Statistical Analyses in Nursing
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D rug-induced injury is common. Independent risk factors for adverse drug events in the ambulatory setting include ad- vanced age, multiple comorbid conditions, and the use of
high-risk medications requiring close monitoring. For example, fail- ure to appropriately monitor older patients receiving drug therapy ac- counts for 36% of preventable adverse drug events in the ambulatory setting.1
Efforts to improve monitoring within organizations are hampered by a lack of comprehensive and specific guidelines for the laboratory moni- toring of high-risk medications.2 Monitoring guidelines for selected drugs exist in recommendations of organizations such as the American Heart Association guidelines to manage heart failure,3 the American Geriatrics Society Assessing Care of Vulnerable Elders medication quality indicators,4 and the National Quality Forum–endorsed mea- sures.5 A nationwide baseline monitoring assessment study6 developed more comprehensive guidelines for medications used through 2000, among which a subset of 14 were updated and adopted for an interven- tion trial between 2002 and 2003 within a single health maintenance organization.7,8
We sought to develop an updated and comprehensive list of drugs requiring laboratory monitoring for an electronic medical record–em- bedded clinical decision support intervention at a multispecialty group practice for medications in clinical use during 2008. The intent of the updated guidelines was to include drugs introduced to the market since December 2000, the date of the literature review for the original drug and laboratory monitoring recommendations published by Raebel et al6
in 2005, as well as to update laboratory test and frequency recommenda- tions based on 2007 changes in monitoring recommendations.9 Herein, we describe the development of guidelines to monitor high-risk medica- tions in the ambulatory setting using a 2-step consensus-based approach, including a national expert advisory panel and local leaders to select candidate medications for monitoring and to determine the frequency of laboratory monitoring. To estimate the potential effect of our guidelines on actual practice, we determined the use frequency of the guideline drugs and the prevalence for each of the recommended laboratory tests.
The specific objectives of this study were (1) to develop recommendations to guide the monitoring of high-risk medications in the ambulatory set- ting, (2) to assess the use prevalence
Development and Pilot Testing of Guidelines to Monitor High-Risk Medications in the Ambulatory Setting
Jennifer Tjia, MD, MSCE; Terr y S. Field, DSc; Lawrence D. Garber, MD; Jennifer L. Donovan, PharmD;
Abir O. Kanaan, PharmD; Marsha A. Raebel, PharmD; Yanfang Zhao, MA; Jacquelyne C. Fuller, MPH;
Shawn J. Gagne, BA; Shira H. Fischer, AB; and Jerr y H. Gur witz, MD
Objectives: To develop guidelines to monitor high-risk medications and to assess the preva- lence of laboratory testing for these medications among a multispecialty group practice.
Study Design: Safety intervention trial.
Methods: We developed guidelines for the laboratory monitoring of high-risk medications as part of a patient safety intervention trial. An advisory committee of national experts and local leaders used a 2-round Internet-based Delphi process to select guideline medications based on the importance of monitoring for efficacy, safety, and drug–drug interactions. Test frequency recommendations were developed by academic pharmacists based on a literature review and local interdisciplinary consensus. To estimate the potential effect of the planned intervention, we determined the prevalence of high-risk drug dispensings and laboratory testing for guideline medications between January 1, 2008, and July 31, 2008.
Results: Consensus on medications to include in the guidelines was achieved in 2 rounds. Final guidelines included 35 drugs or drug classes and 61 laboratory tests. The prevalence of monitor- ing ranged from less than 50.0% to greater than 90.0%, with infrequently prescribed drugs having a lower prevalence of recommended testing (P <.001 for new dispensings and P <.01 for chronic dispensings, nonparametric test for trend). When more than 1 test was recommended for a selected medication, monitoring within a medication sometimes differed by greater than 50.0%.
Conclusions: Even among drugs for which there is general consensus that laboratory monitor- ing is important, the prevalence of monitoring is highly variable. Furthermore, infrequently prescribed medications are at higher risk for poor monitoring.
(Am J Manag Care. 2010;16(7):489-496)
For author information and disclosures, see end of text.
In this article Take-Away Points / p490 www.ajmc.com Full text and PDF
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of candidate medications for monitoring, and (3) to deter- mine completion of recommended testing for medications dispensed among the patient population.
