research

The prompt matters when using Large Language Models (LLMs) and AI in healthcare

by Dana Lewis

I see more and more research papers coming out these days about different uses of large language models (LLMs, a type of AI) in healthcare. There are papers evaluating it for supporting clinicians in decision-making, aiding in note-taking and improving clinical documentation, and enhancing patient education. But I see a wide-sweeping trend in the titles and conclusions of these papers, exacerbated by media headlines, making sweeping claims about the performance of one model versus another. I challenge everyone to pause and consider a critical fact that is less obvious: the prompt matters just as much as the model.

As an example of this, I will link to a recent pre-print of a research article I worked on with Liz Salmi (pre-print here).

Liz nerd-sniped me about an idea of a study to have a patient and a neuro-oncologist evaluate LLM responses related to patient-generated queries about a chart note (or visit note or open note or clinical note, however you want to call it). I say nerd-sniped because I got very interested in designing the methods of the study, including making sure we used the APIs to model these ‘chat’ sessions so that the prompts were not influenced by custom instructions, ‘memory’ features within the account or chat sessions, etc. I also wanted to test something I’ve observed anecdotally from personal LLM use across other topics, which is that with 2024-era models the prompt matters a lot for what type of output you get. So that’s the study we designed, and wrote with Jennifer Clarke, Zhiyong Dong, Rudy Fischmann, Emily McIntosh, Chethan Sarabu, and Catherine (Cait) DesRoches, and I encourage you to check out the pre-print and enjoy the methods section, which is critical for understanding the point I’m trying to make here. 

In this study, the data showed that when LLM outputs were evaluated for a healthcare task, the results varied significantly depending not just on the model but also on how the task was presented (the prompt). Specifically, persona-based prompts—designed to reflect the perspectives of different end users like clinicians and patients—yielded better results, as independently graded by both an oncologist and a patient.

The Myth of the “Best Model for the Job”

Many research papers conclude with simplified takeaways: Model A is better than Model B for healthcare tasks. While performance benchmarking is important, this approach often oversimplifies reality. Healthcare tasks are rarely monolithic. There’s a difference between summarizing patient education materials, drafting clinical notes, or assisting with complex differential diagnosis tasks.

But even within a single task, the way you frame the prompt makes a profound difference.

Consider these three prompts for the same task:

  • “Explain the treatment options for early-stage breast cancer.”
  • “You’re an oncologist. Explain the treatment options for early-stage breast cancer.”
  • “You’re an oncologist. Explain the treatment options for early-stage breast cancer as you would to a newly diagnosed patient with no medical background.”

The second and third prompt likely result in a more accessible and tailored response. If a study only tests general prompts (e.g. prompt one), it may fail to capture how much more effective an LLM can be with task-specific guidance.

Why Prompting Matters in Healthcare Tasks

Prompting shapes how the model interprets the task and generates its output. Here’s why it matters:

  • Precision and Clarity: A vague prompt may yield vague results. A precise prompt clarifies the goal and the speaker (e.g. in prompt 2), and also often the audience (e.g. in prompt 3).
  • Task Alignment: Complex medical topics often require different approaches depending on the user—whether it’s a clinician, a patient, or a researcher.
  • Bias and Quality Control: Poorly constructed prompts can inadvertently introduce biases

Selecting a Model for a Task? Test Multiple Prompts

When evaluating LLMs for healthcare tasks—or applying insights from a research paper—consider these principles:

  1. Prompt Variation Matters: If an LLM fails on a task, it may not be the model’s fault. Try adjusting your prompts before concluding the model is ineffective, and avoid broad sweeping claims about a field or topic that aren’t supported by the test you are running.
  2. Multiple Dimensions of Performance: Look beyond binary “good” vs. “bad” evaluations. Consider dimensions like readability, clinical accuracy, and alignment with user needs, as an example when thinking about performance in healthcare. In our paper, we saw some cases where a patient and provider overlapped in ratings, and other places where the ratings were different.
  3. Reproducibility and Transparency: If a study doesn’t disclose how prompts were designed or varied, its conclusions may lack context. Reproducibility in AI studies depends not just on the model, but on the interaction between the task, model, and prompt design. You should be looking for these kinds of details when reading or peer reviewing papers. Take results and conclusions with a grain of salt if these methods are not detailed in the paper.
  4. Involve Stakeholders in Evaluation: As shown in the preprint mentioned earlier, involving both clinical experts and patients in evaluating LLM outputs adds critical perspectives often missing in standard evaluations, especially as we evolve to focus research on supporting patient needs and not simply focusing on clinician and healthcare system usage of AI.

What This Means for Healthcare Providers, Researchers, and Patients

  • For healthcare providers, understand that the way you frame a question can improve the usefulness of AI tools in practice. A carefully constructed prompt, adding a persona or requesting information for a specific audience, can change the output.
  • For researchers, especially those developing or evaluating AI models, it’s essential to test prompts across different task types and end-user needs. Transparent reporting on prompt strategies strengthens the reliability of your findings.
  • For patients, recognizing that AI-generated health information is shaped by both the model and the prompt. This can support critical thinking when interpreting AI-driven health advice. Remember that LLMs can be biased, but so too can be humans in healthcare. The same approach for assessing bias and evaluating experiences in healthcare should be used for LLM output as well as human output. Everyone (humans) and everything (LLMs) are capable of bias or errors in healthcare.

Prompts matter, so consider model type as well as the prompt as a factor in assessing LLMs in healthcare. Blog by Dana M. LewisTLDR: Instead of asking “Which model is best?”, a better question might be:

“How do we design and evaluate prompts that lead to the most reliable, useful results for this specific task and audience?”

I’ve observed, and this study adds evidence, that prompt interaction with the model matters.

Best practices in communication related to writing a journal article and sharing it with co-authors

by Dana Lewis

I’ve been a single author, a lead author, a co-author, a corresponding author, AND a last author. Basically, I have written a lot of journal articles myself, solo / single, and with other people. One area in this process that I observe frequently gets overlooked is what happens during and after the submission process, as it relates to communicating about the article itself.

I’m not talking about disseminating the article to your target audience or the public, either (although that is important as well). I’m talking about making sure all authors know the article has been accepted; when it is live; have access to a copy of the article (!); etc.

Most people don’t know that by default, not all journals give all authors access to their own articles for free.

Here are some tips about the process of submitting and saving published articles that will help all authors – even solo authors – in the future.

Basically, help you help your future self! (As well as help your co-authors).

Journals typically only notify the lead/corresponding/submitting author about where the manuscript is in terms of revision, acceptance, and publication. That puts the responsibility on the lead/corresponding/submitting author to notify the full team of authors of where the article is in the process. Similarly, some journals will send a PDF/final copy of the proofed, final, version of record article to the lead author (not always, but usually), but that often does not go out to the full author team by default.

This means that it is the lead author’s responsibility to forward the copy of the final, PDF, proofed article to the entire authorship team so everyone has a copy.

(No, most of the time authors do not have free access to the journal they are submitting to. No, most authors do not have budget to make articles open access and free to all, which means unless they manage to snag and save this PDF article when it is sent to them at the time of publication, in the future, they may not have access to their very own article! Just because you, as the lead/corresponding author do have access, this does not mean everyone on your article team will.

I’m a good example of someone who authors frequently but is not at an institution and has zero access to any paywalled journals. If I’m not given a copy of my articles at the time of publication, I have to phone-a-friend (thanks, Liz Salmi, for being the go-to for me here) to help pull articles. There are things like S c i H u b, but they more often than not do not have super recent, fresh off the press articles. So yes, people like me exist on your authorship teams.)

Best practices for authors include:

  • Once you submit a manuscript, mark your file name (somehow) with “Submitted”. This way you know this is the version that was submitted. This is a useful step related to the below, we’ll come back to why we may want to use only the ‘submitted’ version.

    Example: “JournalAcronym-Article-Blah-Blah-SUBMITTED.docx”.

    Even as the non-lead author, when co-writing articles, as any type of author I prefer to have access to this submitted version. This way, I can see all incorporated edits and the ‘final’ version we submitted. There’s also cases where, see below, I need this for sharing it with other people.

  • Usually, the article goes through peer review and you get comments, so you make revisions and re-submit your article. Again, once submitted, make sure you’ve marked this as ‘revision’ somehow (usually people do) and that is was submitted.

    Example: “JournalAcronym-Article-Blah-Blah-SUBMITTED-R1.docx”.

    Again, best practice would be to send out this re-submitted revision version to all authors so everyone has it.

  • You may end up with multiple rounds of revisions and peer review (moving to R2, etc), or you may get an acceptance notice. Your article will then move to copyediting stage and you get proofs. It’s useful to save these for your own purpose, such as making sure that the edits you make are actually executed in the final article. This is less important for dissemination, though, although I do recommend giving all co-authors the ability to edit/review/proof and request changes.
  • Accepted, proofed, published! THIS is the step that I see most people miss, so pay attention.If you are the lead or solo author, you will probably get an email saying your article is now online, either online first or published. You may get an attachment PDF of your article. If not, you should be able to click on your access link and go to access the article online.

    IMPORTANT STEP HERE: go ahead and download the PDF of the article then. Right then, go ahead and save it.

    Example: “JournalAcronym-Article-Blah-Blah-Year.PDF”.

    (Why do you care about this if you are a solo author? Because the link may expire and you may lose access to this article. More on sharing your article below.)

  • Email your entire author team (if you’re not a solo author). Tell them the article was published; provide a link and/or the DOI link; and attach the PDF to the email so everyone on the team has a copy of the final article. Not all of your co-authors will work at an institution that has unlimited library access; if they do, that might change in the future. Give everyone a copy of the article to save for themselves.You can also remind everyone what the sharing permissions (or limitations) are for the article.

    For example, some articles are paywalled but authors have permission to store the final copy (PDF of the final version) on their own repository or not-for-profit website. For an example, see my research page of DIYPS.org/research – you’ll notice how sometimes I link to an “author copy” PDF, which is what this is – the final article PDF like you would get by accessing the paywalled journal.

    Other times, though, you are specifically not permitted to share the final/proofed/formatted copy. Instead, you’ll be allowed to share the “submitted” manuscript (usually prior to the revision stage). Remember how step 1 that I told you was to save a SUBMITTED copy? This is why! You can PDF this up; add a note to the top that references the final version of record (usually, journals give you recommended language for this) and a link/DOI link to it, and share away on your own site. Again, look at DIYPS.org/research and you’ll notice some of my “author copy” versions are these submitted versions rather than the final versions.

    You’ll also notice that sometimes I link to articles that are open access and then also have a link to a PDF author copy. This is in case something changes in the future with open access links breaking, the journal changing, etc. I have actually had free non-paywalled articles get turned into paywalled journal articles years later, which is why I do point to both places (the open access version and a back up author copy).

    Regardless of what the permissions are for sharing on your own website/repository/institutional repository: you as the author always have permission to give this PDF out when you are asked directly. For example, someone emails you and asks for a copy: you can email back and attach the PDF! This is true even if the permissioning for your own website is the submitted version (not the final version), you can still hand out the final, formatted, pretty PDF version when asked directly.

    As a related tip, this is a great way to disseminate your research and build relationships, so if someone does email you and ask for an author copy…please reply and send them a copy. (Saying this as someone without access to articles who sends requests to many authors to get access to their research, and I only get responses from 50% of authors. Sad panda.) Again, this is why it is helpful to get in the habit of saving your articles as you submit and have them published; it makes it easy to jump into the “Published copy” folder (or however you name it) and attach the PDF to the email and send it.

