Limitations to empirical extrapolation studies: the case of BMD ratios.

Extrapolation relationships are of keen interest to chemical risk assessment in which they play a prominent role in translating experimentally derived (usually in animals) toxicity estimates into estimates more relevant to human populations. A standard approach for characterizing each extrapolation relies on ratios of pre-existing toxicity estimates. Applications of this "ratio approach" have overlooked several sources of error. This article examines the case of ratios of benchmark doses, trying to better understand their informativeness. The approach involves mathematically modeling the process by which the ratios are generated in practice. Both closed form and simulation-based models of this "data-generating process" (DGP) are developed, paying special attention to the influence of experimental design. The results show the potential for significant limits to informativeness, and revealing dependencies. Future applications of the ratio approach should take imprecision and bias into account. Bootstrap techniques are recommended for gauging imprecision, but more complicated techniques will be required for gauging bias (and capturing dependencies). Strategies for mitigating the errors are suggested.

Assessing the public health benefits of reduced ozone concentrations.

In this paper we examine scientific evidence and related uncertainties in two steps of benefit-cost analyses of ozone reduction: estimating the health improvements attributable to reductions in ozone and determining the appropriate monetary values of these improvements. Although substantial evidence exists on molecular and physiologic impacts, the evidence needed to establish concentration-response functions is somewhat limited. Furthermore, because exposure to ozone depends on factors such as air conditioning use, past epidemiologic studies may not be directly applicable in unstudied settings. To evaluate the evidence likely to contribute significantly to benefits, we focus on four health outcomes: premature mortality, chronic asthma, respiratory hospital admissions, and minor restricted activity days. We determine concentration-response functions for these health outcomes for a hypothetical case study in Houston, Texas, using probabilistic weighting reflecting our judgment of the strength of the evidence and the possibility of confounding. We make a similar presentation for valuation, where uncertainty is due primarily to the lack of willingness-to-pay data for the population affected by ozone. We estimate that the annual monetary value of health benefits from reducing ozone concentrations in Houston is approximately $10 per person per microgram per cubic meter (24-hr average) reduced (95% confidence interval, $0.70-$40). The central estimate exceeds past estimates by approximately a factor of five, driven by the inclusion of mortality. We discuss the implications of our findings for future analyses and determine areas of research that might help reduce the uncertainties in benefit estimation.

Modeling for health care and other policy decisions: uses, roles, and validity.

The role of models to support recommendations on the cost-effective use of medical technologies and pharmaceuticals is controversial. At the heart of the controversy is the degree to which experimental or other empirical evidence should be required prior to model use. The controversy stems in part from a misconception that the role of models is to establish truth rather than to guide clinical and policy decisions. In other domains of public policy that involve human life and health, such as environmental protection and defense strategy, models are generally accepted as decision aids, and many models have been formally incorporated into regulatory processes and governmental decision making. We formulate an analytical framework for evaluating the role of models as aids to decision making. Implications for the implementation of Section 114 of the Food and Drug Administration Modernization Act (FDAMA) are derived from this framework.

Public attitudes about genetic testing for Alzheimer's disease.

In a general population survey (N = 314), 79 percent of respondents stated that they would take a hypothetical genetic test to predict whether they will eventually develop Alzheimer's disease. The proportion fell to 45 percent for a "partially predictive" test (which had a one in ten chance of being incorrect). Inclination to obtain testing was similar across age groups. Respondents were willing to pay $324 for the completely predictive test. Respondents stated that if they tested positive, they would sign advance directives (84 percent), get their finances in order (74 percent), and purchase long-term care insurance (69 percent). Only a third of respondents expressed concern about confidentiality. The results suggest that people value genetic testingfor personal and financial reasons, but they also underscore the need to counsel potential recipients carefully about the accuracy and implications of test information.

Perceived risks of conventional and organic produce: pesticides, pathogens, and natural toxins.