METHODS Study Setting and Population
This study was conducted in a large multispecialty group practice that provides most medical care to members of a closely associated health plan based in the New England area of the United States. The group practice employs 250 outpatient clinicians at 30 ambulatory clinic sites. The practice uses the EpicCare Ambulatory (Epic, Verona, WI) electronic medical record system and provides medical care to approximately 180,000 individuals. For this analysis, we included patients if they received care from the multispe- cialty group practice, were 18 years or older, and obtained insurance coverage from the health plan between January 1, 2007, and July 31, 2008. Patients had to be continuously enrolled during the observation period and not residing in a long-term care facility. Data about medication exposure were derived from the prescription drug claims of the health plan. Data about laboratory test completion were derived from the multispecialty group practice electronic medical record.
Determination of High-Risk Drugs and Laboratory Monitoring Guidelines
Laboratory monitoring guidelines for high-risk drugs were developed using a sequential process adapted from an approach created and tested for a study6 conducted within the Health Maintenance Organization Research Network Center for Ed- ucation and Research on Therapeutics. This approach used an advisory committee of national experts and local health plan leaders, including practicing clinicians and pharmacists and experts in patient safety and geriatric pharmacotherapy. The charge for this group was as follows: (1) to review a com- prehensive initial list of medications requiring monitoring; (2) to assess the importance of including monitoring recom- mendations to evaluate efficacy, safety, and clinically relevant
drug–drug interactions; and (3) to deter- mine the need to include infrequently prescribed medications in the guidelines. The initial list of high-risk drugs includ- ed those commonly implicated in adverse events among patients in the ambulatory setting1 and those associated with adverse events leading to emergency department visits,10 as well as drugs with low moni- toring rates,6,11 drugs included in national
quality guidelines,4 and drugs with black box warnings.12
We asked panel members to participate in an Internet- based questionnaire administered in a 2-round modified Delphi process13 between August and October 2008. Panel- ists were asked whether electronic monitoring alerts should be sent to primary care physicians, specialists, or both and whether monitoring alerts should be generated for infre- quently dispensed or effectively obsolete medications. Panel- ists were also asked to rate the importance of monitoring each candidate medication for efficacy, toxic effects, and drug–drug interactions. Each question was answered based on a 5-point Likert-type scale to evaluate agreement or disagreement with statements concerning the importance of monitoring each medication or medication class for the domain assessed. The scale ranged from 1 (indicating “strongly agree”) to 5 (indi- cating “strongly disagree”).
After the first round of the survey, we eliminated ques- tions for which there was agreement and readministered questions for which there was lack of consensus. Consistent with other modified Delphi methods, consensus for a ques- tion was defined by agreement on categorization by at least a majority (>50.0%) of respondents.13 We then administered a second questionnaire to participants. In this round, panelists were reminded of their original responses to individual ques- tions and were given the group’s aggregated response to the questions in the first round. At this stage, each participant was given the opportunity to revise his or her response to increase consensus with the succeeding round. The results of the Delphi process informed the selection of the final high- risk drug list.
Determination of Laboratory Test Monitoring Frequency
After selection of the final high-risk drug list, 2 research pharmacists (JLD and AOK) reviewed the literature to de- termine the appropriate frequency of laboratory monitoring for each drug. The review included monitoring recommenda- tions provided in manufacturer labeling information, nation- ally available published guidelines, and clinical guidelines from national organizations and initiatives (eg, American
Take-Away Points This article adds to the existing literature and informs clinical decisions in the following ways:
n By describing a process to develop guidelines for the laboratory monitoring of high- risk medications within a multispecialty group practice.
n By estimating the potential effect of an intervention to improve laboratory testing of high-risk medications by reporting the use frequency of high-risk medications requiring monitoring in 2008 and the prevalence of test completion for high-risk drugs in 2008.
n By demonstrating that infrequently used medications have lower rates of recommend- ed laboratory test monitoring.
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completion. All analyses were conducted using commercially available software (SAS 9.2; SAS Institute Inc, Cary, NC). The study was approved by the institutional review boards of the University of Massachusetts Medical School, Worcester, and the participating group practice.
