Learn More
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially(More)
OBJECTIVE Several groups have reported apparent association between month of birth and multiple sclerosis. We sought to test the extent to which such studies might be confounded by extraneous variables such as year and place of birth. METHODS Using national birth statistics from 2 continents, we assessed the evidence for seasonal variations in birth rate(More)
In drug development, there is often uncertainty about the most promising among a set of different treatments. Multi-arm multi-stage (MAMS) trials provide large gains in efficiency over separate randomised trials of each treatment. They allow a shared control group, dropping of ineffective treatments before the end of the trial and stopping the trial early(More)
Multistage designs allow considerable reductions in the expected sample size of a trial. When stopping for futility or efficacy is allowed at each stage, the expected sample size under different possible true treatment effects (δ) is of interest. The δ-minimax design is the one for which the maximum expected sample size is minimised amongst all designs that(More)
In a recent genome-wide association study (GWAS) based on 12,374 non-synonymous single nucleotide polymorphisms we identified a number of candidate multiple sclerosis susceptibility genes. Here, we describe the extended analysis of 17 of these loci undertaken using an additional 4234 patients, 2983 controls and 2053 trio families. In the final analysis(More)
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as(More)
BACKGROUND Multi-arm trials enable the evaluation of multiple treatments within a single trial. They provide a way of substantially increasing the efficiency of the clinical development process. However, since multi-arm trials test multiple hypotheses, some regulators require that a statistical correction be made to control the chance of making a type-1(More)
Multi-arm multi-stage designs can improve the efficiency of the drug-development process by evaluating multiple experimental arms against a common control within one trial. This reduces the number of patients required compared to a series of trials testing each experimental arm separately against control. By allowing for multiple stages experimental(More)
For most of us, the foundations of our understanding of genetics were laid by considering Mendelian diseases in which familial recurrence risks are high, and mutant alleles are both necessary and sufficient. One consequence of this deterministic teaching is that our conceptualization of genetics tends to be dominated by the notion that the genetic aspects(More)
Reducing the number of patients required for a clinical trial is important for shortening development time. Phase II cancer trials assess the tumour-shrinking effect of a novel compound through a binary end-point formed from the percentage change in total lesion diameter. We compare single-arm two-stage designs which use the binary end-point to those which(More)