Tests in a Case–control Design Including Relatives

Abstract.  We present a new approach to handle dependencies within the general framework of case–control designs, illustrating our approach by a particular application from the field of genetic epidemiology. The method is derived for parent–offspring trios, which will later be relaxed to more general family structures. For applications in genetic epidemiology we consider tests on equality of allele frequencies among cases and controls utilizing well-known risk measures to test for independence of phenotype and genotype at the observed locus. These test statistics are derived as functions of the entries in the associated contingency table containing the numbers of the alleles under consideration in the case and the control group. We find the joint asymptotic distribution of these entries, which enables us to derive critical values for any test constructed on this basis. A simulation study reveals the finite sample behaviour of our test statistics.     

Direct Inference, Probability, and a Conceptual Gulf in Risk Communication

Differences in the conceptual frameworks of scientists and nonscientists may create barriers to risk communication. This article examines two such conceptual problems. First, the logic of "direct inference" from group statistics to probabilities about specific individuals suggests that individuals might be acting rationally in refusing to apply to themselves the conclusions of regulatory risk assessments. Second, while regulators and risk assessment scientists often use an "objectivist" or "relative frequency" interpretation of probability statements, members of the public are more likely to adopt a "subjectivist" or "degree of confidence" interpretation when estimating their personal risks, and either misunderstand or significantly discount the relevance of risk assessment conclusions. If these analyses of inference and probability are correct, there may be a conceptual gulf at the center of risk communication that cannot be bridged by additional data about the magnitude of group risk. Suggestions are made for empirical studies that might help regulators deal with this conceptual gulf.     

Compressed Natural Gas Bus Safety: A Quantitative Risk Assessment

This study assesses the fire safety risks associated with compressed natural gas (CNG) vehicle systems, comprising primarily a typical school bus and supporting fuel infrastructure. The study determines the sensitivity of the results to variations in component failure rates and consequences of fire events. The components and subsystems that contribute most to fire safety risk are determined. Finally, the results are compared to fire risks of the present generation of diesel-fueled school buses. Direct computation of the safety risks associated with diesel-powered vehicles is possible because these are mature technologies for which historical performance data are available. Because of limited experience, fatal accident data for CNG bus fleets are minimal. Therefore, this study uses the probabilistic risk assessment (PRA) approach to model and predict fire safety risk of CNG buses. Generic failure data, engineering judgments, and assumptions are used in this study. This study predicts the mean fire fatality risk for typical CNG buses as approximately 0.23 fatalities per 100-million miles for all people involved, including bus passengers. The study estimates mean values of 0.16 fatalities per 100-million miles for bus passengers only. Based on historical data, diesel school bus mean fire fatality risk is 0.091 and 0.0007 per 100-million miles for all people and bus passengers, respectively. One can therefore conclude that CNG buses are more prone to fire fatality risk by 2.5 times that of diesel buses, with the bus passengers being more at risk by over two orders of magnitude. The study estimates a mean fire risk frequency of 2.2 x 10(-5) fatalities/bus per year. The 5% and 95% uncertainty bounds are 9.1 x 10(-6) and 4.0 x 10(-5), respectively. The risk result was found to be affected most by failure rates of pressure relief valves, CNG cylinders, and fuel piping.     

A family of admissible minimax estimators of the mean of a multivariate,normal distribution

Let X has a p-dimensional normal distribution with mean vector θ and identity covariance matrix I. In a compound decision problem consisting of squared-error estimation of θ, Strawderman (1971) placed a Beta (α, 1) prior distribution on a normal class of priors to produce a family of Bayes minimax estimators. We propose an incomplete Gamma(α, β) prior distribution on the same normal class of priors to produce a larger family of Bayes minimax estimators. We present the results of a Monte Carlo study to demonstrate the reduced risk of our estimators in comparison with the Strawderman estimators when θ is away from the zero vector.     