RESuLTS Consensus Panel Survey
A panel of 3 pharmacists and 6 physicians participated in the consensus survey. All physicians were certified by the American Board of Internal Medicine, 2 had an added quali- fication in geriatric medicine, and 3 had subspecialty board certifications. All respondents completed the 2 rounds of the survey. After the second round of the survey, consensus was achieved for all 40 medications with respect to parameters (ie, efficacy or toxic effects) for laboratory monitoring and for alerts to physicians (ie, primary care physician vs specialist). The consensus panel agreed that alerts for high-risk medi- cations were indicated to monitor efficacy and toxic effects alone or in the presence of significant drug–drug interactions. The panel also agreed that alerts should be sent to special- ists and primary care physicians and should be developed for medications that were frequently and infrequently prescribed. Because strict national prescribing policies already exist to guide the use and monitoring of isotretinoin, we did not in- clude this medication in the newly developed guidelines. The resulting list of drugs included 39 drugs or drug classes.
Pilot Testing of Monitoring Recommendations Once the medication list was established, we exam-
ined overall dispensings of the selected medications. The chronic index dispensings ranged from 0 (procainamide and ganciclovir) to 13,351 (statins), and new index dispens- ings ranged from 0 (procainamide and ganciclovir) to 2463 (statins) during the observation period of January 1, 2008, to July 31, 2008. Based on these results, 4 drugs with fewer than 5 new or chronic users combined (ticlopidine, tolca- pone, ganciclovir, and procainamide) were eliminated from the final drug list, resulting in 35 drugs or drug classes in the final list of monitoring guidelines. There were 61 separate drug–laboratory test combinations for monitoring, with 15 requiring more than 1 laboratory test (eg, amiodarone–thy- roid-stimulating hormone [TSH] and amiodarone–aspartate aminotransferase [AST]) and 20 requiring a single test; for the purpose of this study, we considered a basic metabolic panel that includes sodium, potassium, chloride, bicarbonate, blood urea nitrogen, and creatinine levels as a single test.
Overall, the rates of test completion ranged from 0.0% for aspartate aminotransferase or alanine aminotransferase [ALT]
Heart Association guidelines3 and National Committee for Quality Assurance–developed measures and guidelines5). Be- cause manufacturers’ warnings often describe a nonspecific frequency for monitoring such as “periodically,” we reviewed other authoritative sources that pharmacists and clinicians commonly use to guide decisions about the frequency of monitoring. These sources included the following: (1) the published literature; (2) the Micromedex Healthcare Series14 (Thomson Reuters [Healthcare] Inc, Greenwood Village, CO) database, which sources the primary case report and ex- perimental literature; (3) UpToDate Inc15 (Waltham, MA), an online peer-reviewed reference database; and (4) the Pharmacist’s Letter16 (Therapeutic Research Center, Stock- ton, CA). The final list of laboratory monitoring tests and the associated monitoring frequencies were reviewed by a local panel of academic pharmacists, the clinical pharmacist for the multispecialty group practice, and the medical director of the multispecialty group practice to determine local acceptability and congruence with local quality standards.
Statistical Analysis We used drug dispensing claims between January 1, 2007,
and July 31, 2008, to identify the first dispensing of a high-risk medication for a patient after January 1, 2008. New drug use was defined as an initial dispensing on or after the index date of January 1, 2008, and no drug dispensing in the 6 months preceding the index date. Chronic (ongoing) drug use was de- fined as a dispensing on or after January 1, 2008, with evidence of drug dispensing in the 6 months before that date. Because clinicians might rely on laboratory test results for up to 6 months before initiation of a drug or might order a test within 2 weeks after initiation of a drug, we defined test completion for a new dispensing in 2008 as having occurred if there was at least 1 associated monitoring test completed 180 days before dispensing to 42 days after dispensing (test ordered <14 days after dispensing plus 28 days for test completion). Comple- tion of a test of serum drug levels (eg, serum carbamazepine) for new prescriptions was measured from the day of dispensing to 30 days after initial dispensing. Test completion for chronic medication use was defined as having occurred if there was at least 1 recommended test for the drug test pair that occurred up to 365 days before the index dispensing in 2008 through 42 days after the dispensing if the test was indicated annually (or 180 days before to 42 days after index dispensing if the test was indicated every 6 months). For each drug–laboratory test combination, the proportion of completed recommended tests was determined for all index dispensings in the observa- tion period. We used a nonparametric test for trend across or- dered groups by Cuzick17 to examine whether more frequently dispensed drugs had a higher prevalence of recommended test
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among new users of nefazodone, phenobarbital, and quinidine at baseline to 96.8% for AST or ALT test among chronic users of niacin (Table 1 and Table 2). Drug–laboratory test pair comple- tion differed between new and chronic medication dispensings. For new medication dispensings, less than 20.0% of the recom- mended 61 drug–laboratory test pairs were monitored in the majority (>75.0%) of patients. In contrast, close to 40.0% of the
recommended drug–laboratory test pairs for chronic dispensings were monitored in greater than 75.0% of patients.
