[refurb]

It’s a similar problem you see with all safety related decisions - as the large risks are eliminated you become more concerned about the smaller risks.

Plenty of successful drugs from the 50’s had hERG activity, yet the impact on safety was marginal. Today plenty of programs are killed over it.

Increase safety scrutiny does increase safety, but at a cost.

[mmooss]

> Plenty of successful drugs from the 50’s had hERG activity, yet the impact on safety was marginal.

Is there some evidence of these two claims? Obviously many experts think otherwise.

[refurb]

Lots of examples of older drugs currently in use that are potent hERG inhibitors: haloperidol (antipsychotic), ketoconazole (antifungal), erythromycin (antibiotic), domperidone (anti-emetic), hydroxychloroquine (anti-malarial).

All of these are rather potent hERG inhibitors, yet were approved and widely used before that activity was discovered. Pulling them off the market would have been quite disruptive considering some of them are the only effective treatment for rather serious diseases.

Of course it's a matter of opinion, but I would argue some of these workhorse medications would have had their program killed by the manufacturer (fear the FDA won't approve) or the FDA itself (risk of fatal arrhythmias) if they were developed today.

Yet the risk is managed by flagging the contraindication when combined with other drugs (since the inhibition is often additive).