bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bootstrap investigation of the stability of a cox regression model
Authors: Altman Douglas G. , Andersen Per Kragh 
Published: April 2007

AbstractWe describe a bootstrap investigation of the stability of a Cox proportional hazards regression model resulting from the analysis of a clinical trial of azathioprine versus placebo in patients with primary biliary cirrhosis. We have considered stability to refer both to the choice of variables included in the model and, more importantly, to the predictive ability of the model. In stepwise Cox regression analyses of 100 bootstrap samples using 17 candidate variables, the most frequently selected variables were those selected in the original analysis, and no other important variable was identified. Thus there was no reason to doubt the model obtained in the original analysis. For each patient in the trial, bootstrap confidence intervals were constructed for the estimated probability of surviving two years. It is shown graphically that these intervals are markedly wider than those obtained from the original model.
On correcting for misclassification in twin studies and other matched‐pair studies
Authors: Greenland Sander 
Published: April 2007

AbstractIn twin studies (and other matched‐pair studies) of the effect of a K‐level risk factor on disease risk, one must estimate the proportion of pairs in each of K2 possible pair categories, of which K(K −1) categories represent discordant pairs. In particular, for a binary factor, one must estimate proportions within two discordant‐pair categories and the variances of functions of these estimates. This paper shows how to do so when misclassification is present and stable estimates of the classification rates are available. Unlike methods that estimate only the discordance ratio, one can use the methods presented here to improve estimates of epidemiologic effects.
Comparison of the information in two lung function experiments
Authors: Lim Lynette L‐Y , Whitehead John 
Published: April 2007

AbstractThe amount of ventilation relative to perfusion (the ventilation‐perfusion ratio) received by the lung is a useful indicator of the efficiency of lung function. Two alternative techniques for recovering the ventilation‐perfusion ratio are outlined. While both techniques rely on the use of inert gases, one is well established and the other is only in a developmental stage. This paper focuses on a comparison of the amount of statistical information provided by these two techniques about the ventilation‐perfusion ratio. The criterion applied here for measuring amount of information has roots in communication theory and uses ideas inherent to Bayesian inference.
Correcting reported aids incidence: A statistical approach
Authors: Heisterkamp S. H. , Jager J. C. , Ruitenberg E. J. , Van Druten J. A. M. , Downs A. M. 
Published: April 2007

AbstractThis study is motivated by the time lag between date of diagnosis of AIDS cases and date of reporting, which results in incomplete data about the epidemic. A maximum likelihood procedure has been developed to adjust the actual numbers of diagnosed AIDS cases for reporting delay. If a parametric function for describing past and future incidence is assumed, its parameters and the adjustment for reporting delay can be estimated simultaneously. Data from the WHO Collaborating Centre on AIDS, Paris, are used. Practical problems related to data collection are dealt with.
Efficiency gains from the addition of controls to matched sets in cohort studies
Authors: Raboud J. , Breslow N. E. 
Published: April 2007

AbstractWe evaluate relative efficiencies of added controls in matched cohort studies in terms of the asymptotic variance of the estimate of the log relative risk associated with a single binary exposure variable. We calculate expected contributions to the information based on the Cox proportional hazards model under the assumption that the failure times for exposed and unexposed individuals have independent exponential or Weibull distributions and that the censoring variable, when present, also has an exponential distribution or a Weibull distribution with a shape parameter common to that of the failure time distribution. With estimation of a relative risk of four or less, one gains little with an increase in the ratio of unexposed to exposed cohort members beyond five or so.
A comparison of maximum likelihood and Jewell's estimators of the odds ratio and relative risk in single 2 × 2 tables
Authors: Becker Stan 
Published: April 2007

AbstractThis paper compares the maximum likelihood estimators of the odds ratio and relative risk in 2 × 2 tables with less biased estimators recently proposed by Jewell for small samples. In addition to bias, location in the confidence interval, and relative likelihood are calculated for ranges of sample sizes, probabilities (of exposure or disease) and true values of the odds ratio and relative risk. Jewell's estimators perform poorly from the perspectives of confidence intervals and likelihood. Given these and other problems, continued use of the maximum likelihood estimators is recommended.
Validity of mortality analysis based on retrospective smoking information
Authors: Machlin Steven R. , Kleinman Joel C. , Madans Jennifer H. 
Published: April 2007