For drugs with multiple laboratory tests, the percentage test completion often varied within the drug (Table 2). For example, for new amiodarone use, 52.7% had an AST or ALT test, while 74.6% had a TSH test; for azathioprine use, 28.0% had a baseline AST or ALT test, while 72.0% had a com-
n Table 1. Prevalence of Laboratory Test Completion Among High-Risk Medications With a Single Laboratory Test Indicated by Frequency of New Dispensings Between January 1, 2008, and July 31, 2008
Drug Name or Class
No. of Users
Test
Guideline Recommendation
for Monitoring Frequency
Completion of Recommended
Laboratory Test, %
New ChronicNew Chronic
Statins 2463 13,351 AST or ALT Baseline and yearly 67.2 84.0
Angiotensin-converting enzyme inhibitors
1736 8696 BMP Baseline and yearly 72.1 88.3
Diuretics
Thiazide 1198 5500 BMP Baseline and yearly 71.2 87.4
Loop 1031 2901 BMP Baseline and yearly 83.7 91.1
Warfarin 676 2268 INR Baseline, weekly for first month, and monthly
86.7 96.4
Thyroid replacement 636 4660 TSH Baseline and yearly 48.4 70.0
Potassium supplement 610 1610 K Baseline and yearly 87.7 90.0
Metformin 568 2056 Cr Baseline and yearly 44.7 60.4
Diuretics, potassium sparing 285 1383 BMP Baseline and yearly 71.5 87.4
Imidazole antifungalsa 243 20 AST or ALT Baseline and every 3 mo
28.8 60.0
Gemfibrozil 217 697 AST or ALT Baseline, 3 and 6 mo, and yearly
75.1 81.4
Allopurinol 198 821 Cr Baseline and yearly 85.9 90.9
Thiazolidinediones 120 537 AST or ALT Baseline, every 2 mo for first year, and every 6 mo
73.3 64.8
Terbinafine 50 6 AST or ALT Baseline and every 2 mo
26.0 66.7
Niacin 49 95 AST or ALT Baseline and yearly 83.7 96.8
Angiotensin II receptor blockers
32 69 BMP Baseline and yearly 62.5 82.6
Isoniazid 18 14 AST or ALT Baseline and every 2 mo
33.3 35.7
Rifampin 14 9 AST or ALT Baseline and every 2 mo
35.7 22.2
Theophylline 15 88 Theophylline level
1 wk After initiation and yearly
20.0 61.4
Nefazodone 2 15 AST or ALT Baseline, 3 and 6 mo, and yearly
0.0 26.7
ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; BMP, basic metabolic panel; Cr, creatinine; INR, international normalized ratio; K, potassium; TSH, thyroid-stimulating hormone. aExcluding single-dose fluconazole.
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n Table 2. Prevalence of Laboratory Test Completion Among High-Risk Medications With Multiple Laboratory Tests Indicated by Frequency of New Dispensings Between January 1, 2008, and July 31, 2008
Drug Name or Class
No. of Users
Test
Guideline Recommendation
for Monitoring Frequency
Completion of Recommended
Laboratory Tests, %
New ChronicNew Chronic
Colchicine 289 255 Cr Baseline and yearly 79.6 84.3
CBC Baseline and yearly 74.1 78.4
Digoxin 202 1015 Cr Baseline and yearly 83.2 91.0
K Baseline and yearly 83.2 90.3
Digoxin level 5-7 d After dose changes and yearly
31.7 63.5
Fenofibrate 147 190 CBC Baseline, monthly for 3 mo, and every 6 mo for the first year
55.8 70.0
AST or ALT Baseline and every 3-6 mo 71.4 86.3
Valproic acid 133 248 AST or ALT Baseline, every 2 mo for 6 months, and yearly
21.8 37.9
CBC Baseline and yearly 38.4 62.1
Valproic acid level 2-4 wk After initiation, with changing clinical status, and yearly
10.5 44.8
Cyclosporine 102 76 AST or ALT Baseline, monthly for 3 mo, and yearly
38.2 48.7
Cr Baseline, every 2 wk for 3 mo, and yearly
59.8 34.2
Cyclosporine level Weekly for 2-3 mo and monthly
0.0 18.4
Phenytoin 67 313 AST or ALT Baseline, monthly for 6 mo, and yearly
31.3 46.3
Phenytoin level 2-4 wk After initiation and yearly
37.3a 75.1
Methotrexate 65 213 AST or ALT Baseline and every 2-3 mo 60.0 83.6
CBC Baseline and monthly 72.3 66.2
Cr Baseline and every 2-3 mo 66.2 77.5
Amiodarone 55 79 AST or ALT Baseline and every 6 mo 52.7 59.5
TSH Baseline and every 3-6 mo 74.6 48.1
Carbamazepine 49 193 AST or ALT Baseline and yearly 38.8 57.5
CBC Baseline, monthly for 3 mo, and yearly
57.1 72.5
Carbamazepine level 2-4 wk After initiation, with changing clinical status, and yearly
12.2 27.0
Lithium 36 125 CBC Baseline, 1 mo after stabilized, and yearly
38.9 55.2
Cr Baseline, 1 mo after stabilized, and yearly
41.7 60.8
TSH Baseline, 3 and 6 mo, and yearly
11.1 39.2
Lithium level 2-4 wk After initiation, with changing clinical status, and yearly
16.7 39.2
(Continued)
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plete blood count (CBC). We also found that the frequency of medication use was associated with the frequency of rec- ommended test completion (Table 3). Infrequently dispensed medications had a lower prevalence of test completion. Non- parametric test for trend showed a significant trend toward more frequently dispensed medications having a higher preva- lence of appropriate testing (P <.001).
DISCuSSION Herein, we describe the development of drug–laboratory
test monitoring guidelines based on manufacturers’ recom- mendations and published guidelines. Recently published guidelines to monitor drugs in the long-term care setting included a similar list of medications and laboratory tests.18 To determine the potential effect of our guidelines on actual practice, we determined the use frequency of the guideline drugs and the prevalence of testing for each of the recom- mended laboratory tests. We found that (1) certain high-risk
drugs had very low rates of use among our target population, (2) rates of testing for high-risk drugs varied widely, and (3) infrequently used drugs had lower testing rates. Our study adds to the literature by identifying ways to inexpensively improve patient safety and quality of care (describing a method for formulating monitoring recommendations) and by provid- ing final monitoring recommendations (detailed guidelines are available from the authors) that are useful to practitioners considering similar interventions at their local institutions.
It is important to point out that the level of evidence for each recommended drug test pair varied and that this likely explains some of the variation in testing among our sample. For example, there is increasing controversy about the role of evaluating renal function in patients taking metformin.19 Among our sample, we found that 45.0% to 60.0% of met- formin users had completed a serum creatinine test. Similarly, there is a difference in the role of digoxin-level monitoring depending on indication, with digoxin serum drug levels of less importance when prescribed for heart rate control and of
n Table 2. Prevalence of Laboratory Test Completion Among High-Risk Medications With Multiple Laboratory Tests Indicated by Frequency of New Dispensings Between January 1, 2008, and July 31, 2008 (Continued)
Drug Name or Class
No. of Users
Test
Guideline Recommendation
for Monitoring Frequency
Completion of Recommended
Laboratory Tests, %
New ChronicNew Chronic
Primidone 27 60 CBC Baseline and every 6 mo 55.6 50.0
Phenobarbital level 2-4 wk After initiation, with changing clinical status, and every 6 mo
0.0 11.7
Primidone level 2-4 wk After initiation, with changing clinical status, and every 6 mo
0.0 11.7
Azathioprine 25 58 AST or ALT Baseline and every 3 mo 28.0 25.9
CBC Baseline, every week for first month, every 2 wk for second and third months, then monthly or after treatment changes
72.0 87.9
Methyldopa 12 44 AST or ALT Baseline and every 6-12 mo 16.7 63.6
CBC Baseline and every 6 mo 50.0 47.7
Phenobarbital 9 52 AST or ALT Baseline and every 6 mo 0.0 46.1
CBC Baseline and every 6 mo 22.2 69.2
Phenobarbital level 2-4 wk After initiation, with changing clinical status, and yearly
0.0 53.8
Quinidine 1 13 AST or ALT Baseline and yearly 0.0 92.3
Cr Baseline and yearly 100.0 92.3
K Baseline and yearly 100.0 92.3
Quinidine level 2-4 wk After initiation and yearly
0.0 92.3
ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; BMP, basic metabolic panel; CBC, complete blood count; Cr, creatinine; K, potassium; TSH, thyroid-stimulating hormone.
