Here are my thoughts that you can ignore if you find them argumentative:
1. It is less reliance on historical knowledge and more a reliance on Subject Matter Knowledge. You would want a significant amount of data to support a model which is counter to scientific/engineering theory.
2. I struggle with your use of words....I don't understand what "statistically characterizing" or "statistically built" means. We use statistics as an effective and efficient way of understanding causal structure and to build empirical models.
3. There are principles we use as guidance to developing understanding of causal structure using fractional factorials:
- Scarcity (there are a few of the many factors that are useful for a useful model)
- Hierarchy (first order>2nd order>>3rd order...etc.) We typically build models in Tylor series order.
- Heredity (In order for a higher order effect to be active, at least 1 parent must be active). This is used when there are significant effects of the same order and hierarchy can't provide guidance as to which is the active effect.
These are for guidance and are not always true (they are not rules per se). If, after these guiding principles, you still can't select the significant effect from a string of aliased effects, you will need to run more treatments. Where, in relation to the design space, you run these additional runs is situation dependent.
4. When building models, there are a number of elements to take into account. First (and foremost) is the scientific or engineering justification (hypotheses). Then a number of useful statistics, for example:
- RMSE (the model with the smaller RMSE is better)
- p-Values (statistical significance assuming the MSE is a good estimate of the random errors)
- Delta R-square-R-square adjusted (the larger the delta the more likely the model is over-specified)
- Residuals (NID(0,variance))
Again none are definitive and require interpretation given how the data was gotten and the situation.
5. There is no one DOE strategy that will be the most effective or efficient. Selection of the appropriate experiment strategy is situation dependent. My suggestion is always to design multiple experiments and assess what can be learned from each and contrast that with the resources required. Then pick one and prepare to iterate.
"All models are wrong, some are useful" G.E.P. Box