AbstractWe assess the validity of mortality analysis based on retrospective reporting of smoking habits by subjects and proxies after a time lag of approximately ten years. The analysis is based on 2855 subject respondents and 615 proxy respondents to the NHANES I Epidemiologic Followup Survey (NHEFS), a national followup study of persons examined in the National Health and Nutrition Examination Survey (NHANES I). Persons 45–77 years of age at baseline were selected for analysis. Using three categories of smoking at baseline (current, former, never), the retrospective classification (NHEFS) matched the NHANES I classification for 89 per cent of the subject respondents and 83 per cent of the proxy respondents. Agreement levels were higher for women (92 per cent of subjects and 89 per cent of proxies) than for men (85 and 80 per cent).We used Cox regression models to assess the use of retrospective smoking information in an analysis of the relationship between selected risk factors and mortality for persons 45–64 years of age. There were few substantive differences in results with use of NHEFS smoking data versus NHANES I smoking data. In particular, the effects of age, systolic blood pressure, education; and race on mortality were not sensitive to the source of the smoking data (NHANES I or NHEFS) or the form of the smoking variable (two‐, three‐, or six‐level categorization). The effects of body mass index on mortality were sensitive to the form of the smoking variable but results based on NHANES I and NHEFS were quite similar. These results suggest that smoking information obtained from proxy respondents is adequate for analyses of the risk of total mortality associated with smoking and other risk factors. Further assessment is needed to determine the adequacy of such data for analyses of mortality from specific causes that are sensitive to amount smoked or duration of smoking.
Testing for central mixtures of compartment model parameters
Authors: Zelterman Daniel 
Published: April 2007

AbstractI discuss alternatives to the one compartment model, ℰYt = α + β exp(−γt). Instead of comparing the one and two compartment models, I derive statistics for testing mixtures of the parameters (β, γ) in the one compartment model. I apply the proposed methods to the problem of hydrogen clearance in blood flow measurement and to vanadium depuration data.
The use of dual or multiple reports in epidemiologic studies
Authors: Marshall James R. 
Published: April 2007

AbstractWeak measurement of epidemiologic exposures is an impediment to appreciation of the effects of those exposures. This paper discusses two strategies to assess the true effects of weakly measured exposure. The first is to use external information about the extent of mismeasurement to adjust estimates of the effects of exposure. The second strategy is to use multiple measurement — to repeat the measurement in such a way that measurement errors are not repeated. The major disadvantage of the adjustment strategy is its sensitivity to incorrect specification of mismeasurement structure. The primary disadvantage of the multiple measurement strategy is its inefficiency. Unless epidemiologists are quite confident, about the extent and structure of measurement error in their data, they should rely primarily on multiple measurement, and secondarily on adjustment procedures.
Predicting the range of plasma carbamazepine concentrations in patients with epilepsy
Authors: Racine‐Poon A. , Dubois J. P. 
Published: April 2007

AbstractA statistical model is proposed for predicting the range of plasma carbamazepine concentrations after administration of a controlled‐release formulation at steady state. The model is based on previous clinical studies in patients with epilepsy. The predicted range may be used to monitor and adjust treatment in a patient.
The use of baselines in clinical trials of bronchodilators
Authors: Senn S. J. 
Published: April 2007

AbstractTwo important qualities of controlled clinical trials are that they reduce dependence on historical standards for evaluating therapy and separate the effect of treatment from the confounding influence of time. Whatever the theory of the clinical trial, however, time has not easily been banished from the analysis of medical experiments in practice, and many doctors still prefer to evaluate treatments by comparing now with then rather than treatment with control. This is especially so in trials of bronchodilators in the treatment of asthma where, it is shown, baselines are used in ways which can increase the variability of measurement and even bias the results.
The analysis of relapse clinical trials, with application to a comparison of two ulcer treatments
Authors: Whitehead John 
Published: April 2007

AbstractPatients cured of ulcers, carcinomas or other recurrent conditions are randomized between two treatments designed to maintain their recovery. Spontaneous reporting of relapse is supplemented by periodic asymptomatic screening. Interest centres on the difference in times to relapse between the two treatments. However, the analysis is complicated by the times to diagnoses at screens being qualitatively different from the times to symptomatic diagnoses between screens. In this paper a number of approaches to the analysis of such data are explored, and one of them is recommended. An extensive example with data on ulcer recurrence is presented to illustrate the method.
The superiority of a drug combination over each of its components
Authors: Gibson Janet M. , Overall John E. 
Published: April 2007

AbstractThe requirement for approval of a combination drug treatment AB is its demonstrated superiority over each of its components A and B at their most appropriate dose levels. This has led to frequent use of a three‐group experimental design that permits separate testing of Ho: AB ⩽ A and Ho: AB ⩽ B. A type I error can occur if no true treatment effect is present in either or both of the contrasts. The sampling distribution for the larger of the two observed p‐values, however, depends on whether a non‐null treatment effect is or is not present in one of the contrasts. We propose a strategy in which a conservative experiment‐wide type I error is achieved by defining the criterion for significance of the smaller observed treatment effect contingent on the magnitude of the larger observed treatment effect. We also discuss sample size requirements for the three‐group design.
Comparison of correlated correlations
Authors: Cohen Ayala 
Published: April 2007

