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Animal models are used to predict the effect of an intervention in humans. An example is the prediction of the efficacy of a vaccine when it is considered unethical or infeasible to challenge humans with the target disease to assess the effect of the vaccine on the disease in humans directly. In such cases, data from animal studies are used to develop models relating antibody level to protection probability in the animal, and then data from a study or studies in human subjects vaccinated with the proposed vaccine regimen are used in combination with the relevant animal models to predict protection in humans, and hence estimate vaccine efficacy. We explain the statistical techniques required to provide an estimate of vaccine efficacy and its precision. We present simulated examples showing that precise estimation of the relationship between antibody levels and protection in animals, at levels likely to be induced in humans by the vaccine regimen, is key to precise estimation of the vaccine efficacy. Because the confidence interval for the estimate of vaccine efficacy cannot be expressed in analytical form, but must be estimated from resampling, or bootstrapping, it is not possible to design studies with required power analytically. Therefore we propose that a simulation-based design of experiments approach using preliminary data is used to maximise the power of further studies and thus minimise the human and animal experimentation required. [ABSTRACT FROM AUTHOR]

Abstract: Background: Preclinical and phase I data suggest gemcitabine to be a potent radiosensitiser. This multicentre study addressed whether the addition of low dose gemcitabine to radical radiotherapy improved 2year event-free survival in patients with medically inoperable stages I–II non-small cell lung cancer. Aim: To determine whether low dose gemcitabine increased event–free survival in patients with T1-2 N0-1 M0 NSCLC deemed unfit for surgery. Methods: Patients with T1-2 N0-1 M0 NSCLC deemed unfit for surgery were randomised to 3D conformal radiotherapy delivering 55Gy in 20 fractions over 4weeks to known sites of cancer with (Arm B) or without (Arm A) 100mg/m2 weekly gemcitabine. Results: Study entry was terminated early because of slow accrual. 111 patients were randomised between March 2003 and December 2005, of whom 4 withdrew consent and 2 were lost to follow-up. Median age was 75 (range 49–88)years and 67 (63%) were male. 86 (81%) were PS 0–1 and 31 (30%) Charlson index 2 or greater. Event-free survival in arm A and B, respectively, was 42% and 46% at 2years and 20% and 31% at 5years (p =0.72), while overall survival was 56% and 52% at 2years and 20% and 33% at 5years (p =0.87). Two deaths from accelerated interstitial lung disease were seen in arm B, but toxicity was otherwise mild. Conclusion: No evidence of an improvement in event-free survival was seen with the addition of weekly gemcitabine at this dose for patients with early stage NSCLC unfit for surgery, although the power of the study was low. [Copyright &y& Elsevier]

We introduce a new method for the analysis of enzyme-linked immunosorbent assay (ELISA) data. The new method can use data near the asymptotes and does not give undue weight to responses on the flatter parts of the dose-response curve. We apply it to simulated data and to two real-world assays and show it is more accurate and more precise than the traditional interpolation method. In particular, the new method works much better for very low-concentration samples for which the traditional method is often unable to give a result. [ABSTRACT FROM AUTHOR]