What's an IVD or an LDT and why are new rules a big deal for clinical proteomics?

 

I'm behind the ball on this, it's been a busy year, but Adam's write up on it is a great place to start. 

Some background would probably be helpful - 

An IVD is an in vitro diagnostic assay 

LDT is a laboratory developed test

Sounds the same? Basically is, but how they're regulated has been - until now -very different. 

I only know about the mass spec part, so here is my incomplete and quite likely inaccurate interpretation of how this works - 

Hospital clinics generally have MD/PhDs hanging around helping patients, doing surgeries, training people and doing research in-between getting paged to go to another patient room or surgery.

The outcome of some of their research is that they'll find - in samples they've collected from their own patients - that small molecule A or protein B can help them predict a patient's recovery (or the not recovery). 

They can then go through a process to validate that assay and after getting approval from a whole bunch of regulatory bodies (here I'm hazy, probably ASCP and CLIA, and I bet FDA at least wants to do a solid pile of paperwork).

Generally, though, once that ASSAY is developed, you just need to lock down the method and run it on an FDA approved medical device mass spectrometer. Each vendor has 1 or 2 of those. The vendors go through huge expense to get these instruments approved as medical devices. That's on them, and probably a decent pile of the expenses come to you, the assay developer, when you purchase the instrument, but the time and energy necessary to validate the whole package doesn't fall on you. 

Boom - you've got an LDT

An IVD is a whole lot harder. Imagine you have to go through all of this stuff but then you have a full regulatory investigation and approval process on each and every assay? In this case, all of the expenses for developing the whole thing fall directly on you - the assay inventor. However, the IVD should now we something that other people can purchase as a complete package. 

The number of labs, people, institutes and - heck - commercial organizations that can foot the bill for an LDT is way way larger than the number that can develop an IVD. Then you've got to think about motivation. Of the number of organizations with the resources to develop and IVD - how many have the motivation? It can be a long expensive process and there are probably shareholders involved who are going to be unhappy if it that assay doesn't get approved in Q3. An FDA approved device that can be used for LDTs is going to be a safer relative investment than a whole new IVD. 

Now - that's the background. Adam's article can fill in the rest. I don't know if those rules are proposed or through or when they kick in or when they have, but it could be a big thing for US clinical labs.