AbstractWe consider a problem where k highly correlated variables are available, each being a candidate for predicting a dependent variable. Only one of the k variables can be chosen as a predictor and the question is whether there are significant differences in the quality of the predictors. We review several tests derived previously and propose a method based on the bootstrap. The motivating medical problem was to predict 24 hour proteinuria by protein—creatinine ratio measured at either 08:00,12:00 or 16:00. The tests which we discuss are illustrated by this example and compared using a small Monte Carlo study.
Time series analysis of injuries
Authors: Martinez‐Schnell Beverly , Zaidi Akbar 
Published: April 2007

AbstractWe used time series models in the exploratory and confirmatory analysis of selected fatal injuries in the United States from 1972 to 1983. We built autoregressive integrated moving average (ARIMA) models for monthly, weekly, and daily series of deaths and used these models to generate hypotheses. These deaths resulted from six causes of injuries: motor vehicles, suicides, homicides, falls, drownings, and residential fires. For each cause of injury, we estimated calendar effects on the monthly death counts. We confirmed the significant effect of vehicle miles travelled on motor vehicle fatalities with a transfer function model. Finally, we applied intervention analysis to deaths due to motor vehicles.
Efficiency of the logistic regression and cox proportional hazards models in longitudinal studies
Authors: Annesi Isabella , Moreau Thierry , Lellouch Joseph 
Published: April 2007

AbstractBoth logistic regression and Cox proportional hazards models are used widely in longitudinal epidemiologic studies for analysing the relationship between several risk factors and a time‐related dichotomous event. The two models yield similar estimates of regression coefficients in studies with short follow‐up and low incidence of event occurrence. Further, with just one dichotomous covariate and identical censoring times for all subjects, the asymptotic relative efficiency of the two models is very close to 1 unless the duration of follow‐up is extended. We generalize this result to several qualitative or quantitative covariates. This was motivated by the analysis of mortality data from a study where all subjects are followed up during the same fixed period without loss except by death. Logistic and Cox models were applied to these data. Similar results were obtained for the two models in shorter periods of follow‐up of five years or less, but not in longer periods of ten years or more, where the survival rate was lower.
A cautionary note on the use of autoregressive models in analysis of longitudinal data
Authors: Stanek Edward J. , Shetterley Susan S. , Allen Lindsay H. , Pelto Gretel H. , Chavez Adolfo 
Published: April 2007

AbstractRosner et al. presented a simple, easily implemented modelling method for retaining time order relationships in analyses of longitudinal data when successive measures are correlated. Evaluation of time order is particularly useful in epidemiologic studies concerned with exposure to potentially toxic substances and subsequent outcome, but may also have use in more traditional growth studies that relate intake to subsequent development. The analysis allows for unequally spaced measures and missing data. The estimation method permits varying numbers of observations per subject and, with measures equally spaced, one can fit the model with use of ordinary least squares regression software. We report on a potential false association that can result when both exposure and outcome are related to time. We illustrate this problem with a small scale simulation and example. We also note a more serious problem with Rosner's approach in interpreting parameters. Although the model may be useful for prediction, parameters depend on the autocorrelation and are not readily interpretable. We recommend alternative modelling strategies be used when autocorrelation of errors is suspected.
Single‐stage cluster sampling with a telescopic respondent rule: A variation motivated by a survey of dementia in elderly residents of Shanghai
Authors: Levy Paul S. , Yu Elena S. H. , Liu William T. , Wong Siu‐Chi , Zhang Ming‐Yuan , Wang Zheng‐Yu , Katzman Robert 
Published: April 2007

AbstractIn this report, we consider the situation in which one wishes to identify a cohort of a specified number of individuals within each of several domains for future follow‐up studies based on a single‐stage cluster sampling design. We develop sample size formulae relevant to this situation and introduce a variation of single‐stage cluster sampling that seems more suitable in this situation than is ordinary single‐stage cluster sampling. The basis for this variation is the concept that the definition of eligible respondents is not the same for all clusters. The use of this modified respondent rule (which we call telescopic) enables one to meet specified sample sizes in all domains of interest without the need to sample extra individuals in some domains. We used a version of this sampling design successfully in the field with a survey of elderly persons conducted in Shanghai, People's Republic of China.
Cost and efficiency in clinical trials: The U.S. physicians' health study
Authors: Buring Julie E. , Hennekens Charles H. 
Published: April 2007

AbstractThe U.S. Physicians' Health Study, a primary prevention trial of low‐dose aspirin in the reduction of cardiovascular disease and of beta‐carotene in lowering cancer risk, implemented a number of design strategies to decrease costs and increase efficiency. These included the choice of physicians as the study population, use of a factorial design, implementation of a pre‐randomization run‐in phase, and the collection of pre‐randomization blood specimens. The use of these strategies enabled us to enroll 22,071 subjects and maintain high compliance and long‐term follow‐up at a fraction of the usual cost of large‐scale trials of primary prevention.
Sickle cell anaemia trial
Authors: Gaston Marilyn Hughes , Verter Joel 
Published: April 2007

