In science, when we find evidence that proves some hypothesis, we cannot say that we've found the truth behind the studied phenomenon. We can only say that, until this point, the hypothesis works and it's useful to explain that phenomenon, and that, until refuted, we can use that hypothesis as a provisional working hypothesis, which is subject to eventual modification.
This understanding you have highlights the difference between the pursuit of knowledge vs enlightenment. A hypothesis is a belief. Even when it is tested and vetted, it still can not be said to be truth because the foundation on which science is built relies on what we call in Buddhism, the illusion.
Does this apply to Dhamma as well?
In short, no. Dhamma is a list of instructions and teachings that assist you in seeing through the illusion. It can almost be seen as the opposite of science. In science, we start with a belief in illusion, and then accumulate more and more beliefs based on a detailed analysis done. When pursuing enlightenment, we hold each belief we accumulate, and we ask "Does this hold up to logic? What are the holes in my understanding?". Pursuing enlightenment is a process of breaking down beliefs you hold, and stripping away those that do not accurately reflect our experience.
Evidence, (no matter how much evidence, whether theoretical or experiencial) is not enough to posit that the truth has been reached without any posible future refutation.
Gathering evidence is not how you become enlightened. Hopefully this does not deter you from perusing it, but let me explain myself fully.
The mind of the illusory self has a habit of finding problems, and wishing to solve them in some way. Solving problems is one way the illusory self perpetuates its own existence. If something is being done or solved, there must be a doer of these actions.
If there is still a solution to be solved, the illusory self still persists in some way. After becoming enlightened, the habit of looking for solutions and solving problems drops away naturally.
Let me ask this with an example:
We can say that the khandhas are not the self, but does that imply that there is not self at all? How can we reach that conclusion without any doubts?
Enlightenment does not come after a conclusion. Enlightenment comes when the illusion is seen not as a multitude of objects and concepts, but as Nirvana, the One, the simultaneous creator and created.
It is important to remember that when enlightenment occurs, there is only Nirvana. It is not you who becomes enlightened, for who you believe yourself to be is simply a concept. It is more accurate to say that when enlightenment occurs, it is Nirvana that experiences Nirvana.
Isn't better to simply say that we cannot know, and that it shouldn't matter at all? After all, if something is beyond the realm of experience, we shouldn't be able to say anything about it.
It is 100% accurate to say that you can not know. The "you" you are referring to is the illusory self. The illusory self is a non-existent. A non-existent is incapable of knowledge. Someone who does not exist, can not know anything. This is why enlightened beings in the past have said "All I know, is that I know nothing." Knowledge is simply a label we give the experience of a thought arising, and having it correlate with some other aspect of experience. In reality, there is only Nirvana. Nothing can be known. Not because there is no Truth, but because there is no one there to hold the knowledge.
Again, if you are seeking freedom, gaining knowledge should not be your goal. You should simply be comparing your experience to your beliefs. The more beliefs you are able to verify as invalid, the easier it will become to see through the illusion.
Is Buddhism concerned with ontology (how and what thinfs are by themselves, and not only how we humans perceive them), epistemology (the possiblity of knowing things about reality itself, objectively) or pragmatism (to use whatever seem to work for some specific end)? Is it concerned with all of them, some of them, or none of them?
In my explanations here, it is important to remember the story of the blind men and the elephant. Although what I say below may seem contradictory to those with a limited frame of reference, when you see through the illusion yourself, you will see how all my explanations tie together. My explanations are coming from a place of pure, non-conceptualized experience, so trying to conceptualize will naturally cause paradoxes to arise. Try not to get hung up on the contradictory nature, and just know that they all have a basis in the same foundational experiences.
Ontology does not apply to Buddhism for there is no concept of humans. The concept of being a human that is perceiving something is part of the illusion you are trying to break free from. Nirvana is seeing the "observed" perspective and the "true" perspective are one and the same.
Epistemology somewhat applies. Like I said before, there is no knowledge, so you can drop that on the floor right away. That being said though, there is an objective way of observing experience that will undoubtedly bring about the changes that occur after enlightenment. End of suffering, End of self, End of mind, etc.
Pragmatism does not apply, for when enlightenment occurs, it is seen clearly that there is no "doer of actions". The concepts of "actions" or "cause and effect" do not apply to experience.
Pragmatism, for example, doesn't deny the possibility of knowledge, and technology and scientific progress seem to be evidence for that. The problem lies in assuming that this -unknown- degree of certainty is somehow the same as the truth (or the expression of all possible definition or information about a phenomenon). If we arrive to the truth, how could we know? Because of a certain X amount of evidence? How much evidence is indication of reaching the truth?
All three of these conceptual frameworks were created in an attempt to prop up the belief that knowledge exists. If one definition does not suit you, you can move on to the next and say "Oh yea, that makes sense. This is how knowledge really works." In reality though, there is no one there. There is no one to know anything. There is nothing to be known. If you continue down this path of attempting to gather knowledge, you will never escape. There is no limit to what you can "know". Not because there is infinite knowledge to gain, but because knowledge is imagined, and you can imagine an infinite number of things.
There is only one thing that exists. Only one thing to experience. That one thing is not knowledge, therefore, there is no knowledge.
Or in other words, is enlightenment enough and definitive proof of having reached the truth about reality itself? Does it even matter if it works?
Enlightenment is the end of searching for an answer. It is the end of restlessness. It is peace.
I hope you are well and I hope this information has been helpful to you in some way. I pray for nothing more than your liberation this lifetime.