How to Confirm Monitoring Labs and Follow-Up for Medications: A Practical Guide for Providers

When a patient is on a medication with a narrow therapeutic index-like warfarin, digoxin, or tacrolimus-getting the lab results right isn’t just important. It’s life-or-death. A single point off in the blood level can mean the difference between effective treatment and toxic overdose. Yet, too many providers assume the lab result they see in the EHR is automatically accurate. It’s not. Therapeutic drug monitoring requires more than just ordering a test. It demands confirmation that the lab’s process is reliable, and that follow-up actions are based on trustworthy data.

Why Lab Verification Matters More Than You Think

Every time a doctor adjusts a dose based on a lab result, they’re trusting that the test was done correctly. But labs don’t just plug in a sample and spit out a number. There’s a whole system behind it. The process of confirming that a test works as it should is called verification (for FDA-cleared tests) or validation (for lab-developed tests). These aren’t just paperwork exercises-they’re safety checks.

The Centers for Medicare & Medicaid Services (CMS) requires this under CLIA ’88 regulations. Skip it, and you risk fines up to $7,500 per violation. More importantly, you risk patient harm. Studies show that 5-8% of inaccurate results for drugs like carbamazepine come from undetected interference-like another medication or metabolite skewing the test. In one documented case, a digoxin test failure led to 23 patients getting wrong doses because the lab didn’t check for antibody cross-reactivity. That’s not a rare glitch. It’s preventable.

Verification vs. Validation: Know the Difference

Not all lab tests are created equal. There are two paths to ensuring accuracy:

• Verification is for tests that already have FDA clearance-like lithium or vancomycin assays. The lab doesn’t need to build the test from scratch. They just need to prove it works the way the manufacturer says it does.
• Validation is for tests the lab created themselves, like monitoring clozapine metabolites. These have no FDA-approved kit. The lab must prove everything: accuracy, precision, sensitivity, and interference resistance. It’s more work, more time, and more expensive.

Verification typically takes 80 hours and costs $2,500-$5,000. Validation? 120+ hours and $7,500-$15,000. That’s why most hospitals stick with FDA-cleared tests whenever possible. But if your patient is on an uncommon drug-say, a new biologic or an off-label use-you might need a lab-developed test. In those cases, you need to ask: Has this test been properly validated? Can they show you the data?

The 9-Step Lab Verification Process (What Labs Actually Do)

If you’re wondering how labs make sure their results are solid, here’s what they follow, based on the APHL toolkit used by 98% of U.S. labs:

1. Plan it out. Define what tests to verify, what performance standards to use, and who’s responsible. This step alone takes 8-16 hours.
2. Get approval. The lab director must sign off before any testing starts. No exceptions.
3. Run the tests. For verification, they test the same sample 20+ times over 5 days to check precision. They use reference materials to measure trueness. They spike samples with interfering substances like other drugs to see if the test gets confused.
4. Analyze the numbers. They check if precision is within 1/4 of the total allowable error. For digoxin, that’s a 10% margin. For vancomycin, it’s 15%. If it’s outside, they stop.
5. Re-evaluate if needed. About 30% of verification attempts need adjustments-usually because the instrument isn’t calibrated right or the reagents are off.
6. Write the report. A summary document showing all data, decisions, and outcomes. This is legally required.
7. Create SOPs. Standard Operating Procedures for staff to follow every time the test is run. Training materials are developed here.
8. Final approval. Again, the lab director signs off. This isn’t a formality-it’s accountability.
9. Implement. The test goes live. Staff are trained. The result appears in the EHR.

This isn’t theoretical. One lab director in Ohio used a template from the APHL toolkit to verify a vancomycin test. It caught a linearity issue at 75 mcg/mL-right in the middle of the therapeutic range. Without that check, patients would’ve been overdosed. That’s the kind of thing that saves lives.