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greater importance when used for heart failure.20 Among our sample, we found digoxin levels completed for 30.0% to 60.0% of users. We did not discern the indication for digoxin use in our study, but previous investigations have shown similarly low rates of digoxin-level test- ing.21 Variance in the level of evidence for testing may explain some of the dif- ferences we observed in the prevalence of completion among different tests within the same drug.
We are concerned about the low prevalence of testing for drug test pair recommendations that are much less controversial such as evaluation of thyroid func- tion among amiodarone users. Amiodarone-induced thyroid dysfunction, including thyrotoxicosis and hypothyroidism, can occur in up to 20% of users.22 For this drug test pair, we found that 75.0% of new users and 50.0% of chronic users had completed a TSH test. The reason for the lower rate of testing among new drug users is unclear. Although a possible explanation may be the initiation of drugs in the hospital, as may be the case for amiodarone among using patients with arrhythmias, the prevalence of hospitalizations did not differ among those with versus without appropriate monitoring of amiodarone in a prior study.23 Further investigation is neces- sary to determine whether hospitalizations explain low testing rates among our study population.
An important finding of our study was that patients using infrequently prescribed drugs were less likely to complete rec- ommended laboratory tests. This is consistent with literature showing an association between patient volume and quality of care24 but is not supported by at least 1 study25 examining patient volume in association with process measures such as laboratory testing in diabetes. The rationale supported by the human fac- tors model of medical errors is that physicians will likely have better familiarity of the literature for drugs that they prescribe more frequently than for drugs that they do not prescribe.26
The implication of this finding can be considered in terms of potential relative and absolute effects of an intervention to improve monitoring. There is potential for significant ef- fect from interventions aimed at improving infrequently used medications because baseline rates of testing are low. This is important for drugs such as phenobarbital, whose laboratory monitoring is a Healthcare Effectiveness Data and Information Set measurement for assessing health plan quality of care.27 In contrast, the number of patients affected by infrequently pre- scribed drugs is small from a population health perspective. For example, the number of patients who failed to receive monitoring of statins was 2136, more than 20 times greater
than the number of patients affected by failure to monitor the 7 infrequently prescribed drugs combined (ie, imidazole anti- fungals, terbinafine, angiotensin II receptor blockers, isoniazid, rifampin, theophylline, and nefazodone). Health plans consid- ering the implementation of interventions to improve medi- cation monitoring need to weigh the absolute and relative potential effects of their program. Although the marginal cost of targeting many medications in a health information tech- nology–based intervention to improve monitoring is minimal and allows for the inclusion of many medications, programs using high-cost resources such as pharmacist time need to limit target medications by weighing the relative overall effect care- fully to optimally select target medications.
Other important drugs for inclusion in monitoring guide- lines are those with a high likelihood of a serious adverse outcome. Our guidelines incorporate several drugs commonly implicated in adverse drug events leading to emergency depart- ment visits,10 including hypoglycemics, warfarin, anticonvul- sants, digoxin, theophylline, and lithium. Of these, we found high rates for warfarin, which is often monitored through spe- cial anticoagulation programs, but low-to-moderate rates for digoxin, anticonvulsants, lithium, and theophylline.
