Researchers are making progress toward the artificial pancreas (AP) with 2016 focusing on real-world testing of algorithms. Key areas of interest for 2017 include transparency of researcher methods and data, effort required by patients, and reimbursement discussions. Continuous glucose monitoring accuracy and wear time remain barriers, as do pump reliability and immune responses. Both algorithmic and heuristic approaches are being studied, with personalization seen as important. Success has also come from grassroots integration and sharing of existing technologies.

1. Road to the
Artificial Pancreas
3rd Annual Progress Update
May 23, 2016
kevin@mediself.co

2. Disclosures
- Founder & CEO; Diabetech, LP
- Co-inventor; Telcare BGM
- Co-author; “Sugar Surfing”
- Publisher; MediSelf Press
- Advisor; Dynamic Diabetes Management, Inc.

3. Background
Blood glucose meters remain grossly underutilized but are essential to AP
Goals of AP research:
- Decrease or eliminate severe low blood sugar events, especially at night
- Decrease frequency and duration of severe high blood sugar excursions
- Decrease complications associated with severe highs and lows
- Decrease cost of caring for people with type 1 diabetes
How to accomplish this goal:
According to most researchers we must “Take the patient out of the loop”.

4. Technology Landscape
Continuous Glucose Monitoring: explant vs implant
Hormonal Pumps (Insulin alone or Insulin + Glucagon); explant vs. implant
Software Algorithms (General Purpose vs. Personalization)
Remote Monitoring Systems (Now viewed as essential incl. Monitoring Centers)

5. Continuous Glucose Monitoring
Sensor systems that infer how much glucose is in the body at any given time
Potentially many different sensor technologies
The only commercially available CGM sensors are based on a chemical reaction
of interstitial fluid with wires (‘electrodes’) coated in glucose oxidase
The magical part of a sensor is the coating (‘membrane’) surrounding the wire
- Disguises the electrode from the body’s immune system
- Protects against the body’s immune response
Future research is focused on extending wear and improving accuracy & precision

6. CGM Barriers
Biofouling
Inflammation
Cost
Accuracy & Precision

7. How Researchers Measure Success
Used to be use Clarke Error Grid:
Now we use Mean Avg Relative Difference (MARD):
8%

8. Hormonal Pumps
Insulin alone
- Externally worn vs Fully implanted
Insulin + Glucagon
- “Bi-hormonal pump”

9. Pump Barriers
Pumps battle with:
- human body defenses
- human behavior
- mechanical failure
Can’t injections also be considered along the road to an AP?

10. Software Algorithms
Control Algorithms vs. Safety Algorithms
$12.5M recently awarded to Harvard to field test 2 AP algorithms
● Phase 1 - 240 patients for 6 months (Kovatchev et al (UVA) - Type Zero)
● Phase 2 - 180 of the same patients for 6 months (Zone MPC)
Researchers have finally identified:
● Potential of personalizing algorithms
● Requirement to incorporate behavioral science (a lot depends on the user)
● Heuristics now considered as viable solution for AP vs. Algorithms

11. Remote Monitoring Systems
To identify actionable events or trends by care team & by medical team
24 x 7 x 365 monitoring centers envisioned by researchers
Dexcom, Medtronic, Nightscout
Third parties will be challenged from legally providing real-time
- Dexcom approach relies on ‘Retrospective API’ ~ 3hr lag time
- Negotiated with FDA
Researchers in Europe implementing remote monitoring in upcoming studies

12. AP Cartels - 2016 NIH (USA) Awards $20M
A) $12.4M Harvard, UVA, team formerly from Sansum Diabetes Institute
B) $ 6.4M University of Cambridge (UK)
C) $ 2.0M Diabetes Wireless Artificial Pancreas Consortium (EU)
D) $ 1.5M Mass General (Bionic Pancreas - iLet - includes glucagon)
Typical Academic Overhead …………….……..40%
Avg Researcher Makes ………………………...$100k/yr
Plus Benefits and Overhead …………………..$100k/yr
On average, a $2M budget reflects the work of 5 people over the
course of 1 year less any fixed costs such as hardware not donated.
In other words, $1M doesn’t go that far
● http://j.mp/tlcAPupdate2016-1

13. 2016 Focus: Algorithms
Characteristics
● Repeatable, Efficient & Always Completed in a timely manner
● Thus, algorithms are inherently limited in their application
● Example: “Traveling Salesman” algorithm; $1M prize - no winner yet
● For some things an imperfect algorithm is good enough
Is “Good Enough” good enough when we think
about people with type 1 diabetes?

14. More Than One Way From Paris to Rome
- e.g. Sorting Algorithms (many ways to sort a deck of cards)
- Effective + Inefficient vs. Effective + Efficient vs. Ineffective
- Depends On Known Inputs & Predictability
- How does the algorithm deal with ‘Outliers’?
Algorithms vs. Heuristics
- Algorithms always have a conclusion
- Heuristics are about how to deal with inconclusive results
- Heuristics invites a human decision
- An algorithm is a recipe whereas a heuristic is a guide
Algorithmic AP or Heuristic AP? ------------------------------------------- Place Your Bet!

15. Success Stories
- I can’t afford a CGM:
- GlucoMON-ADMS: Tech can simplify & encourage frequent pattern mgmt
- Cooperation isn’t necessary - just will http://type1techventures.com
- If I can get access to CGM what is the best way to use it?
- Sugar Surfing: A compelling strategy embracing in the moment self-care
- All that’s required is insulin, a brain, motivation and frequent blood sugar data
- http://sugarsurfing.com
- I wish all of these companies would just cooperate:
- NightScout: Technical integration doesn’t have to be hard or expensive
- Cooperation isn’t necessary - just will https://nightscout.info
- I wonder if an ‘AP’ could really work?
- DIY Pancreas: Personalization Is Possibly A Critical Aspect of AP
- If it’s highly personalized, yes! https://diyps.org

16. The Cranial Pancreas:
- Relatively inexpensive
- All components already exist
- Also not yet perfect
- Results depend on you

17. Summary
Researchers continue to make progress
2016 will be about real world results - first time in the history of AP
Areas of Interest for 2017:
● Transparency of researchers with regard to methods and data
● Level of effort by the patient
● Reimbursement discussions must begin now (currently not happening at all)

18. Thank you!
Road to the Artificial Pancreas
3rd Annual Progress Update
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