- Email: [email protected]
Improving Drug Therapy for Patients with Asthma-Part 2: Use of Antiasthma Medications
. . RESEARCH
Improving Drug Therapy for Patients with Asthma-Part 2: Use' of Antiasthma Medications Hanne Herborg. Birthe Soendergaard. Tove .Jorgenaen. Lotte Fonneabaek, Charlea D. Hepler. Helle Holat. and Bente Froekjaer
Objectiva: To describe the use of antiasthma drugs among the study patients and to evaluate whether therapeutic outcomes monitoring (TOM) is associated with improved quality of drug therapy, o..ign: Prospective, controlled, multicenter study, Consumption of antiasthma medications was measured as the number of defined daily doses (DDDs) purchased. Data were collected from the pharmacies' computer systems for a period beginning 6 months before the start of the study (period 1) and during its first and second halfyears (periods 2 and 3). Treatment changes for TOM patients were classified on the basis of drug regimens at periods 1 and 3. Setting: Community pharmacies in Denmark (16 intervention, 15 control). Pati8lJts: Five hundred patients with asthma aged 16to 60 years who were being treated in primary health care; this study used data from 350 patients from this sample. Intervention: TOM. Main
Outcome Measures: Changes in the use of individual drugs and changes in therapeutic patterns-distribution of purchased drugs; proportion of corticosteroid users; frequency of drug regimens used; treatment changes for TOM patients. Raub: TOM patients' consumption of ~2-agonists decreased by 12% overall from period 1 through period 3, while control patients' consumption of these medications decreased by only 1%. TOM patients' use of inhaled corticosteroids increased by more than 50% compared with 9% among controls. In both groups, about one-half of all purchased DDDs were for inhaled ~2-agonists. The proportion of inhaled corticosteroids increased from 27% to 42% of total ODDs for the TOM group and remained constant for controls. Of patients using ~2-agonists, 68% also used inhaled steroids initially in both the TOM and control groups. The proportion of inhaled steroid users in the TOM group increased to 84%, and to 70% among controls. The most common regimen was inhaled short-acting ~2-agonists and corticosteroids in combination, and the second most common regimen was monotherapy with short-acting
~2-agonists.
With time, the regimens changed
more toward consensus guidelines among TOM patients. Changes in drug therapy totaled 451, averaging 2.4 changes per TOM patient. The largest number of changes (49%) involved inhaled corticosteroids. Conclusion: Changes in medication use among TOM patients were toward improved asthma treatment. Our results show that community pharmacists, physicians, and patients, working together, can improve prescribing, solve drug therapy problems, and improve outcomes for patients with moderate-to-severe asthma.
JAm Pharm Assoc. 2001;41:551-9. Received June 16, 2000, and in revised form November 13, 2000. Accepted for publication November 17, 2000. Hanne Herborg, MSc, is head, Division of Research and Development; Birthe Soendergaard, PhD, is project coordinator; Tove Jorgensen, MSc, PhD, is pharmacist; Lotte Fonnesbaek, MSc, is pharmacist, Pharmakon, Danish College of Pharmacy Practice, Hilleroed, Denmark. Charles D. Hepler, PhD, is distinguished professor, pharmacy health care administration, University of Fla., Gainesville, Fla. Helle Holst, MSc, PhD, is associate professor, Department of Mathematical Modelling, Technical University of Denmark, Lyngby, Denmark. Bente Froekjaer, MSc, is project coordinator, Division of Research and Development, Danish College of Pharmacy Practice, Hilleroed, Denmark. Correspondence: Hanne Herborg, Pharmakon, Danish College of Pharmacy Practice, Milnersvej 42, DK-3400 Hilleroed, Denmark. Fax: 01145-4820-6062. E-mail: [email protected]. See related articles on pages 514 and 539.
VoL 41, No 4
July/August 1001
Efforts to improve drug therapy often focus on single components, for example, adherence or prescribing. In pharmaceutical care, the individual patient is the focus, and the goal is to achieve definite outcomes of drug therapy (e.g., improved quality of life) by identifying, resolving, and preventing drug-related problems (DRPs) . Thus, pharmaceutical care shifts the focus of quality management of the medication use process from single process components to outcomes and from use of drug products to care for the patient as a whole. We hypothesized that, for patients with moderate-to-severe asthma, a pharmaceutical care program would cost-effectively improve health status, clinical and psychosocial outcomes, and quality of drug therapy. Patients with asthma were chosen because the disease is associated with a high frequency of drug-related morbidity,l-3 despite the availability of improved treatments.
