Runar Solberg, PhD Scientist
Centre for Epidemic Interventions Research (CEIR)
Norwegian Institute of Public Health
Atle Fretheim, PhD Research Director
Norwegian Institute of Public Health
Keywords
Face Masks; Masking; Respiratory Infection; Public Health; COVID-19
Key Points
Observational evidence supports a reduction in respiratory infection with face mask use. However, randomized trials face challenges–especially in achieving sufficient statistical power–that contribute to uncertainty in their findings.
The study team conducted a pragmatic randomized trial aimed at assessing the personal protective efficacy of wearing a surgical face mask in public settings.
Adherence varied between the control and intervention groups, with higher rates of adherence within the control group (no mask).
Participants were recruited from multiple locations across Norway. Advertising and the researchers’ appearance on Norwegian television, radio, and other media helped raise awareness about the study.
Reviewers acknowledged that the primary outcome–self-reported respiratory symptoms–was clinically meaningful and well-defined. However, the reliance on self-reported data led to concerns about bias and accuracy, as there was no in-person verification of masking.
To mitigate these concerns, future studies may opt to use registry data or incorporate mandatory PCR testing of participants.
Discussion Themes
An open and important question about masking effectiveness relates to the durability of the intervention: Does it flatten the curve early or delay the peak?
Collecting data on components of the primary outcome–i.e. if more objective symptoms like fever were more or less impacted by the intervention than more subjective outcomes like malaise–may help address concerns about the reliability of self-reported outcomes.
Efficacy depends on the degree of risk. Proving efficacy in a randomized controlled trial or pragmatic trial is tricky unless there is something to prevent. This depends on many factors that may cause heterogeneity of treatment effects (e.g. degree of exposure, physical proximity, virulence, etc.).
Deborah J. Wexler, MD, MSc Associate Professor of Medicine and Diabetes Unit Chief
Massachusetts General Hospital and Harvard Medical School
Brendan M. Everett, MD, MPH Associate Professor of Medicine
Divisions of Cardiology and Preventive Medicine
Brigham and Women’s Hospital and Harvard Medical School
Comparative effectiveness of SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) for cardiac and kidney outcomes is a major question in cardiac-kidney-metabolic health.
More broadly, comparative effectiveness of on-patent medications is crucial, yet not mandated, with little incentive (and some disincentive) for pharmaceutical companies to participate.
The PRECIDENTD trial will seek to test one approach to evaluating the comparative effectiveness of expensive new therapies. Their primary aim is to conduct a head-to-head evaluation of SGLT2i versus GLP-1 RA for the prevention of major adverse cardiovascular/kidney events and death.
Partnerships with patients, providers and stakeholders will be crucial to the success of PRECIDENTD. Patient engagement strategies include Community Engagement Studios, a Center for Effective Health Communication, and an interactive text messaging system to assess adherence.
The research team sees the trial, which involves two expensive, brand-name drugs and requires extensive collaboration, as a true test of a pragmatic trial of branded pharmaceutical medications.
Obtaining informed consent isn’t going to be pragmatic; it is time-consuming, challenging, and individualized.
Constrained funding in the feasibility phase may hamper the growth of the trial. In a bureaucratic research environment, the administrative burden can take time and energy from a study.
Discussion Themes
Patients have been more interested in participating given that this trial compares one effective, well-understood active drug to another, so there’s no risk of being assigned to a placebo group.
The pragmatic nature of the trial means that the study team is recruiting participants who can go either way when it comes to the two treatment options. The highest-risk people won’t be enrolled.
There is some overlap between the two public health crises of our time: suicidal behavior and the Opioid Use Disorder (OUD)/opioid overdose crisis.
The research team looked at whether starting (vs not starting) buprenorphine reduces the subsequent risk of a self-harm event or suicide attempt among people diagnosed with OUD.
They conducted an observational study with target trial emulation, emulating a randomized trial where people with an OUD diagnosis might be randomly assigned to start or not start buprenorphine during an outpatient visit. They tracked the rates of self-harm, adverse outcomes more broadly, and overdose over 90 days.