To recap, as a best practice, you should disseminate various versions of articles to your entire co-author team at the following points in time:

  • Original submission.

    Suggestion: Write an email, say you’ve successfully submitted, remind everyone which journal this was submitted to, and attached a copy of your “JournalAcronym-Article-Blah-Blah-SUBMITTED.docx”(If you end up getting a desk rejection, and you are re-submitting elsewhere, it is also nice to email co-authors and tell them so. You don’t necessarily need to send out a newly retitled version, unless there’s new changes to the submission, such as if you did go through a partial round of peer review before getting rejected and you are submitting the revised version to the new target journal.)

  • Revision submission.

    Suggestion: Write an email, say you’ve successfully submitted the revisions, remind everyone which journal this was submitted to, and attached a copy of your “JournalAcronym-Article-Blah-Blah-SUBMITTED-R1.docx” and the reviewer response document so everyone can see how edits/feedback were incorporated (or not).

  • Acceptance.

    Suggestion:

    A) Forward the email if it has the PDF attached to your full author team. Say congratulations; the article was accepted; and point out the article is attached as PDF.

    B) If you don’t have a PDF attachment in your email already, go to the online access link the journal gave you and save a copy of the PDF. Then, email the author team with the FYI that the article is live; provide the link to the online version; and attach the PDF directly to that email so everyone has a final version.

    Regardless of A or B, remind everyone what the permissions are for sharing to their own/institution repository (eg final PDF or use the submitted version, which you previously shared or could also re-share here).

Bonus tip:

Depending on the content of your article, you may also want to think about sending copies of the final PDF article to certain people who are not co-authors with you.

For example, if you are heavily citing someone’s work or talking about their work in a constructive way – you could email them and give them a heads up and provide a copy of the article. It’s a great way to contribute to your relationship (if you have an existing relationship) and/or foster a relationship. Remember that many people will have Google Scholar Alerts or similar with their name and/or citation alerts from various services, so people are likely to see when you talk about them or their work or are heavily citing their work. Again, some of those people may not have access to your article and may reach out to ask for an article; you can (and should) send them a copy! (And again, consider thinking about it as a relationship building opportunity rather than a transactional thing related to this single article.)

I would particularly flag this as something to pay attention to and do if you are someone working in the space of patient engagement in healthcare. For example, if you write an article and mention them or their body of work by name, it would be courteous to email them, let them know about the article, and send them a PDF.

Otherwise, I can speak from the experience of being talked about as a patient like I’m an ant under the microscope where someone cites an article where my work is mentioned; talks about me by name and references my perspective; and I get a notification about this article….but I can’t access it because it’s in a paywalled journal. Awkward, and a little weird in some cases when the very subject of the article(s) are about patient engagement and involving patients in research. Remember, research involvement should include all stages from design, planning, doing the research, and then disseminating the research. So this meta point is that if there is scholarly literature of any kind (whether original research articles or reviews, commentaries, letters in response to other articles, etc) talking about specific patients and their bodies of work – best practice should be to email them and send a copy of the article. Again, think less transactional and more about relationships – it will likely give you benefit in the long run! Plus, less awkward, a short-term benefit.

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best practices for communicating with co-authors about published articles, by Dana M. Lewis from DIYPS.orgAs an example for how I like to disseminate my articles personally, every time a journal article is published and I have access to it, I updated DIYPS.org/research with the title, journal, a DOI link (to help people find it online and/or cite it), and a link to the open access version if available and if not, an author copy PDF of the final or submitted version. So, if you’re ever looking for any of my articles, you can head there (DIYPS.org/research) first and grab copies any time!

If you are looking for a particular article and can’t find it or it’s not listed there yet (e.g. likely because it just came out and I haven’t been sent my own copy by my co-authors yet…), you can always email me directly (Dana@OpenAPS.org) and I’m more than happy to send you a copy of whatever version I have available and/or the final PDF once I have access to it.

Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI): A Diabetes Subgroup Analysis of EPI/PEI-SS Scores – Poster at #ADA2024

by Dana Lewis

Last year, I recognized that there was a need to improve the documentation of symptoms of exocrine pancreatic insufficiency (known as EPI or PEI). There is no standardized way to discuss symptoms with doctors, and this influences whether or not people get the right amount of enzymes (pancreatic enzyme replacement therapy; PERT) to treat EPI and eliminate symptoms completely. It can be done, but like insulin, it requires matching PERT to the amount of food you’re consuming. I also began observing that EPI is underscreened and underdiagnosed, whether that’s in the general population or in people with diabetes. I thought that if we could create a list of common EPI symptoms and a standardized scale to rate them, this might help address some of these challenges.

I developed this scale to address these needs. It is called the “Exocrine Pancreatic Insufficiency Symptom Score” or “EPI/PEI-SS” for short.

I had a handful of people with and without EPI help me test the scale last year, and then I opened up a survey to the entire world and asked people to share their experiences with GI-related symptoms. I specifically sought people with EPI diagnoses as well as people who don’t have EPI, so that we could compare the symptom burden and experiences to people without EPI. (Thank you to everyone who contributed their data to this survey!)

After the first three weeks, I started analyzing the first set of data. While doing that, I realized that (both because of my network of people with diabetes and because I also posted in at least one diabetes-specific group), I had a large sub-group of people with diabetes who had contributed to the survey, and I was able to do a full subgroup analyses to assess whether having diabetes seemed to correlate with a different symptom experience of EPI or not.

Here’s what I found, and what my poster is about (you can view my poster as a PDF here), presented at ADA Scientific Sessions 2024 (#ADA2024):

1985-LB at #ADA2024, “Assessing the Impact of Diabetes on Gastrointestinal Symptom Severity in Exocrine Pancreatic Insufficiency (EPI/PEI): A Diabetes Subgroup Analysis of EPI/PEI-SS Scores”

Exocrine pancreatic insufficiency has a high symptom burden and is present in as many as 3 of 10 people with diabetes. (See my systematic review from last year here). To help improve conversations about symptoms of EPI, which can then be used to improve screening, diagnosis, and treatment success with EPI, I created the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS), which consists of 15 individual symptoms that people separately rate the frequency (0-5) and severity (0-3) for which they experience those symptoms, if at all. The frequency and severity get multiplied for an individual symptom score (0-15 possible) and these get added up for a total EPI/PEI-SS score (0-225 possible, because 15 symptoms times 15 possible points per symptom is 225).

I conducted a real-world study of the EPI/PEI-SS in the general population to assess the gastrointestinal symptom burden in individuals with (n=155) and without (n=169) EPI. Because there was a large cohort of PWD within these groups, I separately analyzed them to evaluate whether diabetes contributes to a difference in EPI/PEI-SS score.

Methods:

I calculated EPI/PEI-SS scores for all survey participants. Previously, I had analyzed the differences of people with and without EPI overall. For this sub-analysis, I analyzed and compared between PWD (n=118 total), with EPI (T1D: n=14; T2D: n=20) or without EPI (T1D: n=78; T2D: n=6), and people without diabetes (n=206 total) with and without EPI.

I also looked at sub-groups within the non-EPI cohorts and broke them into two groups to see whether other GI conditions contributed to a higher EPI/PEI-SS score and whether we could distinguish EPI from other GI and non-GI conditions.

Results:

People with EPI have a much higher symptom burden than people without EPI. This can be assessed by looking at the statistically significant higher mean EPI/PEI-SS score as well as the average number of symptoms; the average severity score of individual symptoms; and the average frequency score of individual symptoms.

This remains true irrespective of diabetes. In other words, diabetes does not appear to influence any of these metrics.

People with diabetes with EPI had statistically significant higher mean EPI/PEI-SS scores (102.62 out of 225, SD: 52.46) than did people with diabetes without EPI (33.64, SD: 30.38), irrespective of presence of other GI conditions (all group comparisons p<0.001). As you can see below, that is the same pattern we see in people without diabetes. And the stats confirm what you can see: there is no significant difference overall or in any of the subgroups between people with and without diabetes.

Box plot showing EPI/PEI-SS scores for people with and without diabetes, and with and without EPI or other GI conditions. The scores are higher in people with EPI regardless of whether they have diabetes. The plot makes it clear that the scores are distinct between the groups with and without EPI, even when the people without EPI have other GI conditions. This suggests the EPI/PEI-SS can be useful in distinguishing between EPI and other conditions that may cause GI symptoms, and that the EPI/PEI-SS could be a useful screening tool to help identify people who need screening for EPI.

T1D and T2D subgroups were similar
(but because the T2D cohort is small, I did not break them out separately in this graph).

For example, people with diabetes with EPI had an average of 12.59 (out of 15) symptoms, with an average frequency score of 3.06 and average severity score of 1.79, and an average individual symptom score of 5.48. This is a pretty clear contrast to people with diabetes without EPI who had had an average of 7.36 symptoms, with an average frequency score of 1.4 and average severity score of 0.8, and an average individual symptom score of 1.12. All comparisons are statistically significant (p<0.001).

A table comparing the average number of symptoms, frequency, severity, and individual symptom scores between people with diabetes with and without exocrine pancreatic insufficiency (EPI). People with EPI have more symptoms and higher frequency and severity than without EPI: regardless of diabetes.

Conclusion 

  • EPI has a high symptom burden, irrespective of diabetes.
  • High scores using the EPI/PEI-SS among people with diabetes can distinguish between EPI and other GI conditions.
  • The EPI/PEI-SS should be further studied as a possible screening method for EPI and assessed as a tool to aid people with EPI in tracking changes to EPI symptoms over time based on PERT titration.

What does this mean if you are a healthcare provider? What actionable information does this give you?

If you’re a healthcare provider, you should be aware that people with diabetes may be more likely to have EPI – rather than celiac or gastroparesis (source) – if they mention having GI symptoms. This means you should incorporate fecal elastase screening into your care plans to help further evaluate GI-related symptoms.

If you want to further improve your pre-test probability of the elastase testing, you can use the EPI/PEI-SS with your patients to assess the severity and frequency of their GI-related symptoms. I will explain the cutoff and AUC numbers we calculated, but first understand the caveat that these were calculated in the initial real-world study that included people with EPI who are already treating with PERT; thus these numbers might change a little when we repeat this study and evaluate it in people with untreated EPI. (However, I actually predict the mean score to go up in an undiagnosed population, because scores should go down with treatment.) But that different population study may change these exact cutoff and sensitivity specificity numbers, which is why I’m giving this caveat. That being said: the AUC was 0.85 which means a higher EPI/PEI-SS is pretty good for differentiating between EPI and not having EPI. (In the diabetes sub-population specifically, I calculated a suggested cutoff of 59 (out of 225) with a sensitivity of 0.81 and specificity of 0.75. This means we estimate that if people are bringing up GI symptoms to you and you have them take the EPI/PEI-SS and their score is greater than or equal to 59, you would expect that out of 100 people that 81 with EPI would be identified (and 75 of 100 people without EPI would also correctly be identified via scores lower than 59). That doesn’t mean that people with EPI can’t have a lower score; or that people with a higher score do have EPI; but it does mean that the chances of having fecal elastase <=200 ug/g is a lot more likely in those with higher EPI/PEI-SS scores.