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Danish TOM Project-Part 2
To test this hypothesis, we evaluated a therapeutic outcomes monitoring (TOM) program in a 12-month controlled trial involving 31 community pharmacies (16 intervention, 15 control) in Denmark. In cooperation with physicians and patients, TOM pharmacists identified and resolved (or referred) DRPs that, if not addressed, might have resulted in therapeutic failure or' adverse effects. The TOM program has been previously described.4 The Danish TOM project, including processes and patient outcomes in the present study, is described in Part 1,5 also in this issue of JAPhA. The present article, Part 2, reports the effects of TOM on patients' use of antiasthma drugs. The results of the outcomes study demonstrate that the strategy used in the Danish TOM project was effective in improving the quality of drug therapy for asthma patients in primary care. Drug therapy outcomes-symptom status, quality of life (health-related and asthma-specific) and days of sicknesstended to improve for intervention patients. Beneficial effects were also found for the following intermediate outcome and process measures: knowledge of asthma and the medications used to treat it, inhalation errors, drug use, and drug therapy problems. Also, as reported elsewhere, the program was costeffective. 6 Appropriate medication use can significantly improve outcomes for many patients with asthma. Therefore, demonstrated improvements in medication use would provide an important explanatory link between the provision of TOM services by pharmacists and the improved outcomes of care described in Part 1.
Objectives Our objectives in this article are to describe the consumption of antiasthma drugs by the study patients and to evaluate whether TOM was associated with improved quality of drug therapy, i.e.,
with drug consumption that is more consistent with consensus treatment guidelines.
Methods The general methods of the controlled, prospective study carried out from August 1994 and through July 1995 are described in Part 1. The specific measures used in this study are described in Table P A total of 500 patients participated in the study. To ensure reliability of data, however, we included data on drug use only for patients purchasing more than 90% of their drugs in a study pharmacy (n =350).
Measures and Sampling We analyzed data on drug consumption (purchased drugs) for three periods: period I-beginning 6 months prior to the start of the study (February 1994 through July 1994); period 2-the frrst half-year of the study (August 1994 through January 1995); and period 3-the second half-year of the study (February 1995 through July 1995). Drug consumption was measured as use of defmed daily doses (DDDs).7 It was possible to identify and quantify the medications patients were purchasing because pharmacies in Denmark use Anatomical and Therapeutic Classification (ATC) codes to identify and track drugs 8 and DDDs to identify the amount of drug consumed. ATC codes and DDDs have been defined by the World Health Organization as a classification standard and a standard for daily drug doses for the purpose of assembling national and international statistics on drug consumption. Consumption of the following categories of antiasthma drugs was measured: inhaled P2-agonists (ATC code R03AC), inhaled adrenergic agonists (R03AK), inhaled cortico-steroids (R03BA), inhaled anticholinergics
Table 1. Indicators and Number of Pharmacies and Patients Studied
Analysis Use of individual drugs Oral corticosteroid use Mean drug consumption Mean individual difference in drug consumption Therapeutic pattern Pattern of purchased drugs Distribution of users Drug treatment regimens Changes in drug therapy for TOM patients
Indicator
No. Pharmacies
No. Patients (TOM/Control) (241/228) (181/169) (181/169) (181/169)
Result
Number of courses per patient Purchased (ODDS/user/day) x 100 a) MID in (ODDS/user/day) x 100 b) MID x 100%/group mean (period 1)
31 298 29 8 298
469 350 350 350
Total ODDs of each drug group as percentage of total ODDs purchased Percentage of inhaled corticosteroid users among users of inhaled f}2-agonists Drug regimens for individual patients (as purchased) Number and type of therapy changes
29
350 (181/169)
Figure 1
29
350 (181/169)
Figure 2
26
302 (133/169)
Figure 3
14
184
Table 3
Text Table 2 (column 1) Table 2 (column 2) Table 2 (column 3)
DOD = defined daily dose; MID = mean individual difference; TOM = therapeutic outcomes monitoring. "The subanalysis for inhaled short- and long-acting f}i-agonists involved 26 pharmacies and 302 patients.
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(R03BB), inhaled antiallergics (sodium cromoglycate, called cnr molyn sodium in the United States, and nedocromil sodium) (R03BC), oral ~2-agonists (R03CC), and theophylline (R03DA).
Use of Individual Drugs We collected drug consumption data, measured as number of DDDs purchased per patient, from the computer systems at 29 of the 31 participating phannacies (both intervention and control) for periods I through 3. Data from two pharmacies were excluded because of a software problem. Four vendors provided additional software tools and service to assist in recording and collecting data in the correct ATC and DDD fonnats. Printouts of pharmacy ftles on asthma drugs purchased each month were collected for all 500 patients. Only data for patients who reported obtaining more than 90% of their asthma drugs from a study pharmacy were entered into an SPSS database, resulting in the inclusion of 350
RESEARCH
patients in the analysis of drug consumption. More detailed information was needed to distinguish between short- and long-acting inhaled 132-agonists; because three TOM pharmacies were unable to provide this level of detail, data on use of inhaled ~2-agonists were collected from only 26 phannacies. . Except for oral corticosteroids, data on consumption of individual drugs were converted to an index of DDDs per user per day x 100. (Hence, if all users consume 1 DDD/day, the index is 100. If the index is below 100, the drug is prescribed or used less frequently or in smaller dosages.) A patient was considered a user of a given group of drugs if he or she purchased a drug in that group during any of the three time periods. . Pharmacists collected information on the number of courses of asthma-specific oral corticosteroids .during evaluation sessions at the ends of periods 1,2, and 3. Oral steroid use was analyzed as the number of courses of therapy used by each patient.
Table 2_ Consumption of Antiasthma Drugs
Mean Value in OOOs/User!Day x 100 (SEM) Period Period Period 1 2 3 Short-acting i32-agonists s.b TOM group (n = 111) Control group (n = 148)
87.1 (9.2) 94.0 (8.9)
Long-acting i32-agonists TOM group (n = 23) Control group (n = 23)
27.4 (7.2) 57.0 (12.1)
91 .4 (9.6) 111 .5 (9.8) 46.6 (9.6) 66.6 (11.8)
Mean Individual Difference (SEM) Period Period 2-1 3-1
PValues (tTest/Nested ANOVA) in Use Period Period Period 2- 1 3-1 3-1
% Change
64.7 (8.9) 90.4 (9.0)
4.3 (5.8) 17.5 (5.5)
-22.4 (6.4) - 3 .6 (8.1)
4.9 18.6
- 25.7 -3.8
.086 .169
72.1 (11 .0) 56.4 (10.8)
19.2 (10.0) 9 .7 (7.5)
44.7 (14.4) -{J.50 (11 .7)
70. 1 17.0
163.1 -{J.9
.019 .114
5 .2 (5.5) 4.4 (5.6)
- 10.0 (6.1) - 1.0 (7.8)
6 .1 4.2
- 11.7 -1 .0
.374 .238
3 .0 249.6
- 26.2 1,584.6
.099 .071
51 .5 24.7
52.5 9 .1
.018 .102
i32-agonists (total) TOM group (n = 162) Control group (n = 155)
85.2 (7.3) 103.6 (9.0)
90.4 (7.9) 108.1 (8.9)
75.4 (7.6) 102.5 (8.7)
Inhaled adrenergic agonists C TOM group (n = 12) Control group (n = 9)
148.0 (58.3) 12.3 (9.3)
152.5 (44.8) 43.0 (17 .8)
109.2 (32.0) 207.2 (140.2)
4.5 (28.3) 30.7 (9.7)
Inhaled corticosteroids TOM group (n = 167) Control group (n = 137)
49.3 (4.9) 62.3 (5.2)
74.7 (4.4) 77.6 (5.8)
75.2 (5.2) 68.0(5.0)
25.4 (4.4) 15.4 (5. 1)
25.9 (6.2) 5 .7 (5.6)
Inhaled anticholinergicsd.e TOM group (n = 7) Control group (n = 9)
196.8 (54.3) 28.4(12.1)
139.8 (28. 1) 29.2 (12.4)
71 .0 (28.8) 34.5 (13.9)
-57.1 (44.4) 0 .7 (8.0)
-125.8 (70.0) 6.0 (14.2)
- 29.0 2 .6
-53.9 21 . 1
. 111 . 101
Inhaled antiallergics TOM group (n = 3) Control group (n = 4)
97.3 (83.4) 65.3 (14.7)
0(0) 31.4 (17.8)
0(0) 35.4 (17.3)
- 97.3 (83.4) -34.0 (14.9)
- 97.3 (83.4) - 30.0 (16.8)
-100.0 - 52.1
- 100.0 -45.9
.507
Oral i32-agonists TOM group (n = 31) Control group (n = 37)
51.6 (10.6) 33.2 (6.9)
48.9 (8.8) 28.8 (6.2)
29.8 (7.4) 33.6 (6.5)
- 2 .7 (8. 1) -4.4 (5.5)
- 21 .8 (9.8) 0 .4(6.2)
-5.2 - 13.2
-42.2 1.2
.053 .079
Theophylline' TOM group (n = 40) Control group (n = 30)
77.9 (10.0) 84.6 (11 .9)
104.3 (10.9) 78.9 (11 .4)
67.3 (10.1) 78.6 (11.7)
26.3 (10.7) - 5.7 (10.8)
- 10.7 (10 .4) -5.0 (11 .0)
33.8
-13.7 -7.1
.763 .618
ANOVA = analysis of varianc e; DOD = defined daily d ose; SEM · Phys ic ian difference e ffect ( P = .0465). bPharmacy difference effect (P = .0001) . CPhysician difference effect (P = .0013) . dPharmacy difference effe ct (P = .0086), ephysician difference e ffe ct (P = .0076). ' Phys ician difference effect (P = .0451).
