This covers the trials not being fully representative, but largely neglects why that is the case.

The paper defines a population "at high risk of drug-induced serious adverse events", which presumably means they're also the most likely people to be harmed or killed by the drug trial itself.

A lot of companies essentially cherry pick healthy patients and write insane inclusion/exclusion criteria to rule out anyone except for the ideal participant, which is why more and more research sites are negotiating payment up front for pre-screening and higher screenfail % reimbursement for into their study budgets.

Study design is sometimes optimized so only the "best" most enticing participants will actually be eligible, I've seen as low as 2% - 12% but frequently 50% randomization rates. Some studies also have 100 to 150 day screening period, a limited AND full screening period, etc.

Overly restrictive inclusion/exclusion criteria to super narrowly defined ideal populations hinders enrollment, causes a large burden to sites for prescreening and ends with trial results that fail to reflect real-world demographics.

Also, if they're known to be at such a high risk of adverse events, would they even be given the treatments, trial or not?