Trials in particular settings

Some diseases and product classes force design, endpoint and analysis choices that the principles every trial shares do not settle. This branch covers trials in those settings, and its parts divide by the setting the trial is run in: the diseases, cancer, Alzheimer's disease and rare diseases, and the product classes, vaccines, allergen immunotherapy products and biosimilars. It leaves the principles every trial shares, such as the estimand, the analysis plan, missing data and who is enrolled, to designing and analysing clinical trials, the science of the disease or product to the scientific background, and the regulatory dossier for a product class to product classes with their own requirements.

• Cancer trials — the endpoints a cancer trial is measured on and what each lets its report claim, how the phases and their designs change for targeted therapies and immunotherapies, and where bias enters the design and its reporting
• Trials in Alzheimer's disease — how the EMA revised its Alzheimer's disease guideline from the 2016 draft to the 2018 guideline, evaluating medicines in earlier disease stages, and the design questions each version addresses: diagnostic criteria for early and asymptomatic stages, outcome measures for each stage, biomarkers, and efficacy and safety studies
• Trials in rare diseases — what makes a trial for a small, scattered and poorly characterised population harder to design, its place in the development plan and the engagement with regulators it needs, choosing the population, design, control and endpoints, and the patient community, sites, participants, protocol amendments and supply around it
• Vaccine trials — the development pathway from exploratory research to post-marketing surveillance, sizing an efficacy trial from disease incidence, follow-up and correlates analysis, efficacy from the cases in each arm and the analysis plan, reactogenicity, vaccine-induced seropositivity, efficacy inferred from the immune response, the population to vaccinate, and the approvals, manufacturing and site capacity a vaccine needs
• Allergen immunotherapy trials — the European framework for allergen products, matching the efficacy claim to the trial's duration, phase I and dose-finding, the confirmatory trial under natural allergen exposure and the patients it selects, the combined symptom and medication score, and assessing safety
• Equivalence trials for biosimilars — showing similarity rather than superiority: the pharmacokinetic similarity study and its three arms for the regional reference products, the confirmatory study's indication and endpoint, the margin derived from the reference's effect against placebo, why the per-protocol set and missing data work differently, switching designs for interchangeability, and which concepts carry over from new-drug development