Limitations of our study should be noted. First, our study was conducted in a single multispecialty group practice. Sec- ond, laboratory tests may have been ordered for another rea- son (ie, not for high-risk medication monitoring), so that we may have overestimated the prevalence of recommended test- ing. Third, we were unable to confirm patient adherence to drugs and were unable to identify patients who did not com- plete tests because they were no longer using the medication. Fourth, in many cases, despite the panel’s conclusions, limited evidence was found to support testing frequency or impor- tance, and that may explain the low prevalence of test order- ing for some drugs. For many drugs, further study is necessary to determine whether laboratory test monitoring improves health outcomes. Furthermore, lower testing for new use may also be explained by drug initiation in the hospital setting for
n Table 3. Completion of Recommended Laboratory Tests by Quartile of Dispensing Frequency
Completion of Recommended Laboratory Tests, Mean (SD), %
Quartile of Dispensing Frequency
New Dispensingsa
Chronic Dispensingsb
1, Low 29.6 (33.7) 60.9 (25.5)
2 47.0 (22.4) 47.8 (23.9)
3 48.1 (27.4) 64.8 (18.5)
4, High 68.5 (17.6) 82.5 (11.7)
aP <.001, nonparametric test for trend. bP <.01, nonparametric test for trend.
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drugs such as amiodarone and antiepileptics. In these cases, it is possible that baseline testing was obtained after initia- tion in the hospital and was not repeated after discharge to the ambulatory setting. However, similarly low rates of TSH and aminotransferase testing have been reported for chronic users of amiodarone23 and for determining serum levels of antiepileptics.21 Fifth, we did not assess all guideline recom- mendations such as monitoring after dose changes, drug–drug interactions, changing renal function, and clinical status.
Our study updates the laboratory monitoring recommenda- tions for high-risk drugs to include drugs used in ambulatory practice until 2008. Our findings and guidelines are generalizable to other institutions seeking to improve monitoring of high-risk medications to enhance the safety for their patient population after review and adaptation by local medical and pharmacy lead- ership to ensure consistency with local standards. Health plans considering similar interventions can use our findings to weigh the potential benefit of targeting drugs of high-frequency and low-frequency use in clinical practice, as our study demonstrates potential for improvement in the laboratory monitoring of drug types. Further research is necessary to understand factors con- tributing to the low monitoring of high-risk drugs, including physician factors resulting in lack of test ordering and patient factors leading to incomplete performance of tests.
Acknowledgments We acknowledge the contributions of the national expert advisory panel,
including Susan Andrade, ScD; Steven Simon, MD; Jerry H. Gurwitz, MD; and Marsha A. Raebel, PharmD. Local experts included Josie Cambia-Kiely, PharmD; Mojgan Hajji, PharmD; Michael Kelleher, MD; Leslie Harrold, MD; Sarah McGee, MD; and Robert Yood, MD.
Author Affiliations: From the Division of Geriatric Medicine (JT, TSF, SJG, SHF, JHG), University of Massachusetts, Worcester, MA; Meyers Pri- mary Care Institute (JT, TSF, YZ, JCF, JHG), Worcester, MA; Fallon Clinic (LDG), Worcester, MA; Massachusetts College of Pharmacy (JLD, AOK), Worcester, MA; and Kaiser Permanente Colorado (MAR), Denver, CO.
Funding Source: This study was funded by grants R18 HS017203, R18 HS017817, and R18 HS017906 from the Agency for Healthcare Research and Quality.
Author Disclosures: The authors (JT, TSF, LDG, JLD, AOK, MAR, YZ, JCF, SJG, SHF, JHG) report no relationship or financial interest with any enti- ty that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (JT, TSF, LDG, JHG); ac- quisition of data (JT, TSF, JCF); analysis and interpretation of data (JT, TSF, LDG, JLD, AOK, MAR, YZ, JCF, SJG, SHF, JHG); drafting of the manuscript (JT, TSF, JLD, AOK, MAR, SJG); critical revision of the manuscript for im- portant intellectual content (JT, TSF, JLD, AOK, MAR, SJG, SHF, JHG); statistical analysis (JT, YZ, JCF); obtaining funding (JT, JHG); and administra- tive, technical, or logistic support (LDG, YZ, JCF, SJG, SHF).
Address correspondence to: Jennifer Tjia, MD, MSCE, Division of Ge- riatric Medicine, University of Massachusetts, 377 Plantation St, Ste 315, Worcester, MA 01605. E-mail: [email protected].
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