Clinical Drug Testing for Pain Medicine
The demand for clinical drug testing in the field of pain management has increased dramatically as clinicians, regulatory agencies and insurance payers seek objective measures to enhance and augment pharmacotherapy, monitor pharmacotherapeutic compliance, assess treatment efficacy, and identify individuals at risk following the use or misuse of illicit substances, prescription drugs, over the counter medications and herbals. Clinical Pharmacology/Toxicology is an evolving and complex discipline whereas many of the current methodologies were designed for non-clinical applications. As the demand for relevant, accurate, quantifiable, cost-effective technologies grows, the need to design, develop, validate, and perform assays that satisfy the requirements of clinicians must keep pace. In addition, the timely dissemination of scientifically sound information regarding laboratory science pertinent to the pain management field is essential.
Diagnostics are fundamental to western medicine and are an essential part of clinical decision making. The technologies that create and satisfy clinician and consumer demand must also be used intelligently to ensure a scientifically sound, clinically efficacious, and financially responsible healthcare system. Clinicians must have a sufficient understanding of, and have access to, the laboratory and its processes. Education at every level (College of American Pathologists, CAP; Clinical Laboratory Information Amendments, CLIA; Food and Drug Administration, FDA; Center for Medicare and Medicaid Services, CMS; Pain Associations; primary; and clinical medical education, etc.) is critical if we are to set realistic expectations and ensure proper utilization and interpretation of results and regulations.
The prevention, diagnosis, measurement, and the interventional and pharmacotherapeutic treatment of pain are difficult tasks. More specifically, the use of many pain medications can result in dependence, addiction, pseudoaddiction, tolerance, withdrawal, and over- or under-medication. Pain can be the result of a disease process, a disease itself, or the cause of other illness (e.g., depression, anxiety, etc.). Two essential elements common to these phenomena are the needs to identify and measure their critical aspects. These are the core functions of the medical laboratory. The methodical integration of laboratory medicine can lead to a diagnostic-based model for pain management, mental health and behavioral medicine (addiction medicine) and assist in improving patient care by objectifying outcomes.
The laboratory should strive to:
- discover, develop, implement, standardize, and augment objective diagnostic procedures for the daily treatment of pain and its downstream effects (i.e., state-of-the-art analytical pharmacology/toxicology [drug testing], therapeutic drug management, quantitative analyses for chemistry, hematology, molecular diagnostics, virology, immunology, microbiology, [where appropriate], pharmacokinetic consulting, integrated training and technical support [access to pharmacologists, toxicologists, pharmacists, physicians, etc.],
- develop and implement data systems that efficiently allow ordering, organizing, analyzing, reporting, billing, and archiving of every aspect of laboratory information, as well as assisting in data mining, bioinformatics applications, cost management, budgeting and patient trending,
- assist in establishing scientific-based curricula for all educational programs pertinent to pain and addiction medicine, regulatory agencies, healthcare payers, and consumers,
- build infrastructure for basic to clinical research and implement programs to obtain extramural funding, and
- help establish the proper diagnostic criteria for objective outcome measurement (evidence-based medicine) and best-practice guidelines.
The type of drug testing used for the pain patient must satisfy many clinical and forensic requirements. Most importantly, the methodologies and their interpretations must always have the capacity to satisfy the clinical needs of the physician. There are many different analyses used for the isolation, identification, and quantification of drug substances. These procedures all have strengths and limitations and are certainly not equivalent. Historically, testing has been divided into two distinct categories: forensic (including workplace applications) and clinical testing. The first testing was performed using the more traditional techniques of chromatography and spectrometry. As the need for workplace testing increased and was driven by federal rules and regulations, rapid and inexpensive technologies became essential and so immunoassays became popular.
Immunoassays are divided into clinical products (therapeutic drug monitoring/ TDM serum assays) and forensic (drugs of abuse/DAU urine assays). These distinct applications can differ in their design, technical capabilities and regulatory approval processes. Listed below are some fundamental general differences:
Therapeutic Drug Monitoring (TDM) Assays
- TDM assays are designed to quantify a single analyte and/or parent drug and major metabolite in serum.
- The therapeutic range is based upon many preclinical and clinical studies where the therapeutic level of compound necessary to produce the desired biological effect has been determined.
- Dosing can be controlled by repeated peak and trough measurements and iterative adjustments to the frequency and amount of drug administered.
- Performed in a fixed compartment model.
Drug of Abuse (DAU) Assays
- DAU assays are designed to identify a single analyte and/or parent drug and metabolites, or congeners within a particular drug class in urine.
- If quantifiable, they can be used to determine patient-specific drug elimination rates or trends following single/ intermittent usage, or steady state rates for compounds administered in a maintenance or chronic administration regimen if normalized for creatinine concentration.
- They are not designed to measure specific, clinically relevant levels of drugs in urine.
- They are performed in an open compartment model.
These differences can cause confusion, as these products can either adhere to very rigorous performance specifications or perform at minimal levels. The same can be said in general for chromatographic (e.g., thin layer chromatography, high pressure liquid chromatography, and gas chromatography) and coupled mass spectrometric techniques (e.g., gas/liquid chromatography/mass spectrometry).
Minimally, for clinical purposes, the Analytical Reportable Range (ARR) and the Clinical Reportable Range (CRR) should overlap in the linear portion of the assays response curves and the assays should adhere to standards regarding accuracy, reproducibility, sensitivity, and selectivity.
In addition to multiple technical considerations during these analytical procedures, there are numerous factors that influence the absorption, distribution, metabolism and elimination of a drug including: