I need an extension for my research project because I spent all month trying to figure out whether learning Dvorak would help me type it faster.
There are often multiple ways in which to deal with a problem or task. There may be a most efficient method, though sometimes the differences in efficiency between methods is only slight. People often try to save unnecessary work by first determining which is the "best" method - either the easiest or the most efficient. This can be a good approach, particularly where the savings prove to be significant. But it can also prove to be more time-consuming than just doing the task using one of the most obvious methods. The comic humorously exaggerates this.
One method of trying to determine the best way of performing a task is to perform A/B testing where a trial is performed where the two strategies, A and B, are implemented and compared. Often the two strategies are simple to implement (for instance, two versions of a web page with different text and colours to determine which provides the better rate of click through) and therefore the amount of time required to implement the strategies (the "time cost") could easily be considerably less than the time to determine if the results are statistically significant.
The title text references a supposed incident in which Randall did not commence writing a research paper because he spent the entire assignment period deciding whether to learn an entirely different keyboard layout just to potentially be slightly more efficient in his typing speed. It refers to the Dvorak keyboard layout, an alternative to the most commonly accepted QWERTY layout. Some believe the Dvorak keyboard offers greater typing efficiency. Efficiency of the Dvorak keyboard layout was mentioned in the title text of 561: Well, where it was stated that it was not more effective, and by now it has become a recurrent theme on xkcd.
Other comics about spending too many resources on decisions that ultimately might not matter include 309: Shopping Teams and 1801: Decision Paralysis. Several other comics address similarly wasted time due to bad time management; see for instance 1205: Is It Worth the Time? or the Time management category.