Their analysis found that starting buprenorphine didn’t reduce the risk of self-harm behavior and (surprisingly) had no protective or beneficial effect when it came to opioid poisoning or overdose.
They found that when they stopped tracking outcomes for those who changed course – i.e. had initiated buprenorphine but stopped or had initially declined but initiated later – they observed protective effects consistent with previous findings. The risk of self-harm for people who stopped or had their treatment interrupted increased four-fold, and the risk of opioid overdose or poisoning increased five- or six-fold.
These findings reinforce concerns about high risk of adverse outcomes soon after stopping or interrupting buprenorphine treatment.
These findings also raise questions about the kind of target trials researchers should be emulating and what pragmatic trials might be considered for follow-up. Given these results, the research team is interested in research questions that center on the stopping or interruption of buprenorphine treatment.
Discussion Themes
Given that buprenorphine is often prescribed in shorter supply (7 – 14 days worth), the researchers were able to track the timing of events more accurately than they’d be able to with other chronic conditions. The profit motive of healthcare systems (i.e. billing insurance for treating an overdose) also improved their ascertainment of those events.
One limitation of the study is that they don’t have any way of ascertaining self-harm events or overdoses that never came to medical attention.
At the individual clinician level and at the policy level, the decision to treat OUD with buprenorphine is informed by the knowledge that interruptions in treatment are fairly common and can have adverse effects.
Another study design option is to compare people before and after initiating buprenorphine treatment, as opposed to comparing people who initiate and people who don’t. The tricky thing about that design is that an individual’s state is not consistent; there may have be an initiating event that precipitates the decision to start treatment.
Adrian Hernandez, MD, MHS Vice Dean and Executive Director
Duke Clinical Research Institute
Duke University School of Medicine
Keywords
CRISPR; Gene Editing Therapies; Population Health
Key Points
The epidemiologic forecast for 2050 is gloomy, with projected increases in the prevalence of diabetes, high cholesterol, hypertension, obesity, and resulting cardiovascular conditions. Innovative technologies and therapies – particularly gene editing – could potentially prevent these conditions and have a positive long-term impact.
Gene editing technology could be used to develop targeted treatments for ultra-rare, rare, and common diseases. Several clinical trials are already underway, testing CRISPR-based therapies for cancers, chronic bacterial infections, lupus, and others.
A little over a decade after the first discovery using CRISPR technology was published in Science, the FDA approved the first CRISPR-based medicine for the treatment of any disease. The recent, rapid, and revolutionary advances in gene editing therapies simultaneously hold promise and indicate the importance of ensuring that this technology is developed safely and effectively.
When thinking through trial design, researchers need to consider durability. This means developing assessment methods for off-target effects and on-target safety validation, as well as planning for long-term monitoring.
There are also ethical and regulatory points to consider, especially around obtaining informed consent, navigating the unknowns and potential permanence of gene editing interventions, engaging underserved communities, preventing misinformation, and defining long-term follow-up.
The Precision Health Alliance was pulled together by Dr. Hernandez and his colleagues in an effort to bring together a variety of stakeholders – clinicians, researchers, healthcare systems, and life-science leaders – to think through what’s needed to develop research-to-care pathways with gene editing.
Many questions still need to be addressed: How do we handle more and more personalized health data appropriately? If we know we can cure someone, should we? How do we ensure we don’t create greater health disparities? How do we overcome mistrust in revolutionary science? How do we address common questions, commonly?
Discussion Themes
– What’s your view on the current temperature of public perception in this space? And as you look to the future, how important do you think it’ll be to improve public understanding and acceptance of these types of therapies as a safe and effective strategy in clinical practice? There’s been some interesting early survey data in terms of, if you had an option for a permanent therapy that you took once, would you like to do it? And the answer was largely yes. Now if you were to say, well, we’re going to edit your genes, then the answer kind of changes. Some of the confusion comes from germline editing. So I think there’s a lot of education that has to be done in this area.
