Past exam of the mathematics course of the University of Cambridge / 2013 / iii / Paper 35 / 1 / c

Use a randomized complete block design, with day as block and each biological cell as an experimental unit. Each day should contain two biological cells at each of the five dose levels. Each level then has ten replicates overall and occurs equally often in every day: the resulting block design is an orthogonal block design.

This spreads any day-to-day changes in preparation, temperature or measurement across all levels instead of confounding dose with day. Treat the zero level as a control with otherwise comparable handling. Keep the treatment-to-measurement delay standardized because the response variable is a diffusion rate measured immediately after preparation.

If the biological cells are initially interchangeable, randomly allocate them to five groups of ten for the days. Within each day, independently choose a uniform distribution on a finite set over assignments having two occurrences of each dose level to the ten experimental units. One implementation is a random permutation of a list containing two labels of each level; the duplicate labels give every admissible assignment the same number of underlying permutations.

Randomize the processing order within each day as well, while pairing each preparation with its immediate measurement. Randomize dose within day, not merely the names of the days. This restricted randomization preserves the planned balance while protecting treatment contrasts against systematic order effects. Conceal the dose labels from the assessor where practical.

The constant subspace has one statistical degree of freedom. Day contrasts have $5-1=4$, and the within-block ANOVA stratum has $50-5=45$. Because the orthogonal block design puts all four independent dose contrasts in that last ANOVA stratum, the residual has $45-4=41$ statistical degrees of freedom.

The corrected total has 49 statistical degrees of freedom; dose is tested against the within-day residual. The quantitative dose scale also permits the dose component to be split into linear, quadratic, cubic and quartic orthogonal polynomial contrasts, each with one statistical degree of freedom. This is optional and does not assume the response is linear in dose.