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Biomedical subjects

T A Louis

Publications and source records attributed to T A Louis.

At least 19 recordsLinked to original sources
PubMed1991

Variance components and their implications for statistical information in medical data.

We discuss general issues concerning the design and analysis of medical experiments involving repeated measures or hierarchical groupings of subjects within larger study units. Depending on the types of questions being investigated, the correlations induced by clustering can have dramatic impact on the effective sample size. The unique aspects of such experiments must be accounted for during analysis and during interpretation of the results. We illustrate these issues by using a variance components model to investigate the role of leadership in medical practice.

Ambulatory Care↗
PubMed1991

Using empirical Bayes methods in biopharmaceutical research.

A compound sampling model, where a unit-specific parameter is sampled from a prior distribution and then observed are generated by a sampling distribution depending on the parameter, underlies a wide variety of biopharmaceutical data. For example, in a multi-centre clinical trial the true treatment effect varies from centre to centre. Observed treatment effects deviate from these true effects through sampling variation. Knowledge of the prior distribution allows use of Bayesian analysis to compute the posterior distribution of clinic-specific treatment effects (frequently summarized by the posterior mean and variance). More commonly, with the prior not completely specified, observed data can be used to estimate the prior and use it to produce the posterior distribution: an empirical Bayes (or variance component) analysis. In the empirical Bayes model the estimated prior mean gives the typical treatment effect and the estimated prior standard deviation indicates the heterogeneity of treatment effects. In both the Bayes and empirical Bayes approaches, estimated clinic effects are shrunken towards a common value from estimates based on single clinics. This shrinkage produces more efficient estimates. In addition, the compound model helps structure approaches to ranking and selection, provides adjustments for multiplicity, allows estimation of the histogram of clinic-specific effects, and structures incorporation of external information. This paper outlines the empirical Bayes approach. Coverage will include development and comparison of approaches based on parametric priors (for example, a Gaussian prior with unknown mean and variance) and non-parametric priors, discussion of the importance of accounting for uncertainty in the estimated prior, comparison of the output and interpretation of fixed and random effects approaches to estimating population values, estimating histograms, and identification of key considerations in the use and interpretation of empirical Bayes methods.

Bayes Theorem↗
PubMed1991

Forecasting the number of future disabled elderly using Markovian and mathematical models.

The accuracy of forecasting the number of future disabled elderly people depends on the accuracy of projecting mortality rates and the rates of transition to and from functional disability. We describe a new two-step method for constructing mathematical models that project these future rates dynamically. (1) A Markovian model of elders' transitions between functional states is specified. (2) A mathematical model of the probability of each transition is created. We conducted pilot studies of the fundamental mathematical processes of this method using data from the Longitudinal Study of Aging. First we constructed prototypic mathematical models of the probabilities of remaining functionally able and of making transitions to disability and to death within 2 years. Then we used these models to project hypothetical rates of transition for white women of selected ages, morbidity ratings and health statuses.

Activities of Daily Living↗
PubMed1991

Assessing, accommodating, and interpreting the influences of heterogeneity.

Heterogeneity, ranging from measurement error to variation among individuals or regions, influences all levels of data collected for risk assessment. In its role as a nemesis, heterogeneity can reduce the precision of estimates, change the shape of a population model, or reduce the generalizability of study results. In many contexts, however, heterogeneity is the primary object of inference. Indeed, some degree of heterogeneity in excess of a baseline amount associated with a statistical model is necessary in order to identify important determinants of response. This report outlines the causes and influences of heterogeneity, develops statistical methods used to estimate and account for it, discusses interpretations of heterogeneity, and shows how it should influence study design. Examples from dose-response modeling, identification of sensitive individuals, assessment of small area variations and meta analysis provide applied contexts.

Animals↗
PubMed1990

Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma.

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).

Adult↗
PubMed1990

Longitudinal and cross-sectional estimates of pulmonary function decline in never-smoking adults.

This paper describes methods for simultaneous cross-sectional and longitudinal analysis of repeated measurements obtained in cohort studies with regular examination schedules, then uses these methods to describe age-related changes in pulmonary function level among nonsmoking participants in the Six Cities Study, a longitudinal study of air pollution and respiratory health conducted between 1974 and 1983 in Watertown, Massachusetts; Kingston and Harriman, Tennessee; St. Louis, Missouri; Steubenville, Ohio; Portage, Wisconsin; and Topeka, Kansas. The subjects, initially aged 25-74, were examined on three occasions at 3-year intervals. Individual rates of loss increased more rapidly with age than predicted from the cross-sectional model. For example, for a male of height 1.75 m, the cross-sectional model predicted an increase in the annual rate of loss of FEV1 from 23.7 ml/yr at age 25 to 39.0 ml/yr at age 75, while the longitudinal model gave rates of loss increasing from 12.9 ml/yr at age 25 to 58.2 ml/yr at age 75. These results contrast with those of other studies comparing longitudinal and cross-sectional estimates of pulmonary function loss.

