摘要:

AbstractThirteen methods for computing binomial confidence intervals are compared based on their coverage properties, widths and errors relative to exact limits. The use of the standard textbook method,x/n± 1.96√[(x/n) (1 −x/n)/n], or its continuity corrected version, is strongly discouraged. A commonly cited rule of thumb stating that alternatives to exact methods may be used when the estimated proportion p̂ is such thatnp̂andn(1 − p̂) both exceed 5 does not ensure adequate accuracy. Score limits are easily calculated from closed from solutions to quadratic equations and can be used at all times. Based on coverage functions, the continuity corrected score method is recommended over exact methods. Its conservative nature should be kept in mind, as should the wider fluctuation of actual coverage that accompanies omission of the continuity c

ISSN:0277-6715    

DOI:10.1002/sim.4780120902

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe propose a conditional analysis for outcome data on numbers of recurrent symptoms arising in a two‐treatment, multiple‐period crossover trial. Conditioning on subject‐specific totals removes any dependence on mean subject‐specific symptom rates and permits the use of standard software to perform regression analysis to examine treatment, period, carryover and interaction effects. The addition of offsets to the regression equations allows the incorporation of data from subjects who do not complete all period in the trial. We apply the proposed method to data from a crossover trial and discuss its advantages and disadv

ISSN:0277-6715    

DOI:10.1002/sim.4780120903

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractIn human immunodeficiency virus clinical trials, the CD4‐lymphocyte count has been regarded as a promising surrogate endpoint for clinical efficacy measures such as time to opportunistic infection and survival time. In the present paper, we test this hypothesis according to a criterion proposed by Prentice. This criterion requires the surrogate variable to capture the entire effect of treatment on the clinical endpoint, and it is satisfied if the hazard rate of the clinical endpoint is not affected by treatment among patients with the same preceding history of the surrogate variable. We analyse data from two completed zidovudine trials using the Cox regression model with the CD4‐lymphocyte count as a time‐varying covariate. The results indicate that the CD4‐lymphocyte count captures part of the relationship between zidovudine and time to a first critical event but does not fulfil the Prentice cr

ISSN:0277-6715    

DOI:10.1002/sim.4780120904

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe acquired immunodeficiency syndrome (AIDS) results from infection with the human immunodeficiency virus (HIV). The time of infection is generally unknown since transmission usually occurs during the course of repeated sexual contacts or needle sharing. Brookmeyer and Gail describe the biases that may arise in survival analyses using the recruitment time rather than the unknown infection time as the origin in prevalent cohorts of HIV‐infected individuals. We apply a non‐parametric hazard estimator, introduced by Nielsen, that assumes the hazard of an AIDS diagnosis depends upon the unknown time of infection solely through the value of possibly multidimensional markers of HIV‐disease progression such as CD4+T lymphocyte cell counts. Essentially, we estimate the hazard for a specific marker valueyby dividing the number of occurrences among subjects with marker measurements in a neighbourhood ofyby the total risk time in that neighbourhood. We present this estimator, which relies upon kernel estimator techniques to produce a smooth estimate, within a counting process framework. We apply this method to marker data from the San Francisco Men's Health

ISSN:0277-6715    

DOI:10.1002/sim.4780120905

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractRetrospective studies of time from initiation of risk (for example, transfusion of HIV‐infected blood) to the occurrence of an endpoint of interest are useful in epidemiology. One example is studies of time to pregnancy, which have evaluated exposures that may affect human fertility. One can reconstruct the non‐contracepting interval required for each woman's most recent pregnancy and then treat the data as if the couples had been studied prospectively. As we illustrate, however, failure‐time models can be dangerously misleading when there have been trends over calendar time in exposures under study. We propose anad hocmethod for evaluating possible effects on fertility despite this bias, by making use of external data on trends in the exposure over time. This approach applies a prospective model and generates an empiricalp‐value, based on comparing the data‐based estimated exposure coefficient with its null distribution estimated by simulation. A second method maximizes a conditional likelihood, and we show that this is equivalent to logistically modelling the relative odds for the subject's exposure as related to the reported time she required to achieve

ISSN:0277-6715    

DOI:10.1002/sim.4780120906

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe discuss a generalization of the logistic response function of the formPr(y= 1|x) = {1 + exp( − θ − β'x)}−α, where α>0. This function coincides with the usual logistic response when the shape parameter α is equal to one. We describe the use of this model for analysing cancer rates in mice for low‐dose exposure to a known carcinogen. When estimating the low‐dose responses, the errors associated with extrapolation are reduced whena prioriknowledge about the rates among unexposed individuals is incorporated into the fitt

ISSN:0277-6715    

DOI:10.1002/sim.4780120907

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractRandom time‐period effects are unexplained increases or decreases in the observed value for all individuals measured at a particular time point in a longitudinal study. They can be caused by learning effects, changes in equipment, personnel and overall subject co‐operation. We investigate the consequences of time‐period effects in random coefficient regression models, where interest is in the average rate of change (slope) of a continuous outcome. In a study with a single group of subjects, they can lead to conditionally biased estimates of the mean slope and its variance (conditional on the time‐period effects). Calculations suggest that the increase in sample size required to maintain a specified precision of the mean slope estimate over repeated studies may be substantial. In a study with a concurrent control group, however, time‐period effects do not distort the expectation, estimated variance or the distribution of the difference between the mean slopes. With missing data, in addition to time‐period effects, an unbaised estimate of a single mean slope remains problematic, but one can use standard maximum likelihood techniques to obtain consistent estimators of the difference in mean slopes and its variance. This suggests the importance of a concurrent control group when potential time‐period effects a

ISSN:0277-6715    

DOI:10.1002/sim.4780120908

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0277-6715    

DOI:10.1002/sim.4780120901

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY