Is universal screening for type 1 diabetes ready for prime time?
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The time has come for universal screening, but we still need to resolve certain issues.
A few months ago, I would have questioned the value of universal screening for type 1 diabetes because we did not have anything to offer people who are at risk for the disease. However, we now have a drug — teplizumab-mzwv — that can delay the onset of type 1 diabetes. That is an important advance.
The Fr1da study in Bavaria, Germany, has shown that the risk for type 1 diabetes for people who test autoantibody-positive is basically the same as relatives of people with type 1 diabetes who test autoantibody-positive, and most people who will develop type 1 diabetes do not have a relative with the disease. So, to identify most individuals at risk, we need to look in the general population.
There are still a lot of unanswered questions regarding implementation of universal screening. What is the most cost-effective and efficient way to do this? How do you screen so many people? These are challenges that need improvements in our technologies, but already there are advances and strategies that may make this work.
Some groups have advocated for starting with genetic screening that narrows the number of individuals who really require follow-up serologic testing since most who will develop type 1 diabetes have genetic markers that identify their risk. New genetic risk scores have refined this technology and offer more precise estimates of risk compared with screening for major histocompatibility genes alone. Conversely, there are now methods for serologic testing that are easy to do and, as costs come down, that could be a very feasible option. I personally have not drawn a conclusion as to whether we should start with genetic or serologic screening. I am very keen to hear how things will go with the CASCADE study as well as others.
There is also a question about at what age to screen as well. Recommendations have been to screen very young, at age 2 years and ages 4 or 5 years. Now, teplizumab is approved for at-risk individuals age 8 years and older, so in the future, the age of recommended screening may depend on whether interventions can be offered to younger children.
In addition, there are important practical considerations about implementing screening. Most children do not routinely get laboratory tests done when they are very young. Using blood spots might obviate the need for a test that requires blood draws, and these could be done by individuals anywhere. Guidelines are needed for follow-up of patients who test positive. For example, what sort of metabolic studies are needed and at what interval should they be done? Finally, if screening becomes more widespread, patients at risk may not want to travel long distances for monitoring or even to receive approved therapies. Since those at risk are not “patients” who have contact with endocrinologists, we need to rethink how new therapies can be administered and by whom.
The endocrine community needs to address these questions as we move into a new era in type 1 diabetes prevention.
- For more information:
- Kevan Herold, MD, is C.N.H. Long Professor of Immunology and Internal Medicine at Yale University and the chair of the National Institute of Diabetes and Digestive and Kidney Diseases’ Type 1 Diabetes TrialNet.
Yes, under certain conditions.
For the PLEDGE study, we are essentially performing universal screening now and find that it is feasible in clinical practice using our current tools across Sanford Health, which is the largest rural health system in the United States. With screening, our objective was to roll this out across our whole footprint, and in the past 2 years, we went from operating in one clinic to 141 clinics. This is only possible with automation and innovation and leveraging the infrastructure that we already have.
Currently, we screen every child in our footprint at ages 2 and 5 years by measuring antibodies using a platform from William Hagopian, MD, PhD, who has the CASCADE program. Measuring antibodies is not particularly innovative, but the way that we are implementing it is. Other clinical trials have used research coordinators to discuss screening and trial participation with parents, which is labor-intensive.
In contrast, we use our electronic medical record system to identify eligible children who have an upcoming appointment, and the system automatically sends an invitation to the patient’s portal asking them to participate in PLEDGE. Children can then come into the clinic, stop off at a lab and then — boom! — we have our sample. The assays are Clinical Laboratory Improvement Amendments (CLIA) grade, and the results are reported to patients and providers via the EMR system. If antibodies are found, we have a monitoring protocol set up or the patient can opt to enter the TrialNet monitoring protocol.
So, is population screening for type 1 diabetes ready for prime time? Yes, but an integrated health system, such as Sanford Health, is necessary. With PLEDGE, we are trying to model what universal screening will look like when it is part of standard care. We found that it was a heavy lift, but it can be done.
That said, there are a lot of pieces that still need to be developed and refined, and we have to build more evidence. We are collecting data on cost-effectiveness, which is important to payers, and we are discussing what level of evidence the International Society for Pediatric and Adolescent Diabetes (ISPAD) needs to implement universal screening into their guidelines. Once it is in the ISPAD guidelines and adopted by the American Academy of Pediatrics’ Bright Futures guidelines, payers will pay attention, tests will get cheaper and it will really be ready for primetime.
As a society, we have to start thinking about this because prevention is better than the cure. Now with teplizumab, we have the ability to identify children in whom we can delay the disease as well as those who are at risk and can enroll in clinical trials that will help us find the next therapy or, hopefully, a way to prevent type 1 diabetes altogether. If we can put ourselves out of work, that would be a good thing.
- For more information:
- Kurt Griffin, MD, is a pediatric endocrinologist and the principal investigator of the PLEDGE study. David Pearce, MD, is president of research, innovation and World Clinic at Sanford Health.
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