Well, as long as transfer to a car seat is practical, that's the best and safest option. At some point it does become impractical. So at that point, all you can do is make sure that the wheelchair being used is the safest one possible and being used and secured as safely as possible in the van.
Any harness or belt being used needs to be crash-rated and tested. It also needs to fit properly. The wheelchair needs to be properly secured (there are different levels of what is better; I'm going to let someone more familiar with wheelchair transport give you that hierarchy, but I know some commonly used systems are not really very crashworthy while others tested well. I can look it up if needed.) Any additional equipment (trays, etc.) that are removed for transport need to be properly secured (strapped down or compartmentalized, etc.) as well, as much as possible.
So the answer is, it depends on the securement system, the belt fit, the chair, a large range of factors how safe it is, and transfer is always safer, but at some point you have to do it, so at that point you need to make sure to do it in the safest way possible. If that makes sense?