ORIGINAL INVESTIGATION

The Impact of Prescribing Safety Alerts

for Elderly Persons in an Electronic Medical Record
An Interrupted Time Series Evaluation
David H. Smith, RPh, PhD; Nancy Perrin, PhD; Adrianne Feldstein, MS, MD; Xiuhai Yang, MS; Daniel Kuang, MS;
Steven R. Simon, MD, MPH; Dean F. Sittig, PhD; Richard Platt, MS, MD; Stephen B. Soumerai, ScD

Background: Considerable effort and attention have fo-
cused on medication safety in elderly persons; one ap-
proach that has been understudied in the outpatient en-
vironment is the use of computerized provider order entry
with clinical decision support. The objective of this study
was to examine the effects of computerized provider or-
der entry with clinical decision support in reducing the
use of potentially contraindicated agents in elderly
persons.
Methods: With data from a 39-month period of a natu-
ral experiment, we evaluated changes in medication dis-
pensing using interrupted time series analysis to esti-
mate changes, controlling for prealert prescribing trends.
The setting was a large health maintenance organiza-
tion in the Pacific Northwest. All adult enrollees of the
health plan participated. The intervention was comput-
erized alerts cautioning against using certain medica-
tions in elderly persons. The main outcome measure was
dispensing per 10 000 members per month.
Results: Following the implementation of the drug-
specific alerts, a large and persistent reduction (5.1 pre-
scriptions per 10 000, P=.004), a 22% relative decrease
from the month before alert implementation, in the ex-
posure of elderly patients to nonpreferred medications
was observed. We found no evidence of a decrease in use
of nonpreferred agents for nonelderly patients. The re-
duction seen in use of nonpreferred agents for elderly per-
sons was driven primarily by decreases in dispensing for
tertiary tricyclic agents.
Conclusions: We found that alerts in an outpatient elec-
tronic medical record aimed at decreasing prescribing of
medication use in elderly persons may be an effective
method of reducing prescribing of contraindicated medi-
cations. The effect of the alerts on patient outcomes is
less certain and deserves further investigation.
Arch Intern Med. 2006;166:1098-1104

Author Affiliations: Kaiser
Permanente Center for Health
Research (Drs Smith, Perrin,
Feldstein, and Sittig and
Messrs Yang and Kuang) and
Oregon Health and Sciences
University (Dr Perrin),
Portland; and Harvard Medical
School and Harvard Pilgrim
Health Care, Boston, Mass
(Drs Simon, Platt, and
Soumerai).
C
ONSIDERABLE EFFORT AND
attention have focused on
the development and dis-
semination of evidence-
based guidelines to re-
duce medication errors. Unfortunately,
these efforts have not yet translated into
wanted changes in physician behavior.1-3
Even when the physician is aware of a
guideline, time and mental processing con-
straints at clinical decision making ham-
per its use.4 Guideline implementation
strategies, including alerts, reminders, and
other clinical decision support,5 are more
likely to be effective because they deliver
specific advice at the time and place of a
consultation. Such strategies have been as-
sociated with reduced medication pre-
scribing errors, improved preventive and
chronic disease care, and improved phy-
sician and patient satisfaction in con-
trolled trials, predominantly in academic
settings or inpatient environments.6-12
However, these studies are difficult to gen-
eralize to community-based care, where
most prescribing occurs. In addition, many
previous analyses have had short fol-
low-up times, limiting inferences regard-
ing erosion of effect over time.13,14
Systems analysis suggests that comput-
erized provider order entry (CPOE) with
clinical decision support systems can re-
duce medication errors.15 A recent sys-
tematic review16 supports the effective-
ness of CPOE with clinical decision
support in reducing the frequency of medi-
cation errors in inpatients. However, there
is little research on the effectiveness of elec-
tronic medical record (EMR) alerts for pro-
moting medication safety in the outpa-
tient environment. This topic is important
because about half of medication errors oc-
cur during the prescribing phase,17,18 and
most prescribing occurs in the outpa-
tient setting.
The goal of this study was to evaluate
the impact of decision support at pro-
vider medication order entry, which sought

