Understanding LDTs with Real-World Examples

Laboratory Developed Tests (LDTs) have become an essential part of healthcare diagnostics. These specialized tests, developed and processed within CLIA-certified laboratories, offer customized solutions that help close diagnostic gaps left by commercial options. They are particularly important in areas where traditional diagnostics fall short, such as personalized healthcare.

LDTs are in vitro diagnostic (IVD) products which analyze biological samples such as blood, saliva, or tissue. The FDA recognizes IVDs, including those developed in single laboratories, as medical devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act). Increasingly, health care professionals are turning to these tests to guide clinical decisions, especially for rare diseases and public health emergencies.

Below are several examples where laboratory-developed diagnostics play a critical role in advancing healthcare:

1. Genetic Screening and Testing

LDTs shine in cases where no FDA-approved test exists. Most clinical genetics tests are LDTs. Here are some common examples:

• Diagnostic testing for rare diseases. Approximately 1 in 10 Americans are living with a rare disease, and 80% are genetic. Genetic testing may be targeted based on symptoms. For example, diagnostic testing for cystic fibrosis when a child presents with specific symptoms. However, some rare diseases present with seemlying urelated symptoms. In this case, clinicans may use Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS) to scan the genome for a genetic diagnosis.    
• Hereditary cancer testing. Up to 10% of cancers are hereditary, caused by a mutation in a hereditary cancer gene which is passing down in a family. One example is genetic testing for BRCA1 or BRCA2, which can detect mutations that significantly increase the risk of breast and ovarian cancers, helping guide preventive or treatment decisions.
• Targeting cancer treatments. For a person with cancer, genetic testing on tumour tissue or circulating tumour cells can reveal mutations that may help with diagnosis, prognosis, and to predict if a targeted therapy or immunotherapy is expected work (or not). This allows doctors to choose therapies that are more personalized to the patient’s specific cancer diagnosis, increasing the chance of success. 

2. Newborn screening

All newborn babies in the US are screened for serious, but treatable, health conditions at birth. Early intervention can prevent severe health and developmental issues. Newborn screening programs are usually offered as LDTs through state public health laboratories. Each State has their own list of conditions. Here are some examples:

• Metabolic diseases. Babies born with a metabolic condition, like Phenylketonuria (PKU), are unable to breakdown parts of food like fats, proteins or sugar. Specific diets or supplementation can promote a healthy life.  
• Endocrine diseases. In these conditions, like congenital hypothyroidism (CH), the body produces too much or too little of certain hormones. Early interventions, often with daily hormone supplement, can lead to normal growth and development.  
• Genetic diseases. These conditions may be inherited or occur sporadically in a child. An example is severe combined immune deficiency (SCID), when a baby is missing important immune cells, where early intervention and medical support can be life-saving.

3. Pharmacogenomic Tests

Pharmacogenomic testing looks at how a person’s genetic makeup impacts the way they process and respond to medications. These LDTs can support health care professionals when making precribing decisions, helping them find the right drug at the right dose for their patient. , Here are some examples:

• CYP450 Genotyping: Identifies genetic variants that affect how the body metabolizes drugs like antidepressants or pain medications, to allow for safer and more effective dosing.
• Warfarin Sensitivity Testing: This test helps customize warfarin dosing based on genetic markers that influence how the body processes this blood thinner, reducing the risk of complications and promoting efficacy.
• Cancer Drug Dosing : Detects mutations in genes like TPMT or DYPD that affect how patients may process chemotherapy drugs, reducing the risk for toxicity and optimizing treatment.

4. Viral & Infectious Disease Tests

LDTs are pivotal during public health crises like pandemics, where rapid and adaptable diagnostics are crucial. Unlike standard tests, LDTs can be quickly developed and deployed to detect infectious agents.

• COVID-19 Tests: Labs developed PCR and antigen tests rapidly during the pandemic to meet urgent testing needs, providing early and accurate virus detection.
• Respiratory Virus Panels: Detect multiple viruses such as flu, RSV, and coronaviruses from one test, helping doctors quickly diagnose and treat infections.
• HIV Viral Load Testing: Measures the amount of HIV in the blood, important for monitoring disease progression and treatment effectiveness, especially when advanced testing isn’t commercially available.

5. Blood Lead Level Tests: Public Health Monitoring

These tests measure lead in the blood, which is crucial for protecting children and workers exposed to lead. Lead exposure can cause severe health problems, including developmental delays and neurological issues.

• Pediatric Lead Testing: Used in children’s hospitals to quickly screen for lead poisoning in young children, particularly those at high risk.
• Capillary Blood Lead Screening: Simple fingerstick tests provide immediate results, often used in community settings like schools and clinics to identify those needing further testing.
• Occupational Lead Exposure Testing: Screens workers in high-risk jobs like construction and battery manufacturing to ensure safety and timely intervention.

6. Transplant Compatibility Tests (HLA Testing)

HLA tests determine organ donor and recipient compatibility, which is crucial for transplant success. These LDTs help reduce the risk of organ rejection and improve patient outcomes.

• HLA Typing: Helps match donors and recipients for organ transplants, reducing the risk of rejection.
• Virtual Crossmatching: Predicts the likelihood of rejection by comparing a recipient’s antibodies to a donor’s HLA profile before surgery.
• HLA Antibody Monitoring: Tracks the development of antibodies that could lead to organ rejection, allowing for timely adjustments in treatment.

Conclusion

LDTs represent a vital tool in modern diagnostics, offering flexibility and precision where standard tests might fall short. They’re particularly impactful in areas such as rare disease diagnosis, personalized medicine, public health crises, and transplant compatibility. As healthcare becomes more personalized, LDTs will continue to lead innovation, improving patient outcomes in ways that traditional tests cannot.