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My wife who is 5'6" routinely captains our tandems. We ride small /small frames. We have 5 tandems that have 700C , 700c/650B, 29r, 26, and fattire tandem with 5.0 tires. The first three have couplers and we travel very frequently in S&S cases. I take the tires off all of the wheels except the 650b to fit easily into the cases. Zero question in my mind that the 700c wheels with 28mm tires are faster by far. The bike that takes 700/650 is faster on the same course with same riders on the 700c by as much as 20%. The 700c with 35-37 is a close compromise with not a huge difference in speed, again same bike ,same riders, on same course . We worked hard with the frame maker to allow a good riding bike with an ability to ride two different wheel sets for different conditions. We can fit up to 47mm tires on the 650b wheels . We do have some toe overlap but it has never been an issue in many thousands of miles of riding. There are a huge number of tire choices for 700C and now many options for 650b. We ride disc brakes on all the bikes now so no adjustment between the wheel sizes. I think an another important issue to decide on a custom frame is the axle system you pick. We use thru axles on all of the tandems. The two road/adventure tandems use 142/12 on the rear and 100/15 on the forks. This is now a very common mtn bike standard and in a pinch if we had a wheel failure we could go into any bike shop and buy a 29r wheel or 650 wheel as a replacement. There are lots of choices to make on a custom frame
but it is a fun process. Enjoy