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©2006 American Medical Association. All rights reserved.

to reduce the use of 2 classes of medications generally
contraindicated in elderly persons. We took advantage
of a natural experiment and 39 months of data at a large
health maintenance organization (HMO), using a strong
quasi-experimental design and interrupted time series
analysis, to examine the effects of CPOE with clinical de-
cision support in reducing the use of potentially contra-
indicated agents in elderly persons. To our knowledge,
this is the first study examining the effects of medica-
tion safety alerts (CPOE with clinical decision support)
in a population-based primary care setting.
METHODS
STUDY DESIGN
By using data from a 39-month period, we evaluated changes
in the use of medications generally contraindicated in elderly
persons, associated with the implementation of a CPOE alert
cautioning against using these 2 classes of medications in el-
derly persons. We used interrupted time series analysis to es-
timate changes in the use of these medications, controlling for
prealert trends.
SETTING AND INTERVENTION
The setting for the study was a group-model HMO in the Pa-
cific Northwest caring for about 450 000 people, with demo-
graphic characteristics closely mirroring those of the surround-
ing metropolitan area. The Research Subjects Protection Office
approved the study. The HMO uses an EMR (EpicCare; Epic
Systems Corporation, Verona, Wis) for all outpatient encoun-
ters, including the ordering of all medications. From Septem-
ber to October 2000, decision support was implemented, which
alerted clinicians to preferred alternative medications when they
ordered certain nonpreferred agents that carry potential con-
traindication in elderly persons.19 These nonpreferred agents
were certain long-acting benzodiazepines (diazepam, fluraz-
epam, triazolam, and chlordiazepoxide) and tertiary amine tri-
cyclic antidepressants (TCAs) (imipramine, amitriptyline, and
doxepin); the shorter-acting and less-sedating alternative ben-
zodiazepines (oxazepam and temazepam), secondary amine
TCAs (nortriptyline and desipramine), or other medications
(buspirone, trazodone, and paroxetine) were suggested as al-
ternatives. Paroxetine was subject to changes in formulary sta-
tus during the period of study, leading to large fluctuations in
use that were unrelated to the alerts, so we did not include it
in any of our analyses.
The alerts (Figure 1) made it possible to change the order
by accepting the alternative medication suggested. These alerts
were drug specific, meaning that they were presented to the
clinician after ordering one of the nonpreferred medications,
regardless of patient characteristics, such as age or comorbidi-
ties. As Figure 1 illustrates, the alert was constructed so that
the warning regarding falls and fractures was prominent. If de-
sired, the user could scroll down the message pane to see the
rest of the text, which contained further information on spe-
cific preferred alternative agents.
STUDY SAMPLE
We collected electronic data on monthly outpatient medica-
tion dispensings from prescriptions written by primary care pro-
viders between October 1, 1999, and December 31, 2002; this
period included 12 months before the alerts were imple-
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mented and 27 months after implementation. We included data
from all 15 primary care clinics. Providers were family practi-
tioners and internal medicine clinicians, including physicians
(n = 152), nurse practitioners (n = 25), and physician assis-
tants (n=32) (the numbers are for the 12 months preceding
the intervention). All members of the HMO during the obser-
vation period were included in the study.
DATA SOURCES AND MEASURES
We were interested in examining the effect of the alerts on
initial medication prescribing, because it is during prescrib-
ing that alerts are presented to the clinician. Our data source
was the prescription-dispensing database. The dispensing
database includes prescription refills, but refills are not sub-
ject to the alert. Prescriptions are given a unique identifica-
tion number, and this identification number is associated
with the entire stream of prescription refills, making it
impossible to directly differentiate between initial dispens-
ings and refills. To minimize inclusion of refills, we included
dispensings only when (1) the patient had not been exposed
to the medication in the previous 6 months and (2) the pre-
scription was the first in a stream of refills for a given pre-
scription identification number.
The alerts in this analysis were presented when any non-
preferred drug was prescribed, regardless of age or clinical char-
acteristics of the patient. It was left to the prescriber to deter-
mine the clinical appropriateness of the advisory. Because of
this, we were interested in whether there was any spillover effect
in nonelderly persons, so we examined results for patients in
the elderly (aged ⱖ65 years) and nonelderly (aged ⬍65 years)
groups.
STATISTICAL ANALYSIS
Outcomes of interest (number of dispensings of nonpreferred
and preferred drugs per 10 000 population) were aggregated
into 39 monthly intervals. We used interrupted time series re-
gression models (segmented regression) to estimate changes
in outcomes that occurred after the alert implementation, con-
trolling for preintervention trends and other autocorrelation
(including seasonal effects).20-23 The models included a con-
stant, a baseline slope term to control for secular trends (eg,
first-, second-, and higher-order autocorrelation), and terms
estimating changes in the level and slope of outcome rates. Analy-
ses were conducted using SAS statistical software (Proc Au-
toreg; SAS Institute Inc, Cary, NC).
RESULTS
At baseline, patients with a dispensing for the nonpre-
ferred agents were older (nonelderly patients, 44.9 vs 31.4
years; and elderly patients, 75.1 vs 74.7 years) and more
likely to be female (nonelderly patients, 72.1% vs 51.7%;
and elderly patients, 69.4% vs 56.2%) compared with the
general HMO population. Data on the use of nonpre-
ferred and preferred medications at baseline are given in
the Table. Controlling for baseline trends, a sudden re-
duction in the rate of initial dispensing of nonpreferred
agents among elderly persons was observed when the
alerts were placed (Figure 2A), from 21.9 to 16.8 per
10 000 (P⬍.01). This decrease of 5.1 prescriptions per
10 000 represented a relative decrease of 22% from the
month before alert implementation and was sustained over
the entire 2-year postalert observation period. For non-
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Figure 1. Example screen shot of an alert for diazepam, a nonpreferred benzodiazepine.

