The first note is on quickly estimating the 95% confidence interval of an event rate when there are no observed events: if you observe n patients, and none of these patients have the event, then a 95% confidence interval for the probability of the event goes from zero to 3/n (source, with more mathematical detail than I care for). So, if you treat 5 patients and none of them respond, the true response rate could still be as high as 60%. Note that there are many drugs on the market now approved for response rates much lower than 60%, possibly because of the flipside of this calculation (5 of 5 responders could still mean that the true response rate is “only” 40%) combined with some persistence on the part of the developers. But are some drugs dropped too quickly? Probably, which increases the urgency of making clinical trials easier and cheaper to run.
Another implications is that in your standard 3+3 dose escalation design, where you go up in dose if the first 3 study participants don’t experience a dose-limiting toxicity, the 95% confidence interval of the DLT rate at that dose level is still 0 to almost 100%. So, the trials we are running aren’t giving us good enough information. Yay!
The second note, much les philosophical, is that there exists and online tool called reference extractor which can go through a document and extract all Zotero and Mendeley references from it for export into a variety of formats. It can also select those references in your Zotero library, which is life-saving for a slob like me who keeps his references haphazardly strewn across dozens of subfolders. This way anyone who asks can get a neat export, files included.