As Jess pointed out in a recent, really touching post about JDRF’s 1-in-20 campaign, the FDA is in the process of putting together a guidance document for the development of a would-be artificial pancreas system — a combo insulin pump/CGM that would take much of the thought and stress out of life with diabetes. (Insert a pause to consider how amazing and wonderful that would be.) Believe me, I know that FDA guidance documents are hardly fun reading — I’m working on a book about the history of nutrition and have been researching the history of supplement regulation for the past week and a half. But this is a very important issue for anyone who knows someone living with Type 1, and JDRF is trying to drum up public support to encourage the FDA to streamline the process (safely, of course). If you haven’t signed it already, here’s another link to JDRF’s petition on the matter.
Anyway, I wanted to call attention to another issue currently under consideration by the FDA that also has to do with an eventual artificial pancreas: low glucose suspend systems. Low-glucose suspend-enabled pumps, which have already been available in Europe for several years, would do exactly what their name implies: stop the delivery of insulin if a person’s blood sugar dropped too low. You could override this suspend, of course, if your blood sugar weren’t actually low. But if you indeed were dangerously hypoglycemic, this feature could prevent the situation from getting worse.
To me, this sounds like a no-brainer: first off, if you’re not eating anything, suspending basal insulin for two hours seems unlikely to lead to intense hyperglycemia. And even if your blood glucose ended up elevated for a few hours, would that really be worse than, I don’t know, dying from hypoglycemia? (I point you again to Jess’s post.)
So I was disappointed that the FDA’s draft low glucose suspend guidance document, which came out in June, was so restrictive. It inspired critical comments from JDRF, Yale’s section of endocrinology, the American Association of Clinical Endocrinologists, American Association of Diabetes Educators, and the American Diabetes Association, all of whom voiced similar concerns which I think are important for people with Type 1 to be aware of. Basically, after praising and thanking the FDA for devoting the time to put together guidance on such a very important topic for the treatment of Type 1, JDRF — to use one example — “strongly warned that the guidance is unreasonable and will further delay the availability of lifesaving technology to patients who need it.” Their core concerns (I’m quoting directly from the press release):
- “The proposed clinical study pathway is excessively burdensome, and would further delay patients’ access to the technology. Without changes, this guidance will require multiple clinical trials (inpatient and outpatient) involving a large number of subjects in order to show statistically significant differences in preventing hypoglycemia. This would be an excessive hurdle in order to make available to patients a simple but important feature which shuts off insulin when someone has or is near severe low blood sugar (hypoglycemia). Instead, the LGS systems should be approved based on data showing safety and equivalent glycemic control. Clinical effectiveness data among larger populations could be collected in post-market studies.
- “There is a lack of clarity in the use of continuous glucose monitors (CGM) in LGS studies. JDRF is pleased the guidance allows the use of CGM data in evaluating the safety and effectiveness of LGS systems. The use of any other outcomes would be considered impractical by the diabetes research community. FDA must express a commitment to the use of CGM data, rather than indicating it may change its standard later after studies have begun.
- “The proposed guidance requires that substitution of substantially equivalent components in the LGS system would be allowed only if additional separate clinical studies of the system for each component variation are conducted. This requirement would severely limit choice for patients and discourage the development of technologies serving a critical public health need. FDA needs to adopt more efficient means to allow sponsors of clinical investigations and holders of approved premarket approval (“PMA”) applications to utilize multiple versions of components or make modifications to their LGS and artificial pancreas systems.”
Now, I know that’s a lot of FDA speak to deal with. But the bottom line is that the FDA appears to be creating guidelines that would be applicable, roughly speaking, to both a low-glucose suspend system AND an actual artificial pancreas. But the two systems’ safety issues are very, very different: the biggest risk of a low-glucose suspend system — versions of which are currently available in more than 40 countries — is temporary hyperglycemia. It would be very hard for such a system to kill you, or even have a noticeable effect on your A1c.
A full automatic pancreas system, on the other hand, would regulate your blood sugar for you. That would include suspending insulin delivery if your glucose dropped too low, but it also would include giving you insulin if your blood sugar were to rise. Too much insulin, as we all know, can kill you — so an artificial pancreas system needs to have a lot of safety redundancies in place. It’s a potentially deadly piece of equipment, and I am very grateful to know that whenever a system does come to market, it will have gone through a lot of testing and research.
I don’t know why the FDA seems to be conflating these two technologies, and while I really am grateful that they’re working on regulatory guidelines, I am disappointed that the proposed guidelines for low glucose suspend systems are so bizarrely restrictive (again, especially since Minimed’s version of the product has been available abroad for several years). The good thing is that this guidance is only a draft, and there is still time for public comments. If you feel similarly and want to encourage the FDA to reconsider its approach, here’s a link to their contact page. I’m not entirely sure when they published the draft in the Federal Register (since they are technically only accepting comments till three months after the fact) — but the FDA typically has to go through several rounds of public comment before any draft guidance becomes official, so it’s still worth making your voice heard.
Also, this helps give context to JDRF’s artificial pancreas petition — the FDA is supposed to come out with a draft guidance document for artificial pancreas systems in December, and JDRF is trying to ensure that, while adequately cautious, those guidelines are not overly restrictive.