elderly persons, no significant (P=.48) changes were ob-
served in the use of nonpreferred agents.
The dispensing rate of preferred agents did not change
significantly (P=.66) for elderly persons, but did con-
tinue an upward trend throughout the observation pe-
riod (Figure 2B). Controlling for preintervention trends,
the use of preferred agents increased suddenly by 4.0 dis-
pensings per 10 000 (P⬍.01) for nonelderly persons, rep-
resenting a 20% increase from the month before alert
implementation. An upward trend continued over the ob-
servation period.
Controlling for baseline trend, the rate of use of non-
preferred TCAs for elderly persons decreased abruptly
by 4.5 dispensings per 10 000, a 35% decrease from the
month before the alert, with a further continued decline
of 0.4 prescription per 10 000 per month (P⬍.01) ob-
served over the entire 39-month study period. The rate
of initial dispensing of the nonpreferred TCAs for el-
derly persons had been increasing at a rate of 0.3 pre-
scription per 10 000 per month (P=.02) before the alerts
were placed—this trend was reversed after alert imple-
mentation. The rate of overall dispensing for nonpre-
ferred TCAs did not change significantly (P=.22) before
or after alert implementation for nonelderly persons.
The medications with the largest observed changes in
dispensing rates were the TCA amitriptyline (nonpre-
ferred) and its metabolite, the preferred TCA, nortrip-
tyline. Nortriptyline was specifically suggested in the alert
as the preferred alternative to amitriptyline. The rate of
dispensings for the nonpreferred TCA (amitriptyline) was

