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Biomedical subjects

D J Finney

Publications and source records attributed to D J Finney.

10 recordsLinked to original sources

Ethical aspects of statistical practice.

This paper embodies a personal view of the ethical considerations that the author believes should be continuously in the mind of any applied statistician or biometrician whose work involves extensive collaboration with other persons and organizations. It looks particularly at the contribution of the International Statistical Institute to the codification of principles, the duties of the statistician in relation to data and the interests of his employer or client, his responsibilities to his professional colleagues and towards society as a whole, and, by no means least; the responsibility of the client towards the statistician who works with him.

Biometry

Repeated measurements: what is measured and what repeats?

This paper expresses a personal view of experiments involving repeated measurements; it attempts to classify types of experiment and approaches to statistical analysis: no novel procedures are proposed, only a systematic outlook on objectives and methods.

Data Interpretation, Statistical

The median lethal dose and its estimation.

An important paper by Zbinden and Fluri-Roversi (1981) has shown the many weaknesses in any policy or regulatory system that regards an estimated LD50 in an animal species as an adequate guide to toxicity in man. The present paper draws attention to some statistical aspects of LD50 estimation that are too often neglected or misunderstood when this quantity is wanted. It is solely concerned with practice when a LD50 must be estimated, and deliberately does not approach the broader issues of whether the LD50 should be estimated. A first need is clear distinction between the true but unknown form of dependence of mortality on dose and the estimate of it (or of a particular property such as the LD50) that is obtainable from an experiment. Some assumptions are necessary before any estimation is possible. The graphical and semi-graphical methods that once were popular because of their simplicity and speed are today only reasonable as a last resort, when data are wholly inadequate and all that can be found is a very rough preliminary indication. Many "simple" arithmetical methods have been shown to be inherently bad, in that equally simple alternatives are usually more precise and less subject to bias. The Spearman-Kärber method remains as a useful possibility, demanding little knowledge of the form of the response curves but often needing other unverifiable assumptions. For most purposes, maximum likelihood estimation of a parametric formulation of the response curve is the best choice, not only because of theoretical merits but also because it can now be performed on a microcomputer in a very few seconds.

Animals

Guidelines for immunoassay data processing.

These guidelines outline the minimum requirements for a data-processing package to be used in the immunoassay laboratory. They include recommendations on hardware, software, and program design. We outline the statistical analyses that should be performed to obtain the analyte concentrations of unknown specimens and to ensure adequate monitoring of within- and between-assay errors of measurement.

Computers

Point and interval estimation in the combination of bioassay results.

A procedure for combining evidence from different biological assays is shown to be equivalent both to generalized least-squares and to maximum-likelihood estimation. By appropriate nesting of hypotheses, the likelihood function can be used to test the agreement between the assays and to obtain probability limits for the combined estimate of potency. The properties of these limits are examined, with particular reference to the situation, unusual but not impossible in practice, in which the values of relative potency that they define consist of several disjoint segments instead of a single interval. The connection with general theory of estimating linear functional relations is pointed out.

Biological Assay

Radioligand Assay.

In radioimmunoassay and immunoradiometric assay, potency estimation involves the relation between counts of radioactivity and dose. Many workers have found the regression function to be satisfactorily represented by a logistic curve with limits that are themselves unknown parameters. This paper discusses estimation of all the parameters under the supposition (supported by empirical evidence) that the variance of a count is proportional to UJ, where U is the mean count at a dose and J is a parameter that almost certainly lies between 1.0 and 2.0. Estimation is found to be very robust, both in respect of the value taken for J and over alternative forms of least squares and maximum likelihood procedures. Special attention is given to whether the assay uses one or more doses of each test preparation, the former having important limitations but permitting some simplification of formulae. Requirements for a comprehensive computer program, suitable for routine use by assayists lacking statistical expertise and designed to produce potency estimates for a series of test preparations in one assay, are described. Data from an assay of oestradiol are used to illustrate various points.

Analysis of Variance

A computer program for parallel line bioassays.

PARLIN is a program for the statistical analysis of biological assays that are either completely randomized, or in randomized blocks, in which the regression on log dose is linear with a constant variance per response. An earlier program (McArthur et al., J. Pharmacol. Exp. Ther. 153: 573-580, 1966) has been completely rewritten, improved and extended in its facilities. PARLIN, written in FORTRAN IV, will handle up to 99 test preparations, up to 100 doses in all, and up to 50 responses per dose. It is designed with special attention to simplicity for routine use, versatility of facilities and output immediately available for all forms of reporting results. A wide choice of transformations of response is available. The output reproduces the data for verification and tabulates potency estimates with limits at probabilities .95, .99; optional output includes an analysis of variance, information on validity, values of residuals and a rough plot of the dose-response relation.

Analysis of Variance

The role of operational research in clinical chemistry.

This paper begins with a critical examination of the published account (Carruthers, 1970) of a pioneering study of simulation in a clinical chemistry laboratory. It next considers the basic requirements for the formal mathematical description of such a laboratory: these include the setting of criteria, the resource and input variates, and the definition of success by means of criterion variates. Investigation of criterion variates can be by direct measurement, or by a theoretical approach which may include simulation. The aims of simulation are discussed and an attempt to simulate the operation of a large clinical chemistry laboratory is described. The difficulty of constructing an overall measure of efficiency is considered in relation to improving performance within an existing framework, to evaluating new equipment such as computers on-line to laboratory apparatus, and to inter-laboratory comparisons of performance. It is concluded that complex operational research techniques, including simulation, have little to offer at least for the present, and may even lead to misleading conclusions.

Chemistry, Clinical