Exact optimum coin bias in Efron's randomization procedure.

Efron's biased coin design is a restricted randomization procedure that has very favorable balancing properties, yet it is fully randomized, in that subjects are always randomized to one of two treatments with a probability less than 1. The parameter of interest is the bias p of the coin, which can range from 0.5 to 1. In this note, we propose a compound optimization strategy that selects p based on a subjected weighting of the relative importance of the two fundamental criteria of interest for restricted randomization mechanisms, namely balance between the treatment assignments and allocation randomness. We use exact and asymptotic distributional properties of Efron's coin to find the optimal p under compound criteria involving imbalance variability, expected imbalance, selection bias, and accidental bias, for both small/moderate trials and large samples.

Balance and randomness in sequential clinical trials: the dominant biased coin design.

Efron's biased coin design (BCD) is a well-known randomization technique that helps neutralize selection bias, while keeping the experiment fairly balanced for every sample size. Several extensions of this rule have been proposed, and their properties were analyzed from an asymptotic viewpoint and compared via simulations in a finite setup. The aim of this paper is to push forward these comparisons by taking also into account the adjustable BCD, which is never considered up to now. Firstly, we show that the adjustable BCD performs better than Efron's coin with respect to both loss of precision and randomness. Moreover, the adjustable BCD is always more balanced than the other coins and, only for some sample sizes, slightly more predictable. Therefore, we suggest the dominant BCD, namely a new and flexible class of procedures that can change the allocation rule step by step in order to ensure very good performance in terms of both balance and selection bias for any sample size. Our simulations demonstrate that the dominant BCD is more balanced and, at the same time, less or equally predictable than Atkinson's optimum BCD.

Is the classical Wald test always suitable under response-adaptive randomization?

The aim of this paper is to analyze the impact of response-adaptive randomization rules for normal response trials intended to test the superiority of one of two available treatments. Taking into account the classical Wald test, we show how response-adaptive methodology could induce a consistent loss of inferential precision. Then, we suggest a modified version of the Wald test which, by using the current allocation proportion to the treatments as a consistent estimator of the target, avoids some degenerate scenarios and so it should be preferable to the classical test. Furthermore, we show both analytically and via simulations how some target allocations may induce a locally decreasing power function. Thus, we derive the conditions on the target guaranteeing its monotonicity and we show how a correct choice of the initial sample size allows one to overcome this drawback regardless of the adopted target.

Sleep quality and motor vehicle crashes in adolescents.

STUDY OBJECTIVES: Sleep-related complaints are common in adolescents, but their impact on the rate of motor vehicle crashes accidents is poorly known. We studied subjective sleep quality, driving habits, and self-reported car crashes in high-school adolescents. METHODS: Self-administered questionnaires (with items exploring driving habits) were distributed to 339 students who had a driver's license and attended 1 of 7 high schools in Bologna, Italy. Statistical analysis were performed to describe lifestyle habits, sleep quality, sleepiness, and their relationship with the binary dependent variable (presence or absence of car crashes) to identify the factors significantly affecting the probability of car crashes in a multivariate binary logistic regression model. RESULTS: Nineteen percent of the sample reported bad sleep, 64% complained of daytime sleepiness, and 40% reported sleepiness while driving. Eighty students (24%), 76% of which were males, reported that they had already crashed at least once, and 15% considered sleepiness to have been the main cause of their crash. As compared with adolescents who had not had a crash, those who had at least 1 previous crash reported that they more frequently used to drive (79% vs 62%), drove at night (25% vs 9%), drove while sleepy (56% vs 35%), had bad sleep (29% vs 16%), and used stimulants such as caffeinated soft drinks (32% vs 19%), tobacco (54% vs 27%), and drugs (21% vs 7%). The logistic procedure established a significant predictive role of male sex (p < 0.0001; odds ratio = 3.3), tobacco use (p < 0.0001; odds ratio = 3.2), sleepiness while driving (p = 0.010; odds ratio = 2.1), and bad sleep (p = 0.047; odds ratio = 1.9) for the crash risk. CONCLUSIONS: Our results confirm the high prevalence of sleep-related complaints among adolescents and highlight their independent role on self-reported crash risk.