Adult↗
PubMed1990

Performance quality, gender, and professional role. A study of physicians and nonphysicians in 16 ambulatory care practices.

The quality of medical care has rarely been evaluated in relation to practitioner or patient gender. Moreover, comparisons between physicians and nonphysicians typically are confounded by practitioner gender. In this study gender and professional role effects were analyzed separately for 162 male and female staff physicians, 191 male and female residents, and 73 female nonphysicians delivering adult and pediatric primary care in 16 ambulatory care practices. Analyses addressed influences of patient and practitioner gender as well as differences between physicians and nonphysicians. Results showed that female staff physicians performed better than male staff physicians for cancer screening in women by breast examination and Pap smears, but that female residents performed worse than male residents for urinary tract infections in children. Patient gender effects occurred for two tasks; for these, superior care was rendered to the gender with higher prevalence for the condition (girls for urinary tract infections, boys for otitis media). The results are considered in the context of the gender-relevance of particular medical tasks or conditions. Comparisons between physicians and nonphysicians were limited to female practitioners. Comparable or superior performance for nonphysicians was found for all tasks but one (cancer screening in women).

Ambulatory Care↗
PubMed1989

Analysis of a random sample of 2-year carcinogen bioassays from the NCI data base.

We take as our primary goals the introduction of novel, methods of analysis that have the potential to control error rates and reconcile results of multiple studies of the same chemical. We develop a selection rule to pick, for each study, a tumor site/type combination for analysis, and then apply random effects models to these study-specific summaries. These models combine evidence over studies; producing a chemical-specific assessment of carcinogenicity. We declare 14 of the 25 chemicals "carcinogens," and find that female mice are the most sensitive sex/species combination. We discuss the benefits and drawbacks of our method and outline developments necessary for their incorporation into the risk assessment process.

Animals↗
PubMed1988

Unfavourable outcomes of drug therapy--subjective probability versus confidence intervals.

To investigate how individual predictions compare with confidence intervals, we asked 50 medical residents and 28 graduate students with biostatistics training to estimate unfavourable outcomes of drug therapy (therapeutic failures and side-effects) in groups of 10 and 20 patients. The predictions made by physicians and graduate students were similar for both sample sizes and types of outcome. The majority (58%) of estimates were greater than the upper limit of the 95% confidence interval, a bias that may hamper the correct interpretation of therapeutic risks in medical decision-making.

Adult↗
PubMed1988

Cumulative and reversible effects of lifetime smoking on simple tests of lung function in adults.

Data from a random sample of 8,191 men and women from 6 U.S. cities are used to fit a model describing the effects of cumulative and current cigarette smoking on pulmonary function. The data show that smokers suffer an irreversible loss of FVC and FEV1, which is described by a linear function of their cumulative cigarette smoking as measured in pack-years. For a typical male 173 cm tall, the estimated loss of FEV1 is 7.4 ml for each pack-year smoked. For a typical woman, 161 cm tall, the estimated effect is 4.4 ml per pack-year. Current cigarette smoking adds an acute deficit over and above the cumulative effect of lifetime smoking. For any lifetime pack-years, exsmokers have higher levels of FEV1, 123 ml for a typical man, 107 ml for a typical woman, than do current smokers of a pack per day (p less than 0.001). A man who starts smoking one pack of cigarettes per day at 25 yr of age would at age 60, after 35 pack-years of exposure, have an expected FEV1 equal to that of a man 69.4 yr of age who had never smoked. If he stopped smoking at 60 yr of age, his expected level would increase to that of a 66.5-yr-old never-smoker. This model therefore estimates how much lung function is irreversibly lost by smoking, estimates how much could be regained with cessation of smoking, and predicts the future loss of lung function in both cases.

Adult↗
PubMed1987

Inter-laboratory variability in Ames assay results.

The Ames test is widely used in the screening of chemicals and compounds for potential carcinogenic effect. There is, however, considerable inter-laboratory variability in results from this assay. Using data from the RTI Collaborative Study of the EPA Ames Test Protocol, we show that their reported standard errors of estimates of mutagenicity fall far short of capturing day-to-day or laboratory-to-laboratory variation. We estimate the factors by which the standard errors must be inflated to account for these sources of variation. The laboratory protocol and previous studies suggest that much of this variation may be caused by factors that are relatively constant within days (e.g. technician, incubation temperature, S9 liver homogenate preparation) but vary over days and across laboratories. Therefore, such variation might be reduced through use of a reference compound tested on the same day and under the same conditions as the test chemical. This conjecture was, however, not supported by analyses that considered the positive control compound and a pure chemical as possible reference assays.

Laboratories↗
PubMed1986

Explaining discrepancies between longitudinal and cross-sectional models.