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higher than for the preferred TCA (nortriptyline) for both
age groups at every time point before the alert (Figure 3).
This trend was suddenly reversed after the alerts. Con-
trolling for baseline trends, there was an abrupt and sus-
tained 34% decrease from 9.8 (1 month before alert imple-
mentation) to 6.4 dispensings per 10 000 (P⬍.01) in the
use of the TCA amitriptyline for elderly persons, with a
further slight decline (−0.3 prescription per 10 000 per
month, P=.004) during the follow-up period of observa-
tion. Use of the TCA amitriptyline also decreased for non-
elderly persons, but not significantly (P=.22) (Figure 3A).
Use of the preferred TCA nortriptyline increased sud-
denly in both age groups, by 3.5 prescriptions per 10 000
for elderly persons (P⬍.01) and by 1.9 prescriptions per
10 000 for nonelderly persons (P⬍.01) (Figure 3B).
Although the monthly rate of initial prescribing for non-
preferred benzodiazepines did not change, the monthly ini-
tial prescribing rate of flurazepam per 10 000 did decrease
immediately following the alert for elderly persons, by 0.3
dispensing per 10 000 (P⬍.10), with a continued de-
crease of 0.04 dispensing per 10 000 per month (P=.02),
which persisted to the end of the study period; no changes
were observed for nonelderly persons. No significant
(P=.36) changes were noted in the rate of use of preferred
benzodiazepines or “other” preferred agents (buspirone and
trazodone) in either age group—the small sample sizes did
not produce stable effects.
COMMENT
Following the implementation of drug-specific alerts in
an outpatient setting aimed at decreasing the use of medi-
cations that are often contraindicated in elderly per-
sons, we found an abrupt, large, and persistent reduc-
tion in the exposure of elderly patients to nonpreferred
medications. Among elderly persons, we found that the
use of nonpreferred agents decreased immediately by 5.1
prescriptions per 10 000 (P⬍.01), a 22% relative de-
crease from the month before alert implementation. This
reduction was sustained over the entire 2-year postalert
period of observation, and was driven primarily by de-
creases in dispensings for nonpreferred TCAs. The re-
duction in the use of nonpreferred TCAs was especially
striking given that their rate of dispensing was increas-
ing significantly before the intervention, then contin-
ued significantly downward at every time point after the
intervention. We found no evidence of a decrease in the
use of nonpreferred agents for nonelderly patients.
Among all the medications studied, the TCAs ami-
triptyline and nortriptyline had the largest changes in dis-
pensing rates. Before the alert, the nonpreferred TCA ami-
triptyline was prescribed more frequently at every time
point than the preferred TCA nortriptyline, but after the
alert, this finding was exactly reversed. One reason may
be that there is a clear therapeutic interchange—
amitriptyline is metabolized to nortriptyline—perhaps
making the exchange more amenable for clinician and
patient acceptance. In addition, for other nonpreferred
medications, specifically the long half-life benzodiaz-
epines, there is conflicting opinion on whether they should
be avoided in elderly persons.24
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Table. Use of Nonpreferred and Preferred
Medications at Baseline*
Nonelderly Elderly
Medication Persons Persons
Nonpreferred prescriptions
Tricyclic antidepressants 5.9 12.8
Benzodiazepines 2.3 10.1
Total 8.2 22.9
Preferred prescriptions
Tricyclic antidepressants 5.2 10.9
Benzodiazepines 5.9 22.5
Other preferred agents 8.8 19.8
Total 19.8 53.3
*Data are given as number of prescriptions per 10 000 enrollees. Data
were calculated at 1 month prealert. The different types of drugs included in
each category are described in the “Setting and Intervention” subsection of
the “Methods” section.
We found that while the use of nonpreferred medi-
cations decreased for elderly persons, there was no off-
setting increase in the use of preferred medications. This
finding suggests that the alerts had the effect of decreas-
ing overall exposure of older patients to these types of
drugs, nonpreferred and preferred. While this may have
been clinically appropriate for some patients, it is pos-
sible that others were denied appropriate medication. Al-
ternatively, clinicians may have switched to other medi-
cations that we did not include in our analysis.
This research suggests there may be some unex-
pected consequences from the alerts, namely, that the rates
of use of preferred medications increased for people in
younger age groups. One reason for this finding may be
the high fraction of prescribing encounters with nonel-
derly patients for whom the alerts were generated. Also,
the alert functioned such that it was easy to choose the
recommended alternative medication, and the clini-
cians’ “reward” for choosing the alternative was a com-
pleted prescription automatically prepopulated (with dose,
directions for use, and refills) that was ready for elec-
tronic signature. Anecdotes from clinicians suggest that
they would start a prescription with the nonpreferred
medication to access the prepopulated prescription.
This study includes alerts with particular character-
istics, potentially limiting generalizability. First, even
though the premise of the safety message contained in
these alerts was related to patient age, because of the func-
tionality constraints of the specific EMR in use at the time
of the study, ordering of specific medications, regard-
less of patient age, triggered the alerts. At the HMO, about
25% of all prescriptions for the nonpreferred drugs are
for people older than 65 years. An alert with more pa-
tient specificity (ie, only present for elderly patients) would
reduce provider burden; whether such an alert would be
differentially effective is unknown.
A remaining unanswered question is the relationship
of the intervention to patient outcomes. The alerts may
have decreased the use of nonpreferred medications, but
that decrease does not necessarily translate into im-
proved outcomes (eg, decreased rate of daytime seda-
tion and fewer falls). In addition, there is some contro-
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 A 30 Intervention Point
Persons ≥65 y
Persons <65 y
25
No. of Dispensings per 10 000

