Voltaire wrote in 1772, “the best is the enemy of the good”, warning against the fallacy that something is worthless if it is not perfect — a sentiment that seems common in scientific peer review today.
The history of science has taught us that most progress has come from exploring flawed hypotheses and imperfect models. We must always strive for the better study, the better model, the better analysis. As experienced reviewers, however, we contend that seeking ultimate perfection is not the same as accepting nothing less here and now. Scientific progress depends on such compromise — provided that potential caveats are recognized.
If a model is the most technically and ethically feasible approach available, and is better than random guessing, then it has some merit in advancing knowledge. Useful developments in biology, for example, have come from in vitro systems that do not reflect in vivo conditions, and from animal models that do not necessarily predict human disorders.
The aim should be to utilize models, despite their imperfections, while continuing to improve them. It is unrealistic to hold progress in science to standards of perfection and certainty: progress is usually incremental and iterative.