FDA-Patient Dialogue on Unmet Needs in Diabetes

November 3, 2014; Silver Spring, MD; Highlights - Draft

Executive Highlights

We are writing from Silver Spring, Maryland, where an unprecedented event took place today – the first-ever FDA-Patient Dialogue on Unmet Needs in Diabetes. Along with nine committed patient representatives, we were thrilled to visit the FDA campus and have an open and direct discussion about the challenges people with diabetes face every day, what tools we would like to see, and what we’d like reviewers to keep in mind as they consider new drugs and devices. The three-hour event included two panels (one with patients interviewed by FDA, one with FDA leaders led by Kelly Close); organizational perspectives from the diaTribe Foundation, JDRF, and ADA; and several presentations from the FDA (including Dr. Courtney Lias who runs the device side). Overall, the day was a success on many key measures – moving patient stories; FDA’s enthusiasm for future dialogue; and a strong need to supplement A1c with additional endpoints (e.g., time-in-range), among others. One major negative was that although FDA had room for 1,000 registrations for patients listening by webcast and although there was planned capacity for many additional to “lurk,” the very high demand from Diabetes Online Community and others jamming the lines shut down the servers at FDA. More on this below; we are working on a video that will include iPhone video coverage to supplement CVENT before it failed – stay tuned.    

Below, we enclose our top 10 highlights from the day, followed by more detailed discussion and commentary.

1. Today’s event was live webcast and saw overwhelming participation – so much so that the FDA’s online feed crashed around the 90 minute mark! There was massive social media surrounding this event, with over three million twitter impressions (#DOCAsksFDA) in just a few hours!

2. FDA leadership used lots of encouraging language throughout the day, suggesting that future patient dialogue would be constructive and desired. We are hopeful that a similar meeting would include more leadership from CDER (the very respected Dr. Courtney Lias was the leader from the diabetes device side along with Dr. Stayce Beck – there was not anyone at this level of seniority from CDER although there was very thoughtful commentary from a former CDER reviewer).

3. A loud-and-clear message from all patient advocates was the desire to have FDA go beyond A1c when assessing trial results and supplement A1c (a valuable measure, all agreed) with metrics such as time-in-range and hypoglycemia.

4. A compelling video captured patients’ diverse wishes for the future - click here to view it.

5. Parent Ms. Angie Platt paired with JDRF’s Dr. Aaron Kowalski shared a truly moving view of the daily struggles of type 1 diabetes.

6. A compelling patient panel shared vivid stories of what it is like to live with diabetes, why it’s difficult, and what tools are needed.

7. Candid patient feedback underscored the challenges of finding and participating in clinical trials along with some related positives; some FDA leadership appeared very surprised at this. 

8. FDA expressed concern with labeling and sought to discuss a “Consumer Reports” for diabetes devices. Patient panelists remarked that they rarely read labels and asked for more user-friendly ways of learning. It’s clear in the iPhone age that expectations are higher than they have been in the past. We think declines in attention span probably contribute to this.

9. In addition to sharing comments on the value of time-in-range and the complexity of diabetes, the diaTribe Foundation called for better or broader regulatory guidance on four fronts: prediabetes; more therapies for type 1 diabetes; BGM accuracy; and re-examining cardiovascular outcomes trials. Some of these were covered in an FDA panel, where leaders also discussed the possibility of approving drugs or devices for certain patient subgroups.

10. Leading up to the meeting, more than 7,000 patients/caregivers responded to a dQ&A survey of the diabetes community. The results were highly illuminating and impactful, particularly the 400-page book of comments delivered to the FDA.

1. Today’s event was live webcast and saw overwhelming participation – so much so that the FDA’s online feed crashed around the 90-minute mark. FDA sent out an email during the event to apologize for the technical difficulties with Adobe Connect – it was disappointing though also a major statement about pent up demand to speak to FDA from the diabetes online community (DOC). Indeed, there was massive social media surrounding this event, with over 3 million twitter impressions (#DOCAsksFDA) in just a few hours – unfortunately the shutdown of the FDA servers also shut down much social media. We believe nearly 1,000 attendees watched the live event, supplementing the more than 7,000 people with diabetes/caregivers that took the survey. We are hopeful that it’s still possible to piece together a video of the event.

  • “So, what did you do today?" "Participated in a nationwide diabetes discussion that brought http://FDA.gov  to its knees" #DOCasksFDA – @OrbingPunk
  • Measure of DOC success: 2 years ago we couldn't organize a response on PDUFA http://www.ydmv.net/search?q=pdufa  Today we crashed #DOCasksFDA” - @StripSafely
  • “Back to my regularly scheduled life. Despite tech issues, I'm happy that #DOCasksFDA happened.” – @SweetenedKate
  • “really don't want to give up on this FDA event. But it looks like a government agency has failed us again. #DOCasksFDA” – @curlysarah56
  • "What did you do while #DOCAsksFDA mtg was down?" Hey, jogging in place for a @bigbluetest seemed like a good plan.” - @MHoskins2179

2. FDA speakers used quite encouraging language throughout the day, suggesting that future patient dialogue would be constructive and desired. Senior FDA diabetes device leadership, Drs. Courtney Lias and Stayce Beck, were highly engaged and smiling throughout the day, and their comments were very patient-centered as well as astute in assessing the situation. FDA diabetes device leadership has trended in a very positive direction over the past year, and we salute Drs. Lias and Beck for taking time to engage in a major way with today’s meeting – their biggest commentary made it clear they believe in time in zone and moving beyond A1c while there were fewer specifics on glucose monitoring accuracy, etc – we also wished we had been able to move to more of these questions, especially related to ISO and guidance. CDER Medical Officer Dr. Naomi Lowy also clearly expressed that she found the day valuable, and we were very moved by her positive comments about much better understanding patient life (she found the comments on clinical trials especially helpful she said). Though she spoke much less specifically to diabetes, we were very impressed by her remarks related to risk/benefit tradeoffs. It was disappointing that CDER’s top leadership was not present today, an absence that did not go unnoticed by some patients who spoke up about it. Still, given Dr. Lowy’s positive experience and encouraging remarks, we believe a similar meeting with CDER leadership is likely in the future. An excellent bright spot was meeting FDA’s Dr. Jonca Bull (Director, Office of Minority Health), a major advocate for patients who spoke passionately about the her desire to bring in more patient input to FDA, the need to highlight patient issues, the need for aspirational work by FDA (!), and the strong desire to boost minority representation in clinical trials, which had been highlighted by multiple patients. We continue to think that this is solvable problem.

  • “I want to thank the patient advocates who spoke. As a clinical reviewer stuck in data summaries, it is really refreshing to hear stories; they are really powerful. Patients are trying to help. At CDER, and CDRH, we are always looking for new ways to understand patient tolerance for risk. That is something that the Division of CDER is open to understanding. We will work with the Office of Health and Constituent Affairs to make that happen.” – Dr. Naomi Lowy
  • “We’re excited about where FDA can take this transformative pilot discussion.” – Dr. Helene Clayton-Jeter (Director of FDA’s Cardiovascular and Endocrine Liaison Program, meeting co-host with Kelly Close)
  • “This is the start of an ongoing dialogue, one that we hope goes forward in a strengthened way.” – Dr. Jonca Bull

3. A clear message from all patient advocates was the need to go beyond A1c and consider metrics such as time-in-range and hypoglycemia. The device division has of course been very forward thinking on this front (e.g., the final Artificial Pancreas guidance, to which JDRF contributed significantly in a major advocacy effort), and we hope today’s meeting planted a seed on this front in other areas of the FDA, especially CDER. The need to supplement A1c was a focus of remarks from both diaTribe (see slides here and below), JDRF, and many patient panelists (Anna McCollister-Slipp, Rebecca Killion, Angie Platt). While it will no doubt take time and effort to truly shift the paradigm, we believe it is essential to move beyond A1c alone, particularly as next-gen therapies come to market that may reduce hypoglycemia and/or hyperglycemia, but might not impact A1c. “Quality of A1c” was just as relevant a decade ago as it is now, but there is now CGM accurate enough to measure it. That said – we are under no illusions that it is easy to use CGM in all trials and obviously it wouldn’t be appropriate to suggest this. Still, we do believe long-term data on this would be highly valuable – Dr. Patricia Beaston insisted there is no science behind “time in zone” and indeed she is right in terms of there being no outcomes trials like DCCT that assess the impact of variability on long term complications. That said, CGM does clearly contribute to less hypoglcyemia. In the meantime, we would love to see funding emerge for a modern-day DCCT and/or UKPDS; although most with whom we speak say this is impossible, and while we recognize it would be very challenging to design and execute these trials, we also think it is important to consider if major government officials insist there is no value to pointing out variability.

4. A compelling video captured patients’ diverse wishes for the future - click here to view it. It was notable that this came before the FDA’s presentations, a highly symbolic move that really framed the day’s focus on patients. Most notably – and in line with the flavor of today’s discussion – it was yet another aspect of the day that appeared to bring together the type 1 and type 2 communities. We believe this could be a key to successful advocacy at other levels – not just FDA, but also CMS, other payers, Congress etc. It was incredible to hear the diversity of patient perspectives; some of our favorite quotes are posted below.

  • “I dream of not having to worry about hypoglycemia. Ever.” – Manny Hernandez, type 1
  • “My dream is to not let diabetes get in the way as I live my life.” – Sue
  • “I’d like the FDA to please make it easier to bring things like Nightscout and the Bionic Pancreas to everyone with type 1 diabetes.” – Andrew
  • “My type 2 diabetes is about more than A1c. My medication should be too.” – Bennet Dunlap
  • “I would really like to see better fast-acting insulin and pump sites that don’t hurt when they’re put in.” – Ben
  • “It’s a dream to actually remove the stigma of living with diabetes. Diabetes is not a character flaw.” – Kelly
  • “My husband has had diabetes for a very long time. The ups and down – it’s a roller coaster. Please help us get off the roller coaster – we want normal blood sugars!” – Lorraine
  • “I dream of diabetes being minimally invasive on my body, on my mind, and on my happiness.” - Kerri Sparling
  • “I’m tired of working so hard and always being 40 or 400. I want something to just even out the blood sugars.” – Michelle

