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Biomedical subjects

T R Fears

Publications and source records attributed to T R Fears.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effects of cluster sampling on epidemiologic analysis in population-based case-control studies.

We consider population-based case-control designs in which controls are selected by one of three cluster sampling plans from the entire population at risk. The effects of cluster sampling on classical epidemiologic procedures are investigated, and appropriately modified procedures are developed. In particular, modified procedures for testing the homogeneity of odds ratios across strata, and for estimating and testing a common odds ratio are presented. Simulations that use the data from the 1970 Health Interview Survey as a population suggest that classical procedures may be fairly robust in the presence of cluster sampling. A more extreme example based on a mixed multinomial model clearly demonstrates that the classical Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) and Woolf-Haldane tests of no exposure effect may have sizes exceeding nominal levels and confidence intervals with less than nominal coverage under an alternative hypothesis. Classical estimates of odds ratios may also be biased with non-self-weighting cluster samples. The modified procedures we propose remedy these defects.

Biometry↗
PubMed1988

The statistical analysis of a carcinogen mixture experiment. II. Carcinogens with different target organs, N-methyl-N'-nitro-N-nitrosoguanidine, N-butyl-N-(4-hydroxybutyl)nitrosamine, dipentylnitrosamine, and nitrilotriacetic acid.

This paper describes factorial experiments designed to determine whether two carcinogens that act on different organ systems act synergistically to produce cancers in Fischer 344 rats. Four carcinogens, N-methyl-N'-nitrosoguanidine (MNNG), N-butanol-N-butylnitrosamine (NBBN), nitilotriacetic acid (NTA), and dipentylnitrosamine (DPN) were studied in pairwise combinations. Each of the six possible pairs was studied by means of a 4 X 4 factorial experiment, each agent being fed at zero and at three non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for single agent studies. Antagonism was demonstrated in some chemical mixtures containing NTA. Other chemical mixtures did not interact. Findings for male and female animals were generally, but not always, in agreement.

Animals↗
PubMed1987

Statistical analysis of a carcinogen mixture experiment. I. Liver carcinogens.

This paper describes factorial experiments designed to determine whether 2 liver carcinogens act synergistically to produce liver cancers in Fischer 344 rats. Four hepatocarcinogens, cycad flour, lasiocarpine (CAS: 303-34-4), aflatoxin B1 (CAS: 1162-65-8), and dipentylnitrosamine (CAS: 13256-06-9), were studied in pairwise combinations. Each of the 6 possible pairs was studied by means of 4 X 4 factorial experiment, each agent being fed at zero and at 3 non-zero doses. Methods of analysis designed explicitly for this study were derived to study interaction. These methods were supplemented by standard statistical methods appropriate for one-at-a-time studies. Antagonism was not discovered in any chemical mixture. Some chemical mixtures did interact synergistically. Findings for male and female animals were generally, but not always, in agreement.

Aflatoxin B1↗
PubMed1987

The association of solar ultraviolet and skin melanoma incidence among caucasians in the United States.

Using recent data from cancer incidence surveys and measures of UVB exposure levels at seven geographic locations within the United States, we estimate the dose-response relation between UVB and skin melanoma incidence. Mathematical models used information from general population interview studies conducted in these locations to adjust for potentially confounding factors such as age, skin color, ancestry, eye color, hair color, sunburn sensitivity, prevalence of moles, freckles, and hours spent outdoors, use of sunscreen/lotion, and other variables. The effect of geographic UVB exposure on incidence was found to be statistically significant (p less than 0.01) after adjusting for each variable and certain combinations of these variables. We found that incidence rates for those skin melanomas arising in the face, head, neck, or upper extremities (i.e, the most exposed sites) were more sensitive to UVB increases than the incidence rates for those lesions occurring in the ordinarily less exposed sites of the trunk and lower extremities.

Female↗
PubMed1986

Logistic regression methods for retrospective case-control studies using complex sampling procedures.

