Good example: the Freestyle Libre CGM is a recently approved glucose monitor for diabetics. The European version lasts 14 days and takes an hour to start up, the US version lasts 10 days and has a 12 hour (!) startup time. It's the exact same hardware with artificial restrictions added to the software for unclear reasons.
Well, a quick search of Google Scholar turns up at least one citation in which the Freestyle Libre CGM was significantly less accurate in the first day of use than in later days, indicating that it needed more time for proper calibration:
https://www.liebertpub.com/doi/pdfplus/10.1089/dia.2014.0378
I expect that the differences are based on some actual findings, not just "unclear reasons," but you may have to do some research to find out.
The FDA is notoriously cautious, possibly somewhat excessively so, but there is some good reason for that caution; medication and medical devices can have unexpected behavior and side effects and it can take a lot of long term study to find them. One example of the caution working out well is the Thalidomide case, which was approved in many other jurisdictions but not in the US, and which had significant side effects on fetuses.
Anecdotally, as a diabetic, the margin of error in that paper is much less scary than going 12 hours without a CGM. Poor data is much better than no data, especially if I know the data is going to be a little questionable the first day. I was completely ready to switch from Dexcom to the Libre until they announced that restriction.
Because the FDA is very conservative, in part because that conservatism prevented the thalidomide incident back in the day.
When it comes to novel treatments, or monitoring devices, we don't know what we don't know. The FDA errs on the side of well-tested treatments and devices.
Extra inaccuracy during the first day could lead people to make mistakes that could prove dangerous or fatal. You don't have no data during the first 12 hours, you just have to fall back to the fingerstick method, which the FreeStyle Libre still supports.
It's possible that as more data is gathered in Europe and the US, it could be found that this extra inaccuracy is not harmful, and the European version approved in the US. Or it could be that the company is able to improve the device to improve accuracy in the first 12 hours, and get a new version approved.
It seems to me that other CGMs like the Dexcom require fingerstick calibration at lest twice a day, so I would think that 12 hours of having to use a fingerstick during calibration would be preferable to twice a day fingersticks.
The decisions were being made by different people. It's not like the FDA decided that Americans require a 12-hour window but Europeans only need 1. The FDA is just more cautious.
People will benefit from those extra 11 hours, but they'll also be hurt by the lower accuracy. It's completely reasonable for different people to weigh these costs and benefits differently.
11 hours without a CGM is a much greater risk than marginally lower accuracy. As a potential user of this system I've been unable to locate research to convince me otherwise.
What's the right regulation? I don't know.
The FDA is necessarily conservative (in the practice, not political sense) but actively pursuing changes like you ask: look at their interest and experiments with adaptive trials.
Out here in the valley they are considered by folks outside life sciences to be stodgy and bureaucratic. But they can move fast. In one (paper) submission I made we dropped one sheet of the 1600+ page document when copying them. Within a week of sending it to them they contacted us for that sheet and we sent it. My board of directors was very interested in how long it took us to reply (down to the minute) and when I said it was less than 10 minutes there was a big sigh of relief. Compare that to the months they gave 22andMe to reply to notices of gross violation that the company had ignored.
They're moving closer to the "move-fast" thinking (although not the "break things" part fortunately) under the new administration: https://www.economist.com/news/leaders/21739157-drug-regulat...
I'm in the US and my Dexcom takes 2 hours to startup, and that's really only because of the sensor temperature adjustment, otherwise it's pretty much instantaneous.
> In the US, FreeStyle Libre’s accuracy has improved a bit with these changes – the average measurement error relative to a reference value is 9.7%, an improvement from around 11% in Europe (and on par with 9.0% for Dexcom’s G5). (https://diatribe.org/abbotts-freestyle-libre-approved-us-rep...)
Which is absolutely ridiculous. 12 hours without a CGM is much, much more dangerous than a 1.3% margin of error.
It looks like on the first day, comparing blood glucose with FreeStyle Libre CGM, there was a significant difference in accuracy, with a lot more (~20% more) readings falling into "zone B", or "points that are outside of 20% but would not lead to inappropriate treatment" (chart https://www.liebertpub.com/action/showImage?doi=10.1089%2Fdi..., from paper https://www.liebertpub.com/doi/pdfplus/10.1089/dia.2014.0378).
This is just one quick thing I found on Google Scholar.
Given that this CGM can also act as a regular fingerprick blood glucose monitor during that 12 hour overlap, I think the FDA likely wanted to err on the safer side of using well known and well tested methods for monitoring to avoid any unexpected issues. Is there sufficient evidence of the benefit of CGM over fingerprick tests to believe that this caution could cause actual harm?
This is a question you could only ask if you were looking only at the data without understanding the problem at hand.
