Clinical and Forensic Testing

Clinical testing is a vital contributor of important clinical information impacting human healthcare decisions. Clinical testing labs will either use in vitro diagnostic assays (IVDs) or lab developed tests (LDTs) as the key diagnostic assay types. These assays will examine a wide range of analytes from a diverse set of human samples to deliver important diagnostic information. Clinical labs also conduct screening and monitoring for therapeutic drugs and identifying drugs of abuse. Forensic testing typically serves the needs of the judicial system as part of investigations and legal procedures.

Some key testing modalities will include immunoassays, such as ELISAs and immunohistochemistry (IHC), Molecular diagnostic techniques like PCR, qPCR and sequencing, and analytical chemistry techniques including liquid chromatography followed by mass spectrometry (LC-MS).

• The role of lab developed tests (LDTs) in clinical diagnostic laboratory testing
• Lab Developed Tests (LDT) - common testing modalities and sample types
• Therapeutic drug monitoring
• Drugs of abuse testing – sample/ test types and testing modalities
• Toxicology - applications in clinical testing and forensics

• Key uses, steps, and components for the LC-MS based testing
• Key uses, steps, and components for the PCR-based testing
• Key uses, steps, and components for the ELISA-based testing
• View LC-MS Workflow

LDTs are a critical, but typically smaller, part in the test menu of a clinical lab and complement the larger volume of offered in vitro diagnostic (IVD) tests.

LDTs typically address a gap in the clinical testing market not covered by available IVD tests, or they offer additional value when compared to the IVD equivalent. In some instances, they cover the esoteric testing needs of rarer conditions where there isn’t a commercial case for developing IVDs. In other cases, LDTs allow a rapid response to emerging infectious diseases, as was seen with the SARS-CoV-2 (COVID-19) pandemic.

One of the notable distinctions between LDT and IVD is the responsibility that the individual labs take in the development and management of these LDT assays which gives them the flexibility and agility to address unmet needs.

LDTs can utilize a wide range of testing modalities but common ones include: Liquid Chromatography Mass Spectrometry (LC-MS), Molecular Diagnostic (MDx) techniques such as quantitative PCR (qPCR) and NextGen sequencing (NGS), and immunoassay (IA) approaches such as enzyme linked immunosorbent assays (ELISA).

Common human sample types used for testing include blood and urine, for more routine analysis, and hair and saliva for specific testing objectives, such as drug screening.

Therapeutic drug monitoring plays an important part in a subset of critical treatment programs to ensure patient compliance and/or safety. An example of usage would be to ensure that the levels of the drug used in treatment are safe and effective. Examples of drugs that can be monitored include:

• Antibiotics
• Heart drugs
• Anti-seizure drugs
• Autoimmune disease drugs
• Bipolar disorder drugs

Drug monitoring is included in clinical approaches to pain management of patients to ensure treatment program compliance and to limit the potential for drug abuse with medications such as opioids

Drugs of abuse testing identifies the presence of illegal drugs or misused prescription medications for patient safety, legal reasons and/or a part of the conditions of employment. Typical drugs tested for can include:

• Amphetamines: Methamphetamine, amphetamine
• Barbiturates: Phenobarbital, secobarbital, pentobarbital, butalbital, amobarbital
• Benzodiazepines : Diazepam, lorazepam, oxazepam, temazepam, alprazolam
• Cannabinoids: Marijuana
• Cocaine: Cocaine and/or its metabolite (benzoylecognine)
• Methadone: Methadone, methadone metabolite (EDDP)
• Opiates: Codeine, morphine, metabolite of heroin, oxycodone, oxymorphone, hydrocodone, hydromorphone
• Phencyclidine: PCP

A typical approach could include a screening urine test and a confirmatory blood test.

Toxicology includes therapeutic drug monitoring and drugs of abuse testing in clinical labs and aspects of crime scene and investigative efforts of the forensics labs. Sample types from forensics are more diverse in origin but many of the downstream analytical techniques are similar based on the analytes being investigated.