Combining several ordinal measures in clinical studies

In medical research, it is rare that a single variable is sufficient to represent all relevant aspects of epidemiological risk, genomic activity, adverse events, or clinical response. Since biological systems tend to be neither linear, nor hierarchical in nature, the assumptions of traditional multivariate statistical methods based on the linear model can often not be justified on theoretical grounds. Establishing concept validity through empirical validation is not only problematic, but also time consuming. This paper proposes the use of u-statistics for scoring multivariate ordinal data and a family of simple non-parametric tests for analysis. The scoring method is demonstrated to be applicable to scoring clinical response profiles in the treatment of psoriasis and then to identifying genomic pathways that best correlate with these profiles.

[1]  H. B. Mann,et al.  On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other , 1947 .

[2]  D. Schoenfeld,et al.  Combining mortality and longitudinal measures in clinical trials. , 1999, Statistics in medicine.

[3]  E. Gehan A GENERALIZED WILCOXON TEST FOR COMPARING ARBITRARILY SINGLY-CENSORED SAMPLES. , 1965, Biometrika.

[4]  K M Wittkowski,et al.  A structured visual language for a knowledge-based front-end to statistical analysis systems in biomedical research. , 1991, Computer methods and programs in biomedicine.

[5]  B. Davis,et al.  Analysis of a clinical trial involving a combined mortality and adherence dependent interval censored endpoint. , 1992, Statistics in medicine.

[6]  Dianne M Finkelstein,et al.  Analysis of Failure Time Data with Dependent Interval Censoring , 2002, Biometrics.

[7]  E. L. Lehmann,et al.  Consistency and Unbiasedness of Certain Nonparametric Tests , 1951 .

[8]  W. Ewens,et al.  Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). , 1993, American journal of human genetics.

[9]  E. Gehan,et al.  A generalized two-sample Wilcoxon test for doubly censored data. , 1965, Biometrika.

[10]  E. Susser,et al.  Reporting sexual risk behavior for HIV: a practical risk index and a method for improving risk indices. , 1998, American journal of public health.

[11]  James G. Krueger,et al.  Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis , 1995, Nature Genetics.

[12]  Knut M. Wittkowski,et al.  A Statistically Valid Alternative to the TDT , 2003, Human Heredity.

[13]  M. Daly,et al.  PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes , 2003, Nature Genetics.

[14]  J. Krueger The immunologic basis for the treatment of psoriasis with new biologic agents. , 2002, Journal of the American Academy of Dermatology.

[15]  F. Wilcoxon Individual Comparisons by Ranking Methods , 1945 .

[16]  A. Gottlieb,et al.  Psoriasis as a model for T-cell-mediated disease: immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD11a antibody. , 2002, Archives of dermatology.

[17]  W. Hoeffding A Class of Statistics with Asymptotically Normal Distribution , 1948 .

[18]  Kerby Shedden,et al.  Dimension Reduction for Multivariate Response Data , 2003 .

[19]  J. Krueger,et al.  Treatment of inflammatory dermatoses with novel biologic agents: a primer. , 2002, Advances in dermatology.

[20]  A. Dorner,et al.  Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions. , 1999, The Journal of clinical investigation.

[21]  P. Sen,et al.  Nonparametric methods in multivariate analysis , 1974 .

[22]  M. Schemper A nonparametric k‐sample test for data defined by intervals , 1983 .

[23]  Q. Mcnemar Note on the sampling error of the difference between correlated proportions or percentages , 1947, Psychometrika.

[24]  W. Kruskal,et al.  Use of Ranks in One-Criterion Variance Analysis , 1952 .

[25]  Knut M. Wittkowski,et al.  Friedman-Type Statistics and Consistent Multiple Comparisons for Unbalanced Designs with Missing Data , 1988 .

[26]  J. Kalbfleisch,et al.  Marginal likelihoods based on Cox's regression and life model , 1973 .

[27]  K. Wittkowski,et al.  Inflammatory Role of Two Venom Components of Yellow Jackets (Vespula vulgaris): A Mast Cell Degranulating Peptide Mastoparan and Phospholipase A1 , 2003, International Archives of Allergy and Immunology.

[28]  C. W. Coakley,et al.  Versions of the Sign Test in the Presence of Ties , 1996 .

[29]  E. Susser,et al.  The protective effect of condoms and nonoxynol-9 against HIV infection. , 1998, American Journal of Public Health.

[30]  Design and analysis of clinical trials with a bivariate failure time endpoint, with application to AIDS Clinical Trials Group Study A5142. , 2003, Controlled clinical trials.

[31]  L. Cronbach,et al.  Construct validity in psychological tests. , 1955, Psychological bulletin.

[32]  K. Wittkowski An Extension to Wittkowski , 1992 .

[33]  M. Friedman The Use of Ranks to Avoid the Assumption of Normality Implicit in the Analysis of Variance , 1937 .