20

15

10

B 70 Intervention Point

60
No. of Dispensings per 10 000

50

40

30

20

10

0
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

1999 2000 2001 2002

Figure 2. Time series of nonpreferred (A) and preferred (B) agent dispensings per 10 000 by age. Fitted trend lines show predicted values from the segmented
regression analysis.

versy surrounding the clinical appropriateness of epam for relief of anxiety in the past to use it again at a
recommendations regarding some of the medications low dosage for the short term, particularly if the patient
targeted by the alerts in this analysis. Specifically, has not responded well to an alternative preferred agent,
some research24 has suggested that long half-life ben- such as oxazepam or buspirone.
zodiazepines are less likely than short half-life benzo- Compared with studies16 conducted in the inpatient
diazepines to be associated with hip fractures. This lit- setting of CPOE with clinical decision support, our
erature may have had some effect on the effectiveness results suggest a similar direction of effect for the out-
of the alerts if, for example, clinicians chose to ignore patient environment (ie, toward decreasing contrain-
the alerts because of their awareness of the contro- dicated prescribing). Comparing the results of these
versy. However, these medications remain on recent studies is difficult because of differing clinical topics,
lists of medications to avoid in elderly persons.19 A study designs, and outcome measures. However, the
recent study 25 suggests that elderly nursing home reduction of 22% in potentially inappropriate prescrib-
patients who are exposed to potentially inappropriate ing of nonpreferred agents in those older than 65
agents (including those in our study) experience a years that we observed is consistent with findings
higher risk of hospitalization and death. That study from studies16 of inpatient CPOE with clinical decision
examined a broader array of agents and a more frail support.
population, but does suggest that decreasing exposure One small Canadian study26 in the outpatient setting
to these agents is beneficial. that examined the effectiveness of clinical decision sup-
The alerts were not entirely successful in eliminating port (but without CPOE) found a reduction of 13%
the use of these medications in elderly persons. Some use (relative rate, 0.77; 95% confidence interval, 0.59-1.00)
of these drugs in elderly persons is probably clinically in inappropriate prescribing of long-acting benzodiaz-
appropriate, however, so we would not expect to see the epines and active metabolite TCAs. Our results rein-
use of the drugs decline to 0. For example, it might be force that finding in a larger population with a mature
reasonable for a patient who has successfully used diaz- EMR.

