How to Confirm Monitoring Labs and Follow-Up for Medications

Getting medication levels right isn’t just about running a blood test. It’s about making sure that test is accurate-because a single wrong result can lead to underdosing, overdose, or even death. For drugs like vancomycin, digoxin, or tacrolimus, the difference between therapeutic and toxic levels is razor-thin. If your lab’s monitoring test isn’t properly verified or validated, you’re not just risking errors-you’re risking lives.

What’s the Difference Between Verification and Validation?

You’ll hear these terms used interchangeably, but they’re not the same. Verification is for tests that already have FDA clearance. You’re not building the test from scratch-you’re confirming it works the way the manufacturer says it does in your lab. That means checking precision, linearity, and whether other substances in the blood interfere with the result.

Validation, on the other hand, is for lab-developed tests (LDTs). These are custom tests you create because no FDA-approved version exists-for example, tracking a rare metabolite of clozapine. Validation requires far more work: you have to prove the test detects the right thing, at the right level, every time, under your conditions. It’s not just checking specs-it’s building the evidence from the ground up.

Most labs use verification. About 98% of U.S. clinical labs follow the APHL toolkit for verification, and for good reason. It cuts time and cost. Verification takes about 80 hours and $2,500-$5,000. Validation? That’s 120+ hours and $7,500-$15,000. And even then, nearly 19% of LDTs fail the first time and need reworking.

The 9-Step Process for Confirming a Medication Monitoring Test

There’s no room for guesswork. Here’s the real-world workflow labs use to make sure a test is ready for patients:

1. Write the plan. Define what you’re testing, which performance criteria matter, and what acceptance limits you’ll use. This isn’t paperwork-it’s your roadmap. Skip this, and you’re flying blind.
2. Get lab director approval. This isn’t a formality. The director is legally responsible for test accuracy. They need to sign off before any testing begins.
3. Run the tests. For verification, you’ll run 20+ replicates over 5 days to check precision. You’ll test with reference materials to confirm trueness. You’ll spike samples with common drugs like ibuprofen or acetaminophen to check for interference.
4. Analyze the data. Don’t just look at averages. Look at the spread. Is your coefficient of variation under 1/4 of the total allowable error? For digoxin, that’s ≤2.5%. For vancomycin, ≤3.75%. If it’s not, you don’t move forward.
5. Re-evaluate if needed. One in three verification attempts hits a snag-maybe the linearity drops off at high concentrations, or interference shows up only at certain levels. You fix it or you scrap it.
6. Write the summary report. This document becomes your legal record. Include all data, deviations, and conclusions. If the FDA or CAP audits you, this is what they’ll check first.
7. Create SOPs and training materials. Your techs need to know how to run the test, how to troubleshoot, and when to flag a result. A poorly trained staff is the #1 reason even good tests fail in practice.
8. Final approval. The lab director signs off again. This time, it’s for implementation.
9. Go live. Start reporting results. But don’t stop monitoring. Run QC daily. Track patient outcomes. If a patient’s drug level doesn’t match their clinical response, go back and check your test.

What Performance Metrics Actually Matter?

Not all tests are created equal. The stakes are higher for narrow therapeutic index drugs. Here’s what you need to hit:

• Precision: ≤1/4 of total allowable error (TEa). For digoxin (TEa=10%), that means CV ≤2.5%. For vancomycin (TEa=15%), CV ≤3.75%.
• Linearity: R² ≥0.99 across the full therapeutic range. Vancomycin? Must work from 5 to 80 mcg/mL. Digoxin? 0.5 to 4.0 ng/mL. If your instrument can’t reliably measure at the low end, you’re missing underdosed patients.
• Limit of Quantitation (LOQ): Only 64% of labs verify this for narrow index drugs. That’s a problem. If your test can’t detect levels below 0.3 ng/mL for digoxin, you’re missing sub-therapeutic doses in 12-15% of patients.
• Interference: This is the #1 cause of errors. Carbamazepine tests can be thrown off by its own metabolites. Immunoassays for tacrolimus can cross-react with other immunosuppressants. You need to test with at least 6 common interfering substances at clinically relevant levels.
• Reportable range: Must cover the therapeutic range plus 20% on both ends. If your test reports up to 80 mcg/mL but your patient’s level is 90, you’re not seeing the danger.