In addition to the cutoff score, there is a notable difference in people with diabetes and EPI compared to people with diabetes without EPI in their top individual symptom scores (representing symptom burden based on frequency and severity). For example, the top 3 symptoms of those with EPI and diabetes include avoiding certain food/groups; urgent bowel movements; and avoiding eating large meals. People without EPI and diabetes also score “Avoid certain food/groups” as their top score, but the score is markedly different: the mean score of 8.94 for people with EPI as compared to 3.49 for people without EPI. In fact, the mean score on the lowest individual symptom is higher for people with EPI than the highest individual symptom score for people without EPI.

QR code for EPI/PEI-SS - takes you to https://bit.ly/EPI-PEI-SS-WebHow do you have people take the EPI/PEI-SS? You can pull this link up (https://bit.ly/EPI-PEI-SS-Web), give this link to them and ask them to take it on their phone, or save this QR code and give it to them to take later. The link (and the QR code) go to a free web-based version of the EPI/PEI-SS that will calculate the total EPI/PEI-SS score, and you can use it for shared decision making processes about whether this person would benefit from a fecal elastase test or other follow up screening for EPI. Note that the EPI/PEI-SS does not collect any identifiable information and is fully anonymous.

(Bonus: people who use this tool can opt to contribute their anonymized symptom and score data for an ongoing observational study.)

If you have feedback about whether the EPI/PEI-SS was helpful – or not – in your care of people with diabetes; or if you want to discuss collaborating on some prospective studies to evaluate EPI/PEI-SS in comparison to fecal elastase screening, please reach out anytime to Dana@OpenAPS.org. 

What does this mean if you are a patient (person with diabetes)? What actionable information does this give you?

If you don’t have GI symptoms that bother you, you don’t necessarily need to take action. (Just put a note in your brain that EPI is more likely than celiac or gastroparesis in people with diabetes so if you or a friend with diabetes have GI symptoms in the future, you can make sure you are assessed for EPI.) You can also choose to take the EPI/PEI-SS regardless, and also opt in to donate your data.

If you do have GI symptoms that are annoying, you may want to take the EPI/PEI-SS to help you evaluate the frequency and severity of your GI symptoms. You can take it for free and anonymously – no identifiable information is needed to access the tool. It will generate the EPI/PEI-SS score for you.

Based on the score, you may want to ask your doctor (which could be the doctor that treats your diabetes, or a primary/general care provider, or a gastroenterologist – whoever you seek routine care from or have an appointment from next) about your symptoms; share the EPI/PEI-SS score; and explain that you think you may warrant screening for EPI.

(You can also choose to contribute your anonymous symptom data to a research dataset, to help us improve the EPI/PEI-SS and help us figure out how to help improve screening and diagnosis and treatment of EPI. Remember, this tool will not ask you for any identifying information. This is 100% optional and you can opt out of doing so if you do not prefer to contribute to research, while still using the tool.)

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You can see a pre-print version of the diabetes sub-study here or pre-print of the general population data here.

If you’re looking for more personal experiences about living with EPI, check out DIYPS.org/EPI, and also for people with EPI looking to improve their dosing with pancreatic enzyme replacement therapy – you may want to check out PERT Pilot (a free iOS app to record enzyme dosing).

Researchers & clinicians, if you’re interested in collaborating on studies in EPI (in diabetes, or more broadly on EPI), whether specifically on EPI/PEI-SS or broader EPI topics, please reach out! My email is Dana@OpenAPS.org

Effective Pair Programming and Coding and Prompt Engineering and Writing with LLMs like ChatGPT and other AI tools

by Dana Lewis

I’ve been puzzled when I see people online say that LLM’s “don’t write good code”. In my experience, they do. But given that most of these LLMs are used in chatbot mode – meaning you chat and give it instructions to generate the code – that might be where the disconnect lies. To get good code, you need effective prompting and to do so, you need clear thinking and ideas on what you are trying to achieve and how.

My recipe and understanding is:

Clear thinking + clear communication of ideas/request = effective prompting => effective code and other outputs

It also involves understanding what these systems can and can’t do. For example, as I’ve written about before, they can’t “know” things (although they can increasingly look things up) and they can’t do “mental” math. But, they can generally repeat patterns of words to help you see what is known about a topic and they can write code that you can execute (or it can execute, depending on settings) to solve a math problem.

What the system does well is help code small chunks, walk you through processes to link these sections of code up, and help you implement them (if you ask for it). The smaller the task (ask), the more effective it is. Or also – the easier it is for you to see when it completes the task and when it hasn’t been able to finish due to limitations like response length limits, information falling out of the context window (what it knows that you’ve told it); unclear prompting; and/or because you’re asking it to do things for which it doesn’t have expertise. Some of the last part – lack of expertise – can be improved with specific prompting techniques –  and that’s also true for right-sizing the task it’s focusing on.

Right-size the task by giving a clear ask

If I were to ask an LLM to write me code for an iOS app to do XYZ, it could write me some code, but it certainly wouldn’t (at this point in history, written in February 2024), write all code and give me a downloadable file that includes it all and the ability to simply run it. What it can do is start writing chunks and snippets of code for bits and pieces of files that I can take and place and build upon.

How do I know this? Because I made that mistake when trying to build my first iOS apps in April and May 2023 (last year). It can’t do that (and still can’t today; I repeated the experiment). I had zero ideas how to build an iOS app; I had a sense that it involved XCode and pushing to the Apple iOS App Store, and that I needed “Swift” as the programming language. Luckily, though, I had a much stronger sense of how I wanted to structure the app user experience and what the app needed to do.

I followed the following steps:

  1. First, I initiated chat as a complete novice app builder. I told it I was new to building iOS apps and wanted to use XCode. I had XCode downloaded, but that was it. I told it to give me step by step instructions for opening XCode and setting up a project. Success! That was effective.
  2. I opened a different chat window after that, to start a new chat. I told it that it was an expert in iOS programming using Swift and XCode. Then I described the app that I wanted to build, said where I was in the process (e.g. had opened and started a project in XCode but had no code yet), and asked it for code to put on the home screen so I could build and open the app and it would have content on the home screen. Success!
  3. From there, I was able to stay in the same chat window and ask it for pieces at a time. I wanted to have a new user complete an onboarding flow the very first time they opened the app. I explained the number of screens and content I wanted on those screens; the chat was able to generate code, tell me how to create that in a file, and how to write code that would trigger this only for new users. Success!
  4. I was able to then add buttons to the home screen; have those buttons open new screens of the app; add navigation back to the home; etc. Success!
  5. (Rinse and repeat, continuing until all of the functionality was built out a step at a time).

To someone with familiarity building and programming things, this probably follows a logical process of how you might build apps. If you’ve built iOS apps before and are an expert in Swift programming, you’re either not reading this blog post or are thinking I (the human) am dumb and inexperienced.

Inexperienced, yes, I was (in April 2023). But what I am trying to show here is for someone new to a process and language, this is how we need to break down steps and work with LLMs to give it small tasks to help us understand and implement the code it produces before moving forward with a new task (ask). It takes these small building block tasks in order to build up to a complete app with all the functionality that we want. Nowadays, even though I can now whip up a prototype project and iOS app and deploy it to my phone within an hour (by working with an LLM as described above, but skipping some of the introductory set-up steps now that I have experience in those), I still follow the same general process to give the LLM the big picture and efficiently ask it to code pieces of the puzzle I want to create.

As the human, you need to be able to keep the big picture – full app purpose and functionality – in mind while subcontracting with the LLM to generate code for specific chunks of code to help achieve new functionality in our project.

In my experience, this is very much like pair programming with a human. In fact, this is exactly what we did when we built DIYPS over ten years ago (wow) and then OpenAPS within the following year. I’ve talked endlessly about how Scott and I would discuss an idea and agree on the big picture task; then I would direct sub-tasks and asks that he, then also Ben and others would be coding on (at first, because I didn’t have as much experience coding and this was 10 years ago without LLMs; I gradually took on more of those coding steps and roles as well). I was in charge of the big picture project and process and end goal; it didn’t matter who wrote which code or how; we worked together to achieve the intended end result. (And it worked amazingly well; here I am 10 years later still using DIYPS and OpenAPS; and tens of thousands of people globally are all using open source AID systems spun off of the algorithm we built through this process!)

Two purple boxes. The one on the left says "big picture project idea" and has a bunch of smaller size boxes within labeled LLM, attempting to show how an LLM can do small-size tasks within the scope of a bigger project that you direct it to do. On the right, the box simply says "finished project". Today, I would say the same is true. It doesn’t matter – for my types of projects – if a human or an LLM “wrote” the code. What matters is: does it work as intended? Does it achieve the goal? Does it contribute to the goal of the project?

Coding can be done – often by anyone (human with relevant coding expertise) or anything (LLM with effective prompting) – for any purpose. The critical key is knowing what the purpose is of the project and keeping the coding heading in the direction of serving that purpose.

Tips for right-sizing the ask

  1. Consider using different chat windows for different purposes, rather than trying to do it all in one. Yes, context windows are getting bigger, but you’ll still likely benefit from giving different prompts in different windows (more on effective prompting below).Start with one window for getting started with setting up a project (e.g. how to get XCode on a Mac and start a project; what file structure to use for an app/project that will do XYZ; how to start a Jupyter notebook for doing data science with python; etc); brainstorming ideas to scope your project; then separately for starting a series of coding sub-tasks (e.g. write code for the home page screen for your app; add a button that allows voice entry functionality; add in HealthKit permission functionality; etc.) that serves the big picture goal.
  2. Make a list for yourself of the steps needed to build a new piece of functionality for your project. If you know what the steps are, you can specifically ask the LLM for that.Again, use a separate window if you need to. For example, if you want to add in the ability to save data to HealthKit from your app, you may start a new chat window that asks the LLM generally how does one add HealthKit functionality for an app? It’ll describe the process of certain settings that need to be done in XCode for the project; adding code that prompts the user with correct permissions; and then code that actually does the saving/revising to HealthKit.

    Make your list (by yourself or with help), then you can go ask the LLM to do those things in your coding/task window for your specific project. You can go set the settings in XCode yourself, and skip to asking it for the task you need it to do, e.g. “write code to prompt the user with HealthKit permissions when button X is clicked”.

    (Sure, you can do the ask for help in outlining steps in the same window that you’ve been prompting for coding sub-tasks, just be aware that the more you do this, the more quickly you’ll burn through your context window. Sometimes that’s ok, and you’ll get a feel for when to do a separate window with the more experience you get.)

  • Pay attention as you go and see how much code it can generate and when it falls short of an ask. This will help you improve the rate at which you successfully ask and it fully completes a task for future asks. I observe that when I don’t know – due to my lack of expertise – the right size of a task, it’s more prone to give me ½-⅔ of the code and solution but need additional prompting after that. Sometimes I ask it to continue where it cut off; other times I start implementing/working with the bits of code (the first ⅔) it gave me, and have a mental or written note that this did not completely generate all steps/code for the functionality and to come back.Part of why sometimes it is effective to get started with ⅔ of the code is because you’ll likely need to debug/test the first bit of code, anyway. Sometimes when you paste in code it’s using methods that don’t match the version you’re targeting (e.g. functionality that is outdated as of iOS 15, for example, when you’re targeting iOS 17 and newer) and it’ll flag a warning or block it from working until you fix it.

    Once you’ve debugged/tested as much as you can of the original ⅔ of code it gave you, you can prompt it to say “Ok, I’ve done X and Y. We were trying to (repeat initial instructions/prompt) – what are the remaining next steps? Please code that.” to go back and finish the remaining pieces of that functionality.

    (Note that saying “please code that” isn’t necessarily good prompt technique, see below).