5. Parent Ms. Angie Platt paired with JDRF’s Dr. Aaron Kowalski shared a truly moving view of the daily struggles of type 1 diabetes. Both emphasized the daily burden of managing diabetes, the calculations, the supplies, the stress, the fraction of time spent in range, and the disease’s complexity. Dr. Kowalski just finished the New York City Marathon with his family the day before and painted an incredible picture for us of the many sacrifices that the parents had made for two children with diabetes. Ms. Platt spoke movingly about the pressure she feels as a parent without diabetes.  In line with many panelists, she highlighted the disease’s unpredictability: “Jonathon wakes up and eats the same breakfast every morning. However, his blood glucose can vary by up to 100 mg/dl at lunch.” Ms. Platt and her husband wake up multiple times every night (11 pm, 1 am, 3 am) to check their son Jonathan’s blood sugar, in addition to checking him at 5:30 am before he wakes up (“That first blood glucose of the day is critical”).

  • Charismatic patient panelists Ms. Rebecca Killion and Ms. Anna McCollister-Slipp also spoke to the challenges and risks of living with diabetes every day. Type 1 advocate Ms. McCollister-Slipp highlighted diabetes complications as a topic; she was among the day’s strongest advocates on the need to move beyond A1c alone (she acknowledged it was helpful though shared her opinion that FDA’s focus on the measure was myopic). Ms. Killion shared how diabetes has robbed her of both independence and the ability to be spontaneous (“there are always logistics and planning with diabetes; you cannot be spontaneous”). Both were paired with ADA’s Dr. Maria Mupanomunda, who gave both patients plenty of time to speak.

6. Close Concerns has always written with patient perspectives top of mind, but hearing real patients share their stories today was truly heart wrenching and vivid. The commentary was truly impactful, and it was actually moving to see FDA employees in attendance nodding and listening intently. The nine patients on today’s panel were brave in their willingness to share vulnerability with those they didn’t know as well as in discussing a myriad of challenges they have faced: misdiagnosis, complications, diet and exercise challenges, weight management challenges, stress, guilt, shame, burden, and much more.

7. Honest patient feedback underscored the challenges of finding and participating in clinical trials; some FDA staff and leaders were clearly surprised to hear it.  We felt this message was critical to convey (and unlike others, we managed to do it), given the burden many trials place on patients and industry, and the Agency’s temptation to “do another trial.” Cited barriers included: hard to find (e.g., ClinicalTrials.gov not patient-friendly); ineffective marketing; not meeting the inclusion criteria (e.g., other medications, presence of complications); too high of a burden; too far away to travel. Ms. Kelly Close also emphasized the uncertain consequences of cardiovascular outcomes trials, highlighting Dr. John Jenkins’ quote from the mid-August CVOT meeting: “… It may be time to revisit the basis of cardiovascular studies for diabetes drugs.” While this was not a focus of the day’s discussion, it was critical to hear this put on the table. diaTribe’s closing remarks suggested a 2015 meeting to re-examine the basis of cardiovascular outcomes trials, given Dr. Jenkins’ impressions.

8. FDA seemed very concerned with labeling and developing a “Consumer Reports” for diabetes devices. diaTribe’s Adam Brown spoke from his own experience, highlighting his opinion that most patients don’t read labels and don’t open instruction manuals (in fact, he shared, diaTribe tests new products by deliberately trying to set them up without an instruction manual). Adam emphasized the need for simple one-page quick-start guides, and ideally, products that are so easy to use that no instruction manual is required. He further noted what most patients do when they have a problem – they do an online or social media search on it. Overall, we believe patient expectations on ease of use are way beyond the FDA’s current thinking. In hallway chatter, when Kelly raised the problem that labels are hard to read simply because they are small, FDA officials expressed surprise that the small print in labels is hard to read. There is a clear disconnect on this front, and FDA’s Dr. Stayce Beck expressed she would leave with a key takeaway: the need to make labels more patient friendly. We hope future dialogue gives patients an opportunity for candid discussion with FDA on this front.

9. In addition to comments on time-in-range and the complexity of diabetes, diaTribe asked for better or broader regulatory guidance on four fronts: a drug pathway for prediabetes; more type 1 therapies, especially type 2 drugs for type 1; BGM accuracy (particularly the convenience tradeoffs that could come with meters forced to meet the proposed 2014 guidelines); and re-examining cardiovascular outcomes trials. See the opening slides here and the closing slides here.

10. Leading up to the meeting, more than 7,000 patients/caregivers responded to a dQ&A survey of the diabetes community. The goal was to provide broad patient input on key challenges and unmet needs. The survey’s high-level findings are noted below; please contact Richard Wood at Richard.wood@d-qa.com for more details. Two open-ended question concluded the survey and provided an impressive 400 pages of material, a major symbolic “thud factor” handed out to all Agency representatives.

  • An online survey of the diabetes community was conducted from October 15 to October 23, 2014 at www.diaTribe.org/survey. The survey had 6,184 respondents as of October 23: 65% patients (n=3,999) and 35% parents of children with diabetes and partners/caregivers of people with diabetes (n=2,182). Among all survey respondents, 17% self-identified as type 2 (n=1,072) and 83% self-identified as type 1 (n=5,112). While a majority of the survey takers were type 1 patients or caregivers, over 1,000 respondents have type 2 diabetes. The survey garnered over 4,000 open-ended comments from patients.
    • A minority of type 1 (19%) and type 2 (37%) respondents met the AACE goal of an A1c <6.5%, and only 35% of type 1s and 54% of type 2s met the ADA goal of an A1c <7.0%. A quarter of type 1 respondents and 16% of type 2 respondents reported a very high A1c >8.1%, putting them at significantly increased risk for long-term complications. It was notable to see such challenging glycemic control, given the plugged-in population that took the survey. We can only wonder how patients not on social media are doing.
    • The presence of certain complications was high in both populations, particularly depression (reported in 45% of type 1 respondents and 30% of type 2 respondents). A majority of type 2s reported high blood pressure (67%) and cholesterol problems (58%) and a sizable percentage of type 1s reported high blood pressure (28%) and cholesterol (32%) problems. Twenty to 25% of all type 1s and type 2s surveyed had eye, feet, and nerve problems. These outcomes were despite extensive use of diabetes technology in type 1 respondents (95% on BGM, 72% on pumps, 46% on CGM) and BGMs and insulin in type 2 survey respondents (98% and 48%, respectively).
    • Diabetes had a “serious negative impact” on many daily activities, especially patients’ ability to take on life’s challenges, success at work or school, and planning for the future. Qualitative data reflected the high psychological burden associated with managing type 1 and type 2 diabetes. In an open-ended question, thousands of patients pointed to high levels of stress, complexity, therapy burden, and time associated with managing diabetes every day. There was significant hope for simpler therapies that require less thought, medications that are more weight neutral (particularly insulin) and cause less hypoglycemia, and technology like better CGM and the artificial pancreas. Many patients expressed concerns about the cost of drugs and devices.

Detailed Discussion and Commentary

Welcome

Opening Remarks

Helene Clayton Jeter (Director, Cardiovascular and Endocrine Liaison Program, FDA, Silver Spring, MD)

Dr. Helene Clayton-Jeter enthusiastically opened the meeting, highlighting the key objectives and goals.

  • Welcome to the FDA Patient Dialogue on Unmet Needs in Diabetes. It’s exciting to be here for this unprecedented interaction between the diabetes community and FDA. Thank you so much to more than 7,000 patients who responded to a recent set of questions from a community survey, as well as to more than 1,000 people who signed up for the event itself. And all those on Twitter: #DOCAsksFDA
  • Today, we’re going to hear from FDA leadership on what they do. Then, we’ll move into the organizational perspectives session with diaTribe, JDRF, and ADA. The heart of the discussion will be two panels: one where I talk to patients and one where Kelly talks to FDA leadership. I will then discuss communicating with FDA and we’ll conclude with a diaTribe/FDA wrap up.”
  • What do we want to accomplish today?
    • Primarily, we want to open up the lines of communication between the FDA and the patient community.
    • We also want to help the reviewers leave with a better sense of what it is like to live with diabetes, what is difficult for patients, and what patients want in terms of new tools.   
    • Last, we hope this could be a pilot for potential future meetings at the FDA.

Opening Remarks

Kelly Close (Founder, The diaTribe Foundation, San Francisco, CA)

Ms. Close discussed the history of the meeting’s development and highlighted the urgency of diabetes. 

  • To give you a little background, this work started nearly 18 months ago, when I was honored to speak with the great Commissioner Margaret Hamburg in Colorado after she gave a couple of tremendous talks on public health. She first helped lead a panel discussion on “Precision Medicine and the Fight Against Chronic and Infectious Disease” on the BBC World Service’s The Forum at the Aspen Institute. She was there with great cancer biotech leader Tony Coles (we hope next time it’s a diabetes leader!) and CDC head Dr. Tom Frieden – they had fascinating conversation about where chronic disease is going. Considering diabetes is the biggest public health problem of our time, I was of course very interested to follow the dialogue. Then, Dr. Hamburg was part of a fascinating and very daunting discussion with well known public health journalist and thinker Dr. Richard Besser and Mt. Sinai CEO Dr. Ken Davis (now THAT is someone who is really committed and concerned about diabetes on behalf of his great institution and New York City) – their discussion was something that affects all of us gravely - “What Will Healthcare Look Like in 25 Years?”
  • After listening to the ever so eloquent Dr. Hamburg, I went to speak to her right after these discussions about the problems in diabetes and how badly patients need help on SO many fronts. I told her a little bit about some of the challenges in diabetes from a patient perspective. Not skipping even a BEAT, she asked me whether patients would want to have more input at the FDA. At diaTribe, we leapt at the opportunity, and after zigging and zagging a bit across the Agency trying to figure out how and where this could happen, with the help of Dr. Clayton Jeter about how exactly we could bring more patient voice into FDA, we’ve worked hard to make today’s meeting happen. At diaTribe, we’ve always believed that the perspective of people with diabetes and their partners and caregivers should be front and center as the FDA reviews new therapies and technologies.
  • And we need it more than ever. Over 5,000 people are diagnosed every day in the United States, adding to 29 million who already have diabetes here. We are now spending nearly $250 billion per year on diabetes in the US, and yet, most patients are not in good glycemic control. This is the biggest public health problem of our time. Today, the diabetes community will share with the FDA how diabetes affects their daily life, what risks they confront daily, and what would make managing the disease easier.
  • We got over 7,000 responses to the survey – thank you much to dQ&A and the diabetes community for making this happen. Helene, here’s the summary plus comments from just TWO open-ended questions – over 400 pages for you and your team.
  • And last …so we give you every media -  diaTribe asked patients to share some big picture thoughts about what they would like to see most for their diabetes management.   Here’s a selection of patient views …  ROLL IT!!!
  • [Click here to watch the video.]

The Role of the FDA in Diabetes

Office of Minority Health

Jonca Bull, MD (Director, Office of Minority Health, FDA, Silver Spring, MD)

Dr. Jonca Bull had a positive tone and focused message, calling for greater inclusion of minority subgroups in clinical trials. She shared the findings of an FDA Safety and Innovation Act report that examined the availability of demographic subgroup data in medical product applications submitted to the FDA, which demonstrated that the proportion of women, minorities, and elderly in industry-sponsored clinical trials does not reflect the prevalence of diabetes in the underlying population. Further, she highlighted that health professionals and patients do not have sufficient demographic information to make informed treatment and diagnostic decisions. In response to these deficiencies, the FDA published an action plan in August 2014 that consists of three overarching priorities: (i) to improve the completeness and quality of demographic subgroup data collection, reporting, and analysis; (ii) to identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage greater participation; and (iii) to make demographic subgroup data more available and transparent. On a high-level, we salute the FDA for recognizing its shortcomings and carrying through with this call to action, though it remains to be seen how these priorities will translate in practice for patients with diabetes. Improving the diversity of clinical trials is a solvable problem in our view, if also a challenging one – it simply comes to better marketing of trials, meeting patients where they are, making trials less burdensome, and thinking more creatively about recruiting.

CDRH

Courtney Lias, PhD (Director, Division of Chemistry and Toxicology, FDA, Silver Spring, MD)

The very positive Dr. Courtney Lias provided a wide-ranging overview of the medical device regulatory process. She stressed that the Agency is patient-focused at its core and believes that the patient voice is an integral component of the decision-making process. As an example, Dr. Lias cited the FDA’s 2014 draft guidance on BGM accuracy – which was released in January and subject to some criticism over the tightened standards relative to ISO 2013 – as an example of the FDA’s intention to integrate patient perspective into the regulatory pathway. She shared that the two guidance documents, one for SMBG devices (i.e., home use setting) and one for point-of-care devices (i.e., healthcare facilities), received a total of ~600 comments in response, of which 400 were from patients; the FDA is apparently making a strong effort to incorporate that feedback into its final guidance. More broadly, it was refreshing to hear Dr. Lias’ candid characterization of the Agency’s inadequate post-market surveillance of blood glucose monitoring testing supplies. She spoke briefly to the need for more effective surveillance that minimizes “dangerous situations” for patients and that ensures that marketed products are sold by reputable dealers. Dr. Lias also highlighted the Nightscout Project as an example of working with patients (they met formally on October 8), and reiterated the Agency’s enthusiasm to bring closed-loop technologies to patients as soon as possible. On the latter, she noted the significant progress on studies, as every recent proposal has been approved in the first round of review.  We thank Dr. Lias for her patient-focused, encouraging remarks and believe she has truly changed the tide in the FDA device division for the better.

CDER

Naomi Lowy, MD (Medical Officer, Center for Drug Evaluation and Research, FDA, Silver Spring, MD)

Dr. Naomi Lowy provided a detailed breakdown of the FDA’s drug approval process, taking attendees step-by-step through the process of beginning a pre-clinical trial to the post-market surveillance of products. Dr. Lowy included a bold quote from FDA’s Dr. John Jenkins: “It is very important for people to understand that we don’t know everything about new drugs at the time we approve them. If we waited until we knew everything you could possibly know, then the process would be too long and patients would be denied access to important new treatments.” The commentary was somewhat ironic, in our view, given the delays in transformational therapies spearheaded by cardiovascular outcomes trials. That said, we do believe that the regulatory climate on the diabetes drug side has improved in the past year, considering the products approved (see below), though it could always move faster if the Agency had more resources. The volume of requests continually increases, especially as newer drug classes (i.e., GLP-1 agonists, DPP-4 inhibitors, SGLT-2 inhibitors) move to next-gen formulations and combination therapies. Overall, Dr. Lowy’s commentary was fairly general in scope, though we found her commentary in panel discussions to be largely positive, warm, and patient-centered.

  • Diabetes/obesity drug approvals in 2014:
    • Farxiga (dapagliflozin);
    • Tanzeum (albiglutide);
    • Afrezza (inhaled human insulin);
    • Jardiance (empagliflozin);
    • Basaglar (biosimilar glargine);
    • Trulicity (dulaglutide);
    • Contrave (naltrexone/bupropion)
    • (Potentially Saxenda [liraglutide 3.0 mg]).

CDRH

Patricia Beaston, MD, PhD (Medical Officer at Center for Devices and Radiological Health, FDA, Silver Spring, MD)

The controversial Dr. Patricia Beaston concluded the session with comments some said they found defensive. First, she highlighted the difficult trade-off between convenience and accuracy – though the FDA is well aware of the need for new technologies and improved accessibility, Dr. Beaston asserted that the Agency will not compromise safety for the sake of convenience. Additionally, she emphasized that the FDA – unlike European regulatory bodies – has limited options to remove a product from market after it has been approved. (This was also a point of emphasis with respect to diabetes devices at the Consensus Conference on Glucose Monitoring.) Indeed, she explained that the market removal process is largely voluntary from a manufacturer’s point-of-view, underscoring the notion that the FDA must more prudent and judicious than Europe in the approval process. It is clear to us that the FDA needs stronger post-market regulatory jurisdiction, and we hope to see greater dialogue on this front moving forward. However, we did not find Dr. Beaston’s participation in the day to be particularly helpful in advancing patient interests; patients characterized her tone as harsh and condescending (though they were happy to hear from her that she saw patients regularly). Her participation was very opposed to the bright, positive, and engaged other FDA leaders. As noted, she sees problems with understanding the value of “time in zone” – we look forward to greater discussion on this.  

Organizational Perspectives

The complexity of diabeteS: key issues impacting patients

Adam Brown (The diaTribe Foundation, San Francisco, CA)

Slides posted here

Mr. Adam Brown focused the diaTribe Foundation’s presentation on three areas: the need to supplement A1c with time-in-range; the sheer complexity of diabetes; and advice on guidance.

  • Mr. Brown explained that, while A1c is valuable in many ways, it leaves out an important aspect of the story: the time patients spend hypoglycemic and hyperglycemic. As an example, Mr. Brown showed three different patients with an A1c of 7% (an average blood glucose of 154 mg/dl) – one spending 100% time in range, one spending 63% time in range (29% high, 8% low), and one spending 18% time in range (58% high, 24% low). In other words, he said, we need to think about “Quality of A1c” and the amount of time patients are spending high and low. In a complementary fashion, Mr. Brown noted that although some therapies may increase A1c, they are still major wins from a patient perspective if they eliminate hypoglycemia. To cap off this section of his presentation, he concluded with an ironic summary quote, “If I stand with one foot in a bucket of ice water and one foot in a bucket of boiling water,
on average, I am comfortable.”
  • “Diabetes is really easy if you don’t eat, if you don’t move, you get eight hours of sleep, and you’re never stressed.” Mr. Brown also spoke to the daily challenges of diabetes management, remarking that over 22 factors impact a patient’s glucose levels. He noted that even with the best access to therapies, technologies, education, and lots of motivation, it’s impossible to manage the slew of variables. Mr. Brown shared his near-daily experience with one of the most frustrating aspects of diabetes management: “I did everything right and my blood sugar was still out of range!”
  • The presentation asked for follow up on regulatory guidance on four fronts:
    • A drug pathway for prediabetes;
    • More type 1 therapies (especially type 2 drugs for type 1);
    • BGM accuracy and associated tradeoffs (e.g., patients don’t benefit from a clinically insignificant increase in accuracy if an enormous meter or large blood droplet is required; also, is enforcement good enough?).
    • Re-examining cardiovascular outcomes trials (billions of dollars, tens of thousands of patients, delays in transformative therapies).

Question and Answers

Mr. Adam Brown (The diaTribe Foundation, San Francisco, CA):  How would you summarize diabetes in two words?

Mr. Francisco Estrada (National Society of Hispanic MBAs, Irving, TX): It stinks! [Laughter]

Mr. Brown: Francisco, you were diagnosed around five years ago. Can you talk about what your diabetes was like when you were diagnosed and over the next four years?

Mr. Estrada: It was a disaster. I had three physicians. They said I was pre-diabetic, or had syndrome x. I was on 1000 mg of metformin, and it didn’t control me. I was gaining weight every year. It didn’t matter how much i exercised or what I did. 

I was a wreck.  My weight was out of control, I couldn’t get a full night’s sleep, I was constantly getting up to drink water to quench my thirst and then getting up to urinate. I was miserable.  

That’s what diabetes does; robs you of your sleep, makes you feel exhausted and depressed. I sought answers and advice from various doctors. I was told that I probably had pre-diabetes and that the best thing I could do to improve my health was to reduce my weight. While it sounded reasonable, it wasn’t enough.