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-38.8 (49.2) 194.9 (142 .2)
-e..7
= standard error of mean ; TOM = therapeutic outcomes monitoring.
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Therapeutic Patterns We calculated the distribution of purchased drugs by therapeutic class for the TOM and control groups for each time period. The distribution was based on the total number of DDDs purchased in each drug group as percentage of the total DDDs purchased. The proportion of inhaled corticosteroid users among uS,ers of inhaled ~2-agonists was analyzed separately. The rationale for the indicator is that users of ~2-agonists constitute a target group likely to need additional steroid treatment.9 We compared proportion of steroid users between the TOM and control groups for each of the three time periods using the Fisher exact test. The most frequent drug regimens were identified among patients in both groups based on the drug groups purchased by each patient. The number of patients on each regimen was calculated, and a ranked list of regimens was produced. 10 Treatment changes for TOM patients were classified on the basis of TOM pharmacists' records of prescribed regimens at the beginning and end of the study. We collected data from 14 of the 16 TOM pharmacists using records for patients who completed the study (n = 184). We did not collect these data for control patients.
Statistical Analyses Changes (differences) in the drug use variables from period 1 to period 2 and from period 1 to period 3 were calculated for each patient. Group mean differences between periods 1 and 3 were then statistically compared between the TOM and control groups. These comparisons were performed by nested analysis of variance (ANOVA). The nested ANOVA included tests for betweenpharmacy and between-physician effects ("pharmacy" and "physician" effects). The ANOVA is, in theory, equivalent to the t test if both pharmacy and physician effects can be considered negligible. For all analyses, we also present results from ordinary Student t tests. After patients reach 45 years of age, asthma may be complicated by concomitant chronic obstructive pulmonary disease. Therefore, we carried out a preliminary analysis comparing drug use in patients older than 45 years with drug use in younger patients. All analyses were performed using SPSS or SAS statistical software. P values are reported in the article. Significance was set atP< .05.
Results Two preliminary analyses showed that use of some antiasthma drugs differed significantly between the TOM and control groups in period 1. However, these differences were in drug categories with small numbers of users '(inhaled long-acting ~2-agonists, inhaled adrenergic agonists, and inhaled anticholinergics). Also, antiasthma drug use did not differ between the two age groups
(younger or older than age 45), so no further distinction was made regarding age. The mean age for TOM patients included in this analysis was 38.7 years versus 42.5 for controls (P .004).
=
Use of Individual Drugs Reliable drug consumption data (see Table 2), defined as data from patients who reported obtaining more than 90% of their asthma drugs from a study phannacy, were obtained from 350 of the initial 500 patients in the study (181 in the TOM group, 169 in the control group, 70% of the total number of patients). A comparison of the 350 included patients and 121 excluded patients showed a lower number of DDDs purchased for most asthma drug groups among the excluded patients, which is consistent with our rationale for excluding them. In Table 2, the values for short- and long-acting inhaled ~2-agonists are based on data from the 26 pharmacies that could report these data, representing a total of 302 patients. The analysis of the overall use of inhaled P2-agonists, therefore, is a secondary analysis. Mean numbers of DDDs of antiasthma drugs (presented as DDDs/user/day x 100) are presented in Table 2 for TOM and control patients, together with the mean differences and P values. Percentage change in use is included as an aid to interpretation. Analyses with significant differences between pharmacies or between physicians are marked with footnotes. The use of short-acting ~2-agonists decreased by 25.7% in the TOM group compared with a 3.8% decrease among patients in the control group from period! to period 3. These differences were not statistically significant. Consumption of long-acting ~2agonists more than doubled from period 1 to period 3 for TOM patients; there was virtually no change for control patients. The result was significant at P .019 (t test). Consumption of total ~2agonists decreased by 11.7% overall from period 1 to period 3, compared with a 1.0% decrease in the control group. The use of inhaled corticosteroids increased by 51.5% in the TOM group; the increase took place in the first 6 months of the study and then leveled off. Use of inhaled steroids increased by a smaller percentage in the control group and was not sustained. The comparison for the 12 months was significant at P .018 (t test). Consumption of oral ~2-agonists decreased by 42.2% for TOM patients from period 1 to period 3, compared with a 1.2% increase in use among con'!Ol patients. This result was significant at P .053 (t test). During the first 6 months, theophylline use increased in the TOM group by 33.8%, while theophylline use decreased in the control group by 6.7%. ln the second half-year (not shown in the table), use of theophylline decreased by 35.6% in the TOM group compared with a decrease of 0.4% in controls. As a result, use of theophylline decreased in the TOM group from period 1 to period 3 by 13.7%, compared with a 7.1% decrease in the control group, but the overall difference was not significant. For all categories of asthma drugs, except adrenergic agonists, the percentage change in use from period 1 to period 3 was larger
=
=
=
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for TOM patien than contr 1 patient . In the 6 month preceding the tudy TOM patient u eel, on average, 0.15 cour e of oral cortico teroid ver us 0.24 cour e for control (P = .145). During the study, the mean for the TOM group wa unchanged (0.16 course per patient). In the control group the number of cour es per patient decrea ed to 0.21 (P = .402). The difference in average number of regimens between TOM and control group during the study year (period 3-period 1) was not significant (P = .32).
