To that extent, what would be a better way to manage flights, flight crew and pilots so that everyone can maintain an adequate (or better, optimal) level of health and well-being?
Do we need more crew (i.e. per flight, per out-station, etc. - this covers both flight deck and cabin attendants), longer "shore breaks" (i.e. more time between having to operate flights), established out-stations (more crew bases at destinations), or do particular timings of flights need to be outlawed?
There have been a bunch of studies done. A very extensive one was done within Oz. The answer is not simple. You don't necessarily need more crew, and in fact you can sometimes have less. These studies have all generated fatigue management plans...but the problem is simply that the operators and regulators seem to be picking only those parts that allow working days to be lengthened. Quite simply, some days can be longer, but that's affected by starting time, number of sectors, what has been happening in previous days, and so on. What is at issue is the generation of arbitrary limits, that have no basis in science. For instance, after the '89 dispute, the domestics were allowed an 'exemption' that let them plan two pilot, multi sector days, out to 14 hours. They took no regard of any previous activity...but simply made it legal. This exemption still exists, and has had its coverage extended...
Longer slips don't necessarily help at all. In some cases they are a bad idea. An example....operating to NYC via LA, the slip in LA is 48 hours. It could be as short as 24, but even a slight delay will breach the current regs. But, people can always sleep on the first night in LA on the way through, but the second night is always difficult. In that case a relaxation of the rules works better. Long slips also have the negative effect of putting you into the local time zone, and given that most long haul departures are in the middle of the night, that's not necessarily good either.
It seems improving pilot or crew comfort on board is not the answer (as often alluded to by yourself that it is very difficult to get adequate rest on an aircraft for any length of time).
Whilst it is often difficult with a good crew rest, it is impossible if an adequate crew rest is not provided. A business class seat within the cabin is a recipe for a crew that will get no rest whatsoever.
Do you think that this will demand much more expensive flights than current? I'm not saying whether this is bad or good, but rather if that is what it would take. After all, it wasn't very long ago (before deregulation ran rampant) that air travel still cost a decent whack (for example, $1500 - $2000 for an Economy return flight to South East Asia, and that's not the "worst" of it).
And there lies the rub. I doubt that decent fatigue management will be expensive at all. It has swings and roundabouts. In some cases it allows reduced crew and shorter slips, but in others it is more restrictive. But, it is not one sided....