How often are there gaps in monitoring prescription drugs that may have potentially life-threatening side effects?

Recommended initial laboratory monitoring was not completed when indicated for 39 percent of the drugs newly prescribed to patients in 10 health plans during 1999–2000. Failure to monitor varied by type of drug studied, from a low of 19 percent to a high of 85 percent.

Why is this important?

Food and Drug Administration-required product labeling known as "Black Box Warnings" and/or clinical guidelines recommend laboratory monitoring for certain drugs that have the potential to cause organ system toxicity or electrolyte imbalance or require dose adjustment in case of organ dysfunction (Raebel, Lyons, Andrade et al. 2005).

Failure to perform timely laboratory monitoring when indicated is a potentially serious medication error. A study in a large multi-specialty practice, for example, found that more than one-third of the preventable adverse drug events experienced by Medicare patients were related to inadequate monitoring of drug therapy (Gurwitz et al. 2003).

Findings

Two of five drugs newly prescribed to ambulatory care patients in 10 health plans were not monitored when indicated during 1999–2000. The failure to perform some or all recommended laboratory blood tests varied considerably across the 35 drugs or drug classes examined (Raebel, Lyons, Andrade et al. 2005).

• In the worst case, the recommended initial laboratory monitoring was not done for 85 percent of patients prescribed oral ketoconazole, an antifungal drug that may cause liver damage in some patients.
• Even in the best case, 19 percent of transplant patients and others taking the immunosuppressant drug cyclosporine did not receive the recommended initial laboratory monitoring.
• Rates of baseline monitoring failure were similar for three widely used cardiovascular drugs that together comprised two-thirds of all new prescriptions written during the study: angiotensin-converting enzyme (ACE) inhibitors (39%), diuretics (40%), and statins (37%).

The failure to order specific laboratory tests occurred about equally often for serum creatinine (32%), hematologic (32%), electrolyte (34%), and liver function (39%) monitoring. Thyroid function was evaluated even less frequently (data not shown).

Implications

The gap in monitoring might be due to ineffective communication of monitoring recommendations leading to a lack of awareness that laboratory testing is indicated for particular drugs, a belief that testing is not needed for patients considered to be at low risk for adverse events, and uncertainty about the usefulness of monitoring (Barclay 2005; Raebel, Lyons, Andrade et al. 2005). Monitoring tended to increase with patient age and chronic disease burden, suggesting that physicians and patients achieve better adherence when there is a stronger sense of risk.

Along with better information on risk of adverse events, systematic approaches are needed to create a more reliable laboratory test management process in ambulatory practice—something that physicians say they desire (Poon et al. 2004). Because some patients may fail to obtain laboratory testing ordered by their physician, proactive systems or processes are needed to routinely follow-up with patients when expected laboratory results are not received in a timely manner.

Improvement Ideas and Resources

Incorporating warnings into electronic medical records and prescribing systems offers one potential approach to address this problem, although more work is needed to determine the most effective methods for doing this. For example:

• Studies of electronic prescribing systems in a hospital and a primary care setting reported increased laboratory monitoring for selected high-risk drugs when physicians received computerized alerts that required acknowledgement or that automatically ordered tests when physicians concurred (Overhage et al. 1997; Steele et al. 2005).
• On the other hand, a controlled study of electronic prescribing in the primary care clinics of a health maintenance organization (HMO) found no overall effect on laboratory monitoring rates when physicians received education and passive computer alerts that did not require or facilitate intervention (Palen et al. 2006).

Interventions involving pharmacists offer another potential approach. In a controlled study in the same HMO mentioned above, recommended laboratory monitoring for newly prescribed drugs was 9 percentage points higher when pharmacists received alerts about missing laboratory results, ordered missing tests, and reminded patients to obtain needed tests (Raebel, Lyons, Andrade et al. 2005b).

Measure:

The denominator includes 279,354 drug dispensings between July 1, 1999 and June 16, 2001 among a sample of 2,000,000 managed care plan members who had pharmacy benefits for at least 180 days before and 14 days after the index dispensing (no dispensing of the same drug for at least the previous 180 days). The study examined 35 drugs or drug classes for which laboratory monitoring is recommended based on FDA Black Box Warnings and for which there was consensus on guideline recommendations among a panel of clinicians at participating health plans. The numerator contains the subset of the denominator population who did not have the indicated monitoring performed within 180 days before or 14 days after the index drug dispensing (Raebel et al. 2005).

Limitations:

A subanalysis found that monitoring failure identified by administrative data was concordant with medical records for 72 percent to 89 percent of the six drugs examined (e.g., administrative data did not capture baseline monitoring for new prescriptions in the hospital) (Raebel et al. 2005). This implies that the actual monitoring failure rate is somewhat lower than estimated. The data did not distinguish the failure to order a test from patient failure to obtain an ordered test; however, patient nonadherence was rare in another study (Lasser et al. 2006).

Source:

Data for the chart were compiled by a collaboration of health care researchers (Raebel et al. 2005) using administrative data on ambulatory care delivered to patients with private, Medicare, and Medicaid coverage through one of 10 geographically dispersed health maintenance organizations (HMOs) participating in the HMO Research Network's Center for Education and Research in Therapeutics (CERTS) project.

References:

* Indicates source of data used in the chart(s).Barclay, L. 2005. Inconsistent Adherence to Black Box Warnings: A Newsmaker Interview with Anita Wagner. Medscape Medical News (Nov 18).

Gurwitz, J. H., T. S. Field, L. R. Harrold et al. 2003. Incidence and Preventability of Adverse Drug Events Among Older Persons in the Ambulatory Setting. Journal of the American Medical Association 289 (9): 1107–16.

Lasser, K. E., D. L. Seger, D. T. Yu et al. 2006. Adherence to Black Box Warnings for Prescription Medications in Outpatients. Archives of Internal Medicine 166 (3): 338–44.

Overhage, J. M., W. M. Tierney, X. H. Zhou et al. 1997. A Randomized Trial of 'Corollary Orders' to Prevent Errors of Omission. Journal of the American Medical Informatics Association 4 (5): 364–75.

Palen, T. E., M. Raebel, E. Lyons et al. 2006. Evaluation of Laboratory Monitoring Alerts Within a Computerized Physician Order Entry System for Medication Orders. The American Journal of Managed Care. 12 (7): 389–95.

Poon, E. G., T. K. Gandhi, T. D. Sequist et al. 2004. 'I Wish I Had Seen This Test Result Earlier!' Dissatisfaction with Test Result Management Systems in Primary Care. Archives of Internal Medicine 164 (20): 2223–8.

* Raebel, M. A., E. E. Lyons, S. E. Andrade et al. 2005. Laboratory Monitoring of Drugs at Initiation of Therapy in Ambulatory Care. Journal of General Internal Medicine 20 (12): 1120–6.

Raebel, M. A., E. E. Lyons, E. A. Chester et al. 2005. Improving Laboratory Monitoring at Initiation of Drug Therapy in Ambulatory Care: A Randomized Trial. Archives of Internal Medicine 165 (20): 2395–401.

Steele, A. W., S. Eisert, J. Witter et al. 2005. The Effect of Automated Alerts on Provider Ordering Behavior in an Outpatient Setting. PLoS Medicine 2 (9): e255.