Changes in Therapeutic Patterns Figure 1 shows the distribution of purchased drugs for the three time periods. For both TOM and control patients, about one-half of all purchased DDDs were for inhaled ~2-agonists (45.3% versus 54.9%). However, the proportion of ~2-agonists decreased somewhat more for the TOM group from period 1 to period 3 (to 40.4% in the TOM group versus 51.0% in the control group). The second most common drug class was inhaled corticosteroids. The proportion of total DDDs represented by these drugs increased from 27.2% to 41.6% for the TOM group and remained approximately constant for controls, with a change from 30.2% to 29.9%. As Figure 1 indicates, in the TOM group overall, use of inhaled ~2-agonists declined while use of inhaled steroids increased. This pattern was not observed in the control group. Figure 2 summarizes data on proportion of inhaled corticosteroid users. In period 1, 68% of ~2-agonist users in both groups also used corticosteroids. This proportion increased in the TOM group during the study year, and in the last 6 months 84.3% of inhaled ~2-agonist users also used inhaled steroids, compared with 70.4% among controls. The differences in use between
RESEARCH
TOM and control patient were ignificant in periods 2 and 3 P = .01 ). There was no difference between the proportion of teroid u er among patients receiving high do age of ~2-agoni t compared with patient on lower do age . Analysis of the mo t frequently u ed drug regimen wa ba ed on data from 26 pharmacie and 302 patients. Figure 3 how the 10 most common regimens found in the study, which cover 83% of the treatments u ed by the patients in the tudy. In both group , the highest proportion of patients used inhaled hort-acting ~2agonists and inhaled corticosteroids in combination. For TOM patients, the second most common regimen in period 1 wa mono therapy with short-acting ~2-agonists; however, by period 3 the second most common therapy in the TOM group had changed to monotherapy with inhaled corticosteroids. Among controls, the second most CCimmon regimen in both periods was short-acting ~2-agonists. These three regimens were used by 62% of the asthma drug users. The other regimens were used relatively infrequently (by 6% or fewer patients) in both groups. A regimen that became more common among TOM patients was short- and long-acting ~2-agonists with inhaled corticosteroids, which increased from 1.7% at period 1 to 6.1 % at period 3. A corresponding decrease was seen for regimens 8, 9, and 10. For an analysis of treatment changes in TOM patients' drug therapy, we relied on data from 14 TOM pharmacists and 184 TOM patients. The number of treatment changes in the TOM group from the beginning to the end of the study totaled 451, averaging 2.4 changes per patient. Changes for each group of asthma drugs are shown in Table 3. The greatest number of changes involved inhaled corticosteroids.
Figure 1 . Changes in D i stribution of Purchased Antiasthma Drugs 100
D I
80
Theophylline
Oral
~2-agonists
D Inhaled antiallergics
60
I
Inhaled anticholinergics
40 Inhaled corticosteroids
D Inhaled adrenergic agonists
20
I
Inhaled
~2-agonists
o TOM (Period 1)
TOM (Period 2)
Control (Period 1)
TOM (Period 3)
Control (Period 2)
Control (Period 3)
Group
TOM = t herapeutic outcom e s monitoring .
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Figure 2. Changes in Proportion of Inhaled Steroid Users Among Inhaled ~2-agonist Users 100
80
(/)
Q) 60
(/)
:l
D
+'"
.~
c::
0
C'l
Nonusers of steroids
40
cp
•
N
C!l.