– As a person with a rare disease, I’ve been spending some time thinking about what I would do if I had this option, what the considerations are, and the ableism that all of these possibilities bring up. Contemplating and discussing with impacted persons is so critical. How would your initiative address that? It’s critically important to have lived experience involved, especially when you’re thinking about something that’s potentially durable over a lifetime. You want to make sure that you’re deriving meaningful benefit for patients that’s substantially beneficial rather than incremental. That’s also important for engaging the population.
Gregg C. Fonarow, MD, FACC, FAHA, FHFSA Eliot Corday Professor of Cardiovascular Medicine and Science
Director, Ahmanson-UCLA Cardiomyopathy Center
Codirector, UCLA Preventative Cardiology Program
UCLA Division of Cardiology
Keywords
Heart failure; HFrEF; guideline-directed medical therapy; implementation; systematic review
Key Points
Despite the availability of effective therapies for heart failure (HF), a large number of eligible patients are not receiving one or more evidence-based, guideline-recommended therapies. This implementation gap has stymied improvements in morbidity and mortality.
The benefits of evidence-based heart failure medications are cumulative. If all therapies are used, there is a relative risk reduction of 74.0% and an absolute risk reduction of 25.9%. Simultaneous or rapid initiation of therapies reduces HF hospitalizations, rehospitalizations, and mortality.
Reasons for underutilization of Guideline-Directed Medical Therapy (GDMT) for heart failure include a lack of systems to reliably implement therapies; gaps in knowledge and awareness of guidelines; therapeutic inertia; and insufficient urgency.
Dr. Fonarow’s team conducted a systematic review of interventions for the optimization of GDMT, including 28 randomized clinical trials with an aggregate sample of over 19,000 patients. They found that the initiatives that used interdisciplinary teams, largely comprised of nurses and pharmacists, most consistently led to improvements in GDMT. Clinician education, electronic health record initiatives, and patient interventions, on the other hand, resulted in no or modest improvements in GDMT.
Implementation of GDMT needs to improve in all clinical settings. Programs that successfully implement GDMT often have access to current and accurate data on treatment outcomes; administrative and clinician support; use care maps and pathways; and use data to provide feedback. There is also a need for further implementation science innovation and testing.
Discussion Themes
– Do you still see lack of education as a major problem that needs to be approached differently, or should we really be focusing on something else? I do think it need to be further studied. I think our educational efforts around the clinician need to center on the really practical aspects, on what the common pitfalls are in trying to apply and uptitrate these medications. Interdisciplinary teams and cross-discipline education are critically important. [The study results] don’t mean that education shouldn’t be part of further interventions, but I think we need to look at what’s truly going to see a meaningful increase in medication titration and persistence of GDMT.
– The polypill could address some of the clinical inertia issues and patient resistance. Patients hate it when you keep adding on four different medications and you’re increasing the doses. Is it being studied in this context? There is work going on, editorials have been written about it, the concept has been laid out. There are small pilot studies that have been done. There are challenges; is titration necessary? You’ll need a series of polypills to uptitrate, or you’ll get the therapy started and then you’ll bring them together as a polypill. One thing I do want to highlight, though, is that starting medications simultaneously defeats that patient question of, “Why are you adding this extra medication? Are the prior medications not working?” It’s a different mindset upfront: “Here are these four medications you’re going to be on.”
Researchers often look at the intention-to-treat (ITT) effect – i.e., the effect of being assigned to an intervention – for randomized trials, and at the per-protocol effect – i.e., the effect of receiving an intervention – for observational studies.
Why are we giving estimates for 2 different effects? If a causal question is important enough to be asked in an observational study, Dr. Hernán posed, then we should also ask it in a randomized trial, and vice versa.
He walked through some of the field’s justifications for asking different causal questions. If adherence patterns vary, the ITT effect may differ across trials that study the same treatment. Arguments in favor of using the ITT effect often include that it preserves the null; it’s conservative; and it measures effectiveness in the real world.