There are a number of possible designs for case-control studies. The simplest uses two separate simple random samples, but an actual study may use more complex sampling procedures. Typically, stratification is used to control for the effects of one or more risk factors in which we are interested. It has been shown (Anderson, 1972, Biometrika 59, 19-35; Prentice and Pyke, 1979, Biometrika 66, 403-411) that the unconditional logistic regression estimators apply under stratified sampling, so long as the logistic model includes a term for each stratum. We consider the case-control problem with stratified samples and assume a logistic model that does not include terms for strata, i.e., for fixed covariates the (prospective) probability of disease does not depend on stratum. We assume knowledge of the proportion sampled in each stratum as well as the total number in the stratum. We use this knowledge to obtain the maximum likelihood estimators for all parameters in the logistic model including those for variables completely associated with strata. The approach may also be applied to obtain estimators under probability sampling.

Clinical Trials as Topic↗
PubMed1985

Psoriasis and susceptibility to nonmelanoma skin cancer.

Using data from a national skin cancer survey, we assessed the risk of basal cell and squamous cell carcinoma among patients with psoriasis compared with the general population. For both male and female psoriatic patients, the risk of basal cell carcinoma was significantly elevated (relative risk = 2.2 and 1.7; p less than 0.05, both comparisons). The risk of squamous cell carcinoma was not significantly or substantially different for persons with a history of psoriasis compared with other persons (relative risk = 1.3; p greater than 0.05). The relative risk of basal cell skin cancer among patients with psoriasis was significantly higher even after stratification for factors associated with both psoriasis and cutaneous malignancy, which include fair complexion, exposure to coal tar or pitch, and exposure to radiation. Contrary to long-standing beliefs, our findings support the hypothesis that even after allowing for possible greater exposures to cutaneous carcinogens, the risk of nonmelanoma skin cancer in patients with psoriasis is at least as great as in the general population. Thus persons with psoriasis who are treated with potential carcinogens such as ultraviolet radiation, tar, and oral methoxsalen photochemotherapy merit careful, long-term monitoring.

Adult↗
PubMed1983

Estimating increases in skin cancer morbidity due to increases in ultraviolet radiation exposure.

It is generally accepted that if ozone levels in the stratosphere are depleted, greater amounts of shortwave ultraviolet radiation (UVB) will reach the earth's surface, resulting in increased morbidity of nonmelanoma skin cancer. The incidence and UVB data are now available from a new epidemiologic study of skin cancer conducted at eight locations of the United States. We found that either a simple power function or a simple exponential function could be used to describe these new data. According to estimates based on the power model, should the amount of exposure to UVB increase by 30%, then the incidence of skin cancer will increase by 60% in males and 45% in females. Estimates based on the exponential model vary by location, (53-96)% in males and (39-68)% in females. These estimates are somewhat lower than those based only on earlier data. We emphasize that skin cancer rates also depend on variables other than UVB which may be location specific.

Adult↗
PubMed1982

Changes in skin cancer morbidity between 1971-72 and 1977-78.

Skin cancer incidence rates for two geographic areas of the United States were analyzed for detection of significant changes in risk over a 6-year period (1971-72 to 1977-78). Changes in rates were examined by cell type, anatomic site, sex, and age. In general risk has increased, but the size of the increase varied by cell type, sex, and anatomic site. Statistically significant increases were limited to tumors of the basal type. The risk of basal cell skin cancer appears to have increased about 18% or almost 3% per year. Increases did not depend on age group. Among males the increases were most notable for sites other than face, head, and neck, whereas among females the increases were not associated with site.

Adult↗
PubMed1981

Exact significance levels for multiple binomial testing with application to carcinogenicity screens.

A simple experimental design consisting of one control group and one or more treatment groups is considered. Relevant research often focuses on the presence or absence of any of several characteristics in the treatment group(s). The statistical analysis frequently includes the comparison of the control group with each treatment group by the use of Fisher-Irwin exact tests for each of many 2 x 2 tables. The multiplicity of comparisons has given rise to concern that individual Fisher-Irwin tests could seriously overstate the experimental evidence in some situations. This paper provides a method for calculating the exact permutational probability of at least one significant Fisher-Irwin test when only one treatment group and one control group is used. For multiple-treatment-group designs, upper and lower bounds on the probability are provided. Emphasis is given throughout to carcinogenesis screening experiments and an example of such an experiment is provided.

Animals↗
PubMed1979

Comparison and evaluation of some experimental designs for use in carcinogen screening.

