Designing strictly by a computer program, with the intent of satisfying a thermostat on the coldest day, is a very non human way of providing humans with the best possible experience.
People report to me, over and over, that their radiant heating system is their favorite part of their home.
If done well it can range from completely unnoticed to a greeting when you enter, to warm in one area at a certain time while cooler in another, etc, etc.
Since humans are the ones sensing it's operation, we want them to not notice it's design, just it's benefits, if they notice anything at all. So, tube spacing and timing, and BTU inputs factor in in ways not necessarily described simply by crunching the numbers. For instance, as tube spacing widens to 12' and beyond, people begin to notice cold and warm as they walk around. Especially if the area is timed with the thermostat. So, we can achieve the set temp with wider spacing, but the recovery is slower and the comfort is reduced. The same is true for where the tube is placed. Placing the tube only around the perimeter of a room will heat it, probably, but that's not where people walk.
We need heat where people step and where they sit at the time they will be there. Then, often, no heat when they are not there. Simply matching the BTU loss on the worst day misses the point. Not only do we have to match the BTU loss of the building, but we must also change the temperature of many tons of concrete and, often but not always, change the temperature of the walls and furnishings as well.
Another huge factor is the difference between night and day as far as heating is concerned. Sleeping in a dark house at night, in a warm bed, often means lower stat settings. But in the morning the sun comes in the window, cooking commences, lights go on, lots of human activity, etc. So, if the floor was too warm during the night, the house overheats during the day. But we want a warm bathroom when they get up. These factors are why we need close tube spacing, relatively high BTU inputs, numerous thermostat zones, somewhat higher input water temperatures, and less regard for simply matching the calculated worst case exterior temperature.
Then you have the guy who wants to work on his car in the garage and the only place the floor needs to be warn in where the car sits. That too will satisfy the garage thermostat, but the heat needs to be where he is.
Designing goes on and on. But never forget the human factor and try to make it so they only notice how nice it is if they notice it at all. Don't try to simply satisfy a worst case heat load, add enough headroom to liven it up. Yes, rules of thumb, knowing your area, understanding the clients lifestyle, and some guesswork all factor into an excellent design. Sooner or later, for a given area, the heat calcs are so redundant that they become just another factor that you already know and can include automatically.