But null preservation is not guaranteed; most pragmatic trials are not blinded, for instance, so assignment may make patients and doctors alter their behavior. Through hypotheticals and case examples, Dr. Hernán made the case that ITT effects are not necessarily a measure of effectiveness, nor are they of primary interest for doctors and patients.
The per-protocol effect represents another causal question that randomized trials could answer. The issue with per-protocol analysis is that valid estimate of the effect requires adjustment for confounding. Historically, trialists have been suspicious of these analyses as potentially biased.
In the past few decades, however, statistical methods have been developed that allow researchers to adjust for confounders at baseline and after baseline. Provided a few criteria are met, there is hope for the estimation of per-protocol effects as a way to contrast generic treatment strategies.
For a long time, regulators were reluctant to consider causal effects other than the ITT effect. Under increasing pressure from industry, a group of methodologists from pharma and regulatory agencies worked together to generate the “estimand framework.” This manifested as an addendum to the ICH E9 guidelines.
The addendum was a great step forward for more rigorous causal influence, Dr. Hernán noted. But it has room for improvement, specifically in terms of choice (of standard terminology and of estimands) and a lack of emphasis on both treatment strategies and trial design.
Researchers do not compare treatments but treatment strategies. Therefore, the causal contrast needs to specify the treatment strategies of interest; typically, these will be the treatment strategies specified in the protocol. Observational studies for causal inference already try to estimate well-defined per-protocol effects when emulating target trials. It’s time to turn to randomized trials.
Discussion Themes
The intention-to-treat effect is not always the primary interest. When there is a safety outcome or in a non-inferiority trial, the per-protocol effect is necessarily the estimand of interest.
When we say the ITT effect is biased towards the null, we mean it’s biased for the per-protocol effect. I.e., “I’m interested in the per-protocol effect because it’s going to be harder to find differences between treatments using ITT analysis.”
One issue with the estimand framework is that it doesn’t give the per-protocol effect much consideration; it is not named and is part of a set of estimands, all of which are given equal importance. Dr. Hernán argued that the per-protocol effect should be made more explicit, as it’s the main question that we can ask of a trial outside of the ITT effect.
The person who designs the trial is responsible for pre-specifying the procedure when a participant switches treatments.
Artificial Intelligence (AI), when implemented thoughtfully in clinical settings, can lead to meaningful results for patients.
Medicine has long fallen short of the ideal of informed consent, in part due to the limited readability of informed consent forms; as of 2020, 54% of Americans were estimated to read below the sixth-grade reading level. This has implications for patient understanding and quality of care.
Using ChatGPT-4, the research team took LifeSpan Healthcare System’s (LHS) surgical consent form from a 12.6 Flesch-Kincaid reading level to a 6.7. After hospital leadership reviewed the revised form and the research team had addressed concerns around biases, approvals, and future needs, the revised form was deployed across LHS.
This real-world implementation demonstrated the potential for AI to make meaningful improvements to patient care and communication. As a proof-of-concept, it sparked the interest of other health systems.
To investigate the clinical implications of consent form readability, the research team analyzed 798 federally funded clinical trials providing accessible informed consent forms. A 16% increase in the dropout rate was associated with each additional Flesch-Kincaid grade-level increase in the language.
The observed association between consent form complexity and participant dropout rate could be attributed to misaligned expectations; erosion of trust; participant surprise and dissatisfaction; and reduced engagement. This highlights the importance of clear, accessible communication throughout the entire trial process, not just enrollment.
Improved readability of consent forms is crucial for the design and implementation of clinical trials, potentially leading to more inclusive, efficient, and impactful clinical research.
Discussion Themes
Medical malpractice attorneys were part of the cohort that reviewed the simplified consent forms. They shared that when these cases go to court, a jury will often review the informed consent document. In these cases, it can more protective to have documentation that people can understand.
There is the potential for tailored chatbots that could personalize the consent process for patients, but expert oversight would be crucial. AI models can “hallucinate,” saying something incorrect with absolute certainty. Dr. Mirza indicated that the field isn’t ready for those bespoke consents; centralized documents, as least for the time being, are the way to go.