Public risk perceptions and demand for safer food are important factors shaping agricultural production practices in the United States. Despite documented food safety concerns, little attempt has been made to elicit consumers' subjective risk judgments for a range of food safety hazards or to identify factors most predictive of perceived food safety risks. In this study, over 700 conventional and organic fresh produce buyers in the Boston area were surveyed for their perceived food safety risks. Survey results showed that consumers perceived relatively high risks associated with the consumption and production of conventionally grown produce compared with other public health hazards. For example, conventional and organic food buyers estimated the median annual fatality rate due to pesticide residues on conventionally grown food to be about 50 per million and 200 per million, respectively, which is similar in magnitude to the annual mortality risk from motor vehicle accidents in the United States. Over 90% of survey respondents also perceived a reduction in pesticide residue risk associated with substituting organically grown produce for conventionally grown produce, and nearly 50% perceived a risk reduction due to natural toxins and microbial pathogens. Multiple regression analyses indicate that only a few factors are consistently predictive of higher risk perceptions, including feelings of distrust toward regulatory agencies and the safety of the food supply. A variety of factors were found to be significant predictors of specific categories of food hazards, suggesting that consumers may view food safety risks as dissimilar from one another. Based on study findings, it is recommended that future agricultural policies and risk communication efforts utilize a comparative risk approach that targets a range of food safety hazards.

Using life expectancy to communicate benefits of health care programs in contingent valuation studies.

BACKGROUND: There is growing interest in the use of contingent valuation (CV) to estimate the monetary value of health program benefits. Ideally, CV could be used to value a specific shift in survival curve. However, a shift in survival curve may prove too complex for widespread use in CV instruments. To facilitate the use of CV in valuing longevity benefits, researchers need alternative summary measures that describe the longevity benefit in a single number that is more readily communicated in a CV context. METHODS: The authors compare 2 methods for communicating longevity benefits in a CV survey. Random subsamples of respondents valued a longevity benefit expressed either as a continuing reduction in annual mortality risk or as a gain in life expectancy. To compare the validity of the alternative descriptions, the authors evaluate willingness to pay (WTP) estimates for consistency with theoretical predictions. RESULTS: It is found that WTP for a longevity benefit is sensitive to the framing of the benefit, with respondents expressing higher WTP for the benefit expressed as a life expectancy gain. The life expectancy format performs better than the risk reduction format in one important regard-sensitivity to scope of the benefit-and no worse than the risk reduction format in other regards. CONCLUSION: Expressing longevity benefits in terms of life expectancy appears to hold promise as a method for enhancing the validity of economic evaluation of health care programs.

A comparison of organic and conventional fresh produce buyers in the Boston area.

Food safety concerns and the demand for organically grown produce have increased significantly in the United States over the last decade. Key differences in lifestyle characteristics, food safety attitudes and beliefs, perceived food safety risks, and valuation of health risk reductions between organic and conventional food buyers remain largely unknown, however. To better characterize how buyers of organic fresh produce differ from their conventional counterparts, over 700 food shoppers were sampled from ten major retail stores in the Boston area. Survey results show that self-reported organic buyers are more likely than conventional buyers to engage in a variety of health-promoting and environmentally friendly behaviors. Organic buyers are less trusting of federal food safety agencies than are conventional buyers, and perceive greater benefits associated with organically grown produce than do their conventional counterparts. Further, organic buyers have significantly higher risk perceptions than do conventional buyers for food safety hazards associated with conventionally grown produce. Compared to conventional buyers, organic produce buyers also perceive significant risk reductions associated with switching to organically grown produce and are willing to pay a higher price to reduce perceived food safety risks. Few sociodemographic differences between buyer types were observed, possibly due to how organic and conventional food stores were matched. Survey findings highlight the need for greater public education about a range of food safety issues and farming practices to ensure that consumers are making informed decisions in the marketplace.

Risk/risk trade-offs in pesticide regulation: an exploratory analysis of the public health effects of a ban on organophosphate and carbamate pesticides.

Efforts to reduce pesticide-related risks to consumers and farmworkers often neglect the possibility that measures to reduce the target risk may introduce or enhance countervailing risks. These may arise from substitute pesticides or pest-control practices, from increased levels of pests or pest-related hazards, from increased levels of toxic natural pesticides in plants, from increased costs and decreased consumption of health-enhancing fruits and vegetables, or from direct income effects on consumers and farmers. The effect of the countervailing risks may partially or completely offset the reduction in the target risk. A risk-trade-off analysis was conducted of a potential ban on the use of organophosphate and carbamate (OP/Carbamate) insecticides in U.S. agriculture. Although this scenario is extreme, it has the analytic virtue of dispensing with the infinite number of "next-best" OP/Carbamates that might be substituted for specific combinations of crops and pests should only selected uses be banned. The analysis relies on detailed descriptions of the alternative pesticides and pest-control measures that would be used for each of 14 major crops. The effects of pest-control cost changes on prices and consumption and effects on consumer and producer incomes are projected using a general-equilibrium economic model. Several countervailing risks that may be significant were found, including acute toxicity to farmworkers from substitute pesticides, cancer and noncancer risks from substitute pesticides, and mortality induced by changes in disposable income. Other countervailing risks are more difficult to estimate or weigh. Potential increases in natural plant pesticides following an OP/Carbamate ban are discussed but data are lacking to quantify the effects. Changes in diet following the ban have both positive and negative effects, and the ultimate change is difficult to estimate. Although a net risk cannot be estimated, several approaches were illustrated that would be useful in risk-trade-off analyses. Key factors complicating comprehensive analysis of risk/risk trade-offs for pesticides were also identified, including data gaps and shortcomings of current risk assessment methods.

