It's certainly the scale of impact difference between some of the charities:

Charities can be useless or actively harmful: https://www.givewell.org/international/technical/criteria/im...

vs.

$4500/life saved: https://www.givewell.org/our-giving-funds#Top_Charities_Fund

They also say why it's that high: https://www.givewell.org/impact-estimates

Another example I've heard is hospitals asking people to stop skydiving to raise money for them, as the mean cost of medial care the average skydiver needs due to skydiving injuries exceeds the average money raised by skydiving.