AI is going to be integrated into our healthcare system. It’s important for clinicians, researchers, and people who really care about patients, as well as the patients themselves, to have a seat at the table discussing these early models.
Reto Auer, MD, MAS Associate Professor in Primary Health Care, Head Substance Use Unit, Institute of Primary Health Care (BIHAM), University of Bern
Adjunct Physician, University Center for Primary Care and Public Health (Unisanté), Switzerland
Keywords
Smoking; cessation; e-cigarettes; nicotine
Key Points
For cigarette smokers who are struggling to quit, e-cigarettes may be a viable and less risky alternative. When it comes to smoking cessation, there is substantial evidence that nicotine e-cigarette usage increases quit rates compared to nicotine replacement therapies (NRTs). Because the nicotine is inhaled, rather than delivered more slowly by way of a patch or gum, e-cigarettes provide quick relief from cravings much in the way a traditional cigarette would.
E-cigarette use is a polarizing topic in the medical field. The somatic health risks posed by e-cigarettes are lower than that of conventional cigarettes. However, their addictive potential is similar. So, while the availability of e-cigarettes could substantially reduce the health risks of nicotine dependence for existing smokers, it poses a substantial risk of nicotine addiction to a new generation.
A study team led by Dr. Reto Auer ran a randomized clinical trial to assess the efficacy and safety of free e-cigarettes in addition to standard care vs standard care alone. Their secondary aim was to assess the effect of the intervention on respiratory symptoms.
1,246 participants at five study sites in Switzerland were randomized at a 1:1 ratio to the control group (standard-of-care smoking cessation counseling, AKA SOC) and the intervention group (SOC + free e-cigarettes, along with advice on use of products). The intervention included a choice between 6 different aromas and 4 different nicotine concentrations. Researchers followed up with participants at 6-months (later extended to 12-, 24-, and 60 months).
At the end of the six months, the proportion of participants who reported zero tobacco use was 21% higher in the intervention group than in the control group; however, the percentage of participants in the intervention group who abstained from nicotine entirely altogether was almost 14% lower. In other words, the intervention group ended up smoking less tobacco, but consuming more nicotine. The intervention resulted in more adverse events but not more serious adverse events.
In conclusion, their study found that e-cigarette use plus standard counseling may be a viable option for tobacco smokers who want to abstain from smoking without necessarily abstaining from nicotine but may be less appropriate for those who want to abstain from both tobacco and nicotine.
Dr. Auer also discussed ethical considerations for the trial, namely the potential consequences if health care professionals were to state that e-cigarettes are less harmful that tobacco cigarettes. On the one hand, some smokers may quit smoking tobacco thanks to e-cigarettes; on the other hand, non-smokers may be more likely to use e-cigarettes and become addicted to nicotine as a result.
Discussion Themes
– There isn’t always heterogeneity in the products presently on the market. So, I have a little consternation about the devices that people are picking up in vape shops. Do you have any thoughts or comments on that? Of course, you need regulation. You cannot have a drug like this without oversight. I think in the U.S., you might be in a better place with FDA review. And there are now e-cigarettes [in the U.S.] that have been have gone through all the regulatory oversight… I’m completely with you, there’s a lot of research to be done before everyone can embrace recommending these.
– From your perspective, how has the conversation about this trade off, this ethical balance that you described, evolved over time? Are you seeing movement, or do people tend to be entrenched in their positions? That question was at the core of our work. If you speak with some people in England, they say “Why do this trial? This is evident, you don’t need to.” But others will say “We will never allow e-cigarettes.” Our job was to be in the middle of it; to be the boring researchers who produced the evidence, who are not involved in the politics, and who try to understand the difference and see how the conversation moves.
– The trial focused on switching away from combustible cigarettes as opposed to nicotine cessation. As a physician, I would not want indefinite e-cigarette use for my patients. Do you think that was the optimal goal, or was it about what was feasible to achieve with a trial? Smoking is a chronic condition. As a clinician, how I translate this, is that the discussion is about shared decision making and your preference as a patient. If someone says, “I want to quit both [cigarettes and nicotine],” I’ll say, “Well, e-cigarettes might not be the best way.” But if someone says, “I don’t care about nicotine, I’ll be using nicotine for the rest of my life,” … At least they don’t smoke. The approach is different, and with e-cigarettes we can address a population we could never address before.
