>Epidemiology and next-generation(s) sequencing.

>I had a very interesting conversation this morning with a co-worker, which ended up as a full fledged conversation about how next generation sequencing will end up spilling out of the research labs to the physician’s office. My co-worker originally stated that it will take 20 years or so for it to happen, which seems kind of off to me. While most inventions take a lot longer to get going, I think that next-gen sequencing will cascade over more quickly to general use a lot more quickly than people appreciate. Let me explain why.

The first thing we have to acknowledge is that pharmaceutical companies have a HUGE interest in making next gen sequencing work for them. In the past, pharma companies might spend millions of dollars getting a drug candidate to phase 2 trials, and it’s in their best interest to get every drug as far as they can. Thus, any drug that can be “rescued” from failing at this stage will decrease the cost of getting drugs to market, and increases revenues significantly for the company. With the price of genome sequencing falling to $5000/person, it wouldn’t be unreasonable for a company to do 5-10,000 genomes for the phase 3 trial candidates, as insurance. If the drug seems to work well for a population associated with a particular set of traits, and not well for another group, it is a huge bonus for the company in getting the drug approved. If the drug causes adverse reactions in a small population of people which associate with a second set of traits, then it’s even better – they’ll be able to screen out adverse responders.

When it comes to getting FDA approval, any company that can clearly specify who the drug will work for – who it won’t work for – and who shouldn’t take it, will be miles ahead of the game, and able to fast track their application though the approval process. That’s another major savings for the company.

(If you’re paying attention, you’ll also notice at least one new business model here: retesting old drugs that failed trials to see if you can find responsive sub-populations. Someone is going to make a fortune on this.)

Where does this meet epidemiology? Give it 5-7 years, and you’ll start to see drugs appear on the shelf with warnings like “This drug is counter-indicated for patients with CYP450 variant XXXX.” Once that starts to happen, physicians will really have very little choice but to start sending their patients for routine genetic testing. We already have PCR screens in the labs for some diseases and tests, but it won’t be long before a whole series of drugs appear with labels like this, and insurance companies will start insisting that patients have their genomes sequenced for $5000, rather than have 40-50 individual test kits that each cost $100.

Really, though, what choice will physicians have? When drugs begin to show up that will help 99% of the patients for which they should be prescribed, but are counter indicated for genomic variations, no physician will be willing to accept the risk of prescribing without the accompanying test. (Malpractice insurance is good… but only gets you so far!) And as the tests get more complex, and our understanding of underlying cause and effect of various SNPs starts to increase, this is going to quickly go beyond the treatment of single conditions.

I can only see one conclusion: every physician will have to start working closely with a genetic councilor of some sort, who can advise on relative risk and reward of various drugs and treatment regimes. To do otherwise would be utterly reckless.

So, how long will it be until we see the effects of this transformation on our medical system? Well, give it 5 years to see the first genetic counter-indications, but it won’t take long after that for our medical systems (on both sides of the border in North America) to feel the full effects of the revolution. Just wait till we start sequencing the genomes of the flu bugs we’ve caught to best figure out which anti-viral to use.

Gone are the days when the physician will be able to eye up his or her patient and prescribe whatever drug he or she comes up with off the top of their head. Of course, the hospitals aren’t yet aware of this tsunami of information and change that’s coming at them. Somehow, we need to get the message to them that they’ll have to start re-thinking the way they treat people, instead of populations of people.

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