| Web: | mayocliniclabs.com |
|---|---|
| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
| Web: | mayocliniclabs.com |
|---|---|
| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
Thermo Fisher Scientific: Illuminating rare cancer prognosis and improving patients’ lives
Case Study
Aiming to advance understanding of hard-to-predict gastroenteropancreatic neuroendocrine tumors (GEP-NETs), Thermo Fisher Scientific joined forces with Mayo Clinic and BioPharma Diagnostics to validate and gain U.S. regulatory clearance of a novel, automated assay aimed at detecting a biomarker associated with the progressive disease.
Classified as a rare disease, GEP-NETs are increasingly detected due to improved diagnostic imaging. Originating most often in the small intestine, GEP-NETs typically grow slowly and can occur anywhere along the gastrointestinal tract.
“Patients often deal with this disease for many, many years, and even decades and the diagnosis is often delayed as symptoms can be very nonspecific,” says Thor Halfdanarson, M.D., professor of medical oncology at Mayo Clinic.
Among the most important indicators of GEP-NET prognosis and disease activity is the protein biomarker chromogranin A (CgA), which is expressed in 80% to 90% of GEP-NET patients. Attaining accurate measurements of CgA concentrations, however, often relies on time-intensive manual approaches, such as enzyme-linked immunosorbent assay (ELISA).
Developing an automated assay that delivers accurate answers to patients and their healthcare teams was an easy choice for Thermo Fisher Scientific.
“Within Thermo Fisher, we look at biomarkers to develop assays which can either improve patient outcomes or the diagnostic process for the clinician, for the lab, and everyone who’s involved in making a decision for the patient,” says Christian Theimer, director and general manager for analyzers and assays at Thermo Fisher Scientific.
Creating and validating a better, faster way to measure CgA concentrations, however, was complicated. “The existing methodologies and availability of CgA measurement have resulted in a highly centralized testing system and have limited the accessibility of medical information required for the development of a new test,” Theimer adds.
“Our objective was to identify a laboratory that possesses a substantial collection of medically recorded patient samples and extensive expertise from both laboratory and clinician perspectives. This collaboration would enable us to effectively implement the necessary measures for introducing our solution to the market, ultimately contributing to our goal of enhancing patient management and lab efficiencies.”
To gain the critical insight and patient samples needed to validate a novel automated assay for CgA quantification, Thermo Fisher tapped into the experience of Mayo Clinic Laboratories BioPharma Diagnostics service line.
“When we develop an assay, we always look to the experience and needs from our customers,” Theimer says. “What are the requirements, how do we need to design it? This is an interaction we have with many customers. Mayo Clinic has developed a lot of testing in the past and by talking to Mayo we gained a lot of advantages and input on how to design this assay.”
In addition to clinical expertise, Mayo Clinic provided hundreds of patient samples to validate the automated immunofluorescent assay, named the B·R·A·H·M·S CgA II KRYPTOR. After validation, the test was launched broadly in Europe in 2011 and exclusively in the U.S. at Mayo Clinic.
The test launch was just the beginning of the collaboration. To widen the impact of the assay in the U.S., Thermo Fisher worked with BioPharma Diagnostics, and three other healthcare institutions, to conduct a surveillance biomarker study and gain clearance of the assay by the U.S. Food and Drug Administration (FDA).
The clinical study, led by Dr. Halfdanarson at Mayo Clinic, established an optimal cutoff for the measurement of CgA concentration in serum.
As part of the study, research staff from BioPharma Diagnostics, with the help of Dr. Halfdanarson, screened GEP-NET patients for enrollment in the study. From March of 2019 through December 2021, eligible patients were asked to participate in the research.
Enrolled patients agreed to submit an additional blood sample for research testing when providing blood for routine, standard-of-care visits. Study samples were routed to Mayo Clinic Laboratories’ Clinical Immunoassay Laboratory and processed through the B·R·A·H·M·S KRYPTOR random access analyzer.
After the test results were recorded in the patient’s electronic medical record, those results were abstracted by BioPharma research staff. In addition to test results, samples of serum collected during each of the patients’ blood draws were sent to Thermo Fisher. In all, a total of 72 Mayo Clinic patients enrolled, providing 226 samples for the trial.
“This was a major advantage for us,” Theimer says. “During test development and the clinical study, you need to have access to a variety of samples in different concentrations and most importantly the medical record for each sample — it’s not just two or three, it is a lot.”
Equipped with data from hundreds of samples, Thermo Fisher demonstrated the utility of its automated immunoassay for measuring CgA concentration in serum. For patients faced with challenging journeys, results can inform disease monitoring and treatment response.
“Bringing up the fully automated random-access analyzer and providing global access to different markets is a win-win situation,” Theimer says.
Whereas manual biomarker testing can take weeks and even months before results are available due to the infrequency of when the test could be run, the KRYPTOR analyzer delivers precise results in as little as 29 minutes.
“This is a time of uncertainty when the patient does now know if their tumor marker value is stable or not,” Theimer says. “We’re dramatically reducing the time of uncertainty for the patient and the physician.”
The study, which was well designed and executed, offers good negative predictive value on whether the biomarker level indicates a change in disease status, says Dr. Halfdanarson. Additionally, the study is likely the most rigorous research on any blood-based neuroendocrine tumor biomarker completed to date, Dr. Halfdanarson says.
“We’d been looking for a good marker to monitor disease activity, ideally hoping that could ultimately help us to decrease clinic visits, decrease the use of imaging, and make it easier to follow patients,” Dr. Halfdanarson says. “There is definitely a population of patients where this could be helpful, especially patients we follow over time and can show the test is reliably predictive for that particular patient.”
The test is now commercially available in the U.S. and more than 100 other countries around the world.
For the collaborators, the engagement reinforced the notion that when healthcare organizations join forces in the interest of patients, substantive change is possible.
“At Thermo Fisher, everything is tailored for the benefit of the patient first and then we look at how we can improve decision-making for clinicians or productivity or how the entire process is working in the lab,” Theimer says. “We achieved our goals, and can really highlight the speed and quality of the result we obtained from Mayo — it was a use case for us on how we can develop assays with collaborators. It’s an outstanding example of how companies can work together to bring something beneficial to patients, physicians, and the lab following our company’s mission to make the world healthier, cleaner, and safer.”
“This is a good example of how we can and should partner with others in the industry — this was the first one for me where we actually collaborated on a diagnostic test and it is worth highlighting that relationships like this can really benefit patients and the field of oncology — these are things that we might not be able to do on our own.” – Thor Halfdanarson, M.D.
