Any metatheory, God, It's all a Simulation, Material Reality is All That Is - whatever, runs into the same problem when you try to validate it:
How can you fully rely on the results of an experiment when you can never truly know whether some invisible outside force is messing with your data?
To detect anything, at a basic level, electrons need to interact. But nobody can say, for certain, where electrons come from or why, only their effects in the reality that we can detect... using electrons.
In theory, we can't ever 100% rule out the possibility of God, simulation programming, or an undetected force biasing all results.
We can only say that it is really really incredibly unlikely. But that infinitesimal unknowability means claims that we must be living in a simulation are identical to claims that God created everything and claims that there is no God at all.
In a purely scientific sense, anyway. Obviously I enjoyed Feyerabend too much.