 Increasing my physical activity, cutting back on meals, taking supplements and dieting didn’t work.  No matter what I tried to do to control it – nothing worked.   The weight continued to pile on each year.  As I got older I felt more sluggish, stiff in the morning, achy and tired from sleepless nights.  This was my life.  A frustrating existence with little hope of change, I was slowly resigning to the fact that my worsening health was part of my life and I just needed to accept it.  But, I couldn’t.

I was not fully aware how sinister this progressive disease was becoming. My family physician suspected that I was a diabetic and he placed me on metformin. However, my A1C numbers didn’t get better. He was not ready to place me on insulin; the next step, and honestly I was not ready. His only advice to me was to try and lose weight: easier said than done.  I had always tried to eat well, not in excess.  I limited, sugars, and was careful about my carbohydrate intake.  I had always worked out, on average, 3 to 4 days a week to manage stress, and abstained from drinking too much.  Regardless of this life style my numbers did not improve.

Q: Once you retired, you resolved to get your diabetes and weight under control. What did you do?

A: I was running around 272-275 lbs. It didn’t matter whether I exercised, or dieted. I said, "screw it." I thought about gastric bypass. I got on the internet, and after doing some research, ran into a doctor testing a new device, used in Europe and going through FDA trials - it’s a sleeve that put down your gastrointestinal track. I thought, “That would be neat. No surgery, pop it in and out." But I didn’t qualify, because I wasn't on 2000 mg on metformin.  

But a week later, my doctor called and passed me onto the GRADE study. I really found out about the trial by accident. They don’t market very well. Dollars are never appropriated for marketing/advertising. They need to do more in terms of advertising. They are constantly looking for more participants. I volunteered to be in a brochure to help try to find more participants.

Q: What has it been like being a part of the GRADE study? 

A: As soon as I started insulin injections, in the first month, I lost 10 lbs. Then close to another 10 lbs; it just kept dropping. I’ve plateaued, but I’ve lost literally 30 lbs. I sleep eight hours now. I don’t have to get up to urinate 2-3 times per night. I feel more rested. Overall, it’s been a 100% improvement in my health and perspective.

JDRF Perspective

Aaron Kowalski, MD (JDRF, New York City, NY)

Dr. Aaron Kowalski briefly presented on his personal relationship to type 1 diabetes (both he and his brother have type 1 diabetes) and the role of JDRF in diabetes research. He echoed diaTribe’s call for increased attention to time in range; Dr. Kowalski underscored that even those testing upwards of ten times a day still spend only a fraction of the day in range. Turning to the role of JDRF, Dr. Kowalski noted that the organization has funded over a billion dollars in research, and though the ultimate goal is a cure, they are also working to improve tools that will help ease the burden of diabetes. Dr. Kowalski ended his presentation by calling on the FDA, industry, community, payers, and researchers to align work on the unmet needs in the diabetes community. The remainder of Dr. Kowalski’s time went to Ms. Angie Platt who spoke on her role as the parent of a son with has type 1 diabetes; the conversation is transcribed below.

Questions and Answers

Dr. Aaron Kowalski (JDRF, New York City, NY): What was it like when Jonathan was diagnosed?

Ms. Angie Platt (Los Angeles JDRF Chapter Board of Directors, Los Angeles, CA): My son Jonathon is 11 years old and was diagnosed with type 1 diabetes when he was six. He has always been a thin kid, but he soon started urinating frequently and was lethargic. He was rushed to the emergency room with a blood glucose level of over 600. We didn’t understand a lot of what was happening at the time, and I wasn’t sure if Jonathon was ever going to live a normal life again. I lived with guilt for a number of years. When we were at the hospital, we were administered a number of supplies – mostly insulin – and it became a heavy burden.

Dr. Kowalski: Can you talk about your daily routine?

Ms. Platt: At 5:30 AM, we check his blood sugar while he is still asleep, because the first blood sugar of the day is really important. Jonathon wakes up and eats the same breakfast every morning. However, his blood glucose can vary by up to 100 mg/dl at lunch. We check his blood glucose at lunch and again after school. If he has basketball practice, we check before and after practice. We check at dinner and at bedtime and at 10:00 PM every night. He is a tall kid and growing and overnight is really hard.

Dr. Kowalski: What are your concerns?

Ms. Platt: Our concerns used to be overnight lows, but now it is the extreme highs and lows everyday. We test his blood glucose all the time and watch what he eats, and Jonathon is a very active kid.

Dr. Kowalski: What do you see as a better world for living with diabetes? What can we do better as a community?

Ms. Platt: At the initial diagnosis, Jonathon was put on multiple injections a day. The calculations are really difficult – there is a different insulin to carb ratio at different meals throughout the day. We also have to correct for the highs, and that requires a lot of math and tracking. Jonathon went on an insulin pump, and it changed our lives. It eased the burden of calculating the multiple daily injections. I’m hopeful for new technology – I’m hopeful for new tools to ease the burden.