Data from longitudinal studies may be analyzed both cross-sectionally and longitudinally. Discrepancies between estimates obtained from these analyses pose questions about the validity of cross-sectional estimates of change. In some cases these discrepancies are the result of period effects, cohort effects, or selective dropout. In others, they are the result of incomplete modeling of the process and are spurious rather than substantive. In this report, we show that when the true relation between a dependent variable and age is non-linear (e.g. quadratic), but is modeled as linear, the estimated age effect will be a function of the age distribution. In a continuous-time idealization, if the age distribution is Gaussian, the estimated age effects agree. If the age distribution is symmetric and the non-linearity is quadratic, cross-sectional and longitudinal results agree. Otherwise they do not. We illustrate these points by analysis of the relation between aging and pulmonary function in middle and old age using data from a large, prospective, longitudinal study.

Adult↗
PubMed1985

A randomized controlled trial of quality assurance in sixteen ambulatory care practices.

A crossover randomized controlled trial of cycles of quality assurance in 16 primary care (8 medical, 8 pediatric) group practices was conducted. Of four medical and four pediatric tasks important to patient outcome, two were randomly assigned to experimental intervention (a quality assurance cycle), and two were also measured and used as blinded controls for each medical or pediatric group practice. Task performance was measured in each group for 12 months prior to, 9 months during, and 9 months after the experimental intervention, using as a performance score the percentage of evaluation criteria failed of those applicable to a case. As a result of quality assurance intervention, quality of performance was significantly improved in two of the tasks (P less than 0.0001, with 6.7, and 9.8 percentage points improvement), and marginally improved in one task (P = 0.06, 5.7 percentage points improvement). Surprisingly, tasks with lower perceived effect on patient health (low physician motivation) had greater improvement in quality. Unimproved tasks were associated with the perceived need for delivery system changes beyond the immediate control of the individual practitioner.

Adolescent↗
PubMed1984

A classification for biomedical research reports.

Biomedical research uses a wide range of designs applied to problems in laboratory, clinical, and population settings. Whatever the nature of the study, a few key features--such as the admission rule, the method of allocating subjects to treatments, and the use of controls--largely determine the strength of scientific inferences. We used these and other features to classify the 332 Original Articles published in the New England Journal of Medicine during 1978-1979. This classification directs attention to critical aspects of study design and performance and can help in the choice of suitable research approaches and protocols. It emphasizes the critical role of the investigators' intent in performing and analyzing a study, and it alerts readers to important aspects of interpretation. We recommend that authors always report enough detail about their work for readers to apply this or a similar classification. Omission of such detail may limit the interpretation of a research study because a study that cannot be classified has probably been incompletely reported.

Clinical Trials as Topic↗
PubMed1984

Studies without internal controls.

Sometimes questions of clinical interest can be addressed only by investigations without concurrent controls that are under the supervision of the investigator (internal controls). Such studies nearly always make use of other types of comparisons (external controls), such as historical controls. In this paper we examine studies of clinical treatments that have weak internal controls or lack internal controls, as illustrated by recent examples from the Journal. These studies have a small but important and unique role in clinical investigation. Five interrelated features can add to the strength of such studies: (1) an intent by the investigator, expressed before the study, that the treatment will affect the outcomes reported; (2) planning of the analysis before the data are generated; (3) articulation of a plausible hypothesis before the results are observed; (4) a likelihood that the results would still have been of interest if they had been "opposite" in some sense; and (5) reasonable grounds for generalizing the results from the study subjects to a substantially broader group of patients. In spite of potential pitfalls, carefully selected and reported studies without internal controls can play a substantial part in the acquisition of scientific knowledge.

Animals↗
PubMed1984

Crossover and self-controlled designs in clinical research.

Crossover studies (clinical trials in which each patient receives two or more treatments in sequence) and self-controlled studies (in which each patient serves as his or her own control) can produce results that are statistically and clinically valid with far fewer patients than would otherwise be required. We investigated the use of the crossover design in the 13 crossover studies that appeared in the Journal during 1978 and 1979. We considered the following important features of design and analysis as they applied to these studies: the method by which patients were assigned to initial treatment (only 7 of 13 studies used random assignment); the determination of when to switch treatments (10 of the 13 used a time-dependent rule, and 3 a less appropriate disease-state-dependent rule); blinding of the crossover point (in only 3 of the 13 studies was the crossover point concealed, but in 4 of the remaining 10 concealment was impossible); assessment of the effects of the order of treatments (included in only 1 of the 13 studies); and the use of at least minimally acceptable statistical analysis (11 of the 13 studies had such an analysis). We also report briefly on 28 additional studies of a single treatment each, in which each patient served as his or her own control before or after treatment or both. The scientific issues were much the same as in crossover studies except that self-controlled comparisons of treatments tended to be less precisely designed and conducted and to focus on clinical problems and patient groups that are especially difficult to study.

Chronic Disease↗