I contend that the insistence of the US National Institutes of Health (NIH) on hypothesis-driven projects in grant proposals could be a factor contributing to irreproducible research reports (see F. S. Collins and L. A. Tabak Nature 505, 612–613; 2014).

Isaac Newton argued that “hypotheses ... have no place in experimental philosophy”, a view echoed by mathematician Roger Cotes: “Those who assume hypotheses as first principles of their speculations ... may indeed form an ingenious romance, but a romance it will still be” (in I. B. Cohen Introduction to Newton's Principia; iUniverse, 1999).

Such criticisms recognize the risk that scientists may filter data through their hypotheses, discounting results that do not validate the hypothesis as evidence that the experiment did not work — rather than as evidence that the hypothesis is false.

The NIH's funding criteria should instead ensure that a pertinent research question is being asked, and that the applicant has the means to answer it (see D. J. Glass Experimental Design for Biologists; Cold Spring Harbor Laboratory Press, 2006).