Medical Laboratory Observer connects laboratory professionals with industry trends every year. There have been important diagnostic updates for laboratories from the U.S. Food and Drug Administration and the National Institutes of Health in 2023 — MLO staff put together this article to summarize those updates for its readers.
With this new research, medical experts are closer to identifying better cancer treatments, determining blood donor eligibility, having a deeper understanding of long COVID, and diagnosing severe COVID-19 in pediatric patients.
FDA launches pilot program to help reduce risks associated with using laboratory developed tests to identify cancer biomarkers
The U.S. Food and Drug Administration announced a new voluntary pilot program for certain oncology drug products used with certain corresponding in vitro diagnostic tests to help clinicians select appropriate cancer treatments for patients.
Through the pilot program, the FDA will request, from drug manufacturers, performance information for the tests used to enroll patients into the clinical trials that support drug approval. Based on an assessment of that information, the FDA will post to the FDA website the minimum performance characteristics recommended for similar tests that may be used to select patients for treatment with the approved drug. Laboratories may use this information to guide their development of LDTs to identify specific biomarkers used for selecting cancer treatment. This transparency aims to help facilitate better and more consistent performance of these tests, resulting in better drug selection and improved care for patients with cancer.
As discussed in the guidance, the initial phase of the pilot program is anticipated to last up to one year, during which the FDA will evaluate no more than nine drug sponsors for possible acceptance into the pilot. The minimum recommended performance characteristics for in vitro diagnostic tests used with each approved drug product under the pilot, based on the clinical trial assays, will be made publicly available on the FDA’s website following drug approval.1
FDA finalizes move to recommend individual risk assessment to determine eligibility for blood donations
The U.S. Food and Drug Administration finalized recommendations for assessing blood donor eligibility using a set of individual risk-based questions to reduce the risk of transfusion-transmitted HIV. These questions will be the same for every donor, regardless of sexual orientation, sex, or gender. Blood establishments may now implement these recommendations by revising their donor history questionnaires and procedures.
These final recommendations are consistent with the policy initially proposed in January 2023.
This policy eliminates time-based deferrals and screening questions specific to men who have sex with men (MSM) and women who have sex with MSM. Under the final guidance issued, all prospective blood donors will answer a series of individual, risk-based questions to determine eligibility. All prospective donors who report having a new sexual partner, or more than one sexual partner in the past three months, and anal sex in the past three months, would be deferred to reduce the likelihood of donations by individuals with new or recent HIV infection who may be in the window period for detection of HIV by nucleic acid testing.
Additionally, under these final recommendations, those taking medications to treat or prevent HIV infection (e.g., antiretroviral therapy (ART), pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP)), will also be deferred. Though these antiretroviral drugs are safe, effective, and an important public health tool, the available data demonstrate that their use may delay detection of HIV by currently licensed screening tests for blood donations, which may potentially give false negative results. Although HIV is not transmitted sexually by individuals with undetectable viral levels, this does not apply to transfusion transmission of HIV because a blood transfusion is administered intravenously, and a transfusion involves a large volume of blood compared to exposure with sexual contact. As stated in the guidance, individuals should not stop taking their prescribed medications, including PrEP, or PEP, in order to donate blood.2
Large study provides scientists with deeper insight into long COVID symptoms
Initial findings from a study of nearly 10,000 Americans, many of whom had COVID-19, have uncovered new details about long COVID, the post-infection set of conditions that can affect nearly every tissue and organ in the body. Clinical symptoms can vary and include fatigue, brain fog, and dizziness, and last for months or years after a person has COVID-19. The research team, funded by the National Institutes of Health, also found that long COVID was more common and severe in study participants infected before the 2021 Omicron variant.
The study, published in JAMA, is coordinated through the NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, a nationwide effort dedicated to understanding why some people develop long-term symptoms following COVID-19, and most importantly, how to detect, treat, and prevent long COVID. The researchers hope this study is the next step toward potential treatments for long COVID, which affects the health and wellbeing of millions of Americans.
Researchers examined data from 9,764 adults, including 8,646 who had COVID-19 and 1,118 who did not have COVID-19. They assessed more than 30 symptoms across multiple body areas and organs and applied statistical analyses that identified 12 symptoms that most set apart those with and without long COVID: post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements.
They then established a scoring system based on patient-reported symptoms. By assigning points to each of the 12 symptoms, the team gave each patient a score based on symptom combinations. With these scores in hand, researchers identified a meaningful threshold for identifying participants with long COVID. They also found that certain symptoms occurred together and defined four subgroups or “clusters” with a range of impacts on health.
Based on a subset of 2,231 patients in this analysis who had a first COVID-19 infection on or after Dec. 1, 2021, when the Omicron variant was circulating, about 10% experienced long-term symptoms or long COVID after six months. The results are based on a survey of a highly diverse set of patients and are not final. Survey results will next be compared for accuracy against an array of lab tests and imaging.