Users of steroids
'#. 20
0
TOM
TOM
Control (Period 1)
(Period 1)
Control (Period 2)
(Period 2)
TOM (Period 3)
Control (Period 3 )
Group
TOM = therapeutic outcomes monitoring.
Figure 3. The 10 Most Frequently Used Regimens Among TOM and Control Patients 40
35
30
25
I D
(/)
Period 1
~
(/)
:::l
20
'#
Period 3
15
10
5
0 A (1)
B (1)
A (2)
8 (2)
A (3)
B (3)
A (4)
8 (4)
A (5)
B (5)
A (6)
8 (6)
A (7)
8 (7)
A (8)
B (8)
A (9)
8 (9) A (1 0) 8 (10)
A = intervention group; B = control group; TOM = therapeutic outcomes monitoring . (1) = Inhaled short-acting i32-agonists and inhaled steroids; (2) = Inhaled corticosteroids; (3) = Inhaled short-acting 13 2-agonists ; (4) = Inhaled shortand long-acting 132-agonists and inhaled corticosteroids ; (5) = Inhaled short-acting 132-agonists, inhaled steroids, and theophylline ; (6) = Inhaled short-acting and oral132-agonists and inhaled corticosteroids; (7) = Inhaled long-acting i32-agonists and inhaled steroids ; (8) = Inhaled short-acting and oral i32-agonists, inhaled steroids, and theophylline; (9) = Inhaled short-acting 13 2-agonists and theophyline ; (10) = Inhaled short-acting and oral 13 2-a gon ists.
We excluded data from two phannacies (one TOM and one control) because of a oftware problem. The 15 TOM patients excluded from this analysis for this reason were older than the other TOM patients included in the study; 60% of tho e excluded
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were 45 years of age or older, compared with 33% among those included. The 14 excluded control patients showed no demographic differences from the included control patients.
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Table 3. Changes in Drug Therapy for Individual TOM Patients Short-acting Inhaled 13 2-agonists (n = 146)
Long-acting Inhaled 132-agonists (n = 24)
4
13
Withdrawn
6
2
Self-regulation
17
60
Increased dosage
5
50
Initiated
Oral 13 2 agonists (n = 17)
Inhaled Corticosteroids (n = 220)
Oral Corticosteroids (n =
Anticholinergic and Antiallergic Agents
10)
34 15
2
(n =
2
10
Decreased dosage
34
2
15
2
23
3
17
2
Change of drug within drug group
15
22
2
As
dosage~As
needed~fixed
needed
32
dosage
10
Prescribed but not used
Theophylline (n =
24)
3 19
Changed formulation
Fixed
10)
20
~used
TOM = therapeutic outcomes monitoring .
Discussion
A Systems Approach
The quality of drug therapy among TOM patients improved during the study; medication use became more consistent with consensus guidelines for drug therapy of asthma. Drug consumption (in DDDs) changed for TOM patients toward relatively more use of long-acting P2-agonists, inhaled corticosteroids, and recommended combination therapies. The data on proportions of drugs used suggest that older therapies were relinquished and newer ones adopted. In the TOM group, changes in corticosteroid use were toward patient self-regulation of dosage, increased dosages, and initiation of new therapy. Changes in the use of P2-agonists showed decreased dosages and more as-needed use of short-acting agents, with initiation of long-acting P2-agonists. Nearly 80% of changes in theophylline use involved discontinuation of the drug. In an earlier Danish study of 20- to 44-year-old patients with asthma, users of corticosteroids in combination with inhaled P2agonists were analyzed as a proportion of all users of inhaled P2agonists. 9 The proportion did not exceed 75% for any group of P2-agonist users. In -our study (see Figure 2), the proportion increased among TOM patients from 68% at the 6-month baseline to almost 85% by the end of the study. The TOM program led to a more appropriate therapeutic pattern, considering that all patients had moderate-to-severe asthma. In another Danish study, this one performed in 1994,10 the most common regimen was inhaled P2-agonists, followed by inhaled P2-agonists in combination with inhaled corticosteroids. Monotherapy with inhaled corticosteroids was third. Our results from period 1 included the same regimens, except that the order of fIrst and second place was reversed, with steroid monotherapy in third place. Our patient sample was chosen from the whole of Denmark, while that of Gaist et al.IOwas from a single county.
