Sample size and sample composition for constructing growth reference centiles

Growth reference centile charts are widely used in child health to assess weight, height and other age-varying measurements. The centiles are easy to construct from reference data, using the LMS method or GAMLSS (Generalised Additive Models for Location Scale and Shape). However, there is as yet no clear guidance on how to design such studies, and in particular how many reference data to collect, and this has led to study sizes varying widely. The paper aims to provide a theoretical framework for optimally designing growth reference studies based on cross-sectional data. Centiles for weight, height, body mass index and head circumference, in 6878 boys aged 0–21 years from the Fourth Dutch Growth Study, were fitted using GAMLSS. The effect on precision of varying the sample size and the distribution of measurement ages (sample composition) was explored by fitting a series of GAMLSS models to simulated data. Sample composition was defined as uniform on the age λ scale, where λ was chosen to give constant precision across the age range. Precision was measured on the z-score scale, and was the same for all four measurements, with a standard error of 0.041 z-score units for the median and 0.066 for the 2nd and 98th centiles. Compared to a naïve calculation, the process of smoothing the centiles increased the notional sample size two- to threefold by ‘borrowing strength’. The sample composition for estimating the median curve was optimal for λ=0.4, reflecting considerable over-sampling of infants compared to children. However, for the 2nd and 98th centiles, λ=0.75 was optimal, with less infant over-sampling. The conclusion is that both sample size and sample composition need to be optimised. The paper provides practical advice on design, and concludes that optimally designed studies need 7000–25,000 subjects per sex.

Integrating subgroups with mixed-type endpoints in early phase oncology trials

Testing anti-cancer agents with multiple disease subtypes is challenging and it becomes more complicated when the subgroups have different types of endpoints (such as binary endpoints of tumor response and progression-free survival endpoints). When this occurs, one common approach in oncology is to conduct a series of small screening trials in specific patient subgroups, and these trials are typically run in parallel, independent of each other. However, this approach does not consider the possibility that some of the patient subpopulations respond similarly to therapy. In this article, we developed a simple approach to jointly model subgroups with mixed-type endpoints, which allows borrowing strength across subgroups for efficient estimation of treatment effects.

Bayesian state-space models with multiple CPUE data: the case of a mullet fishery

We propose a novel Bayesian hierarchical structure of state-space surplus production models that accommodate multiple catch per unit effort (CPUE) data of various fisheries exploiting the same stock. The advantage of this approach in data-limited stock assessment is the possibility of borrowing strength among different data sources to estimate reference points useful for management decisions. The model is applied to thirteen years of data from seven fisheries of the lebranche mullet (Mugil liza) southern population, distributed along the southern and southeastern shelf regions of Brazil. The results indicate that this modelling strategy is useful and has room for extensions. There are reasons for concern about the sustainability of the mullet stock, although the wide posterior credibility intervals for key reference points preclude conclusive statistical evidence at this time

The need for statistical contributions to bioinformatics at scale, with illustration to mass spectrometry

In their article, Morris and Baladandayuthapani clearly evidence the influence of statisticians in recent methodological advances throughout the bioinformatics pipeline and advocate for the expansion of this role. The latest acquisition platforms, such as next generation sequencing (genomics/transcriptomics) and hyphenated mass spectrometry (proteomics/metabolomics), output raw datasets in the order of gigabytes; it is not unusual to acquire a terabyte or more of data per study. The increasing computational burden this brings is a further impediment against the use of statistically rigorous methodology in the pre-processing stages of the bioinformatics pipeline. In this discussion I describe the mass spectrometry pipeline and use it as an example to show that beneath this challenge lies a two-fold opportunity: (a) Biological complexity and dynamic range is still well beyond what is captured by current processing methodology; hence, potential biomarkers and mechanistic insights are consistently missed; (b) Statistical science could play a larger role in optimizing the acquisition process itself. Data rates will continue to increase as routine clinical omics analysis moves to large-scale facilities with systematic, standardized protocols. Key inferential gains will be achieved by borrowing strength across the sum total of all analyzed studies, a task best underpinned by appropriate statistical modelling.