The development and evaluation of experimental designs for routine in vivo screening of chemicals for potential carcinogenic activity were considered. Such designs have played an important role in the Carcinogenesis Bloassay Program of the National Cancer Institute (NCI). In particular, the current one-stage 50-animal/group screen used by the NCI was considered. A specific two-stage alternative was proposed in which 35 animals/group were used; this alternative allowed for retesting of equivocal compounds. The proposed designs were evaluated in terms of sensitivity, specificity, and throughout. Despite the large number of tests made for each compound, the false-positive rate was found to be less than 0.07 for the current screen and less than 0.05 for the proposed two-stage alternative. The power of the one-stage and two-stage screens was comparable. The two-stage screen was shown to make about 30% more decisions per test period with a savings of around 28% in the expected number of animals needed per compound tested.

Animals↗
PubMed1979

Evaluation of procedures suggested for reducing the pathology workload in a carcinogenesis testing program.

A sampling procedure for reducing the pathology workload in evaluating a carcinogenicity bioassay was utilized for a rodent bioassay. The use of the procedure resulted in 50 percent fewer tissues being examined histologically, in the control groups and 12 percent fewer tissues in the treatment groups. The obvious saving in pathologist's time was negated by an increase in technician time, interference with quality control procedures and loss of nontumor pathology information.

Animals↗
PubMed1978

Skin cancer epidemiology: research needs.

The basis data currently being used to estimate and evaluate the dose-response relationship of UV-B and skin cancer are from a 6-month survey for four areas that participated in the TNCS, 1971-1972. Although most investigators from various fields of interest outside of cancer research, i.e. aviation, environmental ecology, physics, chemistry, and photobiology, etc., may admit an association between nonmelanoma skin cancer and UV-B exists, they point out that 1) the epidemiologic data currently available are too sparse and lack certain detail, such as exposure patterns and skin types, and 2) more data of this type are needed over a broad geographical range to allow for more precise measurements of the effects of stratospheric ozone depletion. They argue that the present relationships could change drastically with the addition even of a few more points (geographical locations) and that location-specific and demographic factors should be evaluated. Therefore, these data need to be updated and expanded to include more locations over a longer study period. The National Cancer Institute and the Environmental Protection Agency undertook a special skin cancer study from June 1, 1977 to May 31, 1978. The objectives of this study were: 1) to determine the incidence of nonmelanoma skin cancer (basal cell and squamous cell carcinomas) in various population groups within the United States, and 2) to ascertain and measure epidemiologic factors that may contribute toward the excess risk of nonmelanoma skin cancer in specific population groups.

Adolescent↗
PubMed1977

Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States.

That sunlight leads to skin cancer has been generally accepted for nearly a century. Physical data are, for the first time, available which support this hypothesis. The authors have found that a simple power relationship can be used to describe the data and that the form of this power function suggests that the risk of nonmelanoma skin cancer is related to cumulative lifetime ultraviolet (UV) exposure and that the risk of melanoma skin cancer is related to annual UV exposure. The authors emphasize that skin cancer risk also depends on location-specific demographic variables other than ultraviolet radiation.

Adult↗
PubMed1977

False-positive and false-negative rates for carcinogenicity screens.

The implementation of a number of chemical carcinogen screening programs has been accompanied by the observation that some screens might have high false-positive error rates. With designs presently used at the National Cancer Institute and historical spontaneous tumor rates based upon control animals in previous experiments, we compute upper bounds on the false-positive error rates for several screening strategies. False-positive results are much less likely to occur at tissue sites with low spontaneous tumor rates; hence the site at which a significant tumor increase occurs is important. There is danger in relying solely upon the finding of statistical significance without incorporating biological knowledge and corroborative evidence such as the presence of a dose-response relationship or experimentally consistent results in different species or sexes. A report by the National Cancer Institute Carcinogenesis Program demonstrates these concepts.

Animals↗
PubMed1976

Cancer mortality and asbestos deposits.

Asbestos deposits are found in many parts of the United States. In this paper the question is asked: Is there an increase in risk from cancer associated with naturally-occurring asbestos? In an attempt to control for the urban effect, geographic gradient and socioeconomic class, each county in the United States with asbestos deposits was matched for percent of area that was urban and for median years in school with two nearby counties that did not have known asbestos deposits. The study of cancer mortality rates in these matched counties provides no evidence that naturally-occurring asbestos is a great hazard to the general population of counties with asbestos depostis.

Age Factors↗