The medication use process is complex and influenced by many factors. Drug therapy outcomes may be influenced directly by the quality of at least fIve activities and the effectiveness with which they are coordinated into a system: response to medical problems, prescribing, dispensing, patient advice and education, and patient behavior and monitoring of results by patients and professionals. Furthermore, according to the theory of continuous quality improvement, one would predict that management of drug use as a system (e.g., with process and outcome indicators) would be necessary to achieve and sustain improvements. ll Pharmaceutical services and other programs aimed at optimizing drug therapy can be divided into two categories: external controls and treatment modifIers.1 2,13 Services in the fIrst category influence prescribing and availability of pharmaceuticals. Examples are drug use review, therapeutic substitution programs, drug target programs, and fonnularies. Treatment modifiers are factors that influence but do not control the choice of drugs. Example are patient and physician education, therapeutic monitoring with appropriate interventions, and methods that improve therapeutic information available for decision makers. The TOM project fIts into the latter group. According to the philosophy of pharmaceutical care, health care professional and patients should work in close cooperation to optimize therapeutic outcomes. Taking a systems view that focuses on all components of the drug use process, many DRPs that are not considered preventable in the more traditional biomedical paradigm become potentially preventable. i l Traditionally, community pharmacist have focu ed on dispensing and, to a Ie ser extent, on influencing prescribing. In thi study, pharmacists in 16 TOM pharmacies increased their efforts to monitor drug therapy outcomes, advise patients and foster cooperation among patients, physicians, and pharmacists. These
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activities were associated with improved outcomes among TOM patients compared with control patients, as shown in Part 1.5 In this article we have described how TOM services led to improvements in medication use, which is consistent with the improved patient processes and outcomes reported in our earlier article.5 Some of the changes in drug consumption--for example, the increase in long-acting inhaled ~2-agonist use-may reflect changes in prescribing. The increase in inhaled corticosteroid use might also reflect new prescriptions, perhaps in addition to increased patient adherence to long-term regimens for inhaled steroids. The decreases in use of oral ~2-agonists and theophylline could also have resulted from prescribing changes as well as better management of drug therapy on the part of clinicians and more informed self-care on the part of the patient. It is noteworthy that the TOM training program emphasized patient care and improved outcomes over direct improvement of prescribing. There was no ''TOM formulary." TOM pharmacists did not contact physicians to discuss asthma therapy in general, as in "academic detailing." When pharmacists approached physicians, it was to discuss patient care (drug therapy problems), and communications were focused on individual outcomes. The improved outcomes shown in this study are consistent with those described in other studies that used a similar strategy of changing the structure of the drug use process. I 4-16 Systems strategies stand in sharp contrast to direct prescribing interventions, which rarely lead to improved patient outcomes and may even worsen patient outcomes and increase total costs of care. 17-20
Limitations Some limitations of this nonrandomized control group design are described in Part 1. We noted few additional methodological issues in this part of the study. We chose to include patients who purchased most of their asthma medications at a TOM pharmacy, since this made the drug data more reliable. Comparing included patients with those who were excluded because of their purchasing practices, we found no evidence that the exclusion of these patients biased the results. The TOM patients excluded because of a computer problem were older compared with participating TOM patients. However, in terms of drug use, older patients (> 45 years) showed no differences from the sample as a whole; therefore, excluding these patients did not appear to affect the results to any large extent. The analyses of changes in drug therapy and regimens, and the separate analyses of short- and long-acting ~2-agonists, were done on subsamples of patients. Thus, the results may not represent the total sample, although we found no evidence that these subsamples biased the results. The alternative would have been to ignore some potentially interesting information about changes in medication use. We analyzed our data on the basis of drug purchases ("intention to treat"). We know the drugs were purchased by patients
with a diagnosis of asthma, but we cannot be certain how much medication was actually consumed. However, the purchase of drugs must be considered a better proximal measure of actual use than the prescribing of drugs. Some practically significant changes in drug consumption in the hypothesized direction did not achieve statistical significance at the .05 level. For example, the lack of statistical significance for the relatively large reduction in use of inhaled short-acting ~2-ago nists could be the result of a type II error. The power of the t test to detect the observed difference was less than 0.50. For some drug groups, the lack of significance was probably a result of small numbers, but this is not likely for short-acting ~2-agonists.
Conclusion The changes in drug consumption among TOM patients were toward better asthma treatment according to consensus guidelines; that is, toward increased use of inhaled corticosteroids and more conservative use of oral asthma medication. Our data suggest that most changes in drug therapy were initiated as a result of the collaborative nature of the TOM process. Our results show that community pharmacists, patients, and physicians, working together, can improve prescribing, solve drug therapy problems, and improve patient outcomes for patients with moderate-tosevere asthma. The project was funded by Apotekerfonden of 1991. The authors declare no conflicts of interest or financial interests in any product or service mentioned in the article, including grants, employment, gifts, stock holdings, and honoraria. Acknowledgments: We thank all the patients, pharmacists, and general practitioners who made this project possible. We are also very grateful to the scientific committee that supported us: Professor Ebba Holme Hansen; Dr. Jens Peter Kampmann; Peter Lund Nielsen, PhD; Dr. Poul A. Pedersen; and Mette Rasmussen, PhD.
