6 ms·

It boils down to people, logistics, and efficiency: Yes, we can produce the primers, develop the tests, ramp up the supply of RNA extraction kits, swabs, tips,

by nkrumm 7y ago

It boils down to people, logistics, and efficiency: Yes, we can produce the primers, develop the tests, ramp up the supply of RNA extraction kits, swabs, tips, etc. Individually easy, but together more challenging, especially when the entire world is also trying to acquire the same products. Yes, large, fast and high-scale instruments exist. But, they need to be set up and calibrated. They need adequate power, cooling, water, space, etc. The technicians need training. They need network interfaces, etc. Yes, it's a simple test. But there are still SO MANY steps needed to generate a result from a sample, and those take people. Just looking at the laboratory workflow: 1) Sample received in shipment -- unbox, scan manifest (if provided) 2) Unbag sample + requisition 3) Check sample label (usually handwritten) and verify accuracy to requisition (possibly handwritten). In an ideal case, orders are coming in as "interfaced orders" (meaning electronically) but many smaller clinics/hospitals will not have this. 4) Enter all demographics of the patient into laboratory system 5) Have second person verify the information 6) Re-bag and send sample to location in lab with test instrumentation 7) Technicians unbag, verify label + order accuracy 8) Decant sample from non-standardized tube sent to lab to standard tube used in lab 9) Scan into liquid handling robot... ...et cetera, et cetera As I will probably find out in the replies there are "solutions" to all of these problems, and many labs utilize them. However, to scale such a complex system so quickly means that there is no room for a "test environment", and all changes have to be made "in production". Even simple changes to the workflow require days of prep to communicate to all of the staff across three daily shifts-- you get the idea. source: i'm a laboratory medicine resident at the UW lab. We scaled from 0 to 3000 tests in 2 weeks and it's been an incredible all-hands effort.

deleted 7y ago
[deleted]
Reelin 7y ago
I appreciate what's going on at UW regarding this and realize that it must have been a huge amount of work to say the least. However, I'd like to point out that most of what you've described is related to the bureaucracy and paperwork of certified medical procedures. Under ordinary circumstances that's all well and good, but given the severity of the situation it seems like it would have been better to eliminate much of that at least a month ago. Put another way, combat medics don't let someone die just because they're short some official FDA approved widget. Why keep such detailed records? Barcode it on the way in, run the test, and report the result - forget demographic data and any other paperwork, whoever ordered the test can deal with that. The supplies for RNA extraction are common and readily available (I think all the raw components are mass produced?), but only specific kits are FDA approved. Only specific swabs are FDA approved. (https://khn.org/news/as-coronavirus-testing-gears-up-specialized-swabs-running-out/ https://khn.org/news/as-coronavirus-testing-gears-up-special...) > the government is considering expanding its recommended testing material options to allow for more general nasal swabs to keep up with the increased testing demand Standard qPCR machines are incredibly common in both academia and industry and have 96 wells at minimum. The protocol published by the CDC has an 80 minute runtime. That's 1000 tests per day for a _single_ low-end machine. The US response has been an absolute shitshow of bureaucratic dysfunction as far as I'm concerned, and people will likely end up dead as a direct result.
- omar_a1 7y ago
  > Why keep such detailed records? Barcode it on the way in, run the test, and report the result - forget demographic data and any other paperwork, whoever ordered the test can deal with that. Detailed records and redundancies ensure you don't mix up any of the tens of thousands of samples coming in. These systems are crucial for being able to scale up as they have without complete chaos breaking out in the lab. You are right that barcodes are far more efficient, after implementation. But implementation takes months, and requires diverting resources that would otherwise be used to run more samples. The lab would face significant downtime putting a barcode setup in place and retraining. (See nkrumm's comment about labs not having a "test" environment.) > Standard qPCR machines are incredibly common in both academia and industry and have 96 wells at minimum. The protocol published by the CDC has an 80 minute runtime. That's 1000 tests per day for a _single_ low-end machine. That's only if we ignore the sample preparation time (orders of magnitude longer than analysis time), and the many control wells necessary to ensure the technique was successful. While I suspect these will also be dismissed as bureaucratic inefficiency, they're needed to make sure your newly-installed instrument running 24/7 hasn't broken down, and that the high throughput sample prep wasn't botched for a given prep batch. The stakes for these tests are high enough that cutting corners on QA/QC isn't acceptable, because it means more lives lost. Doing a mediocre job for testing at this scale will have a very real impact on our population.
  - Reelin 7y ago
    My calculation (1000 tests per day) left space for 12 controls per batch - is that not sufficient under the circumstances? Alternatively, at 500 tests per day (again, this is _per_ low-end machine!) you could run each sample twice in addition to the 12 controls. (And I would _never_ dismiss controls as an inefficiency, even the most trivial exploratory experiment is highly suspect without one.) The point I was trying to make with those numbers was just how readily accessible the necessary instrumentation is. Regarding sample preparation, I'm well aware that it's a time sink (I've done DNA and RNA extractions before). But it's fairly trivial and can be done fully in parallel by multiple people; the primary bottleneck is likely to be available bench space. (Unless the sample prep has been fully mechanized, in which case I'm really not seeing the issue.) My point being that multiple, parallel sample prep pipelines can feed a single qPCR machine to keep it running just about 24/7. Regarding barcodes, I didn't mean it had to be fully automated. Just drop the excess data entry and switch to a serial number scheme with built-in redundancy (or at least error detection). Many academic labs employ such schemes by hand. Given just how dire the circumstances are, I'm afraid I'd have to strenuously disagree that cutting corners on QA/QC (as compared to standard medical diagnostic testing) would be unacceptable. None of what I described is at all out of place for handling research samples, and in my experience those are quite reliable. I used the combat medic analogy in my previous post for a reason - a significant number of people are likely to end up dead due to our having blindly stuck to the rules. A bit of pragmatism could have saved them, and I view that as a tragic systemic failure on the part of the US government.
hcknwscommenter 7y ago
Much of this is BS. Sorry, but all you need to address many of the strawman problems you invent is a barcoding system. Generate barcode, slap it on tube, have drive through visitor spit in tube, ask them to take a pic of barcode with phone using app, send sample tube with barcode for testing. None of the verify label etc. etc. BS is required.
wbl 7y ago
Then let's be about it. South korea did this, why can't we?