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 A 14 Intervention Point
Persons ≥65 y
Persons <65 y
12

No. of Dispensings per 10 000

10

B 14 Intervention Point

12
No. of Dispensings per 10 000

10

0
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

1999 2000 2001 2002

Figure 3. Time series of the dispensings per 10 000 of the tricyclic antidepressants amitriptyline (A) and nortriptyline (B) by age. Fitted trend lines show predicted
values from the segmented regression analysis.

There are alternative explanations for our findings Accepted for Publication: December 27, 2005.
that should be considered. Specifically, the issue of Correspondence: David H. Smith, RPh, PhD, Kaiser
avoiding certain drugs in elderly persons has gained Permanente Center for Health Research, 3800 N Inter-
press in recent years,19,27 raising awareness in the clinical state Ave, Portland, OR 97227 (David.H.Smith@kpchr
community. However, given our strong quasi-experi- .org).
mental methods, and the sudden decrease we observed Financial Disclosure: None.
contemporaneous with the alert initiation, this is an Funding/Support: This study was supported by grant 1
unlikely explanation for the observed changes in medi- U18 HS11843 from the Agency for Healthcare Research
cation use. In addition, we are unaware of any ongoing and Quality, Rockville, Md.
cointervention that could explain these results. We did Role of the Sponsor: The funding body had no role in
investigate this possibility thoroughly by directly inquir- data extraction and analyses, in the writing of the manu-
ing with appropriate personnel in pharmacy and other script, or in the decision to submit the manuscript for
relevant departments at the HMO. publication.
In conclusion, we found that alerts in an outpatient Acknowledgment: We thank the many individuals who
EMR aimed at decreasing prescribing of medication use assisted with this project, particularly those on the Re-
in elderly persons may be an effective method of reduc- gional Formulary and Therapeutics Committee and in
ing prescribing of contraindicated medications. Addi- Information Technology.
tional work on the impact of more patient-specific clini-
cal decision support will be useful to determine whether REFERENCES
an intervention method with less clinician burden can
have similar effects in the outpatient setting. More im- 1. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice: a sys-
portant, the effect of the alerts on patient outcomes is less tematic review of rigorous evaluations. Lancet. 1993;342:1317-1322.
certain and deserves further investigation. 2. Grimshaw JM, Thomas RE, MacLennan G, et al. Effectiveness and efficiency of

(REPRINTED) ARCH INTERN MED/ VOL 166, MAY 22, 2006 WWW.ARCHINTERNMED.COM
1103

©2006 American Medical Association. All rights reserved.

