Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

Statistical Distributions of Daily Breathing Rates for Narrow Age Groups of Infants and Children

Children may be more susceptible to toxicity from some environmental chemicals than adults. This susceptibility may occur during narrow age periods (windows), which can last from days to years depending on the toxicant. Breathing rates specific to narrow age periods are useful to assess inhalation dose during suspected windows of susceptibility. Because existing breathing rates used in risk assessment are typically for broad age ranges or are based on data not representative of the population, we derived daily breathing rates for narrow age ranges of children designed to be more representative of the current U.S. children's population. These rates were derived using the metabolic conversion method of Layton (1993) and energy intake data adjusted to represent the U.S. population from a relatively recent dietary survey (CSFII 1994–1996, 1998). We calculated conversion factors more specific to children than those previously used. Both nonnormalized (L/day) and normalized (L/kg-day) breathing rates were derived and found comparable to rates derived using energy estimates that are accurate for the individuals sampled but not representative of the population. Estimates of breathing rate variability within a population can be used with stochastic techniques to characterize the range of risk in the population from inhalation exposures. For each age and age-gender group, we present the mean, standard error of the mean, percentiles (50th, 90th, and 95th), geometric mean, standard deviation, 95th percentile, and best-fit parametric models of the breathing rate distributions. The standard errors characterize uncertainty in the parameter estimate, while the percentiles describe the combined interindividual and intra-individual variability of the sampled population. These breathing rates can be used for risk assessment of subchronic and chronic inhalation exposures of narrow age groups of children.     

Non-ignorable missing covariate data in survival analysis: a case-study of an International Breast Cancer Study Group trial

Summary.  Non-ignorable missing data, a serious problem in both clinical trials and observational studies, can lead to biased inferences. Quality-of-life measures have become increasingly popular in clinical trials. However, these measures are often incompletely observed, and investigators may suspect that missing quality-of-life data are likely to be non-ignorable. Although several recent references have addressed missing covariates in survival analysis, they all required the assumption that missingness is at random or that all covariates are discrete. We present a method for estimating the parameters in the Cox proportional hazards model when missing covariates may be non-ignorable and continuous or discrete. Our method is useful in reducing the bias and improving efficiency in the presence of missing data. The methodology clearly specifies assumptions about the missing data mechanism and, through sensitivity analysis, helps investigators to understand the potential effect of missing data on study results.     

A class of count models and a new consistent test for the Poisson distribution

We define a class of count distributions which includes the Poisson as well as many alternative count models. Then the empirical probability generating function is utilized to construct a test for the Poisson distribution, which is consistent against this class of alternatives. The limit distribution of the test statistic is derived in case of a general underlying distribution, and efficiency considerations are addressed. A simulation study indicates that the new test is comparable in performance to more complicated omnibus tests.     

Intersensory Redundancy Enhances Memory in Bobwhite Quail Embryos

Information presented concurrently and redundantly to 2 or more senses (intersensory redundancy) has been shown to recruit attention and promote perceptual learning of amodal stimulus properties in animal embryos and human infants. This study examined whether the facilitative effect of intersensory redundancy also extends to the domain of memory. We assessed bobwhite quail chicks' ability to remember and prefer an individual maternal call presented either unimodally or redundantly and synchronously with patterned light during the period prior to hatching. Embryos provided with unimodal auditory exposure failed to prefer the familiar call over a novel maternal call postnatally at 48 hr and 72 hr following exposure. In contrast, embryos provided with redundant, synchronous audiovisual stimulation significantly preferred the familiar call at 48 hr following exposure, but not at 72 hr. A second experiment provided chicks with a single 10‐min refamiliarization with the familiar call at either 48 hr or 72 hr following hatching. Chicks given only unimodal auditory exposure prior to hatching did not appear to benefit from this brief postnatal refamiliarization, showing no preference for the familiar call at either 72 or 96 hr. Chicks that received redundant audiovisual stimulation prenatally showed a significant preference for the familiar call (following the brief reexpo sure 24 hr earlier) at both 72 and 96 hr of age. These results are the first to demonstrate that redundantly specified information is remembered longer and reactivated more easily than the same information presented unimodally. These findings provide further evidence of the salience of intersensory redundancy in guiding selective attention and perceptual learning during early development.     

Consumption and Saving Behavior of Older and Younger Baby Boomers in Korea

The 1998 Korean Survey of Family Income and Expenditures was used to examine the overall consumption and saving behavior of Korean baby boomers and compared the differences in consumption and saving behavior between older and younger boomers. The t -test results indicated that the younger boomers allocated a significantly higher percentage of their expenditures on food away from home, household appliances, transportation and communication than did the older boomers, whereas the older boomers spent higher amounts and allocated larger budget shares on their children's education than did the younger boomers. The results of Ordinary Least-Squares (OLS) regression analysis showed that, holding other factors constant, older boomers not only spent significantly more in the total consumption expenditures and education expenditures, but older boomers also saved significantly less than did younger boomers.     

Automobile prices and protection: The U.S.-Japan trade restraint

We examine the effects of the U.S.-Japan trade restraint on automobile prices and quality upgrading, for both Japanese imports and American small cars. From April 1981 to April 1984 the suggested retail price of all Japanese models increased by 15.8 percent, or 5.3 percent per year. We find that nearly the entire amount of this rise can be explained by the upgrading of individual models. This upgrading may benefit consumers who would purchase a luxury import in any case, but harms those who desire the basic imports. In addition to upgrading, we conclude that a second cost of the trade restraint has been to prevent the yen depreciation from being passed onto American consumers, in terms of lower imported auto prices. For U.S. small cars we find a 9.1 percent rise in the suggested retail price, or 3 percent per year, with a fraction of this amount due to model upgrading. If the yen depreciation had led to lower import prices without the trade restraint, then we expect that U.S. auto prices would have been lower, too.     

Expectations, Capital Gains, and Income

A theoretical framework for the measurement of income under uncertainty is developed that addresses some long-standing controversies about the treatment of capital gains. The consequences for economic analysis and policy making are potentially serious, because the treatment of capital gains can significantly affect some major macroeconomic aggregates, including national income and savings, balance of payments deficits, government deficits, and depreciation. (JEL O47 , P44 , Q32 )