    Again, much of this is paying attention to how the sub-task is getting done in service of the overall big picture goal of your project; or the chunk that you’ve been working on if you’re building new functionality. Keeping track with whatever method you prefer – in your head, a physical written list, a checklist digitally, or notes showing what you’ve done/not done – is helpful.

Most of the above I used for coding examples, but I follow the same general process when writing research papers, blog posts, research protocols, etc. My point is that this works for all types of projects that you’d work on with an LLM, whether the output generation intended is code or human-focused language that you’d write or speak.

But, coding or writing language, the other thing that makes a difference in addition to right-sizing the task is effective prompting. I’ve intuitively noticed that has made the biggest difference in my projects for getting the output matching my expertise. Conversely, I have actually peer reviewed papers for medical journals that do a horrifying job with prompting. You’ll hear people talk about “prompt engineering” and this is what it is referring to: how do you engineer (write) a prompt to get the ideal response from the LLM?

Tips for effective prompting with an LLM

    1. Personas and roles can make a difference, both for you and for the LLM. What do I mean by this? Start your prompt by telling the LLM what perspective you want it to take. Without it, you’re going to make it guess what information and style of response you’re looking for. Here’s an example: if you asked it what caused cancer, it’s going to default to safety and give you a general public answer about causes of cancer in very plain, lay language. Which may be fine. But if you’re looking to generate a better understanding of the causal mechanism of cancer; what is known; and what is not known, you will get better results if you prompt it with “You are an experienced medical oncologist” so it speaks from the generated perspective of that role. Similarly, you can tell it your role. Follow it with “Please describe the causal mechanisms of cancer and what is known and not known” and/or “I am also an experienced medical researcher, although not an oncologist” to help contextualize that you want a deeper, technical approach to the answer and not high level plain language in the response.

      Compare and contrast when you prompt the following:

      A. “What causes cancer?”

      B. “You are an experienced medical oncologist. What causes cancer? How would you explain this differently in lay language to a patient, and how would you explain this to another doctor who is not an oncologist?”

      C. “You are an experienced medical oncologist. Please describe the causal mechanisms of cancer and what is known and not known. I am also an experienced medical researcher, although not an oncologist.”

      You’ll likely get different types of answers, with some overlap between A and the first part of answer B. Ditto for a tiny bit of overlap between the latter half of answer B and for C.

      I do the same kind of prompting with technical projects where I want code. Often, I will say “You are an expert data scientist with experience writing code in Python for a Jupyter Notebook” or “You are an AI programming assistant with expertise in building iOS apps using XCode and SwiftUI”. Those will then be followed with a brief description of my project (more on why this is brief below) and the first task I’m giving it.

      The same also goes for writing-related tasks; the persona I give it and/or the role I reference for myself makes a sizable difference in getting the quality of the output to match the style and quality I was seeking in a response.

  • Be specific. Saying “please code that” or “please write that” might work, sometimes, but more often or not will get a less effective output than if you provide a more specific prompt.I am a literal person, so this is something I think about a lot because I’m always parsing and mentally reviewing what people say to me because my instinct is to take their words literally and I have to think through the likelihood that those words were intended literally or if there is context that should be used to filter those words to be less literal. Sometimes, you’ll be thinking about something and start talking to someone about something, and they have no idea what on earth you’re talking about because the last part of your out-loud conversation with them was about a completely different topic!

    LLMs are the same as the confused conversational partner who doesn’t know what you’re thinking about. LLMs only know what you’ve last/recently told it (and more quickly than humans will ‘forget’ what you told it about a project). Remember the above tips about brainstorming and making a list of tasks for a project? Providing a description of the task along with the ask (e.g. we are doing X related to the purpose of achieving Y, please code X) will get you better output more closely matching what you wanted than saying “please code that” where the LLM might code something else to achieve Y if you didn’t tell it you wanted to focus on X.

    I find this even more necessary with writing related projects. I often find I need to give it the persona “You are an expert medical researcher”, the project “we are writing a research paper for a medical journal”, the task “we need to write the methods section of the paper”, and a clear ask “please review the code and analyses and make an outline of the steps that we have completed in this process, with sufficient detail that we could later write a methods section of a research paper”. A follow up ask is then “please take this list and draft it into the methods section”. That process with all of that specific context gives better results than “write a methods section” or “write the methods” etc.

  • Be willing to start over with a new window/chat. Sometimes the LLM can get itself lost in solving a sub-task and lose sight (via lost context window) of the big picture of a project, and you’ll find yourself having to repeat over and over again what you’re asking it to do. Don’t be afraid to cut your losses and start a new chat for a sub-task that you’ve been stuck on. You may be able to eventually come back to the same window as before, or the new window might become your new ‘home’ for the project…or sometimes a third, fourth, or fifth window will.
  • Try, try again.
    I may hold the record for the longest running bug that I (and the LLM) could. Not. solve. This was so, so annoying. No users apparently noticed it but I knew about it and it bugged me for months and months. Every few weeks I would go to an old window and also start a new window, describe the problem, paste the code in, and ask for help to solve it. I asked it to identify problems with the code; I asked it to explain the code and unexpected/unintended functionality from it; I asked it what types of general things would be likely to cause that type of bug. It couldn’t find the problem. I couldn’t find the problem. Finally, one day, I did all of the above, but then also started pasting every single file from my project and asking if it was likely to include code that could be related to the problem. By forcing myself to review all my code files with this problem in mind, even though the files weren’t related at all to the file/bug….I finally spotted the problem myself. I pasted the code in, asked if it was a possibility that it was related to the problem, the LLM said yes, I tried a change and…voila! Bug solved on January 16 after plaguing me since November 8. (And probably existed before then but I didn’t have functionality built until November 8 where I realized it was a problem). I was beating myself up about it and posted to Twitter about finally solving the bug (but very much with the mindset of feeling very stupid about it). Someone replied and said “congrats! sounds like it was a tough one!”. Which I realized was a very kind framing and one that I liked, because it was a tough one; and also I am doing a tough thing that no one else is doing and I would not have been willing to try to do without an LLM to support.

    Similarly, just this last week on Tuesday I spent about 3 hours working on a sub-task for a new project. It took 3 hours to do something that on a previous project took me about 40 minutes, so I was hyper aware of the time mismatch and perceiving that 3 hours was a long time to spend on the task. I vented to Scott quite a bit on Tuesday night, and he reminded me that sure it took “3 hours” but I did something in 3 hours that would take 3 years otherwise because no one else would do (or is doing) the project that I’m working on. Then on Wednesday, I spent an hour doing another part of the project and Thursday whipped through another hour and a half of doing huge chunks of work that ended up being highly efficient and much faster than they would have been, in part because the “three hours” it took on Tuesday wasn’t just about the code but about organizing my thinking, scoping the project and research protocol, etc. and doing a huge portion of other work to organize my thinking to be able to effectively prompt the LLM to do the sub-task (that probably did actually take closer to the ~40 minutes, similar to the prior project).

    All this to say: LLMs have become pair programmers and collaborators and writers that are helping me achieve tasks and projects that no one else in the world is working on yet. (It reminds me very much of my early work with DIYPS and OpenAPS where we did the work, quietly, and people eventually took notice and paid attention, albeit slower than we wished but years faster than had we not done that work. I’m doing the same thing in a new field/project space now.) Sometimes, the first attempt to delegate a sub-task doesn’t work. It may be because I haven’t organized my thinking enough, and the lack of ideal output shows that I have not prompted effectively yet. Sometimes I can quickly fix the prompt to be effective; but sometimes it highlights that my thinking is not yet clear; my ability to communicate the project/task/big picture is not yet sufficient; and the process of achieving the clarity of thinking and translating to the LLM takes time (e.g. “that took 3 hours when it should have taken 40 minutes”) but ultimately still moves me forward to solving the problem or achieving the tasks and sub-tasks that I wanted to do. Remember what I said at the beginning:

    Clear thinking + clear communication of ideas/request = effective prompting => effective code and other outputs

 

  • Try it anyway.
    I am trying to get out of the habit of saying “I can’t do X”, like “I can’t code/program an iOS app”…because now I can. I’ve in fact built and shipped/launched/made available multiple iOS apps (check out Carb Pilot if you’re interested in macronutrient estimates for any reason; you can customize so you only see the one(s) you care about; or if you have EPI, check out PERT Pilot, which is the world’s first and only app for tracking pancreatic enzyme replacement therapy and has the same AI feature for generating macronutrient estimates to aid in adjusting enzyme dosing for EPI.) I’ve also made really cool, 100% custom-to-me niche apps to serve a personal purpose that save me tons of time and energy. I can do those things, because I tried. I flopped a bunch along the way – it took me several hours to solve a simple iOS programming error related to home screen navigation in my first few apps – but in the process I learned how to do those things and now I can build apps. I’ve coded and developed for OpenAPS and other open source projects, including a tool for data conversion that no one else in the world had built. Yet, my brain still tries to tell me I can’t code/program/etc (and to be fair, humans try to tell me that sometimes, too).

    I bring that up to contextualize that I’m working on – and I wish others would work on to – trying to address the reflexive thoughts of what we can and can’t do, based on prior knowledge. The world is different now and tools like LLMs make it possible to learn new things and build new projects that maybe we didn’t have time/energy to do before (not that we couldn’t). The bar to entry and the bar to starting and trying is so much lower than it was even a year ago. It really comes down to willingness to try and see, which I recognize is hard: I have those thought patterns too of “I can’t do X”, but I’m trying to notice when I have those patterns; shift my thinking to “I used to not be able to do X; I wonder if it is possible to work with an LLM to do part of X or learn how to do Y so that I could try to do X”.

    A recent real example for me is power calculations and sample size estimates for future clinical trials. That’s something I can’t do; it requires a statistician and specialized software and expertise.

    Or…does it?

    I asked my LLM how power calculations are done. It explained. I asked if it was possible to do it using Python code in a Jupyter notebook. I asked what information would be needed to do so. It walked me through the decisions I needed to make about power and significance, and highlighted variables I needed to define/collect to put into the calculation. I had generated the data from a previous study so I had all the pieces (variables) I needed. I asked it to write code for me to run in a Jupyter notebook, and it did. I tweaked the code, input my variables, ran it..and got the result. I had run a power calculation! (Shocked face here). But then I got imposter syndrome again, reached out to a statistician who I had previously worked with on a research project. I shared my code and asked if that was the correct or an acceptable approach and if I was interpreting it correctly. His response? It was correct, and “I couldn’t have done it better myself”.

    (I’m still shocked about this).

    He also kindly took my variables and put it in the specialized software he uses and confirmed that the results output matched what my code did, then pointed out something that taught me something for future projects that might be different (where the data is/isn’t normally distributed) although it didn’t influence the output of my calculation for this project.

    What I learned from this was a) this statistician is amazing (which I already knew from working with him in the past) and kind to support my learning like this; b) I can do pieces of projects that I previously thought were far beyond my expertise; c) the blocker is truly in my head, and the more we break out of or identify the patterns stopping us from trying, the farther we will get.

    “Try it anyway” also refers to trying things over time. The LLMs are improving every few months and often have new capabilities that didn’t before. Much of my work is done with GPT-4 and the more nuanced, advanced technical tasks are way more efficient than when using GPT-3.5. That being said, some tasks can absolutely be done with GPT-3.5-level AI. Doing something now and not quite figuring it out could be something that you sort out in a few weeks/months (see above about my 3 month bug); it could be something that is easier to do once you advance your thinking ; or it could be more efficiently done with the next model of the LLM you’re working with.

  • Test whether custom instructions help. Be aware though that sometimes too many instructions can conflict and also take up some of your context window. Plus if you forget what instructions you gave it, you might get seemingly unexpected responses in future chats. (You can always change the custom instructions and/or turn it on and off.)

I’m hoping this helps give people confidence or context to try things with LLMs that they were not willing to try before; or to help get in the habit of remembering to try things with LLMs; and to get the best possible output for the project that they’re working on.

Remember:

  • Right-size the task by making a clear ask.
  • You can use different chat windows for different levels of the same project.
  • Use a list to help you, the human, keep track of all the pieces that contribute to the bigger picture of the project.
  • Try giving the LLM a persona for an ask; and test whether you also need to assign yourself a persona or not for a particular type of request.
  • Be specific, think of the LLM as a conversational partner that can’t read your mind.
  • Don’t be afraid to start over with a new context window/chat.
  • Things that were hard a year ago might be easier with an LLM; you should try again.
  • You can do more, partnering with an LLM, than you can on your own, and likely can do things you didn’t realize were possible for you to do!

Clear thinking + clear communication of ideas/request = effective prompting => effective code and other outputs

—

Have any tips to help others get more effective output from LLMs? I’d love to hear them, please comment below and share your tips as well!

Tips for prompting LLMs like ChatGPT, written by Dana M. Lewis and available from DIYPS.org

Accepted, Rejected, and Conflict of Interest in Gastroenterology (And Why This Is A Symptom Of A Bigger Problem)

by Dana Lewis

Recently, someone published a new clinical practice update on exocrine pancreatic insufficiency (known as EPI or PEI) in the journal called Gastroenterology, from the American Gastroenterology Association (AGA). Those of you who’ve read any of my blog posts in the last year know how much I’ve been working to raise awareness of EPI, which is very under-researched and under-treated clinically despite the prevalence rates in the general population and key sub-populations such as PWD. So when there was a new clinical practice update and another publication on EPI in general, I was jazzed and set out to read it immediately. Then frowned. Because, like so many articles about EPI, it’s not *quite* right about many things and it perpetuates a lot of the existing problems in the literature. So I did what I could, which was to check out the journal requirements for writing a letter to the editor (LTE) in response to this article and drafting and submitting a LTE article about it. To my delight, on October 17, 2023, I got an email indicating that my LTE was accepted.

You can find my LTE as a pre-print here.

See below why this pre-print version is important, and why you should read it, plus what it reminds us about what journal articles can or cannot tell us in healthcare.

Here’s an image of my acceptance email. I’ll call out a key part of the email:

A print of the acceptance email I received on October 17, 2023, indicating my letter would be sent to authors of the original articles for a chance to choose to respond (or not). Then my LTE would be published.

Letters to the Editor are sent to the authors of the original articles discussed in the letter so that they might have a chance to respond. Letters are not sent to the original article authors until the window of submission for letters responding to that article is closed (the last day of the issue month in which the article is published). Should the authors choose to respond to your letter, their response will appear alongside your letter in the journal.

Given the timeline described, I knew I wouldn’t hear more from the journal until the end of November. The article went online ahead of print in September, meaning likely officially published in October, so the letters wouldn’t be sent to authors until the end of October.

And then I did indeed hear back from the journal. On December 4, 2023, I got the following email:

A print of the email I received saying the LTE was now rejected
TLDR: just kidding, the committee – members of which published the article you’re responding to – and the editors have decided not to publish your article. 

I was surprised – and confused. The committee members, or at least 3 of them, wrote the article. They should have a chance to decide whether or not to write a response letter, which is standard. But telling the editors not to publish my LTE? That seems odd and in contrast to the initial acceptance email. What was going on?

I decided to write back and ask. “Hi (name redacted), this is very surprising. Could you please provide more detail on the decision making process for rescinding the already accepted LTE?”

The response?

Another email explaining that possible commercial affiliations influenced their choice to reject the article after accpeting it originally
“In terms of this decision, possible commercial affiliations, as well as other judgments of priority and relevance among other submissions, dampened enthusiasm for this particular manuscript. Ultimately, it was not judged to be competitive for acceptance in the journal. “

Huh? I don’t have any commercial affiliations. So I asked again, “Can you clarify what commercial affiliations were perceived? I have none (nor any financial conflict of interest; nor any funding related to my time spent on the article) and I wonder if there was a misunderstanding when reviewing this letter to the editor.”

The response was “There were concerns with the affiliation with OpenAPS; with the use of the term “guidelines,” which are distinct from this Clinical Practice Update; and with the overall focus being more fit for a cystic fibrosis or research audience rather than a GI audience.”

A final email saying the concern with my affiliation of OpenAPS, which is not a commercial organization nor related to the field of gastroenterology and EPI

Aha, I thought, there WAS a misunderstanding. (And the latter makes no sense in the context of my LTE – the point of it is that most research and clinical literature is a too-narrow focus, cystic fibrosis as one example – the very point is that a broad gastroenterology audience should pay attention to EPI).

I wrote back and explained how I, as a patient/independent researcher, struggle to submit articles to manuscript systems without a Ringgold-verified organization. (You can also listen to me describe the problem in a podcast, here, and I also talked about it in a peer-reviewed journal article about citizen science and health-related journal publishing here). So I use OpenAPS as an “affiliation” even though OpenAPS isn’t an organization. Let alone a commercial organization. I have no financial conflict of interest related to OpenAPS, and zero financial conflict of interest or commercial or any type of funding in gastroenterology at all, related to EPI or not. I actually go to such extremes to describe even perceived conflicts of interest, even non-financial ones, as you can see this in my disclosure statement publicly available from the New England Journal of Medicine here on our CREATE trial article (scroll to Supplemental Information and click on Disclosure Forms) where I articulate that I have no financial conflicts of interest but acknowledge openly that I created the algorithm used in the study. Yet, there’s no commercial or financial conflict of interest.

A screenshot from the publicly available disclosure form on NEJM's site, where I am so careful to indicate possible conflicts of interest that are not commercial or financial, such as the fact that I developed the algorithm that was used in that study. Again, that's a diabetes study and a diabetes example, the paper we are discussing here is on exocrine pancreatic insufficiency (EPI) and gastroenterology, which is unrelated. I have no COI in gastroenterology.

I sent this information back to the journal, explaining this, and asking if the editors would reconsider the situation, given that the authors (committee members?) have misconstrued my affiliation, and given that the LTE was originally accepted.

Sadly, there was no change. They are still declining to publish this article. And there is no change in my level of disappointment.

Interestingly, here is the article in which my LTE is in reply to, and the conflict of interest statement by the authors (committee members?) who possibly raised a flag about supposed concern about my (this is not true) commercial affiliation:

The conflict of interest statement for authors from the article "AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency 2023"

The authors disclose the following: David C. Whitcomb: consultant for AbbVie, Nestlé, Regeneron; cofounder, consultant, board member, chief scientific officer, and equity holder for Ariel Precision Medicine. Anna M. Buchner: consultant for Olympus Corporation of America. Chris E. Forsmark: grant support from AbbVie; consultant for Nestlé; chair, National Pancreas Foundation Board of Directors.

As a side note, one of the companies with consulting and/or grant funding to two of the three authors is the biggest manufacturer of pancreatic enzyme replacement therapy (PERT), which is the treatment for EPI. I don’t think this conflict of interest makes these clinicians ineligible to write their article; nor do I think commercial interests should preclude anyone from publishing – but in my case, it is irrelevant, because I have none. But, it does seem weird given the stated COI for my (actually not a) COI then to be a reason to reject a LTE, of all things.

Here’s the point, though.

It’s not really about the fact that I had an accepted article rejected (although that is weird, to say the least…).

The point is that the presence of information in medical and research journals does not mean that they are correct. (See this post describing the incorrect facts presented about prevalence of EPI, for example.)

And similarly, the lack of presence of material in medical and research journals does not mean that something is not true or is not fact! 

There is a lot of gatekeeping in scientific and medical research. You can see it illustrated here in this accepted-rejected dance because of supposed COI (when there are zero commercial ties, let alone COI) and alluded to in terms of the priority of what gets published.

I see this often.

There is good research that goes unpublished because editors decide not to prioritize it (aka do not allow it to get published). There are many such factors in play affecting what gets published.

There are also systemic barriers.

  • Many journals require fees (called article processing charges or “APC”s) if your article is accepted for publication. If you don’t have funding, that means you can’t publish there unless you want to pay $2500 (or more) out of pocket. Some journals even have submission fees of hundreds of dollars, just to submit! (At least APCs are usually only levied if your article is accepted, but you won’t submit to these journals if you know you can’t pay the APC). That means the few journals in your field that don’t require APCs or fees are harder to get published in, because many more articles are submitted (thus, influencing the “prioritization” problem at the editor level) to the “free” journals.
  • Journals often require, as previously described, your organization to be part of a verified list (maintained by a third party org) in order for your article to be moved through the queue once submitted. Instead of n/a, I started listing “OpenAPS” as my affiliation and proactively writing to admin teams to let them know that my affiliation won’t be Ringgold-verified, explaining that it’s not an org/I’m not at any institution, and then my article can (usually) get moved through the queue ok. But as I wrote in this peer-reviewed article with a lot of other details about barriers to publishing citizen science and other patient-driven work, it’s one of many barriers involved in the publication process. It’s a little hard, every journal and submission system is a little different, and it’s a lot harder for us than it is for people who have staff/support to help them get articles published in journals.

I’ve seen grant funders say no to funding researchers who haven’t published yet; but editors also won’t prioritize them to publish on a topic in a field where they haven’t been funded yet or aren’t well known. Or they aren’t at a prestigious organization. Or they don’t have the “right” credentials. (Ahem, ahem, ahem). It can be a vicious cycle for even traditional (aka day job) researchers and clinicians. Now imagine that for people who are not inside those systems of academia or medical organizations.

Yet, think about where much of knowledge is captured, created, translated, studied – it’s not solely in these organizations.

Thus, the mismatch. What’s in journals isn’t always right, and the process of peer review can’t catch everything. It’s not a perfect system. But what I want you to take away, if you didn’t already have this context, is an understanding that what’s NOT in a journal is not because the information is not fact or does not exist. It may have not been studied yet; or it may have been blocked from publication by the systemic forces in play.

As I said at the end of my LTE:

“It is also critical to update the knowledge base of EPI beyond the sub-populations of cystic fibrosis and chronic pancreatitis that are currently over-represented in the EPI-related literature. Building upon this updated research base will enable future guidelines, including those like the AGA Clinical Practice Update on EPI, to be clearer, more evidence-based, and truly patient-centric ensuring that every individual living with exocrine pancreatic insufficiency receives optimal care. “

PS – want to read my LTE that was accepted then rejected, meaning it won’t be present in the journal? Here it is on a preprint server with a DOI, which means it’s still easily citable! Here’s an example citation:

Lewis, D. Navigating Ambiguities in Exocrine Pancreatic Insufficiency. OSF Preprints. 2023. DOI: 10.31219/osf.io/xcnf6

New Survey For Everyone (Including You – Yes, You!) To Help Us Learn More About Exocrine Pancreatic Insufficiency

by Dana Lewis

If you’ve ever wanted to help with some of my research, this is for you. Yes, you! I am asking people in the general public to take a survey (https://bit.ly/GI-Symptom-Survey-All) and share their experiences.

