multivariate rank analysis. Under mild conditions this test provides a maximin efficient test of the null hypothesis of no difference between treatment groups for all outcomes versus the alternative hypothesis that the experimental treatment is better than control for some or all of the component outcomes, and not worse for any. Herein applications are described to a simultaneous test for multiple differences in means, proportions or life-times, and combinations thereof, all on potentially different scales. The evaluation of sample size and power for such analyses is also described. For a test of means of two outcomes with a common unit variance and correlation 0.5, the sample size needed to provide 90% power for two separate one-sided tests at the 0.025 level is 64% greater than that needed for the single Wei-Lachin multivariate one-directional test at the 0.05 level. Thus, a Wei-Lachin test with these operating characteristics is 39% more efficient than two separate tests. Likewise, compared to a T2-like omnibus test on 2 df, the Wei-Lachin test is 32% more efficient. An example is provided in which the Wei-Lachin test of multiple components has superior power to a test of a composite outcome.

SUBMITTER: Lachin JM

PROVIDER: S-EPMC4201485 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Applications of the Wei-Lachin multivariate one-sided test for multiple outcomes on possibly different scales.

Lachin John M JM

PloS one 20141017 10

Many studies aim to assess whether a therapy has a beneficial effect on multiple outcomes simultaneously relative to a control. Often the joint null hypothesis of no difference for the set of outcomes is tested using separate tests with a correction for multiple tests, or using a multivariate T2-like MANOVA or global test. However, a more powerful test in this case is a multivariate one-sided or one-directional test directed at detecting a simultaneous beneficial treatment effect on each outcome ...[more]

PMID: 25329662

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Project description:Background/aimsCardiovascular outcome trials, among others, aim to assess the beneficial effects of a treatment on multiple event-time outcomes, such as the time to a myocardial infarction and the time to a stroke. The traditional approach is to conduct a simple analysis of a composite outcome defined as the time to the first component event using a logrank test or the Cox Proportional Hazards regression model. This ignores information from other component events after the first. The composite outcome analysis also treats all initial outcome events as equally important, for example, non-fatal myocardial infarction is as important as cardiovascular death.MethodsHerein, we describe the application of the Wei-Lachin multivariate one-sided (or one-directional) test to the analysis of multiple event-time outcomes. The test is based on the unweighted mean of the treatment group coefficients from individual Cox proportional hazards models fit to the outcomes, where the covariance of the set of coefficients is obtained from a partitioning of the information sandwich estimate. A weighted test is also described, weighing the outcomes by a scoring of their clinical importance. These and other methods are compared with application to the Prevention of Events with Angiotensin-Converting Enzyme Inhibition cardiovascular outcome study.ResultsThe Wei-Lachin test provides an inference with strong control of the type 1 error probability on the difference between groups for the set of outcomes considered. However, it does not provide an inference on the individual components specifically with control of the overall type 1 error probability. By direct computation of relative efficiency and by simulation, we show that the power of the Wei-Lachin one-directional test can be greater than that of the traditional composite outcome analysis based on the time to the first observed component event.ConclusionThe Wei-Lachin multivariate one-directional test may be more powerful than the traditional analysis of a composite outcome defined as the time to the first component outcomes experienced by each subject.

Project description:BackgroundConsensus-orientated Delphi studies are increasingly used in various areas of medical research using a variety of different rating scales and criteria for reaching consensus. We explored the influence of using three different rating scales and different consensus criteria on the results for reaching consensus and assessed the test-retest reliability of these scales within a study aimed at identification of global treatment goals for total knee arthroplasty (TKA).MethodsWe conducted a two-stage study consisting of two surveys and consecutively included patients scheduled for TKA from five German hospitals. Patients were asked to rate 19 potential treatment goals on different rating scales (three-point, five-point, nine-point). Surveys were conducted within a 2 week period prior to TKA, order of questions (scales and treatment goals) was randomized.ResultsEighty patients (mean age 68?±?10?years; 70% females) completed both surveys. Different rating scales (three-point, five-point and nine-point rating scale) lead to different consensus despite moderate to high correlation between rating scales (r?=?0.65 to 0.74). Final consensus was highly influenced by the choice of rating scale with 14 (three-point), 6 (five-point), 15 (nine-point) out of 19 treatment goals reaching the pre-defined 75% consensus threshold. The number of goals reaching consensus also highly varied between rating scales for other consensus thresholds. Overall, concordance differed between the three-point (percent agreement [p]?=?88.5%, weighted kappa [k]?=?0.63), five-point (p?=?75.3%, k?=?0.47) and nine-point scale (p?=?67.8%, k?=?0.78).ConclusionThis study provides evidence that consensus depends on the rating scale and consensus threshold within one population. The test-retest reliability of the three rating scales investigated differs substantially between individual treatment goals. This variation in reliability can become a potential source of bias in consensus studies. In our setting aimed at capturing patients' treatment goals for TKA, the three-point scale proves to be the most reasonable choice, as its translation into the clinical context is the most straightforward among the scales. Researchers conducting Delphi studies should be aware that final consensus is substantially influenced by the choice of rating scale and consensus criteria.

Project description:The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.

Dataset Information

Applications of the Wei-Lachin multivariate one-sided test for multiple outcomes on possibly different scales.

Publications

Applications of the Wei-Lachin multivariate one-sided test for multiple outcomes on possibly different scales.

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