 guideline dissemination and implementation strategies. Health Technol Assess.
2004;8:iii-iv, 1-72.
3. Gilbody S, Whitty P, Grimshaw J, Thomas R. Educational and organizational in-
terventions to improve the management of depression in primary care: a sys-
tematic review. JAMA. 2003;289:3145-3151.
4. McBride PE, Pacala JT, Dean J, Plane MB. Primary care residents and the man-
agement of hypercholesterolemia. Am J Prev Med. 1990;6:71-76.
5. Shiffman RN, Liaw Y, Brandt CA, Corb GJ. Computer-based guideline implemen-
tation systems: a systematic review of functionality and effectiveness. J Am Med
Inform Assoc. 1999;6:104-114.
6. Balas EA, Boren SA, Griffing G. Computerized management of diabetes: a syn-
thesis of controlled trials. Proc AMIA Symp. November 1998:295-299.
7. Balas EA, Weingarten S, Garb CT, Blumenthal D, Boren SA, Brown GD. Improv-
ing preventive care by prompting physicians. Arch Intern Med. 2000;160:301-
308.
8. Elson RB, Connelly DP. Computerized patient records in primary care: their role
in mediating guideline-driven physician behavior change. Arch Fam Med. 1995;
4:698-705.
9. Rind DM, Safran C, Phillips RS, et al. Effect of computer-based alerts on the treat-
ment and outcomes of hospitalized patients. Arch Intern Med. 1994;154:1511-
1517.
10. Jha AK, Kuperman GJ, Teich JM, et al. Identifying adverse drug events: devel-
opment of a computer-based monitor and comparison with chart review and stimu-
lated voluntary report. J Am Med Inform Assoc. 1998;5:305-314.
11. Classen DC, Pestotnik SL, Evans RS, Burke JP. Computerized surveillance of ad-
verse drug events in hospital patients. JAMA. 1991;266:2847-2851.
12. Bates DW. Using information technology to reduce rates of medication errors in
hospitals. BMJ. 2000;320:788-791.
13. Demakis JG, Beauchamp C, Cull WL, et al. Improving residents’ compliance with
standards of ambulatory care: results from the VA Cooperative Study on Com-
puterized Reminders. JAMA. 2000;284:1411-1416.
14. Abookire SA, Teich JM, Sandige H, et al. Improving allergy alerting in a com-
puterized physician order entry system. Proc AMIA Symp. November 2000:
2-6.
15. Leape LL, Bates DW, Cullen DJ, et al; ADE Prevention Study Group. Systems
analysis of adverse drug events. JAMA. 1995;274:35-43.
(REPRINTED) ARCH INTERN MED/ VOL 166, MAY 22, 2006
1104
©2006 American Medical Association. All rights reserved.
16. Kaushal R, Shojania KG, Bates DW. Effects of computerized physician order en-
try and clinical decision support systems on medication safety: a systematic review.
Arch Intern Med. 2003;163:1409-1416.
17. Bates DW, Cullen DJ, Laird N, et al; ADE Prevention Study Group. Incidence of
adverse drug events and potential adverse drug events: implications for prevention.
JAMA. 1995;274:29-34.
18. Kaushal R, Bates DW, Landrigan C, et al. Medication errors and adverse drug
events in pediatric inpatients. JAMA. 2001;285:2114-2120.
19. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the
Beers criteria for potentially inappropriate medication use in older adults: re-
sults of a US consensus panel of experts. Arch Intern Med. 2003;163:2716-
2724.
20. Wagner AK, Soumerai SB, Zhang F, Ross-Degnan D. Segmented regression analy-
sis of interrupted time series studies in medication use research. J Clin Pharm
Ther. 2002;27:299-309.
21. Soumerai SB, McLaughlin TJ, Ross-Degnan D, Casteris CS, Bollini P. Effects of
a limit on Medicaid drug-reimbursement benefits on the use of psychotropic agents
and acute mental health services by patients with schizophrenia. N Engl J Med.
1994;331:650-655.
22. Soumerai SB, Ross-Degnan D, Gortmaker S, Avorn J. Withdrawing payment for
nonscientific drug therapy: intended and unexpected effects of a large-scale natu-
ral experiment. JAMA. 1990;263:831-839.
23. Gillings D, Makuc D, Siegel E. Analysis of interrupted time series mortality trends:
an example to evaluate regionalized perinatal care. Am J Public Health. 1981;
71:38-46.
24. Wagner AK, Zhang F, Soumerai SB, et al. Benzodiazepine use and hip fractures
in the elderly: who is at greatest risk? Arch Intern Med. 2004;164:1567-1572.
25. Lau DT, Kasper JD, Potter DE, Lyles A, Bennett RG. Hospitalization and death
associated with potentially inappropriate medication prescriptions among el-
derly nursing home residents. Arch Intern Med. 2005;165:68-74.
26. Tamblyn R, Huang A, Perreault R, et al. The medical office of the 21st century
(MOXXI): effectiveness of computerized decision-making support in reducing in-
appropriate prescribing in primary care. CMAJ. 2003;169:549-556.
27. Beers MH. Explicit criteria for determining potentially inappropriate medication
use by the elderly: an update. Arch Intern Med. 1997;157:1531-1536.
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