bluuebunny/crossref_metadata_2025_split huggingface dataset:
GENETIC epidemiology: A review of the statistical basis
Authors: Thompson E. A. 
Published: April 2007

AbstractGenetic epidemiology is the analysis of the familial distributions of traits, with a view to understanding any possible genetic basis; the fundamentals of this area are reviewed. The terminology of genetic models is fully described, since it is this wealth of terminology which can make it difficult for a statistician to enter the area. The statistical approaches to the analysis of data on sets of interrelated individuals are then discussed, and resulting problems of sampling design and analysis are considered.
Calculating expected mortality
Authors: Keiding Niels , Væth Michael 
Published: April 2007

AbstractThe widely used ‘person‐years method’ of calculating expected mortality has been discussed recently by several authors. In studies where mortality is either lower or higher than the standard mortality of some reference population, the use of exposure to death as an estimator of the expected number of deaths will generally lead to bias, always exaggerating the difference between study and standard mortality. This bias is examined in a proportional hazards model. The recent suggestion by Hartzet al.1of calculating the mortalities of individuals during their ‘potential follow‐up time’ is claimed to be only rarely feasible in practice.
The use of the binomial distribution in establishing an association between high‐risk donors and transfusion‐associated aids
Authors: Kaplan Jonathan E. , Schonberger Lawrence B. , Lui Kung‐Jong 
Published: April 2007

AbstractIn the first seven cases of transfusion‐associated acquired immunodeficiency syndrome (TA‐AIDS) with completion of blood donor investigations, there was identification of at least one person (a high‐risk donor‐ HRD) in each donor set who might have transmitted the disease. Using three definitions of an HRD, we estimated the prevalence of HRDs in the overall donor population and used the binomial distribution to calculate the probabilities of finding at least the observed numbers of donor sets with one or more HRDs. These probabilities‐0.028, 0.007 and 0.014, respectively‐allowed us to reject the null hypothesis that the number of cases of TA‐AIDS exposed to an HRD was not greater than that expected by chance, based on the total number of donors to which each case was exposed and the estimated proportion of HRDs in the overall donor population. We concluded that there was a statistically significant association between HRDs and TA‐AIDS.
Probabilistic prediction in patient management and clinical trials
Authors: Spiegelhalter D. J. 
Published: April 2007

AbstractIt is argued that the provision of accurate and useful probabilistic assessments of future events should be a fundamental task for biostatisticians collaborating in clinical or experimental medicine, and we explore two aspects of obtaining and evaluating such predictions. When covariate information on patients is available, logistic regression and other multivariate techniques are often used to select prognostic factors and create predictive models. An example shows how the explicit aim of prediction needs to be taken into account in such modelling, and how predictive performance may be assessed by decomposition of a scoring rule. Secondly, results from a program that provides pretrial and interim predictions in clinical trials are displayed, bringing together the use of subjective opinion, Bayesian methodology and techniques for evaluating and criticizing predictions.
Clinical trials of cancer prevention agents: True versus observed prevention effect
Authors: Moon Thomas E. 
Published: April 2007

AbstractImportant considerations in the design and conduct of cancer and other long‐term prevention trials include intervention compliance and frequency of events during follow‐up. Each of these can produce observed proportions of events for control and test groups that differ less than anticipated. Methods and approximate ‘rules of thumb’ are presented that relate power and sample size to the impact of compliance and latent intervention effect. Results are based upon specific modifications in well‐known formulae that reflect long‐term prevention trials. Data from an ongoing cancer prevention trial illustrate the methods. Compliance was estimated accurately using the low cost capsule count method.
The determination of practically useful doses of new drugs: Some methodological considerations
Authors: Turri M. , Stein G. 
Published: April 2007

AbstractAn important aim of Phase 2 clinical trials is the firm determination of the doses and the dose regimes to be used both in later clinical trials and in clinical practice. Comparisons of findings made during clinical development and recommendations contained in the package leaflets of marketed preparations indicate that this objective is rarely achieved.The possible reasons for this difficulty are investigated by reviewing the methodology used in the so‐called dose‐finding trials performed during drug development. Since the terminology used in this context is frequently misleading, definitions are given and alternative approaches, referring to the direct and indirect methods of bioassay, are suggested. The practical use of these models depends on a number of medical and ethical considerations, on the indications for treatment and on the characteristics of the drug under investigation.Some examples are given, indicating that dose‐response relationships can be determined more easily for efficacy, where endpoints more reliably fit commoner distributions, than for tolerability, where the responses frequently follow irregular patterns. This area deserves further investigation to improve the criteria for assessment and to develop adequate statistical methods.
Patient accrual and interim statistical analysis in long‐term randomized clinical trials: The French chronic lymphocytic leukemia CLL 80 protocol as a case study
Authors: Chastang Claude , Travade Philippe , Benichou Jacques , Dighiero Guillaume , Binet Jacques‐Louis 
Published: April 2007