by nkrumm 7y ago

deleted 7y ago

[deleted]

Reelin 7y ago

I appreciate what's going on at UW regarding this and realize that it must have been a huge amount of work to say the least. However, I'd like to point out that most of what you've described is related to the bureaucracy and paperwork of certified medical procedures. Under ordinary circumstances that's all well and good, but given the severity of the situation it seems like it would have been better to eliminate much of that at least a month ago. Put another way, combat medics don't let someone die just because they're short some official FDA approved widget. Why keep such detailed records? Barcode it on the way in, run the test, and report the result - forget demographic data and any other paperwork, whoever ordered the test can deal with that. The supplies for RNA extraction are common and readily available (I think all the raw components are mass produced?), but only specific kits are FDA approved. Only specific swabs are FDA approved. (https://khn.org/news/as-coronavirus-testing-gears-up-specialized-swabs-running-out/ https://khn.org/news/as-coronavirus-testing-gears-up-special...) > the government is considering expanding its recommended testing material options to allow for more general nasal swabs to keep up with the increased testing demand Standard qPCR machines are incredibly common in both academia and industry and have 96 wells at minimum. The protocol published by the CDC has an 80 minute runtime. That's 1000 tests per day for a _single_ low-end machine. The US response has been an absolute shitshow of bureaucratic dysfunction as far as I'm concerned, and people will likely end up dead as a direct result.

omar_a1 7y ago
> Why keep such detailed records? Barcode it on the way in, run the test, and report the result - forget demographic data and any other paperwork, whoever ordered the test can deal with that. Detailed records and redundancies ensure you don't mix up any of the tens of thousands of samples coming in. These systems are crucial for being able to scale up as they have without complete chaos breaking out in the lab. You are right that barcodes are far more efficient, after implementation. But implementation takes months, and requires diverting resources that would otherwise be used to run more samples. The lab would face significant downtime putting a barcode setup in place and retraining. (See nkrumm's comment about labs not having a "test" environment.) > Standard qPCR machines are incredibly common in both academia and industry and have 96 wells at minimum. The protocol published by the CDC has an 80 minute runtime. That's 1000 tests per day for a _single_ low-end machine. That's only if we ignore the sample preparation time (orders of magnitude longer than analysis time), and the many control wells necessary to ensure the technique was successful. While I suspect these will also be dismissed as bureaucratic inefficiency, they're needed to make sure your newly-installed instrument running 24/7 hasn't broken down, and that the high throughput sample prep wasn't botched for a given prep batch. The stakes for these tests are high enough that cutting corners on QA/QC isn't acceptable, because it means more lives lost. Doing a mediocre job for testing at this scale will have a very real impact on our population.
- Reelin 7y ago
  My calculation (1000 tests per day) left space for 12 controls per batch - is that not sufficient under the circumstances? Alternatively, at 500 tests per day (again, this is _per_ low-end machine!) you could run each sample twice in addition to the 12 controls. (And I would _never_ dismiss controls as an inefficiency, even the most trivial exploratory experiment is highly suspect without one.) The point I was trying to make with those numbers was just how readily accessible the necessary instrumentation is. Regarding sample preparation, I'm well aware that it's a time sink (I've done DNA and RNA extractions before). But it's fairly trivial and can be done fully in parallel by multiple people; the primary bottleneck is likely to be available bench space. (Unless the sample prep has been fully mechanized, in which case I'm really not seeing the issue.) My point being that multiple, parallel sample prep pipelines can feed a single qPCR machine to keep it running just about 24/7. Regarding barcodes, I didn't mean it had to be fully automated. Just drop the excess data entry and switch to a serial number scheme with built-in redundancy (or at least error detection). Many academic labs employ such schemes by hand. Given just how dire the circumstances are, I'm afraid I'd have to strenuously disagree that cutting corners on QA/QC (as compared to standard medical diagnostic testing) would be unacceptable. None of what I described is at all out of place for handling research samples, and in my experience those are quite reliable. I used the combat medic analogy in my previous post for a reason - a significant number of people are likely to end up dead due to our having blindly stuck to the rules. A bit of pragmatism could have saved them, and I view that as a tragic systemic failure on the part of the US government.

hcknwscommenter 7y ago

Much of this is BS. Sorry, but all you need to address many of the strawman problems you invent is a barcoding system. Generate barcode, slap it on tube, have drive through visitor spit in tube, ask them to take a pic of barcode with phone using app, send sample tube with barcode for testing. None of the verify label etc. etc. BS is required.

wbl 7y ago

Then let's be about it. South korea did this, why can't we?