Mother's willingness to pay for her own and her child's health: a contingent valuation study in Taiwan.

We use the contingent valuation (CV) method to estimate mothers' willingness to pay (WTP) to protect themselves and their children from suffering a minor illness-a cold-in Taiwan. WTP is specified as a hedonic function of the duration and severity of the cold (measured alternatively by symptoms experienced and the Quality of Well-Being (QWB) index) and of respondents' socioeconomic characteristics. The average mother is willing to pay more to protect her child than herself from suffering a cold. Median WTP to avoid the average mother's and child's colds are US$37 and US$57, respectively. Adjusting for the greater duration and severity of the average mother's cold suggests that WTP to prevent comparable illnesses is approximately twice as large for the child as for the mother. We also find that mother's WTP is about 20% greater to prevent a son's than a daughter's illness.

Estimating the mortality impacts of particulate matter: what can be learned from between-study variability?

Epidemiologic studies of the link between particulate matter (PM) concentrations and mortality rates have yielded a range of estimates, leading to disagreement about the magnitude of the relationship and the strength of the causal connection. Previous meta-analyses of this literature have provided pooled effect estimates, but have not addressed between-study variability that may be associated with analytical models, pollution patterns, and exposed populations. To determine whether study-specific factors can explain some of the variability in the time-series studies on mortality from particulate matter [less than/equal to] 10 microm in aerodynamic diameter (PM(10)), we applied an empirical Bayes meta-analysis. We estimate that mortality rates increase on average by 0.7% per 10 microg/m(3) increase in PM(10) concentrations, with greater effects at sites with higher ratios of particulate matter [less than/equal to] 2.5 microm in aerodynamic diameter (PM(2.5))/PM(10). This finding did not change with the inclusion of a number of potential confounders and effect modifiers, although there is some evidence that PM effects are influenced by climate, housing characteristics, demographics, and the presence of sulfur dioxide and ozone. Although further analysis would be needed to determine which factors causally influence the relationship between PM(10) and mortality, these findings can help guide future epidemiologic investigations and policy decisions.

Equity, efficiency, uncertainty, and the mitigation of global climate change.

Policies to mitigate potential damages from global climate change impose costs on the current generation to provide benefits to future generations. This article examines how comparisons among three stylized policies-business-as-usual, mitigation of climate change, and compensation for climate damages-depend on social preferences with respect to risk and intertemporal equity. Also examined is the opportunity-cost criterion, which asserts that mitigation should not be chosen if its net present value is smaller than that of business-as-usual. Analysis reveals that the discount factor used to evaluate whether mitigation satisfies this criterion depends on preferences regarding risk and intertemporal inequality of consumption, and on the risk of the compensation policy. Risk aversion favors mitigation over business-as-usual. If society is neutral to inequality, risk aversion disfavors compensation, but if society is inequality averse, the effect of risk aversion on preferences between compensation and business-as-usual is ambiguous. Inequality aversion tends to favor business-as-usual over both alternative policies provided that, roughly speaking, the anticipated future improvements in welfare exceed the anticipated climate damages.

Residential building codes, affordability, and health protection: a risk-tradeoff approach.

