It is a valid question: at what point has a concept been tested ad infinitum such that further testing is not worthwhile? There are at least three reasons why additional study of a concept may not be justified:
- Because the prior probability of success is so low (based on extant trials) that a subsequent trial is unlikely to influence the posterior probability that any success represents the truth. (This is a Bayesian or meta-analytic worldview.)
- Because the low probability of success does not justify the expense of additional trials
- Because the low probability of success violates bioethical precepts mandating that trials must have added value for patients and society
And so we have, in the November 6th edition of JAMA, the CRISTAL trial of colloids versus crystalloids for resuscitation in the ICU. As is customary, I will leave it to interested readers to peruse the manuscript for details. My task here is to provide some background and nuance.