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Biomedical subjects

N Mantel

Publications and source records attributed to N Mantel.

At least 73 records · Page 4Linked to original sources
PubMed1978

Breast cancer at a psychiatric hospital before and after the introduction of neuroleptic agents.

No association between breast cancer and treatment with neuroleptic agents agents was detected in a study of 5463 women who died or underwent breast biopsy at the Norristown State Hospital between 1940 and 1974. The method of proportionality was used to evaluate the frequency with which breast cancer occurred at the hospital; cases of breast cancer were related to deaths from other cancers and to deaths from all causes other than breast cancer. Deaths and cancers that occurred within 1 year of hospital admission were excluded from the analysis. To allow for a 10-year transition period and for latency in the development of breast cancer, comparison was made between the 15 years preceding the introduction of neuroleptic agents into medical practice (1940 to 1954) and the second decade after the introduction (1965 to 1974). Although neuroleptic agents were used extensively for treatment of patients at the hospital, there was no statistically or medically significant change in the indicated incidence of breast cancer at the hospital during the neuroleptic period. The study did not rule out the possibility that neuroleptic agents might have some effect on breast cancer after a very long latency period.

Adolescent↗
PubMed1977

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Drug Evaluation↗
PubMed1977

Tests for homogeneity of effect in an epidemiologic investigation.

A test for homogeneity of the effect of a factor in inducing disease in the various strata of a population should relate to the scaling in which homogeneity is anticipated. Popularity, it is the multiplicative effect on the odds ratio in which homogeneity is anticipated. An asymptotic test by M. Zelen (Biometrika 58:129-137, 1971) for homogeneity in this scaling is indicated to be invalid. Further, a test by J. L. Fleiss (Statistical Methods for Rates and Proportions. NY, Wiley, 1973) for homogeneity of the standardized difference is shown to be the same as the Zelen test, to be invalid in any case, and not to correspond to any scaling. The examples given include one in which results of two studies are apparently inhomogeneous by the test even though they give effectively identical results. It is advised that tests for homogeneity be conducted with care, and that thought be given to how effects might be made homogeneous rather than to trying to demonstrate the existence of heterogeneity.

Epidemiologic Methods↗
PubMed1977

Mantel-Haenszel analyses of litter-matched time-to-response data, with modifications for recovery of interlitter information.

The Mantel-Haenszel procedure for comparing sets of time-to-response data is adaptable to data that can be stratified on other variables. A particular adaptation, which we have used, is one in which animals from the same litter have been assigned to different treatment groups, e.g., some to a control group and some to a drug treatment group. The time to response used was that of tumor appearance; death from other causes was considered a loss to observation. The initial litter-adjusted analysis seemed to have only limited advantages compared to analysis that ignored litters and could be interpreted as suggesting that litter matchihg was not advantageous. Contributing to the difficulty was the fact that in the litter-matched analysis no further information was forthcoming from the remaining similarly treated animals in a litter when there were no remaining contrastingly treated littermates. Several devices for recovering interlitter information from such remnants and for combining it with intralitter information are examined and applied.

Animals↗
PubMed1976

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

Clinical Trials as Topic↗
PubMed1976

Is Hodgkin's disease infectious? Discussion of an epidemiologic method used to impute that it is.

A method proposed by MacMahon for the differentiation between familial and environmental causes for disease has recently been applied to demonstrate an environmental etiology for Hodgkin's disease. It is shown that the method, which depends on the comparison of time-of-onset differences with age-at-onset differences for familial pairs with disease, is biased toward results suggestive of an environmental etiology when applied to data of the kind typically analyzed--data restricted to instances in which both members of a familial pair develop disease in a specified, limited time interval. Other features of such data are discussed.

Age Factors↗
PubMed1976

Tables and formulas for extended use of the Ederer-Myers-Mantel disease-clustering procedure.

The principles of the Ederer-Myers-Mantel procedure for seeking evidence of disease clustering are reviewed. The procedure is based on cumulative empirical clusters, i.e., the largest frequency in a single time period or in two successive time periods, and comparing that cumulation with the expected cumulation of largest frequencies under random occurrence. Original tabulations covered totals of up to 15 cases distributed among three, four or five time periods. Present tabulations of expectations and variances cover up to 500 cases distributed among two or three time periods and 200 cases distributed among four or five time periods. Asymptotic formulas are provided for the expectation and variance of the largest frequency in a single period when arbitrarily many cases are distributed at random among two, three, four or five time periods.

Epidemiologic Methods↗
PubMed1975

From mouse to man--or how to get from the laboratory to Park Avenue and 59th Street.