Common Pitfalls and How to Avoid Them

Even experienced labs mess this up. Here’s what goes wrong-and how to stop it:

• Assuming manufacturer claims are accurate. A 2023 survey found 63% of labs got poor or incomplete performance data from manufacturers. Don’t trust the brochure. Test it yourself.
• Skipping interference testing. Dr. James Nichols at Vanderbilt says 5-8% of carbamazepine results are wrong because labs didn’t test for metabolites. That’s avoidable.
• Not verifying the low end. If your test can’t detect 0.4 ng/mL of digoxin, you’re letting patients slip through the cracks. Sub-therapeutic levels lead to rejection of transplants, seizures, or heart failure.
• Using the wrong instrument. Not all platforms are equal. Roche, Abbott, and Siemens all have different performance profiles. Make sure your instrument is validated for the specific drug and matrix (serum vs. plasma).
• Ignoring staff training. 89% of labs say they need dedicated QA staff for verification. If your techs don’t understand why precision matters, they’ll skip QC steps. Train them. Document it.

Regulatory Risks and Consequences of Skipping Steps

This isn’t optional. CLIA ’88 makes verification and validation mandatory. CMS fines labs $7,500 per violation. And it’s not just money-your lab can lose certification.

Between 2018 and 2022, 32% of therapeutic drug monitoring recalls came from inadequate cross-reactivity testing. The FDA’s 2024 draft guidance now requires testing for 15 metabolites for immunosuppressants-not 8. If you’re still using old protocols, you’re already out of compliance.

CAP’s checklist INS.40850 requires labs to verify therapeutic ranges. Labs using the APHL toolkit reduce non-conformities by 63%. That’s not just better practice-it’s better protection.

What’s Changing in 2025?

The landscape is shifting fast:

• VALID Act: The FDA is moving to regulate LDTs more tightly. Many labs are already cutting back on developing custom tests and switching to FDA-cleared ones.
• EHR integration: Epic Systems now has built-in therapeutic drug monitoring modules in 45% of U.S. hospitals. These systems auto-flag low or high levels and alert prescribers. If your lab doesn’t feed accurate data into the EHR, you’re creating a gap in patient safety.
• Staff shortages: 68% of lab directors say they can’t find enough qualified staff to run verification properly. That’s why standardized tools like APHL’s templates are more important than ever.
• ISO 15189:2022: Labs accredited under this standard have 47% fewer medication errors. If you’re not aiming for accreditation, you’re falling behind.

Real-World Wins and Failures

Mayo Clinic’s 2022 tacrolimus validation caught 17% of samples with metabolite interference-preventing dangerous dosing errors in transplant patients. That’s the kind of impact this work has.

On the flip side, a 2021 FDA MAUDE report details a case where a digoxin test failed to detect antibody cross-reactivity. Twenty-three patients got wrong doses. One died.

These aren’t hypotheticals. They’re documented events. The difference between success and disaster is whether you followed the steps.

Where to Start Today

If you’re not doing this yet, don’t panic. Start small:

1. Identify your most critical medication monitoring tests-digoxin, vancomycin, lithium, tacrolimus.
2. Download the APHL Laboratory Test Verification and Validation Toolkit. It’s free. It’s the industry standard.
3. Choose one test. Run the verification plan step by step. Document everything.
4. Train your team on why each step matters-not just how to do it.
5. Repeat. Add one test per quarter.

This isn’t about checking a box. It’s about making sure every blood draw leads to the right decision. In medicine, accuracy isn’t optional. It’s the foundation of care.