Why?

Many people have stomach or digestion problems occasionally. For some people, these symptoms happen more often. In some cases, the symptoms are related to exocrine pancreatic insufficiency (known as EPI or PEI). But to date, there have been few studies looking at the frequency of symptoms – or the level of their self-rated severity – in people with EPI or what symptoms may distinguish EPI from other GI-related conditions.

That’s where this survey comes in! We want to compare the experiences of people with EPI to people without EPI (like you!).

Will you help by taking this survey?

Your anonymous participation in this survey will help us understand the unique experiences individuals have with GI symptoms, including those with conditions like exocrine pancreatic insufficiency (EPI). In particular, data contributed by people without EPI will help us understand how the EPI experience is different (or not).

A note on privacy:

  • The survey is completely anonymous; no identifying information will be collected.
  • You can stop the survey at any point.

Who designed this survey:

Dana Lewis, an independent researcher, developed the survey and will manage the survey data. This survey design and the choice to run this survey is not influenced by funding from or affiliations with any organizations.

What happens to the data collected in this survey:

The aggregated data will be analyzed for patterns and shared through blog posts and academic publications. No individual data will be shared. This will help fill some of the documented gaps in the EPI-related medical knowledge and may influence the design of targeted research studies in the future.

Have Questions?
Feel free to reach out to Dana+GISymptomSurvey@OpenAPS.org.

How else can you help?
Remember, ANYONE can take this survey. So, feel free to share the link with your family and friends – they can take it, too!

Here’s a link to the survey that you can share (after taking it yourself, of course!): https://bit.ly/GI-Symptom-Survey-All

You (yes you!) can help us learn about exocrine pancreatic insufficiency by taking the survey linked on this page.

You’d Be Surprised: Common Causes of Exocrine Pancreatic Insufficiency

by Dana Lewis

Academic and medical literature often is like the game of “telephone”. You can find something commonly cited throughout the literature, but if you dig deep, you can watch the key points change throughout the literature going from a solid, evidence-backed statement to a weaker, more vague statement that is not factually correct but is widely propagated as “fact” as people cite and re-cite the new incorrect statements.

The most obvious one I have seen, after reading hundreds of papers on exocrine pancreatic insufficiency (known as EPI or PEI), is that “chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency”. It’s stated here (“Although chronic pancreatitis is the most common cause of EPI“) and here (“The most frequent causes [of exocrine pancreatic insufficiency] are chronic pancreatitis in adults“) and here (“Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI“) and here (“Numerous conditions account for the etiology of EPI, with the most common being diseases of the pancreatic parenchyma including chronic pancreatitis, cystic fibrosis, and a history of extensive necrotizing acute pancreatitis“) and… you get the picture. I find this statement all over the place.

But guess what? This is not true.

First off, no one has done a study on the overall population of EPI and the breakdown of the most common co-conditions.

Secondly, I did research for my latest article on exocrine pancreatic insufficiency in Type 1 diabetes and Type 2 diabetes and was looking to contextualize the size of the populations. For example, I know overall that diabetes has a ~10% population prevalence, and this review found that there is a median prevalence of EPI of 33% in T1D and 29% in T2D. To put that in absolute numbers, this means that out of 100 people, it’s likely that 3 people have both diabetes and EPI.

How does this compare to the other “most common” causes of EPI?

First, let’s look at the prevalence of EPI in these other conditions:

  • In people with cystic fibrosis, 80-90% of people are estimated to also have EPI
  • In people with chronic pancreatitis, anywhere from 30-90% of people are estimated to also have EPI
  • In people with pancreatic cancer, anywhere from 20-60% of people are estimated to also have EPI

Now let’s look at how common these conditions are in the general population:

  • People with cystic fibrosis are estimated to be 0.04% of the general population.
    • This is 4 in every 10,000 people
  • People with chronic pancreatitis combined with all other types of pancreatitis are also estimated to be 0.04% of the general population, so another 4 out of 10,000.
  • People with pancreatic cancer are estimated to be 0.005% of the general population, or 1 in 20,000.

What happens if you add all of these up: cystic fibrosis, 0.04%, plus all types of pancreatitis, 0.04%, and pancreatic cancer, 0.005%? You get 0.085%, which is less than 1 in 1000 people.

This is quite a bit less than the 10% prevalence of diabetes (1 in 10 people!), or even the 3 in 100 people (3%) with both diabetes and EPI.

Let’s also look at the estimates for EPI prevalence in the general population:

  • General population prevalence of EPI is estimated to be 10-20%, and if we use 10%, that means that 1 in 10 people may have EPI.

Here’s a visual to illustrate the relative size of the populations of people with cystic fibrosis, chronic pancreatitis (visualized as all types of pancreatitis), and pancreatic cancer, relative to the sizes of the general population and the relative amount of people estimated to have EPI:

Gif showing the relative sizes of populations of people with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and the % of those with EPI, contextualized against the prevalence of these in the general population and those with EPI. It's a small number of people because these conditions aren't common, therefore these conditions are not the most common cause of EPI!

What you should take away from this:

  • Yes, EPI is common within conditions such as cystic fibrosis, chronic pancreatitis (and other forms of pancreatitis), and pancreatic cancer
  • However, these conditions are not common: even combined, they add up to less than 1 in 1000!
  • Therefore, it is incorrect to conclude that any of these conditions, individually or even combined, are the most common causes of EPI.

You could say, as I do in this paper, that EPI is likely more common in people with diabetes than all of these conditions combined. You’ll notice that I don’t go so far as to say it’s the MOST common, because I haven’t seen studies to support such a statement, and as I started the post by pointing out, no one has done studies looking at huge populations of EPI and the breakdown of co-conditions at a population level; instead, studies tend to focus on the population of a co-condition and prevalence of EPI within, which is a very different thing than that co-condition’s EPI population as a percentage of the overall population of people with EPI. However, there are some great studies (and I have another systematic review accepted and forthcoming on this topic!) that support the overall prevalence estimates in the general population being in the ballpark of 10+%, so there might be other ‘more common’ causes of EPI that we are currently unaware of, or it may be that most cases of EPI are uncorrelated with any particular co-condition.

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(Need a citation? This logic is found in the introduction paragraph of a systematic review found here, of which the DOI is 10.1089/dia.2023.0157. You can also access a full author copy of it and my other papers here.)

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You can also contribute to a research study and help us learn more about EPI/PEI – take this anonymous survey to share your experiences with EPI-related symptoms!

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New Systematic Review of Exocrine Pancreatic Insufficiency (EPI) In Type 1 Diabetes and Type 2 Diabetes – Focusing on Prevalence and Treatment

by Dana Lewis

I’m thrilled that the research I did evaluating the prevalence and treatment of EPI in both Type 1 diabetes and Type 2 diabetes (also presented as a poster at #ADA2023 – read a summary of the poster here) has now been published as a full systematic review in Diabetes Technology and Therapeutics.

Here is a pre-edited submitted version of my article that you can access if you don’t have journal access; and as a reminder, copies of ALL of my research articles are available on this page: DIYPS.org/research!

And if you don’t want to read the full paper, this is what I think you should take away from it as a person with diabetes or as a healthcare provider:

    1. What is EPI? 

      Exocrine pancreatic insufficiency (known as EPI in some places, and PEI or PI in other places) occurs when the pancreas no longer produces enough enzymes to digest food. People with EPI take pancreatic enzyme replacement therapy (PERT) whenever they eat (or drink anything with fat/protein).

    2. If I have diabetes, or treat people with diabetes, why should I be reading the rest of this about EPI?EPI often occurs in people with cystic fibrosis, pancreatitis, and pancreatic cancer. However, since these diseases are rare (think <0.1% of the general population even when these groups are added up all together), the total number of people with EPI from these causes is quite low. On the other hand, EPI is also common in people with diabetes, but this is less well-studied and understood. The research on other co-conditions is more frequent and often people confuse the prevalence WITHIN those groups with the % of those conditions occurring overall in the EPI community.This paper reviews every paper that includes data on EPI and people with type 1 diabetes or type 2 diabetes to help us better understand what % of people with diabetes are likely to face EPI in their lifetime.
    3. How many people with type 1 diabetes or type 2 diabetes (or diabetes overall) get EPI?TLDR of the paper: EPI prevalence in diabetes varies widely, reported between 5.4% and 77% when the type of diabetes isn’t specified. For Type 1 diabetes, the median EPI prevalence is 33% (range 14-77.5%), and for Type 2 diabetes, the median is 29% (range 16.8-49.2%). In contrast, in non-diabetes control groups, the EPI prevalence ranges from 4.4% to 18% (median 13%). The differences in ranges might be due to geographic variability and different exclusion criteria across studies.Diabetes itself is prevalent in about 10% of the general population. As such, I hypothesize that people with diabetes likely constitute one of the largest sub-groups of individuals with EPI, in contrast to what I described above might be more commonly assumed.
    4. Is pancreatic enzyme replacement therapy (PERT) safe for people with diabetes? 

      Yes. There have been safety and efficacy studies in people with diabetes with EPI, and PERT is effective just like in any other group of people with EPI.

    5. What is the effect of pancreatic enzyme replacement therapy (PERT) on glucose levels in people with diabetes?
      PERT itself does not affect glucose levels, but PERT *d0es* impact the digestion of food, which then changes glucose levels! So, most PERT labels warn to watch for hypoglycemia or hyperglycemia but the medicine itself doesn’t directly cause changes in glucose levels. You can read a previous study I did here using CGM data to show the effect of PERT actually causing improved glucose after meals in someone with Type 1 diabetes. But, in the systematic review, I found only 4 articles that even made note of glucose levels, and only 1 (the paper I linked above) actually included CGM data. Most of the studies are old, so there are no definitive conclusions on whether hypoglycemia or hyperglycemia is more common when a person with diabetes and EPI starts taking PERT. Instead, it’s likely very individual depending on what they’re eating, insulin dosing patterns before, and whether they’re taking enough PERT to match what they’re eating.TLDR here: more studies are needed because there’s no clear single directional effect on glucose levels from PERT in people with diabetes.Note: based on the n=1 study above, and subsequent conversations with other people with diabetes, I hypothesize that high variability and non-optimal post-meal glucose outcomes may be an early ‘symptom’ of EPI in people with diabetes. I’m hoping to eventually generate some studies to evaluate whether we could use this type of data as an input to help increase screening of EPI in people with diabetes.
    6. How common is EPI (PEI / PI) compared to celiac and gastroparesis in Type 1 diabetes and Type 2 diabetes? 

      As a person with (in my case, Type 1) diabetes, I feel like I hear celiac and gastroparesis talked about often in the diabetes community. I had NEVER heard of EPI prior to realizing I had it. Yet, EPI prevalence in Type 1 and Type 2 diabetes is much higher than that of celiac or gastroparesis!The prevalence of EPI is much higher in T1 and T2 than the prevalence of celiac and gastroparesis.Celiac disease is more common in people with diabetes (~5%) than in the general public (0.5-1%). Gastroparesis, when gastric emptying is delayed, is also more common in people with diabetes (5% in PWD).However, the  prevalence of EPI is 14-77.5% (median 33%) in Type 1 diabetes and 16.8-49.2% (median 29%) in Type 2 diabetes (and 5.4-77% prevalence when type of diabetes was not specified). This again is higher than general population prevalence of EPI.