Residential building codes intended to promote health and safety may produce unintended countervailing risks by adding to the cost of construction. Higher construction costs increase the price of new homes and may increase health and safety risks through "income" and "stock" effects. The income effect arises because households that purchase a new home have less income remaining for spending on other goods that contribute to health and safety. The stock effect arises because suppression of new-home construction leads to slower replacement of less safe housing units. These countervailing risks are not presently considered in code debates. We demonstrate the feasibility of estimating the approximate magnitude of countervailing risks by combining the income effect with three relatively well understood and significant home-health risks. We estimate that a code change that increases the nationwide cost of constructing and maintaining homes by $150 (0.1% of the average cost to build a single-family home) would induce offsetting risks yielding between 2 and 60 premature fatalities or, including morbidity effects, between 20 and 800 lost quality-adjusted life years (both discounted at 3%) each year the code provision remains in effect. To provide a net health benefit, the code change would need to reduce risk by at least this amount. Future research should refine these estimates, incorporate quantitative uncertainty analysis, and apply a full risk-tradeoff approach to real-world case studies of proposed code changes.

The price elasticity of opium in Taiwan, 1914-1942.

Between 1895 and 1945, the Japanese colonial government virtually eliminated opium use in Taiwan by licensing and treating existing users, prohibiting sales to others, and raising the price. We evaluate these policies using a two-part model to describe the fraction of the population using opium and consumption among users, and the rational addiction model by Becker et al. (1991). We confirm that opium is addictive and find no evidence supporting the rational addiction hypothesis. Demand is price-elastic with estimated short- and long-run demand elasticities of -0.48 and -1.38. These results have implications for control of other addictive substances.

Estimating general-population utilities using one binary-gamble question per respondent.

This study used a single binary-gamble question per health state per respondent to obtain societal preferences for the health states intermittent claudication and major amputation and compare those with Health Utilities Indices obtained from patients, to test the feasibility of this method, and to investigate whether the utility depends on the presentation of a vignette as generic vs disease-specific. A random sample of the general U.S. population (n = 1,003) was randomly divided into ten subgroups. In telephone interviews, subjects answered one binary-gamble question in a standard-gamble format for each of two health states. The risks of death varied across subgroups but not between health states. Mean utility was estimated by the area above the proportional distribution of responses indicating acceptance of the gamble. The method is based on the binary-choice method used in contingent-valuation studies of willingness to pay. The health states were alternatively described by generic and disease-specific vignettes in two subsamples. The results suggest that the binary-gamble question can be used to obtain societal preferences for health states, and that disease-specific descriptions yield lower utilities compared with generic descriptions of health states.

Finding the optimal multiple-test strategy using a method analogous to logistic regression: the diagnosis of hepatolenticular degeneration (Wilson's disease).

Finding the optimal strategy among a battery of tests may be cumbersome for decision analytic models. The authors present a method of examining multiple test combinations that is based on a modified Bayes' formula analogous to logistic regression. They examined all 16 combinations of four tests used to diagnose hepatolenticular degeneration. The four tests examined were: serum ceruloplasmin level, 24-hour urinary copper excretion, free serum copper level, and liver biopsy copper concentration. They also simulated the diagnostic workup of the disease for a hypothetical cohort of 15,000 patients at risk. Assuming the disutilities of false positives and false negatives to be equal, and considering sensitivity analysis of test characteristics, the following test combinations were found to be optimal for making the diagnosis at a prior probability of disease equal to 0.05: positive serum ceruloplasmin and 24-hour urinary copper excretion, combined with either positive liver biopsy or free serum copper (or both). The strategies obtained by the modified Bayes' formula were the same as those found using the simulated data set with a standard logistic-regression software package. The logistic model's diagnostic accuracy is 0.98 as measured by the area under the receiver operating characteristic curve. The optimal strategy for diagnosing hepatolenticular degeneration varies with the prior probability of disease. For prior probabilities of 0.05, 0.25, and 0.9, and the optimal strategy, model sensitivities are 0.801, 0.880, and 0.997, and model specificities are 0.991, 0.985, and 0.814, respectively. The new method provides a convenient alternative to decision trees when examining multiple diagnostic tests.

Risk perceptions and food choice: an exploratory analysis of organic- versus conventional-produce buyers.

Consumer choice between organically (without pesticides) and conventionally grown produce is examined. Exploratory focus-group discussions and questionnaires (N = 43) suggest that individuals who purchase organically grown produce believe it is substantially less hazardous than the conventional alternative and are willing to pay significant premiums to obtain it (a median 50% above the cost of conventional produce). The value of risk reduction implied by this incremental willingness to pay is not high relative to estimates for other risks, since the perceived risk reduction is relatively large. Organic-produce consumers also appear more likely than conventional-produce consumers to mitigate other ingestion-related risks (e.g., contaminated drinking water) but less likely to use automobile seatbelts.