AbstractThe CLL 80 clinical trial of treatment for chronic lymphocytic leukemia was designed using a three‐stage prognostic classification. Within each stage patients received one of two treatments allocated by randomization, two adjacent stages having a common treatment. The fixed‐sample design required 850 patients entered over a period of 8.5 years.Active patient recruitment led to 741 patients being randomized in four years. The first interim analysis, carried out at this point, showed a treatment difference in one stage which was statistically significant (p = 0.001) and justified an early termination of the protocol. This paper discusses practical aspects of patient accrual and interim analysis in this study.
The changing face of cancer epidemiology
Authors: Wahrendorf Jürgen 
Published: April 2007

AbstractThis paper is concerned with discussing various methodological components of cancer epidemiology. Developments in measuring disease frequency are acknowledged as well as the high level of sophistication of statistical methodology. Several examples are given to illustrate that methods for measuring exposure to factors which cause or protect against cancer have developed considerably over the last few years and allow new approaches in cancer epidemiology. The potential links with clinical research are highlighted.
On the role of ‘habitual aborters’ in the analysis of spontaneous abortion
Authors: Gladen Beth C. 
Published: April 2007

AbstractAnalyses of spontaneous abortion rates often include special provisions to account for the presumed distorting effects that arise because of the presence of habitual aborters. In this paper, I establish a framework for investigating the effects of the presence in study groups of such women. I then examine the strengths and weaknesses of some of the analysis strategies in current use, both in situations where the study group is homogeneous and where there are high‐risk women present. I show that the concept of habitual aborter is not useful and can be misleading, and I suggest that one take a broader view of heterogeneity.
On surveillance methods for congenital malformations
Authors: Gallus G. , Mandelli C. , Marchi M. , Radaelli G. 
Published: April 2007

AbstractThis paper presents an ‘optimal’ procedure for the use of the ‘sets’ method, a system proposed for surveillance of congenital malformations.1 Comparisons over a number of examples shows that the given procedure represents a clear improvement over the one originally proposed, and, in some conditions, is more efficient than the cusum scheme.
Estimating incidence from age‐specific prevalence for irreversible diseases with differential mortality
Authors: Podgor Marvin J. , Leske M. Cristina 
Published: April 2007

AbstractWe present a method for estimating incidence from age‐specific prevalence data for an irreversible disease where the mortality risks may differ for persons with and without the disease. This method is an extension of previously presented methodology1 for estimating incidence from prevalence for a disease that does not entail differential mortality. An application to senile cataract illustrates the method.
A model for variability in arteriographic reading
Authors: Hertzberg Vicki Stover , Fisher Lloyd D. 
Published: April 2007

AbstractWe propose a class of models for the joint cumulative distribution function (c.d.f.) of the values of two independent readings of percentage stenosis from a coronary arteriography. We show that these models are identifiable and that a certain subclass has unique consistent estimators for the parameters in question. We obtain these estimates for a data set from a substudy of the Coronary Artery Surgery Study (CASS).
Simultaneous non‐parametric confidence intervals for survival probabilities from censored data
Authors: Afifi A. A. , Elashoff R. M. , Lee J. J. 
Published: April 2007

AbstractIn medical studies with censored data Kaplan and Meier's product limit estimator has frequent use as the estimate of the survival function. Simultaneous confidence intervals for the survival function at various time points constitute a useful addition to the analysis. This study compares several such methods. We consider in a simulation investigation two whole curve confidence bands and four methods based on the Bonferroni inequality. The results show that three Bonferroni‐type methods are essentially equivalent, all being better than the other methods when the number of time points is small (3 or 5).
Sample size requirements and the cost of a randomized clinical trial with repeated measurements
Authors: Bloch Daniel A. 
Published: April 2007

AbstractThis paper discusses the advantage of using repeated outcome measurements on subjects in a clinical trial. We choose the number of subjects and the number of repeated outcome measurements to minimize a given cost function so that the clinical trial has power (1 −β) for specified significance level < α. An example illustrates the results and emphasizes the importance of study design and of critical evaluation of how one measures the study endpoint.
What do doctors know about statistics?
Authors: Wulff Henrik R. , Andersen Bjørn , Brandenhoff Preben , Guttler Flemming 
Published: April 2007