Previously observed improvements in post-Myocardial Infarction (MI) prognosis have reached a plateau in recent years. Given that SGLT-2 inhibitors have positive effects on almost all cardiometabolic parameters, investigators at the Uppsala Clinical Research Center (UCR) hypothesized that dapagliflozin could reduce the risk of heart failure following MI. SGLT-2 inhibition could become the first new beneficial pharmacological treatment concept for patients with MI in over a decade. Dapagliflozin is already known to be beneficial to patients with diabetes or chronic heart failure, and has a known safety profile.
The DAPA-MI team conducted a pragmatic, registry-based, double-blind randomized clinical trial using national registry data, also known as an R-RCT, from 103 sites in the U.K. and Sweden. Their objective was to evaluate the effect of dapagliflozin on cardiometabolic outcomes in patients with acute myocardial infarction without diabetes or chronic heart failure. Data was collected as part of routine clinical care and transferred to the UCR web application, which helped the PIs to identify and enroll patients. That data was then transferred to the DAPA-MI database.
An R-RCT is a prospective randomized controlled trial that uses a clinical quality registry for one or several major functions for trial conduct and outcomes reporting. The DAPA-MI study team saw this approach as combining the best of two worlds: real-world registry data with the features of a randomized trial.
The registry would allow them to enroll as many patients as possible, in a pragmatic setting, at a lower cost, while the RCT would allow them to draw causal inference and understand the efficacy of the agent. The team’s other objective in conducting this trial was to evaluate the possibility to conduct a registrational clinical trial in a very new way for a marketed product with a known safety profile.
Their initial primary endpoint was a composite of hospitalization for heart failure and cardiovascular death, the traditional standard outcome for heart failure trials. During the course of the trial, however, it became evident that the number of collected primary composite outcomes in the DAPA-MI trial was substantially lower than anticipated. In February 2023, the trial was modified from an event-driven time-to-event approach to a hierarchical composite outcome approach including clinically relevant cardiometabolic outcomes.
They found that DAPA-MI met the primary endpoint and dapagliflozin treatment demonstrated significant clinical benefit compared to the placebo. With a Win ratio of 1.34, the likelihood for a better cardiometabolic outcome with dapagliflozin is 34% higher compared to placebo.
The feasibility of the R-RCT design was confirmed with the recruitment of 4017 patients with acute MI without diabetes and chronic HF in only two countries and 103 sites. Collaboration between UCR and NICOR enabled the success of the trial; excellent data quality confirmed the regulatory-grade of R-RCT design; and the registry-based approach was appreciated and attracted Investigators all over Sweden and the UK representing both large and small hospitals.
Discussion Themes
-Why did you reduce the power of the study when you shifted to the hierarchical endpoint? What would’ve been the power of the hierarchical endpoint if you’d stayed at 6,000 patients? The trial enrolled well, but we realized we wouldn’t be able to double the number of patients from 6,000 to 12,000, which might have been required to get power on the first primary endpoint. I think many of us would like to have continued to enroll patients above 6,000 or 6,500, but there with multiple issues with that. If we had a sufficient power to stop at 4,000 patients, it was difficult to convince the sponsor, perhaps the trial organization to continue enrolling if it wasn’t absolutely necessary.
–What were your interactions with the regulators like? It was interesting to have these regulatory discussions with the different agencies, with very different comments and requests on our trial for the proposal. I would frankly say that the FDA was the easiest regulatory agency to discuss with, very supportive of a new way of doing trials, very supportive of not adjudicating events, finding pragmatic solutions. The U.K, they requested that we do specific, cumbersome safety testing with blood tests, renal function tests. They were afraid that dapagliflozin would hurt the kidneys. The journals were even more difficult. They wanted us to not do a pragmatic trial at all; they wanted us to understand the mechanisms of the drug with repeated echo measurements. So very different ideas.
