Past exam of the mathematics course of the University of Cambridge / 2013 / iii / Paper 35 / 3

A completely randomized design uses $2m$ eligible animals, randomly selecting $m$ to receive $P$ and assigning the remainder to $Q$. Use comparable follow-up and assess the same response variable in both groups. Its advantage is simplicity and freedom from previous-treatment carryover effects; its disadvantage is that between-animal variation enters the residual and can make a treatment contrast imprecise.

A randomized complete block design with matched pairs first forms $m$ pairs using pre-treatment characteristics such as initial disease severity, age or breed. Independently choose which animal in each pair receives $P$, with its partner receiving $Q$. The experimental units are animals; pairs are blocks. The average within-pair difference estimates the treatment contrast, and positive within-pair similarity can reduce its variance. Its advantage is control of known heterogeneity; its disadvantage is the need for useful matching, with fewer residual statistical degrees of freedom and little gain if the matching variables are uninformative. Do not construct pairs using outcomes observed after assignment.

A two-period crossover design randomly assigns half the animals to sequence $PQ$ and half to $QP$. Each animal receives both treatments in separate periods, with a scientifically justified interval between them and the same outcome assessment after each period. Animal blocks remove persistent between-animal differences, while the two sequences balance treatment against period. Its advantage is potentially high precision from within-animal comparisons; its disadvantage is vulnerability to carryover effects, changing disease state and irreversible effects. It is suitable only when comparing the treatments in both periods remains meaningful and residual effects of the first treatment are adequately controlled. A two-period crossover design does not by itself disentangle arbitrary treatment-specific carryover effects.

First agree the scientific question and primary response variable. Ask the vet about the disease's course, the proposed mechanism and duration of each treatment, the eligible population, baseline severity, and what outcome and follow-up time would represent worthwhile improvement. Is the disease transmissible, is recovery reversible, and can treating one cow affect another's outcome? These answers determine whether a crossover design is credible, whether the experimental unit should be a cow or a whole herd, and whether individual randomization would leave interference between groups. Agree welfare and rescue arrangements with the vet when deciding which comparisons are feasible; the statistical plan cannot determine these from an unfamiliar disease name.

Second agree feasible allocation and adequate independent replication. Discuss numbers of available cows and herds, variation in the chosen outcome, a scientifically meaningful treatment difference, and the desired statistical power. Use these to plan sample size, rather than choosing a number solely from convenience. Discuss herd, lactation stage and initial severity as potential blocks in experimental design, then specify randomization, comparable management, concealed allocation and blinded outcome assessment where feasible. Repeated milk or health records from the same cow are observational units, not extra independent experimental units; pseudoreplication would give misleading standard errors. Availability of enough independent cows or herds, together with expected variation, governs the precision actually achievable.