      This data emphasizes that endocrinologists and other diabetes care providers should be more prone to initiate screening (using the non-invasive fecal elastase test) for individuals presenting with gastrointestinal symptoms, as the rates of EPI in diabetes are much higher in both Type 1 and Type 2 diabetes than the rates of celiac and gastroparesis.

    7. What should I do if I think I have EPI?
      Record your symptoms and talk to your doctor and ask for a fecal elastase (FE-1) screening test for EPI. It’s non-invasive. If your results are less than or equal to 200 (μg/g), this means you have EPI and should start on PERT. If you or your doctor feel that your sample may have influenced the results of your test, you can always re-do the test. But if you’re dealing with diarrhea, going on PERT may resolve or improve the diarrhea and improve the quality of the sample for the next test result. PERT doesn’t influence the test result, so you can start PERT and re-run the test any time.Symptoms of EPI can vary. Some people experience diarrhea, while others experience constipation. Steatorrhea or smelly, messy stools that stick to the side of the toilet are also common EPI symptoms, as is bloating, abdominal pain, and generally not feeling well after you eat.

      If you’ve been diagnosed with EPI, you may also want to check out some of my other posts (DIYPS.org/EPI) about my personal experiences with EPI and also this post about the amount of enzymes needed by most people with EPI. You may also want to check out PERT Pilot, a free iOS app, for recording and evaluating your PERT dosing.

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If you want to read the full article, you can find copies of all of my research articles at DIYPS.org/research

If you’d like to cite this specific article in your future research, here’s an example citation:

Lewis, D. A Systematic Review of Exocrine Pancreatic Insufficiency Prevalence and Treatment in Type 1 and Type 2 Diabetes. Diabetes Technology & Therapeutics. http://doi.org/10.1089/dia.2023.0157

Why DIY AID in 2023? #ADA2023 Debate

by Dana Lewis

I was asked to participate in a ‘debate’ about AID at #ADA2023 (ADA Scientific Sessions), representing the perspective that DIY systems should be an option for people living with diabetes.

I present this perspective as a person with type 1 diabetes who has been using DIY AID for almost a decade (and as a developer/contributor to the open source AID systems used in DIY) – please note my constant reminder that I am not a medical doctor.

Dr. Gregory P. Forlenza, an Associate Professor from Barbara Davis Center, presented a viewpoint as a medical doctor practicing in the US.

FYI: here are my disclosures and Dr. Forlenza’s disclosures:

On the left is my slide (Dana M. Lewis) showing I have no commercial support or conflicts of interest. My research in the last 3 years has previously been funded by the New Zealand Health Research Council (for the CREATE Trial); JDRF; and DiabetesMine. Dr. Forlenza lists research support from NIH, JDRF, NSF, Helmsley Charitable Trust, Medtronic, Dexcom, Abbott, Insulet, Tandem, Beta Bionics, and Lilly. He also lists Consulting/Speaking/AdBoard: Medtronic, Dexcom, Abbott, Insulet, Tandem, Beta Bionics, and Lilly.

I opened the debate with my initial presentation. I talk about the history of DIY in diabetes going back to the 1970s, when people with diabetes had to “DIY” with blood glucose meters because initially healthcare providers did not want people to fingerstick at home because they might do something with the information. Similarly, even insulin pumps and CGMs have been used in different “DIY” ways over the years – notably, people with diabetes began dosing insulin using CGM data for years prior to them being approved for that purpose. It’s therefore less of a surprise in that context to think about DIY being done for AID. (If you’re reading this you probably also know that DIY AID was done years before commercial AID was even available; and that there are multiple DIY systems with multiple pump and CGM options, algorithms, and phone options).

And, for people with diabetes, using DIY is very similar to how a lot of doctors recommend or prescribe doing things off label. Diabetes has a LOT of these types of recommendations, whether it’s different types of insulins used in pumps that weren’t approved for that type of insulin; medications for Type 2 being used for Type 1 (and vice versa); and other things that aren’t regulatory approved at all but often recommended anyway. For example, GLP-1’s that are approved for weight management and not glycemic control, but are often prescribed for glycemic control reasons. Or things like Vitamin D, which are widely prescribed or recommended as a supplement even though it is not regulatory-approved as a pharmaceutical agent.

I always like to emphasize that although open source AID is not necessarily regulated (but can be: one open source system has received regulatory clearance recently), that’s not a synonym for ‘no evidence’. There’s plenty of high quality scientific evidence on DIY use and non-DIY use of open source AID. There’s even a recent RCT in the New England Journal of Medicine, not to mention several other RCTs (see here and here, plus another pending publication forthcoming). In addition to those gold-standard RCTs, there are also reviews of large-scale big data datasets from people with diabetes using AID, such as this one where we reviewed 122 people’s glucose data representing 46,070 days’ worth of data; or another forthcoming publication where we analyzed the n=75 unique (distinct from the previous dataset) DIY AID users with 36,827 days’ of data (average of 491 days per participant) and also found above goal TIR outcomes (e.g. mean TIR 70-180 mg/dL of 82.08%).

Yet, people often choose to DIY with AID not just for the glucose outcomes. Yes, commercial AID systems (especially now second-generation) can similarly reach the goal of 70+% TIR on average. DIY helps provide more choices about the type and amount of work that people with diabetes have to put IN to these systems in order to get these above-goal OUTcomes. They can choose, overall or situationally, whether to bolus, count carbs precisely, announce meals at all, or only announce relative meal size while still achieving >80% TIR, no or little hypoglycemia, and less hyperglycemia. Many people using DIY AID for years have been doing no-bolus and/or no meal announcements at all, bringing this closer to a full closed loop, or at least, an AID system with very, very little user input required on a daily basis if they so choose. I presented data back in 2018(!) showing how this was being done in DIY AID, and it was recently confirmed in a randomized control trial (hello, gold standard!) showing that between traditional use (with meal announcements and meal boluses); meal announcement only (no boluses); and no announcement nor bolusing, that they all got similar outcomes in terms of TIR (all above-goal). There was also no difference in those modes of total daily insulin dose (TDD) or amount of carb intake. There was a small difference in time below range being slightly higher in the first mode (where people were counting carbs and bolusing) as compared to the other two modes – which suggests that MORE user input may actually be limiting the capabilities of the system!

The TLDR here is that people with diabetes can do less work/provide less input into AID and still achieve the same level of ideal, above-goal outcomes – and ongoing studies are showing the increased QOL and other patient-reported outcomes that also improve as a result.

Again, people may be predisposed to think that the main difference between commercial and DIY is whether or not it is regulatory approved (and therefore prescribable by doctors and able to be supported by a company under warranty); the bigger differences are instead around interoperability across devices, data access, and transparency of how the system works.

There’s even an international consensus statement on open source AID, created by an international group of 48 medical and legal experts, endorsed by 9 national and international diabetes organizations, supporting that open source AID used in DIY AID is a safe and effective treatment option, confirming that the scientific evidence exists and it has the potential to help people with diabetes and reduce the burden of diabetes. They emphasize that doctors should support patient (and caregiver) autonomy and choice of DIY AID, and state that doctors have a responsibility to learn about all options that exist including DIY. The consensus statement is focused on open source AID but also, in my opinion, applies to all AID: they say that AID systems should fully disclose how they operate to enable informed decisions and that all users should have real-time and open access to their own data. Yes, please! (This is true of DIY but not true of all commercial systems.)

The elephant in the room that I always bring up is cost, insurance coverage, and therefore access and accessibility of AID. Many places have government or insurance that won’t cover AID. For example, the proposed NICE guidelines in the UK wouldn’t provide AID to everyone who wants one. In other places, some people can get their pump covered but not CGM, or vice versa, and must pay out of pocket. Therefore in some cases, DIY has out of pocket costs (because it’s not covered by insurance), but is still cheaper than AID with insurance coverage (if it’s even covered).

I also want to remind everyone that choosing to DIY – or not – is not a once-in-a-lifetime decision. People who use DIY choose every day to use it and continue to use it; at any time, they could and some do choose to switch to a commercial system. Others try commercial, switch back to DIY, and switch back and forth over time for various reasons. It’s not a single or permanent decision to DIY!

The key point is: DIY AID provides safety and efficacy *and* user choice for people with diabetes.

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Dr. Forlenza followed my presentation, talking about commercial AID systems and how they’ve moved through development more quickly recently. He points to the RCTs for each approved commercial system that exist, saying commercial AID systems work, and describing different feature sets and variety across commercial systems. He shared his thoughts on advantages of commercial systems including integration between components by the companies; regulatory approval meaning these systems can be prescribed by healthcare providers; company-provided warranties; and company provided training and support of healthcare providers and patients.

He makes a big point about a perceived reporting bias in social media, which is a valid point, and talks about people who cherry pick (my words) data to share online about their TIR.

He puts an observational study and the CREATE Trial RCT data up next to the commercial AID systems RCT data, showing how the second generation commercial AID reach similar TIR outcomes.

He then says “what are you #notwaiting for?”, pointing out in the US that there are 4 commercial systems FDA approved for type 1 diabetes. He says “Data from the DIY trials themselves demonstrate that DIY users, even with extreme selection bias, do not achieve better glycemic control than is seen with commercial systems.” He concludes that commercial AID has a wide variety of options; commercial systems achieve target-level outcomes; a perception that both glucose outcomes and QOL are being addressed by the commercial market, and that “we do not need Unapproved DIY solutions in this space”.

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After Dr. Forlenza’s presentation, I began my rebuttal, starting with pointing out that he is incorrectly conflating perceived biases/self-reporting of social media posts with gold-standard, rigorously performed scientific trials evaluating DIY. Data from DIY AID trials do not suffer from ‘selection bias’ any more than commercial AID trials do. (In fact, all clinical trials have their own aspects of selection bias, although that isn’t the point here.) I reminded the audience of the not one but multiple RCTs available as well as dozens of other prospective and retrospective clinical trials. Plus, we have 82,000+ data points analyzed showing above-goal outcomes, and many studies that evaluate this data and adjust for starting outcomes still show that people with diabetes who use DIY AID benefit from doing so, regardless of their starting A1c/TIR or demographics. This isn’t cherry-picked social media anecdata.

When studies are done rigorously, as they have been done in DIY, we agree that now second-generation commercial AID systems reach (or exceed, depending on the system) ADA standard of care outcomes. For example, Dr. Forlenza cited the OP5 study with 73.9% TIR which is similar to the CREATE Trial 74.5% TIR.

My point is not that commercial systems don’t work; my point is that DIY systems *do* work and that the fact that commercial systems work doesn’t then override the fact that DIY systems have been shown to work, also! It’s a “yes, and”! Yes, commercial AID systems work; and yes, DIY AID systems work.

The bigger point, which Dr. Forlenza does not address, is that the person with diabetes should get to CHOOSE what is best for them, which is not ONLY about glucose outcomes. Yes, a commercial system- like DIY AID – may help someone get to goal TIR (or above goal), but DIY provides more choice in terms of the input behaviors required to achieve those outcomes! There’s also possible choice of systems with different pumps or CGMs, different (often lower) cost, increased data access and interoperability of data displays, different mobile device options, and more.

Also, supporting user choice of DIY is in fact A STANDARD OF CARE!

It’s in the ADA’s Standards of Care, in fact, as I wrote about here when observing that it’s in the 2023 Standards of Care…as well as in 2022, 2021, 2020, and 2019!

I wouldn’t be surprised if there are people attending the debate who think they don’t have any – or many – patients using DIY AID. For those who think that (or are reading this thinking the same), I ask a question: how many patients have you asked if they are using DIY AID?