What You Should Ask Your Lab

You don’t need to run the tests yourself. But you do need to know if the lab you’re relying on is doing them right. Here’s what to ask:

• Is this test FDA-cleared or lab-developed? If it’s lab-developed, ask for the validation report.
• What’s the total allowable error for this drug? For digoxin, it’s 10%. For tacrolimus, it’s 15%. If they don’t know, that’s a red flag.
• Did you test for interference? Ask specifically about metabolites. For example, carbamazepine can be skewed by its own epoxide metabolite. Tacrolimus can be affected by cyclosporine. If they didn’t test for those, the result could be wrong.
• What’s your lower limit of quantitation? Many labs skip checking this for narrow therapeutic drugs. But if the test can’t detect levels below 0.3 ng/mL, and your patient’s level is 0.25 ng/mL? You’ll think they’re therapeutic when they’re actually sub-therapeutic. That’s dangerous.
• Do you follow CLIA and ISO 15189? These are the gold standards. If they don’t mention them, dig deeper.

Common Pitfalls (And How to Avoid Them)

Even good labs make mistakes. Here are the top three problems-and how to protect your patients:

1. Skipping interference testing. This is the #1 cause of false results. Always ask if the lab tested for common drug interactions. If they say “we use the manufacturer’s claims,” push back. Manufacturer data isn’t always real-world.
2. Not verifying the lower limit. 64% of labs don’t check this for narrow index drugs. That means they’re missing patients who are under-dosed. Always request the lower quantitation limit data.
3. Assuming EHR alerts are enough. EHR systems can flag low or high levels, but they’re only as good as the lab data feeding them. If the lab result is wrong, the alert is meaningless. Don’t rely on automation to catch what the lab missed.

What’s Changing in 2025

The rules are tightening. In January 2024, the FDA released new draft guidance requiring labs to test for 15 metabolites for immunosuppressants-not just 8. That’s a big shift. Labs that haven’t updated their protocols are already behind.

Also, the CLSI is finalizing EP44-Ed2, a new standard specifically for narrow therapeutic index drugs. It will make verification even more rigorous. Meanwhile, more labs are moving away from lab-developed tests (LDTs) and toward FDA-cleared kits. Why? Because validation is expensive, slow, and risky. If a test is available as FDA-cleared, most labs will choose that path.

And EHRs are catching up. Epic Systems now has built-in therapeutic drug monitoring modules in 45% of U.S. hospitals. These systems can auto-flag trends, compare results over time, and even suggest dose adjustments based on validated reference ranges. But again-this only works if the underlying lab data is accurate.

Your Role as a Provider

You’re not responsible for running the lab tests. But you are responsible for knowing whether the results you’re acting on are trustworthy. Here’s your checklist:

• Only order tests from labs that follow CLIA and ISO 15189 standards.
• For high-risk drugs (digoxin, lithium, tacrolimus, cyclosporine), ask for the verification/validation report before using the lab regularly.
• If a result seems odd-too high, too low, inconsistent with clinical signs-request a repeat test from a different lab.
• Document your rationale for dose changes. If a patient has a bad outcome, you’ll need to show you acted on reliable data.
• Stay updated. If your lab switches to a new assay or vendor, ask for a summary of the verification process.

When to Refer to a Specialist

If you’re managing complex cases-transplant patients on multiple immunosuppressants, oncology patients on targeted therapies, or those with renal/hepatic impairment-consider working with a clinical pharmacologist or a specialized therapeutic drug monitoring service. These teams don’t just read results. They interpret them in context, know which tests are reliable, and can advise on dosing adjustments based on real-world data.

Frequently Asked Questions

Next Steps for Providers

Start small. Pick one high-risk medication your patients are on-digoxin, for example. Call your lab and ask: “Have you verified this test? Can I see the data on interference testing and lower limit of quantitation?” If they can’t provide it, find a lab that can. Don’t wait for a bad outcome. The systems are in place to prevent errors. You just need to know how to use them.