AbstractA multiple choice test with nine statistical questions was sent to a random sample of Danish doctors to assess their knowledge of elementary statistical expressions (SD, SE, p < 0·05, p > 0·05 and r). One hundred and forty eight (59 per cent) of 250 doctors answered the questions. The test was also completed by 97 participants in postgraduate courses in research methods, mainly junior hospital doctors. The median number of correct answers was 2·4 in the random sample and 4·0 in the other sample of doctors. It is concluded that the statistical knowledge of most doctors is so limited that they cannot be expected to draw the right conclusions from those statistical analyses which are found in papers in medical journals. Sixty‐five per cent of the doctors in the random sample stated that it is very important that this problem is raised.
Analysis of data arising from a stratified design with the cluster as unit of randomization
Authors: Donner Allan , Donald Alan 
Published: April 2007

AbstractThis paper discusses statistical techniques for the analysis of dichotomous data arising from a design in which the investigator randomly assigns each of two clusters of possibly varying size to interventions within strata. The problem addressed is that of assessing the statistical significance of the intervention effect over all strata. We propose a weighted paired t‐test based on the empirical logistic transform for designs that randomize large aggregate clusters in each of several strata.
Sample size and power for pair‐matched case‐control studies
Authors: Connett John E. , Smith Judith A. , McHugh Richard B. 
Published: April 2007

AbstractA new sample size formula is derived herein for matched‐pair case‐control studies. This result is based on an unconditional approach to the use of McNemar's statistic. We contrast this method for determining sample size and power with Schlesselman's conditional approach and compare the results numerically in a Monte Carlo study.
The three‐decision problem in medical decision making
Authors: Emerson John D. , Tritchler David 
Published: April 2007

AbstractMedical researchers and policy makers face decisions that require a choice from among two or more alternatives. Whereas traditional hypothesis tests cannot always serve the needs of the practitioner who needs to make a decision, a problem formulation that assigns losses to various incorrect decisions offers several advantages. With three possible decisions this approach offers a precise representation of the pragmatic and explanatory views of decision making. It enables the investigator to incorporate in the problem specification his attitudes about the seriousness of various errors by guiding him, before he sees the data, to a choice of asymmetric tail probabilities. It also suggests a reformulation of the P‐value that can accommodate some of the difficulties practitioners face.
An approximation for the distribution of the scan statistic
Authors: Wallenstein Sylvan , Neff Norman 
Published: April 2007

AbstractThe scan statistic evaluates whether an apparent cluster of disease in time is due to chance. The statistic employs a ‘moving window’ of lengthwand finds the maximum number of cases revealed through the window as it scans or slides over the entire time periodT. Computation of the probability of observing a certain size cluster, under the hypothesis of a uniform distribution, is infeasible whenN, the total number of events, is large, andwis of moderate or small size relative toT. We give an approximation that is an asymptotic upper bound, easy to compute, and, for the purposes of hypothesis testing, more accurate than other approximations presented in the literature. The approximation applies both whenNis fixed, and whenNhas a Poisson distribution. We illustrate the procedure on a data set of trisomic spontaneous abortions observed in a two year period in New York City.
Avoidance of large biases and large random errors in the assessment of moderate treatment effects: The need for systematic overviews
Authors: Collins Rory , Gray Richard , Godwin Jon , Peto Richard 
Published: April 2007

AbstractIn order to avoid selective biases and to minimize random errors, inference about the effects of treatment on serious endpoints needs to be based not on one, or a few, of the available trial results, but on a systematic overview of the totality of the evidence from all the relevant unconfounded randomized trials. But, only where coverage of all, or nearly all, randomized patients in all relevant trials (or a reasonably unbiased sample of such trials) can be assured, is a systematic overview of trials reasonably trustworthy, for then any selective biases are likely to be small in comparison with any moderate effects of treatment. Checks for the existence of such biases can best be conducted if reasonably detailed data are available from each trial. Future trials should take into account the results of any relevant overviews in their design, and should plan to obtain sufficient numbers of events to contribute substantially to such overviews. In many cases, this implies the need for randomized trials that are much larger than is currently standard.
An overview of six clinical trials of aspirin in coronary heart disease
Authors: Canner Paul L. 
Published: April 2007

AbstractData from six randomized, placebo‐controlled clinical trials of aspirin, involving a total of 10,703 post‐myocardial infarction patients, have been compared and combined. An apparent heterogeneity of findings among the six trials with respect to all‐cause mortality is noted (P = 0.08). The reasons for this heterogeneity are explored. Two common methods of combining the results of several trials – the logrank and the log odds ratio methods – yield two‐sided P‐values of 0.112 and 0.110, respectively, for the aspirin‐placebo effect on all‐cause mortality. Alternative statistical methods of combining the results of the six trials give two‐sided P‐values ranging from 0.017 to 0.487.
Obtaining medically meaningful answers from an overview of randomized clinical trials
Authors: Yusuf Salim 
Published: April 2007

AbstractAnswers that have medical value can often be obtained from overviews of randomized clinical trials if care is taken in formulating a biologically sensible question and unbiased and careful methods are used in collecting, extracting and analysing the results. This article discusses some of the pitfalls that are encountered during this process, outlines some solutions and emphasizes the need for a conservative interpretation of the results.
Lessons from overviews of cardiovascular trials
Authors: Furberg Curt D. , Morgan Timothy M. 
Published: April 2007

AbstractOverviews of clinical trials in the cardiovascular field have been critically reviewed. Six reasons for the overviews were identified. An impression, at least from a scientific viewpoint, is that the pooled analyses have been valuable. Six potential problems are discussed and recommendations given based on lessons learned. These include the avoidance of three types of biases – publication bias, overviewer bias and investigator bias. The role of time‐dependent treatment effects, the complex issue of ‘mixing of apples and oranges’ and the problem of errors are also addressed.
Potential pooling opportunities: Cancer
Authors: Friedman Michael A. 
Published: April 2007

AbstractThe pooling of large amounts of clinical data from all available and relevant (diverse) sources in order to achieve greater statistical confidence may be appropriate for most modern and well conducted clinical investigations. However, in order to arrive at specific and meaningful conclusions, such exercises absolutely depend upon the homogeneity (or at least comparability) of the study population and therapy under scrutiny. There are currently many opportunities for pooling studies of cancer treatment. The most attractive disease situations are those with a sufficiently large number of completed randomized studies. Some to be considered are colon cancer, gastric cancer, hepatoma, ovarian cancer and lymphoma.
Inter‐study differences: How should they influence the interpretation and analysis of results?
Authors: Bailey Kent R. 
Published: April 2007

AbstractIn determining the role inter‐study variation should play in an overview analysis, it is important to consider three factors: (1) which question one is trying to answer; (2) the degree of similarity or dissimilarity of design, and (3) the degree to which heterogeneity of outcomes can be explained. Three questions one might be interested in are: (1) whether treatment can be effective in some circumstances; (2) whether treatment is effective on average, and (3) whether treatment was effective on average in the trials at hand. Under the assumption of no qualitative interaction, the answers to these questions coincide. The O – E analysis most directly answers the third question. Other analyses are suggested when the first question is of interest, using the aspirin post‐MI studies as an example.
Internal quality control in clinical chemistry: A teaching review
Authors: Nix A. B. J. , Rowlands R. J. , Kemp K. W. , Wilson D. W. , Griffiths K. 
Published: April 2007

AbstractThis survey introduces the subject of internal quality assessment from a historical point of view, presents a unified approach to notation, concepts and definitions, and describes briefly those quality control procedures that are used most commonly in clinical chemistry. It is not the aim of this report to comment on all the individual contributions made in this field, but rather to concentrate on the principles. Particular emphasis is centred around assessment criteria to compare the efficiencies of selected control procedures for monitoring analyte concentrations in biological fluids. The question of whether to compare control schemes by means of average run lengths, run length distribution functions or average cost functions is considered. A rationalized approach based on the comparison of optimal procedures, using average run length, is adopted.
Adjustments to the Mantel–Haenszel chi‐square statistic and odds ratio variance estimator when the data are clustered
Authors: Donald Alan , Donner Allan 
Published: April 2007

AbstractDependence between observations on a dichotomous variable renders invalid the usual chi‐square tests of independence and inflates the variances of parameter estimates. Such a situation occurs, for example, when subjects consist of members of the same family or with repeated observations on the same person. In this paper we describe methods of measuring the extent of correlation (or clustering). We also develop methods of adjusting the Mantel–Haenszel chi‐square test statistic and the variance of the Mantel–Haenszel estimate of a common odds ratio in sets of 2 × 2 contingency tables.
Analysis of total mortality in the rotterdam sample of the Kaunas–Rotterdam intervention study (KRIS)
Authors: Mulder Paul G. H. , Hempenius Anton L. 
Published: April 2007

AbstractIn 3284 middle‐aged Rotterdam men, the dependency of 9‐year survival on a number of cardiovascular risk factors is analysed. The purpose of this analysis is twofold. First, there is interest in the relationship between total mortality and the continuous variables blood pressure and plasma cholesterol. In accordance with other studies, the results provide further evidence for a U‐shaped relationship. The second purpose is to compare three models theoretically as well as empirically: a piecewise exponential distribution of survival time, Cox's proportional hazards model (both with a log‐linear dependency specification of the mortality rate), and a logistic model. The disadvantage of a logistic model is that it is theoretically not appropriate in longitudinal (prospective) epidemiologic studies. The theoretical advantage of the piecewise exponential distribution to Cox's model is that longitudinal (time) effects on the mortality rate can be specified and estimated directly. Empirically, with 342 deaths all three methods yield quite similar estimates and therefore are almost equally capable of detecting relationships between mortality and the risk factors in the data set at hand.