A convenient formula for sample size calculations in clinical trials with multiple co-primary continuous endpoints

The clinical efficacy of a new treatment may often be better evaluated by two or more co-primary endpoints. Recently, in pharmaceutical drug development, there has been increasing discussion regarding establishing statistically significant favorable results on more than one endpoint in comparisons between treatments, which is referred to as a problem of multiple co-primary endpoints. Several methods have been proposed for calculating the sample size required to design a trial with multiple co-primary correlated endpoints. However, because these methods require users to have considerable mathematical sophistication and knowledge of programming techniques, their application and spread may be restricted in practice. To improve the convenience of these methods, in this paper, we provide a useful formula with accompanying numerical tables for sample size calculations to design clinical trials with two treatments, where the efficacy of a new treatment is demonstrated on continuous co-primary endpoints. In addition, we provide some examples to illustrate the sample size calculations made using the formula. Using the formula and the tables, which can be read according to the patterns of correlations and effect size ratios expected in multiple co-primary endpoints, makes it convenient to evaluate the required sample size promptly.     

Behavior of Victims and Information Processing during the Great Hanshin-Awaji Earthquake

Abstract  The Great Hanshin-Awaji earthquake revealed the inadequacy of research in the area of information studies. There is a lack of research on the availability of information on daily life which could alleviate suffering during the reconstruction period. The purpose of this paper is to confirm whether residents receive sufficient information to assist them in making rational decisions during the Great Hanshin-Awaji Earthquake. Our research findings are as follows: (1) People's capacity to send information was very low early in the emergency period. (2) The channel of communication depended on whether people stayed in their own homes or lived elsewhere during the evacuation period. (3) The use of mass media by the aged (both in terms of receiving and sending information) was low. (4) The higher the damage to utilities, the higher was the levels of dissatisfaction with the existing means of information. Most people wished direct communications between the municipality and the victims. (5) Consummatory information on the actual situation was offered effectively by mass media in the stricken area. Similarly important information to support life in the stricken areas was offered by many volunteer groups.     

Sequential parallel comparison design with two coprimary endpoints

A placebo‐controlled randomized clinical trial is required to demonstrate that an experimental treatment is superior to its corresponding placebo on multiple coprimary endpoints. This is particularly true in the field of neurology. In fact, clinical trials for neurological disorders need to show the superiority of an experimental treatment over a placebo in two coprimary endpoints. Unfortunately, these trials often fail to detect a true treatment effect for the experimental treatment versus the placebo owing to an unexpectedly high placebo response rate. Sequential parallel comparison design (SPCD) can be used to address this problem. However, the SPCD has not yet been discussed in relation to clinical trials with coprimary endpoints. In this article, our aim was to develop a hypothesis‐testing method and a method for calculating the corresponding sample size for the SPCD with two coprimary endpoints. In a simulation, we show that the proposed hypothesis‐testing method achieves the nominal type I error rate and power and that the proposed sample size calculation method has adequate power accuracy. In addition, the usefulness of our methods is confirmed by returning to an SPCD trial with a single primary endpoint of Alzheimer disease‐related agitation.     

On Z-estimation by rounded data

It is often assumed in statistics that the random variables under consideration come from a continuous distribution. However, real data is always given in a rounded (discretized) form. The rounding errors become serious when the sample size is large. In this paper, we consider the situation where the mesh of discretization tends to zero as the sample size tends to infinity, and give some sets of sufficient conditions under which the rounding errors can be asymptotically ignored, in the context of Z-estimation. It is theoretically proved that the mid-point discretization is preferable.     

Sample size determination for clinical trials with co‐primary outcomes: exponential event times

Clinical trials with event‐time outcomes as co‐primary contrasts are common in many areas such as infectious disease, oncology, and cardiovascular disease. We discuss methods for calculating the sample size for randomized superiority clinical trials with two correlated time‐to‐event outcomes as co‐primary contrasts when the time‐to‐event outcomes are exponentially distributed. The approach is simple and easily applied in practice. Copyright © 2012 John Wiley & Sons, Ltd.     

Child Poverty as a Determinant of Life Outcomes: Evidence from Nationwide Surveys in Japan

We attempt to examine the extent to which poverty in childhood adversely affects success in adulthood, using micro data from nationwide surveys in Japan and taking into account the recursive structure of life outcomes. We use retrospective assessments of income class at the age of 15, because longitudinal data on household income are not available. After controlling for its endogeneity, we confirm that children from poor families tend to have lower educational attainment, face higher poverty risks, and assess themselves as being less happy and as suffering from poorer health.     

The biology of the voleClethrionomys rufocanus: A review

The biology of the gray-sided voleClethrionomys rufocanus in Hokkaido, concerning taxonomy, morphology, phylogeny, distribution, and natural history, is reviewed. Applied issues in forest management (damage, control and census) are also mentioned. AlthoughClethrionomys rufocanus of Hokkaido was originally identified as a distinct species,Evotomys (=nowClethrionomys) bedfordiae Thomas, 1905, current literature generally refers to the gray-sided vole of Hokkaido asClethrionomys rufocanus or asC. rufocanus bedfordiae (vernacular name, the Bedford’s red-backed vole). The gray-sided vole is the most common small mammal in Hokkaido. It inhabits open areas as well as forests, and mainly feeds on green plants. The gray-sided vole has a high reproductive potential; litter size: 4–7; gestation period: 18–19 days; maturation age: 30–60 days old. Although spring-born individuals usually attain sexual maturity in their summer/fall of birth, their maturation is sometimes suppressed under high densities. The breeding season is generally from April to October, but with some regional variation.Clethrionomys rufocanus has a rather specialized diet (folivorous), particularly during winter when it feeds on bamboo grass. Many predators specialize on the grey-sided vole in Hokkaido; even the red fox, which is a typical generalist predator, selectively feeds on this vole. Damage by voles’ eating bark used to be sever on forest plantations in Hokkaido. Censuses of small rodents have been carried out for management purpose since 1954.     

Spontaneous Facial Expressions Reveal New Action Units for the Sad Experiences

Facial expressions related to sadness are a universal signal of nonverbal communication. Although results of many psychology studies have shown that drooping of the lip corners, raising of the chin, and oblique eyebrow movements (a combination of inner brow raising and brow lowering) express sadness, no report has described a study elucidating facial expression characteristics under well-controlled circumstances with people actually experiencing the emotion of sadness itself. Therefore, spontaneous facial expressions associated with sadness remain unclear. We conducted this study to accumulate important findings related to spontaneous facial expressions of sadness. We recorded the spontaneous facial expressions of a group of participants as they experienced sadness during an emotion-elicitation task. This task required a participant to recall neutral and sad memories while listening to music. We subsequently conducted a detailed analysis of their sad and neutral expressions using the Facial Action Coding System. The prototypical facial expressions of sadness in earlier studies were not observed when people experienced sadness as an internal state under non-social circumstances. By contrast, they expressed tension around the mouth, which might function as a form of suppression. Furthermore, results show that parts of these facial actions are not only related to sad experiences but also to other emotional experiences such as disgust, fear, anger, and happiness. This study revealed the possibility that new facial expressions contribute to the experience of sadness as an internal state.