Where does this all leave us? It leaves us able to develop rather good animal data at dose levels that do not really interest us. That is a first-class highway that takes us where we do not want to go. It leaves us unlikely to be able to develop good data at "realistic" doses. To extrapolate animal results to man exposed at these "realistic" doses today requires assuming a mathematical model of dose-response in the animal and conservative use of this model. Then we have to jump from one species to another in ignorance of the terrain of the landing site, i.e., the many species differences. However, we will have knowledge of some important species similarities and that makes the jump a lot less dangerous. With respect to costs and benefits we are just beginning to understand some of the implications of the arithmetic. We have begun to see that there are few, if any, good ways of totaling the costs or computing the benefits. Cost-benefit may be another blind alley. Tomorrow and the next day we must do the appropriate research on species differences in metabolism and in the mathematics of the modeling and extrapolation--as a minimum. The socially related issues, such as what is an acceptable risk, what are the costs, what are the benefits, must be discussed in the open, freely. This implies recognizing that someone's costs may be someone else's benefits. (Our medical costs are our physician's source of living.) The inputs to the cost-benefit algebra are not well worked out. Our ways of working must include the adversary approach as well as the pleasanter way of cooperation. And today, we must get to precautionary decisions for man's safety and health based on the road maps from animal data--inadequate as they are. We have gotten to the neighborhood of Park Avenue and 59th Street and we can probably one day get to a lot of other places.

Animals↗
PubMed1975

An improved Mantel-Bryan procedure for "safety" testing of carcinogens.

A published method by Mantel and Bryan for calculating "safe" doses of carcinogens is updated by incorporating several improvements. These improvements include more effective procedures for taking into account any spontaneous tumor rate and for combining data at several dose levels. An added feature is that it permits the combining of data from several experiments by postulating that it is only the spontaneous rate that differs between experiments. The improved method is illustrated with data from five hypothetical experiments, using a risk level of 10-8, a conservative slope of one probit or normal deviate per tenfold dose increase, and a nominal assurance level of 99%. The hypothetical experiments were geared to bring out particular pointsas, for example, the applicability of the model in the absence of control data. A large variety of issues involved in the determination of "safe" doses are discussed, including questions of experiment design and extrapolitan between species. A statistical appendix is provided, laying the framework for the calculating procedure and detailing complications therein. The "safe" dose approach helps resolve certain dilemmas in questions relating to food additives. A "no-detectable-level" prescription for chemical residues may be dangerous to the public where detection techniques are insufficiently sensitive, but it can become far too restrictive as exquisitely sensitive detection techniquesare developed. Only levels in excess of the "safe" dose would require detection. Calculated values for the "safe" dose could be updated and increased as more clear evidence of safety becomes available.

Animals↗
PubMed1975

Estimating "safe" levels, a hazardous undertaking.

Various problems beset the question of identifying chemical carcinogens in the environment or setting permissible levels for potential carcinogens. Issues arising are cost-benefit questions, existence of thresholds, appropriate experimental designs, how to extrapolate to man, results from tests on laboratory animals, etc. Certain approaches implicitly involve use of a double standard, with much more stringent measures taken when clearer evidence of carcinogenicity is found. Such double standards may discourage careful testing of carcinogens as this could more probably lead to imposition of the stricter measure. Even-handed application of devices like that recommended by Mantel and Bryan for setting "safe" levels could avoid this difficulty and would encourage more adequate testing. Why laboratory testing should be at high or moderately high levels is explained and the futility of "mega-mouse" experiments at very low dose levels is indicated. A surface-area rule for extrapolating dose levels from laboratory animal to man is suggested, but this is indicated to lead approximately to direct equivalence when dose levels are expressed as dietary concentrations.

Animals↗
PubMed1975

Non-parametric interval estimation of relative potency for dilution assays, including the case of non-monotone dosage response curves.

Interval estimates of the relative potency of two preparations based on data from a dilution assay can be made using an extension of the Mantel-Haenszel procedure, this requiring only the assumption of a monotone dosage-response curve. An assay-design requirement is that dosage levels be equi-spaced logarithmically with a common logarithmic interval for both preparations. By use of ranks the method can be made independent of the scale in which responses are measured. The approach is illustrated using untransformed data, a logarithmic transform, a quantal transform, and a ranking scale. A procedure under which even the monotonicity assumption can be dropped is described and similarly illustrated.

Animals↗
PubMed1975

The equivalence of the generalized McNemar tests for marginal homogeneity in 2(3) and 3(2) tables.

The McNemar test for correlated proportions has been generalized to test for marginal homogeneity of either a 2c or an m2 contingency table. The tests for 2(3) and 3(2) tables turn out to be equivalent since each involves six non-diagonal elements; equal numbers of degrees of freedom in the associated chi square tests, m - 1 = c - 1 = 2; identical constraints on the fits to the non-diagonal elements; and identical measures of discrepancy between observed and fitted values to be optimized.

Biometry↗
PubMed1975

Some interrelationships among the regression coefficient estimates arising in a class of models appropriate to response-time data.

Interrelationships among three response-time models which incorporate covariate information are explored. The most general of these models is the logistic-exponential in which the log odds of the probability of responding in a fixed interval is assumed to be a linear function of the covariates; this model includes a parameter W for the width of discrete time intervals in which responses occur. As W leads to O this model is equivalent to a continuous time exponential model in which the log hazard is linear in the covariates. As W leads to infininity it is equivalent to a continuous time exponential model in which the hazard itself is a linear function of the covariates. This second model was fitted to the data used in an earlier publication describing the logistic exponential model, and very close agreement of the estimates of the regression coefficients is demonstrated.

Models, Biological↗