–Did you have any feedback that was different across the different agencies around safety reporting? Yes, safety reporting was also viewed differently. The FDA were also supportive of not doing specific safety reporting more than we do in regular care. The EMA and the other European agencies were more concerned about safety reporting, but we were able to get support on doing minimal safety reporting since the agent and the safety profile were so well known. We also set up a study in which we are now retrospectively comparing safety reporting with what we can get from registries. So that’s an ongoing process to compare and see if the safety reporting that we can achieve from registries allows us to understand the safety profile as good as or better than the safety reporting.
Russell Rothman, MD, MPP Professor, Internal Medicine, Pediatrics, & Health Policy
Senior Vice President, Population and Public Health
Director, Institute for Medicine and Public Health
Jason Block, MD Assistant Professor, Harvard Medical School
Faculty Member, Harvard Center for Population and Development Studies
Physician, Brigham and Women’s Hospital
Keywords
CODA, PCORnet, diabetes, COVID-19, pragmatic research
Key Points
PCORnet has been around for 10 years and was designed to bring together health systems, clinicians and researchers as well as harnessing medical electronic data and other partners to focus on patient-centered research. The network can support real-world evidence studies, population health research, comparative effectiveness research, pragmatic research, health systems research, and more.
PCORnet includes 8 clinical research networks at more than 75 large health systems health systems, including academic health centers and community clinics, which gives a diverse population to recruit into clinical trials with reach across the U.S. The PCORnet sites have a common data model so it is standardized across systems.
The COVID-19 Diabetes Assessment (CODA) Study worked with PCORnet Front Door to rapidly identify diverse sites for the study. PCORnet Front Door is the access point for PCORnet resources and services and can support study design, connections to network collaborators, and PCORnet study designation.
CODA will recruit and follow a cohort of 1,600 adult and pediatric participants with recent diagnosis of Type 1 (T1D) and Type 2 (T2D) diabetes to examine the relationship between SARS-CoV-2 exposure and glycemic control, metabolic function, inflammation, cardiovascular risk, and patient-reported outcomes.
CODA will explore the role of genomic/social/environmental factors on glycemic control, inflammation, and metabolic function, and it will also leverage EHR data from 38 PCORnet health systems participating in the NIH RECOVER program to explore the role of COVID-19 infection on diabetes development and progression.
There is epidemiologic evidence that suggests increases in the incidence of T1 and T2 diabetes in both adults and children plus possible worsening of preexisting disease after COVID-19 infection. Mechanisms may include direct effects on pancreatic beta cells that produce insulin, increase in inflammation, immune dysregulation, and other metabolic changes caused by infection with SARS-CoV-2. Other factors may contribute to increased rates of diabetes and worsening of disease including social factors, environmental stressors, health disparities, and other issues.
The study will take place at 15 PCORnet sites across the U.S. Five sites are from PEDSnet with large children’s hospitals to help recruit pediatric participants. Participants with a new diagnosis of T1D and T2D, English and Spanish speakers, age 11 and older are eligible for the study, with an enrollment goal of 1,000 adults and 600 children at 3 levels (surveys, mixed meal tolerance test (MMTT), and SphygmoCor to assess arterial stiffness) over 24 months.
CODA also will integrate and leverage supplement EHR data to explore the role of COVID on diabetes development and potential remission in T2D.
Discussion Themes
-What are your expectations about the folks who will participate and if there are differences between the pops who will participate at the different levels. We do provide additional compensation to engage participants at different levels. Particularly with participants with T1D who are younger, families are very interested in understanding more about the diabetes. Our plans are to recruit 400 total patients (25% of total) for MMTTs and 200 total patients (12.5%) for the vascular stiffness study.
–How did you develop your patient recruitment materials? The infographic that we developed to explain the different levels of participation was created by someone on our team with experience in health literacy. We tried designing materials at a sixth grade reading level, with white space on the page to help with the recruitment and consent process and increase participant understanding.