There’s a bunch of reasons why it may not come up, if you haven’t asked:

  • They may use the same consumables (sites, reservoirs) with a different or previous pump in a DIY AID system.
  • Their prescribed pump (particularly in Europe and non-US places that have Bluetooth-enabled pumps) may be usable in a DIY AID.
  • They may not be getting their supplies through insurance, so their prescription doesn’t match what they are currently using.
  • Or, they have more urgent priorities to discuss at appointments, so it doesn’t come up.
  • Or, it’s also possible that it hasn’t come up because they don’t need any assistance or support from their healthcare provider.

Speaking of learning and support, it’s worth noting that in DIY AID, because it is open source and the documentation is freely available, users typically begin learning more about the system prior to initiating their start of closed loop (automated insulin delivery). As a result, the process of understanding and developing trust in the system begins prior to closed loop start as well. In contrast, much of the time there is limited available education prior to receiving the prescription for a commercial AID; it often aligns more closely with the timeline of starting the device. Additionally, because it is a “black box” with fewer available details about exactly how it works (and why), the process of developing trust can be a slower process that occurs only after a user begins to use a commercial device.

With DIY AID, because it is open source and the documentation is freely available, users typically begin learning more about the system prior to initiating their start of closed loop (automated insulin delivery). As a result, the process of understanding and developing trust in the system begins prior to closed loop start as well. In contrast, much of the time there is limited available education prior to receiving the prescription for a commercial AID; it often aligns more closely with the timeline of starting the device. Additionally, because it is a black box with less available details about exactly how it works (and why), the process of developing trust can be a slower process that occurs only after a user begins to use a commercial device. The learning & trust in AID timelines is something that needs more attention in commercial AID moving forward.

I closed my rebuttal section by asking a few questions out loud:

I wonder how healthcare providers feel when patients learn something before they do – which is often what happens with DIY AID. Does it make you uncomfortable, excited, curious, or some other feeling? Why?

I encouraged healthcare providers to consider when they are comfortable with off-label prescriptions (or recommending things that aren’t approved, such as Vitamin D), and reflect on how that differs from understanding patients’ choices to DIY.

I also prompted everyone to consider whether they’ve actually evaluated (all of) the safety and efficacy data, of which many studies exist. And to consider who benefits from each type of system, not only commercial/DIY but individual systems within those buckets. And to consider who gets offered/prescribed AID systems (of any sort) and whether subconscious biases around tech literacy, previous glucose outcomes, and other factors (race, gender, other demographic variables) result in particular groups of people being excluded from accessing AID. I also remind everyone to think about what financial incentives influence access and available of AID education, and where the education comes from.

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Although Dr. Forlenza’s  rebuttal followed mine, I’ll summarize it here before finishing a recap of my rebuttal: he talks about individual selection bias/cherry picked data, acknowledging it can occur in anecdotes with commercial systems as well; talks about the distinction of regulatory approval vs. off label and unapproved; legal concerns for healthcare providers; and closes pointing out that many PWD see primary care providers, he doesn’t believe it is reasonable to expect PCPs to become familiar with DIY since there are no paid device representatives to support their learning, and that growth of AID requires industry support.

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People probably wanted to walk out of this debate with a black and white, clear answer on what is the ‘right’ type of AID system: DIY or commercial. The answer to that question isn’t straightforward, because it depends.

It depends on whether a system is even AVAILABLE. Not all countries have regulatory-approved systems available, meaning commercial AID is not available everywhere. Some places and people are also limited by ACCESSIBILITY, because their healthcare providers won’t prescribe an AID system to them; or insurance won’t cover it. AFFORDABILITY, even with insurance coverage, also plays a role: commercial AID systems (and even pump and CGM components without AID) are expensive and not everyone can afford them. Finally, ADAPTABILITY matters for some people, and not all systems work well for everyone.

When these factors align – they are available, accessible, affordable, and adaptable – that means for some people in some places in some situations, there are commercial systems that meet those needs. But for other people in other places in other situations, DIY systems instead or also can meet that need.

The point is, though, that we need a bigger overlap of these criteria! We need MORE AID systems to be available, accessible, affordable, and adaptable. Those can either be commercial or DIY AID systems.

The point that Dr. Forlenza and I readily agree on is that we need MORE AID – not less.

This is why I support user choice for people with diabetes and for people who want – for any variety of reasons – to use a DIY system to be able to do so.

People probably want a black and white, clear answer on what is the ‘right’ type of AID system: DIY or commercial. It depends on whether a system is even AVAILABLE. Not all countries have regulatory-approved systems available, meaning commercial AID is not available everywhere. Some places and people are also limited by ACCESSIBILITY, because their healthcare providers won’t prescribe an AID system to them; or insurance won’t cover it. AFFORDABILITY, even if insurance coverage, also plays a role: commercial AID systems (and even pump and CGM components without AID) are expensive and not everyone can afford them. Finally, ADAPTABILITY matters for some people, and not all systems work well for everyone. The point is that we need a bigger overlap of these criteria! We need more alignment of these factors - more AID (DIY and commercial) available, accessible, affordable, and adaptable for people with diabetes. I support user choice for people with diabetes, which includes DIY AID systems

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PS – I also presented a poster at #ADA2023 about the high prevalence rates of exocrine pancreatic insufficiency (EPI / PEI / PI) in Type 1 and Type 2 diabetes – you can find the poster and a summary of it here.

Exocrine Pancreatic Insufficiency (EPI/PEI) In Type 1 and Type 2 Diabetes – Poster at #ADA2023

by Dana Lewis

When I was invited to contribute to a debate on AID at #ADA2023 (read my debate recap here), I decided to also submit an abstract related to some of my recent work in researching and understanding the prevalence and treatment of exocrine pancreatic insufficiency (known as EPI or PEI or PI) in people with diabetes.

I have a personal interest in this topic, for those who aren’t aware – I was diagnosed with EPI last year (read more about my experience here) and now take pancreatic enzyme replacement therapy (PERT) pills with everything that I eat.

I was surprised that it took personal advocacy to get a diagnosis, and despite having 2+ known risk factors for EPI (diabetes, celiac disease), that when I presented to a gastroenterologist with GI symptoms, EPI never came up as a possibility. I looked deeper into the research to try to understand what the correlation was in diabetes and EPI and perhaps understand why awareness is low compared to gastroparesis and celiac.

Here’s what I found, and what my poster (and a forthcoming full publication in a peer-reviewed journal!) is about (you can view my poster as a PDF here):

1304-P at #ADA2023, “Exocrine Pancreatic Insufficiency (EPI / PEI)  Likely Overlooked in Diabetes as Common Cause of Gastrointestinal-Related Symptoms”

Exocrine Pancreatic Insufficiency (EPI / PEI / PI) occurs when the pancreas no longer makes enough enzymes to support digestion, and is treated with pancreatic enzyme replacement therapy (PERT). Awareness among diabetes care providers of EPI does not seem to match the likely rates of prevalence and contributes to underscreening, underdiagnosis, and undertreatment of EPI among people with diabetes.

Methods:

I performed a broader systematic review on EPI, classifying all articles based on co-condition. I then did a second specific diabetes-specific EPI search, and de-duplicated and combined the results. (See PRISMA figure).

A PRISMA diagram showing that I performed two separate literature searches - one broadly on EPI before classifying and filtering for diabetes, and one just on EPI and diabetes. After filtering out irrelevant, animal, and off topic papers, I ended up with 41

I ended up with 41 articles specifically about EPI and diabetes, and screened them for diabetes type, prevalence rates (by type of diabetes, if it was segmented), and whether there were any analyses related to glycemic outcomes. I also performed an additional literature review on gastrointestinal conditions in diabetes.

Results:

From the broader systematic review on EPI in general, I found 9.6% of the articles on specific co-conditions to be about diabetes. Most of the articles on diabetes and EPI are simply about prevalence and/or diagnostic methods. Very few (4/41) specified any glycemic metrics or outcomes for people with diabetes and EPI. Only one recent paper (disclosure – I’m a co-author, and you can see the full paper here) evaluated glycemic variability and glycemic outcomes before and after PERT using CGM.

There is a LOT of work to be done in the future to do studies with properly recording type of diabetes; using CGM and modern insulin delivery therapies; and evaluating glycemic outcomes and variabilities to actually understand the impact of PERT on glucose levels in people with diabetes.

In terms of other gastrointestinal conditions, healthcare providers typically perceive the prevalence of celiac disease and gastroparesis to be high in people with diabetes. Reviewing the data, I found that celiac has around ~5% prevalence (range 3-16%) in people with type 1 diabetes and ~1.6% prevalence in Type 2 diabetes, in contrast to the general population prevalence of 0.5-1%. For gastroparesis, the rates in Type 1 diabetes were around ~5% and in Type 2 diabetes around 1.3%, in contrast to the general population prevalence of 0.2-0.9%.

Speaking of contrasts, let’s compare this to the prevalence of EPI in Type 1 and Type 2 diabetes.

  • The prevalence of EPI in Type 1 diabetes in the studies I reviewed had a median of 33% (range 14-77.5%).
  • The prevalence of EPI in Type 2 diabetes in the studies I reviewed had a median of 29% (16.8-49.2%).

You can see this relative prevalence difference in this chart I used on my poster:

The prevalence of EPI is much higher in T1 and T2 than the prevalence of celiac and gastroparesis.

Key Findings and Takeaways:

Gastroparesis and celiac are often top of mind for diabetes care providers, yet EPI may be up to 10 times more common among people with diabetes! EPI is likely significantly underdiagnosed in people with diabetes.

Healthcare providers who see people with diabetes should increase the screening of fecal elastase (FE-1/FEL-1) for people with diabetes who mention gastrointestinal symptoms.

With FE-1 testing, results <=200 μg/g are indicative of EPI and people with diabetes should be prescribed PERT. The quality-of-life burden and long-term clinical implications of undiagnosed EPI are significant enough, and the risks are low enough (aside from cost) that PERT should be initiated more frequently for people with diabetes who present with EPI-related symptoms.

EPI symptoms aren’t just diarrhea and/or weight loss: they can include painful bloating, excessive gas, changed stools (“messy”, “oily”, “sticking to the toilet bowl”), or increased bowel movements. People with diabetes may subconsciously adjust their food choices in response to symptoms for years prior to diagnosis.

Many people with diabetes and existing EPI diagnoses may be undertreated, even years after diagnosis. Diabetes providers should periodically discuss PERT dosing and encourage self-adjustment of dosing (similar to insulin, matching food intake) for people with diabetes and EPI who have ongoing GI symptoms. This also means aiding in updating prescriptions as needed. (PERT has been studied and found to be safe and effective for people with diabetes.)

Non-optimal PERT dosing may result in seemingly unpredictable post-meal glucose outcomes. Non-optimal postprandial glycemic excursions may be a ‘symptom’ of EPI because poor digestion of fat/protein may mean carbs are digested more quickly even in a ’mixed meal’ and result in larger post-meal glucose spikes.

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As I mentioned, I have a full publication with this systematic review undergoing peer review and I’ll share it once it’s published. In the meantime, if you’re looking for more personal experiences about living with EPI, check out DIYPS.org/EPI, and also for people with EPI looking to improve their dosing with pancreatic enzyme replacement therapy – you may want to check out PERT Pilot (a free iOS app to record enzyme dosing).

Researchers, if you’re interested in collaborating on studies in EPI (in diabetes, or more broadly on EPI), please reach out! My email is Dana@OpenAPS.org