To answer your question: as a user I'm not sweating Zone B. That doesn't even register as a problem. Zone C is the only zone I care about, and Zone C situations can happen quite easily with fingersticks too. The entire game is imprecise -- every single day I make decisions based on incomplete data. You're going to have a very hard time convincing me that 11 hours of moderately imprecise data is more dangerous than having 11 hours of no data.
There are many users who would not. They might make a rash decision based on that data. If the data is in Zone B a larger percentage of the time in testing, in much wider general use there will likely be cases that weren't caught in clinical trials in which it could land in Zone C.
During this 12 hour calibration window, you can still use fingersticks, which you have to do for calibration purposes with other CGMs anyhow. And it likely would be a fairly minor change for them to support doubling up on sensors, so that you could overlap them in order to avoid the 12 hour window; but that change would require further testing and approval, so for now the 12 hour calibration window is left in. It was only fairly recently approved with this 12 hour calibration window, so I wouldn't be surprised if the company is working on support for pairing two sensors to one device to support doubling up like this.
Those aren't comparable situations. With my Dexcom I test in the early afternoon and before bed and that gives me 24 hours worth of extremely reliable information.
Here's a hypothetical: let's say you test and your blood sugar is 150 mg/dl. What does that tell you? Almost nothing. Maybe your sugar was 200mg/dl 15 minutes ago and you're dropping like a rock or it was 100mg/dl 15 minutes ago and you're spiking. Maybe you've been at 150mg/dl for the last two hours. You can't really tell, so you test again in 15 minutes. Let's say it's 100mg/dl -- looks like it is dropping, unless your last reading was on the high side and this one on the low meaning nothing's really changed. So you test again in another 15m and maybe you can start putting together a picture of what's actually happening.
This is a terrible process and only works if you're sitting at home doing nothing. What if you're stuck in traffic or on a crowded subway car? In a meeting at work? At the gym? On a date? In a movie theater? It can become overwhelming quickly and that's when mistakes happen. And remember this is all compounded by your body's biology: you have to think about the food you ate, how much insulin you took and when you took it, when the last time you exercised was, how much stress you're under, etc, etc, etc.
And keep in mind fingersticks don't perform that much better than CGMs. They're still susceptible to error (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317395/) and much more susceptible to human error. Failing to wash your hands properly, not drying your hands properly, not letting the alcohol dry completely after a swab, or leaving your strips in a hot car can all cause your readings to be wildly incorrect.
Another thing to note is even if your Libre is off by a huge amount (say 50mg/dl) the trend will still be accurate. Meaning if your blood sugar is constant over an hour the Libre will give you a reading that's also constant. This is extremely important because I'm much more likely to take action on trends (e.g. rising/falling blood sugars) than on individual data points.
You said this in the other thread:
> I would think that 12 hours of having to use a fingerstick during calibration would be preferable to twice a day fingersticks.
I will tell you it is definitively not. Currently Dexcom takes two hours to calibrate and those are the longest two hours of my week. The ability to schedule those two fingersticks is much preferable to 12 hours of radio silence.
> You are on HN, and likely reasonably technically inclined.
Sure. I'm a "good diabetic" but that's the nature of the beast for a disease who's only treatment is constant vigilance. There's a reason why I've never gone into a hypoglycemic coma yet know people my age who are already struggling with neuropathy. The lowest common denominator here is extremely low, and if an error margin of 30mg/dl or a single false reading is going to cause you serious problems you have much greater issues with your diabetes management than your CGM.
But what it comes down to is, there was something about the accuracy during the first 12 hours that gave the FDA cause for concern. Whether the FDA is overly cautious or not is an open question; I do know that in the US we get worse health outcomes for more money than most other developed countries. How much of that is due to our terrible system for paying for health care, which is privatized but with enough regulatory capture and inefficiency to drive prices way up, and how much of that is due to higher costs and lower access to medication and devices not being available due to excessively stringent regulations from the FDA would be something interesting to study.
I think that the FDA could probably loosen up its regulatory process just a little bit and provide a net benefit. Not sure with how much there is wrong with health policy in the US, and partisan politics around it, that's very likely, however. It would be interesting to see if there have been any studies done on this.
I don't really care that much if I'm 70mg/dl or 100mg/dl if the line is horizontal. Both values are, roughly, in the "OK Zone" that I just don't care about better precision.
Even if I'm going low, the difference between 50 or 70 isn't nearly as relevant as the rate of change. If I'm going down, but the slope is gentle enough, I know I probably don't need much to get back to normal, while if it's steep going down, I probably need to eat something regardless if I'm 50 or 70, or 80.
It may be that the device is more highly variable in the first hours giving the impression of spikes or drops where there are none.
It's hard to tell without the raw data.