There's no good candidate for a simple, legible, easily-obtained, and agreeable-to-most metric. Before-and-after polling of patients is probably closest we can get.
That said, the dimensions of quality that the FDA concerns itself with (including physical functioning, self-reported pain, and other easily- and not-easily-measured things) is likely close enough to "improves quality of life" that it's not necessary to have a new direction.
Perhaps you could identify some drugs that you think would improve quality of life, and work backwards to the metrics that prove to you that they do so.
That said, the dimensions of quality that the FDA concerns itself with (including physical functioning, self-reported pain, and other easily- and not-easily-measured things) is likely close enough to "improves quality of life" that it's not necessary to have a new direction.
Athletic performance. Cognitive performance. Work performance. Also ability to accomplish the things needed in every day life to have uh fun..
The best way is probably to have an excellent investigator rank the research subjects by their quality of life. If you've got a good idea about what a high-quality life is, you could probably do the ranking of them yourself.
Currently, to get a drug approved by the FDA you need to prove that it helps with a particular illness and while having an acceptable side effect profile.
If you have a drug that improves people's quality of life but you aren't curing an ICD-11 accepted illness, you don't get your drug approved.
If the FDA would change and approve drugs for improving quality of life, how should they measure it? What's the best way to measure quality of life that's hard to goodhart?