Dr. Kowalski: There is a common misconception about people with diabetes that they we’re non-compliant; we just don’t work hard enough. It’s an incredible amount of work. What are your other children like?

Ms. Platt: Jonathon has two little brothers. I’m almost embarrassed, but when we found out I was pregnant, my first thought was about whether or not they would have diabetes. We don’t know – they could still develop the disease. However, we are hopeful that if they do start to develop type 1 diabetes, we will be able to slow the onset even if we cannot stop the development. We are hopeful for prevention. This is why we love JDRF – because it is working for a cure and prevention. We are hopeful that this will also help Jonathon have access to better technology sooner.

Dr. Kowalski: I know you told me you worried about getting choked up on stage, and now I’m choking up – thinking about all my parents did for me. Diabetes is more than A1c and glucose control, and it impacts more than the person with type 1 diabetes.

FDA Virtual Town Hall Meeting

Maria Mupanomunda, MD, PhD (ADA, Alexandria, VA)

Dr. Maria Mupanomunda provided an overview of the diabetes population in the US, highlighting the 29.1 million diagnosed patients (8.1 million of whom are undiagnosed), and 86 million people with prediabetes. She also remarked that despite improvements in care, diabetes is still the leading cause of blindness and end-stage renal disease, and many patients are not meeting their glycemic goals. Hypoglycemia, she noted, is a limiting factor in the fight against hyperglycemia. Dr. Mupanomunda outlined the ADA’s position: Outcomes are important to patients, and the community needs to work to lower A1c without increasing hypoglycemia or weight gain while, hopefully, maintaining favorable side effects. She also noted the need to address issues of absenteeism, cost, and quality of life. Dr. Mupanomunda ended her presentation by bringing two patient advocates to the stage to talk about their experience with the disease – highlights of the conversation are outlined below.

Questions and Answers

Dr. Maria Mupanomunda (ADA, Alexandria, VA): What compromises have you had to make as a person with diabetes and why?

Ms. Rebecca Killion (Patient Advocate, Washington, DC): I experienced adult-onset diabetes. The first thing I had to give up was my independence. I was training for a marathon and was stopping to drink out of people’s hoses in their backyards – I kept thinking to myself, this is normal, I’m thirsty because I’m running, and I’m urinating because I’m drinking a lot. There was denial at first. When I finally said out loud to my husband that something might be wrong, he said, “you’re fine.” I exploded at him because I was finally coming to terms with it. My first compromise that I make everyday is acknowledging my loss of independence. It is still a struggle; loss of control is very humbling.

I was first diagnosed with type 2 diabetes, and then later diagnosed with type 1 diabetes after I experienced severe diabetic ketoacidosis. As I started out my journey with diabetes, I first realized that I am dependent on multiple drugs. I tried to convince my doctor that I would cure my diabetes with my sheer force of will – but I have yet to do that. My therapy failed me, and I needed insulin; that’s when I realized I would need to do this every day in order to have a life.

[Editor’s note: The live webcast cut out at this point, and the diaTribe team began filming and recording onsite. Hence, we were unable to take detailed notes at this time. We are working to add to this Q&A.]

Closing Remarks

Conclusion and Next Steps

Dr. Clayton-Jeter: Thank you so much to my colleagues at FDA and to so many patient advocates for participating today. I think we’ve gotten great perspective on the challenges patients face and how reviewers can keep those in mind as they think ambitiously about new devices and drugs. As for wrap up and next steps, we’re excited about where FDA can take this transformative pilot discussion.

Kelly: What a tremendous afternoon, capping off a major year for patient advocacy.

[Clicks through closing slides]

Dr. Clayton-Jeter: Wow, external patient advocacy as moderator of the novel March “Live chat” and internal patient advocacy with securing Manny’s remote access to the open public session of the Afrezza Advisory Committee meeting and now today’s webcast, the FDA has stepped up stakeholder engagement with the diabetes community and I look forward to more opportunities to come.

Kelly: And don’t forget next week on November 13 – Public Workshop - Regulatory Science Considerations for Software Used in Diabetes Management, thank you to Dr. Lias and team. This meeting might have more patient input than we’ve ever seen.

What are the collective hopes for next steps? Here’s what we’ve heard:

  • Making it easier for patients to participate virtually in FDA dialogue
    • Webcasts
    • Videos
    • Easy ways to submit opinions
  • Discussion on more patient-centered study outcome measurements, building on “time in zone” AP guidance
  • Discussion re-examining cardiovascular outcomes trials
  • More patient-centered guidance across multiple fronts (pre-diabetes, BGM accuracy, type 1 cure prevention)
  • Continuing the conversation from today

Kelly: So from all of us on stage and those watching online, thank you so much to Dr. Clayton Jeter - in the Commissioner’s Office of Health and Constituent Affairs, all of her colleagues and team at FDA, all of the patients, caregivers and patient  advocates who have joined us here and online. Here’s to shared responsibility and a more collaborative and actionable partnership between patients and the FDA.

 

-- by Adam Brown, Varun Iyengar, Hannah Martin, and Kelly Close