The evaluation of specific treatments in specific diseases are generally investigated in trials of modest size – high hundreds or low thousands. The outcomes of interest, when binary, typically have baseline (control) rates of 5% to 10%. Worthwhile (say 20% risk ratio) improvements can be detected with reasonable precision by trials of this size. When we move to screening, vaccinations, and mass treatment programs, however, things become more difficult, and mega (10,000–100,000) or even ultra (>100,000) trials are necessary. The vitamin A trials in neonates discussed above collectively enrolled 100,038 participants, while the current cohort of vitamin D trials in adults is expected to enroll in excess of 100,000 participants, and the UK Collaborative Trial of Ovarian Cancer Screening has just over 200,000 participants. Given the shape of the graph relating marginal gains in precision to marginal increases in participants (the power function ) we may be reaching the ‘horizon of science’ in these topics.
— Richard Lilford, CLAHRC WM Director
- Manson JAE, & Bassuk SS. Vitamin D Research and Clinical Practice. At a Crossroads. JAMA. 2015; 313: 1311-2.
- United Kingdom Collaborative Trial of Ovarian Cancer Screening Overview. [Online]. 2015.
- Watson S. Mega- and Ultra-Trials. [Online]. 2015.