According to an editorial, the Alzheimer disease literature is full of phase 3 or pivotal trials that were undertaken without prior demonstration of proof of concept, efficacy evidence, or despite prior negative phase 2 efficacy studies. It adds that these industry-sponsored trials were massive undertakings, international in scope, included large samples, made extensive use of biomarkers, used many secondary and exploratory outcomes, were expensive, and consumed considerable human capital. It notes that all showed disappointing results, whereas the minocycline trial, funded by the UK’s Medical Research Council, was intended to pragmatically assess effectiveness and longer-term safety in a clinical population. It, too, can be criticised because prior efficacy for Alzheimer disease had not been demonstrated in previous trials, and similar to many industry-sponsored trials, it skipped phase 2 and relied instead on a rationale that minocycline was worthwhile to test based on preclinical and indirect evidence. However, the minocycline trial differs from industry-sponsored phase 3 trials in terms of its pragmatism.
The editorial notes that compared with explanatory or mechanistic trials, pragmatic trials are designed to be straightforward and externally valid by using practical clinical procedures and outcomes that are important to patients and easily interpretable. Furthermore, it considers that under many circumstances, pragmatic and cheap clinical trials can accomplish as much or more than complicated and expensive trials in learning safety, tolerability, effectiveness, and whether a particular drug has a future or not. They can be done with smaller samples than in most phase 3 trials at a fraction of the cost in both time and money, allowing the testing of many more repurposed and novel proprietary drugs than we test now. It suggest that this minocycline trial is an example of an efficient use of resources, a potentially rapid way to bring a repurposed drug forward and to get an answer.