How to Confirm Monitoring Labs and Follow-Up for Medications

When a patient is on a medication with a narrow therapeutic index-like lithium, digoxin, vancomycin, or tacrolimus-getting the dose right isn’t just important. It’s life-or-death. Too little, and the drug doesn’t work. Too much, and it can cause organ damage, seizures, or even death. That’s why medication monitoring isn’t optional. It’s a critical safety step. But here’s the catch: the lab results you’re relying on to make those decisions? They have to be accurate. And that means confirming the lab’s testing process before you trust the number on the report.

What’s the Difference Between Verification and Validation?

Not all lab tests are created equal. If a test kit is FDA-cleared or approved (like most common drug level tests), the lab does a verification. That means they check if the test performs the way the manufacturer says it will. They run samples, measure precision, check for interference, and confirm the range matches what’s listed on the package insert. This usually takes 80 hours or less and costs between $2,500 and $5,000.

If there’s no FDA-cleared test available-like for certain metabolites of clozapine or newer biologics-the lab has to build the test from scratch. That’s called a validation. It’s much more complex. They have to prove accuracy, sensitivity, linearity, and stability across dozens of variables. Validation can take 120+ hours and cost up to $15,000. It’s also more likely to fail the first time. About 18.7% of validation attempts need to be redone.

Bottom line: Verification is for standard tests. Validation is for custom or rare ones. Either way, the lab must document everything. If they haven’t, you shouldn’t trust the result.

The 9-Step Process Labs Must Follow

Every lab that does therapeutic drug monitoring (TDM) should follow a clear, documented process. The Association of Public Health Laboratories (APHL) toolkit is the gold standard, and 98% of U.S. labs use it. Here’s what it looks like in practice:

1. Develop the plan - What test? What equipment? What acceptance criteria? This step takes 8-16 hours and must be approved by the lab director.
2. Get approval - The lab director signs off before any testing begins. This isn’t a formality-it’s a legal requirement under CLIA.
3. Run the tests - For verification, that’s 20+ replicates over 5 days. For validation, it’s even more: interference testing with 6+ substances, linearity checks across the full therapeutic range, and limit-of-quantitation verification.
4. Analyze the data - Is precision under 1/4 of the total allowable error? Is bias under 1/2? Is linearity R² ≥ 0.99? These aren’t suggestions-they’re requirements.
5. Re-evaluate if needed - About 30% of tests need adjustments. Maybe the instrument isn’t calibrated right, or there’s hidden interference.
6. Write the summary report - This document proves compliance. It includes all raw data, statistical analysis, and conclusions.
7. Create SOPs and training materials - Staff need to know how to run the test, troubleshoot it, and interpret results. This takes 20-40 hours.
8. Final approval - The lab director reviews everything again before the test goes live.
9. Implement the test - Only then can the lab report results to clinicians.

Why Interference Testing Is the Most Common Failure Point

One of the biggest reasons labs get it wrong? Interference. That’s when something in the patient’s blood-like another drug, metabolite, or even a supplement-tricks the test into giving a false result.

For example, carbamazepine’s main metabolite can cross-react with some immunoassays, making levels look 20-30% higher than they really are. Digoxin tests are notorious for false highs due to antibody interference. In one 2021 FDA report, 23 patients got wrong doses because the lab didn’t test for this.

Dr. James Nichols from Vanderbilt says, “The most common error in medication monitoring is inadequate interference testing.” And he’s right. A 2023 CAP survey found only 64% of labs verify the lower limit of quantitation for narrow therapeutic index drugs. That means they might miss patients who are under-dosed-because the test can’t detect levels below a certain point.

The fix? Labs must test for at least 6-12 common interfering substances at clinically relevant concentrations. For immunosuppressants like tacrolimus, the FDA now requires testing against 15 metabolites-not just 8.

What You Need to Ask Your Lab

As a provider, you don’t run the tests-but you rely on them. So ask these questions before prescribing or adjusting doses:

• Is this test FDA-cleared or a lab-developed test (LDT)?
• Have you verified or validated this test per CLIA and APHL guidelines?
• What’s the total allowable error for this drug? (For digoxin, it should be ≤10%; for vancomycin, ≤15%)
• Have you tested for interference from common drugs or metabolites?
• What’s the lower limit of quantitation? Can it detect levels at the bottom of the therapeutic range?
• Do you use the same instrument platform consistently? Switching platforms without re-verification can cause spikes in results.

If they can’t answer clearly-or if they say, “We’ve always done it this way”-that’s a red flag.

What Happens When Labs Skip the Steps?

Non-compliance isn’t just risky-it’s expensive. CMS fined labs an average of $7,500 per violation between 2021 and 2023. But the real cost is to patients.

In 2022, a community hospital skipped interference testing for vancomycin. Their assay couldn’t detect levels above 75 mcg/mL, but the therapeutic range goes up to 80. Five patients got overdosed. Two developed acute kidney injury. One needed dialysis.

And it’s not just big hospitals. A 2023 AHA survey found only 37.8% of community hospitals have full verification protocols. Meanwhile, 98.7% of academic medical centers do. That’s a huge gap in care quality.

How EHRs Are Changing the Game

Technology is helping. Epic Systems, Cerner, and other EHR platforms now include built-in therapeutic drug monitoring modules. By 2025, 45% of U.S. hospitals will have them.

These systems automatically flag results that are out of range. They can compare current levels to past trends. They can even alert the prescriber if a patient’s level is trending upward despite unchanged dosing-hinting at possible drug interactions or declining kidney function.

But here’s the catch: EHR alerts only work if the underlying lab data is accurate. If the lab’s test isn’t verified, the alert might tell you to increase a dose when you should be decreasing it.

What’s Next for Medication Monitoring?

The FDA is cracking down on lab-developed tests. The VALID Act, expected to pass in 2025, will require all LDTs to meet the same standards as commercial tests. That means more labs will switch to FDA-cleared assays, even for rare drugs.

Meanwhile, personalized medicine is growing. More drugs now require individualized dosing based on genetics, kidney function, or drug interactions. That means more monitoring. More tests. More need for rigor.

But staffing is a problem. A 2023 ASCP survey found 68% of lab directors can’t hire enough qualified staff to keep up with verification demands. That’s why shortcuts happen.

Final Takeaway: Trust But Verify

You wouldn’t prescribe a drug without checking the patient’s history. Don’t trust a lab result without checking the lab’s process. Medication monitoring isn’t just about drawing blood and sending it out. It’s about ensuring every step-from sample collection to result reporting-is reliable.

If you’re unsure whether your lab is compliant, ask for their verification or validation documentation. If they don’t have it, find a lab that does. One wrong number can change a patient’s life-and it’s not worth the risk.