Type-I-error rate inflation in mixed models for repeated measures caused by ambiguous or incomplete model specifications

Pre-specification of the primary analysis model is a pre-requisite to control the family-wise type-I-error rate (T1E) at the intended level in confirmatory clinical trials. However, mixed models for repeated measures (MMRM) have been shown to be poorly specified in study protocols. The magnitude of a resulting T1E rate inflation is still unknown. This investigation aims to quantify the magnitude of the T1E rate inflation depending on the type and number of unspecified model items as well as different trial characteristics. We simulated a randomized, double-blind, parallel group, phase III clinical trial under the assumption that there is no treatment effect at any time point. The simulated data was analysed using different clusters, each including several MMRMs that are compatible with the imprecise pre-specification of the MMRM. T1E rates for each cluster were estimated. A significant T1E rate inflation could be shown for ambiguous model specifications with a maximum T1E rate of 7.6% [7.1%; 8.1%]. The results show that the magnitude of the T1E rate inflation depends on the type and number of unspecified model items as well as the sample size and allocation ratio. The imprecise specification of nuisance parameters may not lead to a significant T1E rate inflation. However, the results of this simulation study rather underestimate the true T1E rate inflation. In conclusion, imprecise MMRM specifications may lead to a substantial inflation of the T1E rate and can damage the ability to generate confirmatory evidence in pivotal clinical trials.     

Infant locomotion shapes proximity to adults during everyday play in the U.S.

Learning to walk expands infants’ access to the physical environment and prompts changes in their communicative behaviors. However, little is known about whether walking also shapes infants’ proximity to their adult social partners during everyday activities at home. Here we followed 89 infants (42 boys, 47 girls; 92% White, not Hispanic or Latino) longitudinally and documented connections between infant locomotion and infant-adult proximity on two timescales: (1) across developmental time, by comparing data from a session when infants could only crawl to a later session when they could walk (M walk onset = 12.15 months, range = 8-15); and (2) in real time, by testing whether the amount of time that infants spent in motion (regardless of their locomotor status) related to their interpersonal distance to adults. The developmental transition to walking corresponded to a significant, but modest, decrease in infant-adult proximity. Infants’ moment-to-moment locomotion, however, was strongly related to patterns of interpersonal distance: infants who spent more time in motion spent less time near adults and instigated more proximity transitions, resulting in shorter and more dispersed bouts of proximity throughout sessions. Findings shed new light on how infants’ motor achievements can reverberate across other domains of development, and how changes in infant development that researchers often observe over months arise from infants’ moment-to-moment experiences.     

JOINT PRODUCT COST ALLOCATION IN THE CONTEXT OF COST-PLUS PRICING DETERMINATIONS WITH NON-UNIFORM MARKUPS

Companies that use cost-based pricing sometimes manufacture products that involve joint cost allocation. A problem with this is that, while product prices are a function of the full cost, joint cost allocation methods using net realizable values depend on the product prices. This paper demonstrates that when all costs and production quantities are known or can be budgeted, it is possible to simultaneously determine unique product prices (having non-uniform markup rates) and cost allocations using the net realizable value method.