AbstractThe major cause of death in sickle cell anaemia is from infection, especially infection caused by Streptococcus pneumoniae. Meningitis, pneumonia and septicaemia caused by this organism are the primary types of infection leading to death. Children under three years of age are at highest risk. We have known for over twenty years that approximately 30 per cent of the infants born with sickle cell anaemia will become infected in the first three years of life and one‐third can be expected to die from the infection. These data were the reason that we conducted the Prophylactic Penicillin Study (PROPS), a trial to investigate the effectiveness of oral prophylactic penicillin in preventing severe infection due to S. pneumoniae.This investigation was a very efficient, cost effective study because of its timeliness and its conduct within the framework of an ongoing study. Moreover, the question being answered was simple and focused with up‐to‐date data that permitted accurate estimates of sample size and incidence.
Factorial and reciprocal control designs
Authors: Byar David P. 
Published: April 2007

AbstractThe basic principles of factorial designs are briefly reviewed and estimating equations for a 23 factorial design are presented in order to show how easily the basic idea of the 2 × 2 factorial design generalizes to higher dimensions. Fractional factorial designs are explained and advocated for situations in which the number of experimental groups might otherwise become unmanageably large or costly. Actual examples of use in medical settings are presented for both a 23 full factorial and a half‐fractional 24 design. A new class of designs called reciprocal control designs is proposed for certain disease screening studies. An example is provided by a study designed to screen for lung, colorectal, and prostate cancers.
The role of internal pilot studies in increasing the efficiency of clinical trials
Authors: Wittes Janet , Brittain Erica 
Published: April 2007

AbstractInvestigators often design clinical trials without knowing precisely the values of such necessary parameters as the variances or the event rates in the control group. In order to determine reasonable values for such parameters, they may design a small pilot study external to the main trial. In this paper we propose designs, which we term internal pilot studies, that designate a portion of the main trial as a pilot phase. At the end of the internal pilot study, the investigators recompute preselected parameters and recalculate required sample size. The study then proceeds with the modifications dictated by the internal pilot. Final analyses of the results incorporate all data, disregarding the fact that part of the data came from a pilot phase. As one example of this type of design, we consider a study to compare two normally distributed means. By simulation, we show a numerical example for which the effect of the procedure on the α‐level is negligible, but the potential gain in power considerable. We urge considering a similar approach for a number of types of endpoints.
An examination of the efficiency of some quality assurance methods commonly employed in clinical trials
Authors: Neaton James D. , Duchene Alain G. , Svendsen Kenneth H. , Wentworth Deborah 
Published: April 2007

AbstractThe cost and efficiency of training clinical centre staff and of duplicate data entry in clinical trials is reviewed. Training is an essential component of quality assurance programmes and it is usually carried out at regular intervals in long‐term clinical trials. Initial training of staff and regular retraining is important to assure standardization and it can lead to reduced trial costs. Interim training for new staff and for remedial purposes is less efficient than regularly scheduled training sessions. Regional centres for training and the use of computer aided instruction are two ways such interim training can be made more efficient and standardized. Duplicate data entry or verification can result in a substantial reduction in data entry errors depending on the nature of the data being keyed. Selective verification should especially be considered for important fields for which consistency checks cannot be performed, that are alphabetic or that are several characters in length. Quality assurance procedures should be implemented to monitor data entry accuracy in clinical trials.
Efficient use of endpoints in clinical trials: A clinical perspective
Authors: Terrin Michael L. 
Published: April 2007

AbstractEfficiencies in the use of endpoints in clinical trials are hard won, not easy. They depend upon the shifting of study resources among clinical centres and central units, as well as between numbers of participants and the costs of the endpoint measurement. Costs of endpoint measurement and evaluation do not tell the whole story; nor do costs multiplied by the total number of patients to be recruited; other costs generated by a particular endpoint must also be taken into account. Each clinical trial must be considered separately for the efficient use of endpoints.
The applicability of results of streamlined trials to clinical practice: The myocarditis treatment trial
Authors: O'connell John B. , Mason Jay W. 
Published: April 2007

AbstractThe application of the results of clinical trials to medical practice depends in part upon the understanding and acceptance of study results by the practising physician. Involving non‐academic practitioners as investigators in streamlined trials is an effective means to increase enrolment and minimize cost. Streamlining data collection to accommodate the needs of the practitioner, however, decreases the amount of scientifically and clinically relevant data that are collected. More important, biased enrolment is more likely in this setting. Modifications in organization and design of the Myocarditis Treatment Trial form an example of streamlining an ongoing clinical trial to enhance enrolment.