The researchers explain studying the underlying biological mechanisms of long COVID is central to advancing informed interventions and identifying effective treatment strategies.
In addition to establishing the scoring system, the researchers found that participants who were unvaccinated or who had COVID-19 before the Omicron strain emerged in 2021 were more likely to have long COVID and more severe cases of long COVID. Further, reinfections were also linked to higher long COVID frequency and severity, compared to people who only had COVID-19 once.3
NIH funds eight studies to advance rapid diagnosis of COVID-19–related inflammatory syndrome in children
The National Institutes of Health has awarded eight research grants to refine new technologies for early diagnosis of severe illnesses resulting from SARS-CoV-2 infection in children. The new awards follow grants issued in 2020 to foster methods for diagnosing children at high risk for Multisystem Inflammatory Syndrome in Children (MIS-C), a rare, severe and sometimes fatal after-effect of SARS-CoV-2 infection or exposure in children.
The awards are from NIH’s Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence (PreVAIL kIds) initiative. They are part of the Rapid Acceleration of Diagnostics Radical (RADx-rad) program to support new, non-traditional approaches and reimagined uses of existing tools to address gaps in COVID-19 testing and surveillance.
Although some children develop mild or no symptoms from COVID-19, others will develop more severe effects, including MIS-C, which results in inflammation of one or more organs, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal tract.
The 2020 awards supported studies involving more than 7,400 research participants in four countries and yielded prototype methods and techniques for potential use in clinics, emergency departments and for hospital inpatients. These PreVAIL kIds studies were supported through NIH’s RADx-rad initiative and were part of an NIH collaborative research effort called CARING for Children with COVID. Results from these studies include a laboratory technique for detecting specific immune cells associated with MIS-C; databases that help diagnose children at risk for MIS-C and severe COVID-19, based on certain blood proteins and genetic biomarkers; and a database that can distinguish between MIS-C, Kawasaki disease (which has similar symptoms) and fever-causing viral and bacterial infections.
The new awards will allow researchers to continue their efforts to develop ways to rapidly diagnose MIS-C and identify those at risk for serious and long-term effects of SARS-CoV-2. Earlier identification of those most at risk will allow for earlier interventions to prevent severe health effects.
Awardees
- Jane C. Burns, University of California, San Diego Diagnosing and predicting risk in children with SARS-CoV-2-related illness
- Cedric Manlhiot, Johns Hopkins University, Baltimore Data science approach to MIS-C identification and management associated with SARS
- Ananth V. Annapragada, Baylor College of Medicine, Houston AICORE-kids: Artificial intelligence COVID-19 risk assessment for kids
- Audrey R. Odom John, Children’s Hospital of Philadelphia Diagnosis of MIS-C in febrile children
- Usha Sethuraman, Central Michigan University, Mount Pleasant Severity predictors integrating salivary transcriptomics and proteomics with multineural network intelligence in SARS-CoV2 infection in children
- Juan C. Salazar, Connecticut Children’s Medical Center, Hartford Identifying biomarker signatures of prognostic value for MIS-C
- Charles Yen Chiu, University of California, San Francisco Discovery and clinical validation of host biomarkers of disease severity and MIS-C with COVID-19
- Lawrence Kleinman, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey COVID-19 network of networks expanding clinical and translational approaches to predict severe illness in children4
References
1. FDA launches pilot program to help reduce risks associated with using laboratory developed tests to identify cancer biomarkers. U.S. Food and Drug Administration. Published June 20, 2023. Accessed June 23, 2023. https://www.fda.gov/news-events/press-announcements/fda-launches-pilot-program-help-reduce-risks-associated-using-laboratory-developed-tests-identify.
2. FDA finalizes move to recommend individual risk assessment to determine eligibility for blood donations. U.S. Food and Drug Administration. Published May 11, 2023. Accessed June 23, 2023. https://www.fda.gov/news-events/press-announcements/fda-finalizes-move-recommend-individual-risk-assessment-determine-eligibility-blood-donations.
3. Large study provides scientists with deeper insight into long COVID symptoms. National Institutes of Health (NIH). Published May 25, 2023. Accessed June 23, 2023. https://www.nih.gov/news-events/news-releases/large-study-provides-scientists-deeper-insight-into-long-covid-symptoms.
4. NIH funds eight studies to advance rapid diagnosis of COVID-19-related inflammatory syndrome in children. National Institutes of Health (NIH). Published January 9, 2023. Accessed June 23, 2023. https://www.nih.gov/news-events/news-releases/nih-funds-eight-studies-advance-rapid-diagnosis-covid-19-related-inflammatory-syndrome-children.