A general guideline for management of risk from carcinogens

A simple relationship is formulated that helps to discriminate between acceptable and unacceptable individual lifetime risks (RL) to populations that are exposed to chemical carcinogens. The relationship is an empirical one and is developed using objective risk data as well as subjective risk levels that have found substantial acceptance among those concerned with carcinogenic risk assessment issues. The expression sets acceptable levels of lifetime carcinogenic risk and is a function of the total population exposed to the carcinogen. Its use in risk assessment and risk management provides guidance in distinguishing those carcinogens that should be regulated because of the health hazard they pose from those whose regulation may not be needed.     

Does a Reactor Need a Safety Backfit? Case Study on Communicating Decision and Risk Analysis Information to Managers

An approach to communicating decision and risk analysis findings to managers is illustrated in a real case context. This article consists essentially of a report prepared for senior managers of the Nuclear Regulatory Commission to help them make a reactor safety decision. It illustrates the communication of decision analysis findings relating to technical risks, costs, and benefits in support of a major risk management decision: whether or not to require a safety backfit. Its focus is on the needs of decision makers, and it introduces some novel communication devices.     

Bayesian incorporation of repeated measurements in logistic discrimination

A common problem in medical statistics is the discrimination between two groups on the basis of diagnostic information. Information on patient characteristics is used to classify individuals into one of two groups: diseased or disease-free. This classification is often with respect to a particular disease. This discrimination has two probabilistic components: (1) the discrimination is not without error, and (2) in many cases the a priori chance of disease can be estimated. Logistic models (Cox 1970; Anderson 1972) provide methods for incorporating both of these components. The a posteriori probability of disease may be estimated for a patient on the basis of both current measurement of patient characteristics and prior information. The parameters of the logistic model may be estimated on the basis of a calibration trial. In practice, not one but several sets of measurements of one characteristic of the patient may be made on a questionable case. These measurements typically are correlated; they are far from independent. How should these correlated measurements be used? This paper presents a method for incorporating several sets of measurements in the classification of a case.     

Errors in Estimates of Smoking-Related Deaths Derived from Nonsmoker Mortality

A number of recent analyses have computed present and future costs associated with a risk by estimating what would happen if the risk were absent. Two sources of bias are associated with this approach: (1) differences in confounding factors between present risk avoiders and risk takers, and (2) the difficulty of selecting an unbiased sample of risk avoiders. A staff memo from the Office of Technology Assessment used this approach to estimate mortality due to smoking. Numbers of deaths and age at death distributions of U.S. smokers and nonsmokers for all causes, all cancers, lung cancers, heart disease, and cerebrovascular lesions are used to assess the accuracy of these estimates. Large errors in the OTA estimates are found. Conditions are discussed that might help reduce errors from this approach.     

Hazardous Waste Incineration at Sea: EPA Decision Making on Risk

This paper critiques the Environmental Protection Agency's assessment of risk for hazardous waste incineration at sea. It reviews operational and transportation risks and considers alternative approaches for managing chlorinated organic hazardous wastes. It concludes that depending on the scale of the program, ocean incineration will either contribute little to the overall management of this waste stream or else it will engender significant risks, especially in the coastal environment. Furthermore, past assessments on the part of EPA have tended to understate the risks of incineration at sea while simultaneously holding out the promise of the technology as a commercial-scale management option. Finally, this paper observes that the Western European countries that pioneered incineration in the North Sea are now finding practical alternatives. It is recommended that waste reuse, on-site treatment, and techniques of waste reduction provide viable alternatives and obviate the need for incineration at sea.     

The Risks of Using Nuclear Energy Sources in Space: Some Lay Activists'Perceptions

A combination of directive and nondirective techniques was used to study the mental models of 30 lay activists regarding the risks of nuclear energy sources in space. Respondents'perceptions were compared with an "expert model" of the processes generating and controlling these risks, in terms of both the substance of their beliefs and several statistical measures of their performance. These analyses revealed a complex pattern of strengths and weaknesses. Their details are used to derive recommendations for formulating messages about these risks.