I've had some questions about animal models and testing, so I thought I'd go over the general picture. As far as I can tell, my experience has been pretty representative.
There are plenty of animal models used in my line of work, but some of them you see more than others. Mice and rats are, of course, the front line. I’ve always been glad to have a reliable mouse model, personally, because that means the smallest amount of compound is used to get an in vivo readout. Rats burn up more hard-won material. That's not just because they're uglier, since we don’t dose based on per cent ugly, but rather because they're much larger and heavier. The worst were some elderly rodents I came across years ago that were being groomed for a possible Alzheimer’s assay – you don’t see many old rats in the normal course of things, but I can tell you that they do not age gracefully. They were big, they were mean, and they were, well, as ratty as an animal can get. (They were useless for Alzheimer's, too, which must have been their final revenge).
You can’t get away from the rats, though, because they’re the usual species for toxicity testing. So if your pharmacokinetics are bad in the rat, you’re looking at trouble later on – the whole point of tox screens is to run the compound at much higher than usual blood levels, which in the worst cases you may not be able to reach. Every toxicologist I’ve known has groaned, though, when asked if there isn’t some other species that can be used – just this time! – for tox evaluation. They’d much rather not do that, since they have such a baseline of data for the rat, and I can’t blame them. Toxicology is an inexact enough science already.
It’s been a while since I’ve personally seen the rodents at all, though, not that I miss them. The trend over the years has been for animal facilities to become more and more separated from the other parts of a research site – separate electronic access, etc. That’s partly for security, because of people like this, and partly because the fewer disturbances among the critters, the better the data. One bozo flipping on the wrong set of lights at the wrong time can ruin a huge amount of effort. The people authorized to work in the animal labs have enough on their hands keeping order – I recall a run of assay data that had an asterisk put next to it when it was realized that a male mouse had somehow been introduced into an all-female area. This proved disruptive, as you’d imagine, although he seemed to weather it OK.
Beyond the mouse and rat, things branch out. That’s often where the mechanistic models stop, though – there aren’t as many disease models in the larger animals, although I know that some cardiovascular disease studies are (or have been) run in pigs, the smallest pigs that could be found. And I was once in on an osteoporosis compound that went into macaque monkeys for efficacy. More commonly, the larger animals are used for pharmacokinetics: blood levels, distribution, half-life, etc. The next step for most compounds after the rat is blood levels in dogs – that’s if there’s a next step at all, because the huge majority of compounds don’t get anywhere near a dog.
That’s a big step in terms of the seriousness of the model, because we don’t use dogs lightly. If you’re getting dog PK, you have a compound that you’re seriously considering could be a drug. Similarly, when a compound is finally picked to go on toward human trials, it first goes through a more thorough rat tox screen (several weeks), then goes into two-week dog tox, which is probably the most severe test most drug candidates face. The old (and cold-hearted) saying is that “drugs kill dogs and dogs kill drugs”. I’ve only rarely seen the former happen (twice, I think, in 19 years), but I’ve seen the second half of that saying come true over and over. Dogs are quite sensitive – their cardiovascular systems, especially – and if you have trouble there, you’re very likely done. There’s always monkey data – but monkey blood levels are precious, and a monkey tox screen is extremely rare these days. I’ve never seen one, at any rate. And if you have trouble in the dog, how do you justify going into monkeys at all? No, if you get through dog tox, you're probably going into man, and if you don't, you almost certainly aren't.