References 1. International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health. Bethesda, Md. 20892. Publication No. 92-3091. March 1992. Eur Respir J. 1992:5:601-41. 2. Hallas J, Davidsen 0, Grodum E, et a!. Drug-related illness as a cause of admission to a department of respiratory medicine. Respiration. 1992;59:30-4. 3. Juel K, Pedersen PA Increasing asthma morbidity in Denmark 1969-88 not a result of a changed coding practice. Ann Allergy. 1992;68:180-2. 4. Grainger-Rousseau TJ, Miralles MA, Hepler CD, et a!. Therapeutic outcomes monitoring: application of pharmaceutical care guidelines to community pharmacy. JAm Pharm Assoc. 1997;NS37:647-61. 5. Herborg H, SI/lndergaard B, Froekjaer B, et al. Improving drug therapy for patients with asthma-Part 1: patient outcomes. JAm Pharm
Assoc. 2001; 41:~. 6. SI/lndergaard B, Thorleifsson S, Herberg H, et al. Kvalitetssikring af astmapatienters Imgemiddelbehandling. Sundhedsl/lkonomisk analyse [Quality improvement of drug therapy for asthma patients: health ec0nomic analysis). Ugeskr LtBger. 2000;162:480-6. 7. World Health Organization Collaborating Centre for Drug Statistics Methodology. Guidelines for DOD. Oslo, Norway: WHO; 1993.
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Danish TOM Project-Part 2 8. World Health Organization Collaborating Centre for Drug Statistics Methodology. Guidelines for A TC Classification; Oslo, Norway: WHO; 1993. 9. Hallas J, Hansen NC. Individual utilization of antiasthma medication by young adults: a prescription database analysis. J Intern Med. 1993;234:65-70.
10. Gaist 0, Hallas J, Hansen NC, Gram LF. Are young adults with asthma treated sufficiently with inhaled steroids? A population-based study of prescription data from 1991 and 1994. Br J Clin Pharmacol. 1996;41 :285-9. 11. Hepler CO, Grainger-Rousseau TJ. Pharmaceutical care versus traditional drug treatment. Is there a difference? Drugs. 1995;49: 1-1 O. 12. Holdfold OA, Smith S. Improving the quality of outcomes research involving pharmaceutical services. Am J Health Syst Pharm. 1997;54: 1434-42. 13. Kozma CM, Reeder CE, Schultz RM. Economic, clinical and humanistic outcomes: a planning model for pharmacoeconomic research. Clin Ther.1993;15:1121-32.
RES EAR C H
15. Borgsdorf LR, Knapp KK, Miano JS. Pharmacist-managed medication review in a managed care system. Am J Hosp Pharm. 1994;51 :772-7. 16. Clapham CE, Hepler CD, Reinders TP, et al. Economic consequences of two drug-use control systems in a teaching hospital. Am J Hosp Pharm.1988;45:232~0.
17. Horn SO, Sharkey PO, Tracy OM, et al. Intended and unintended consequences of HMO cost-containment strategies: results from the Managed Care Outcomes Project. Am J Managed Care. 1996;2:25~. 18. Kozma CM, Schulz RM, Dye JT, et al. Economic impact of cost-containment strategies in third party programmes in the U.S. Part II. Pharmacoeconomics. 1993;4: 187-202. 19. Soumerai SB, Ross Degnan 0, Avorn J, et al. Effects of Medicaid drug-payment limits on admission to hospitals and nursing homes. N Engl J Med.1991;325:1072-7. 20. Hepler CD. Where is the evidence for formulary effectiveness? Am J Health Syst Pharm. 1997;54:95.
14. Wilt VM, Gums JG, Ahmed 01, Moore LM. Outcome analysis of a pharmacist-managed anticoagulation service. Pharmacotherapy. 1995;15:732-9.
APhA SESQUICENTENNIAL: VOICES FROM PAST ISSUES OF JAPbA
APhA's Headquarters: Dreams into Re ality "Members of the American Pharmaceutical Association, all who have given to the project of establishing the Headquarters Building in Washington, and pharmacists generally will be interested in the letter printed herewith. The Committee on Public Buildings and Grounds of the United States Senate and the Commission on Fine Arts pass on buildings to be erected and those who will occupy the area to be developed, improved and beautified in the section wherein the Headquarters Building of the American Phannaceutical Association will be a unit. The letter of Chairman Charles Moore, of the Fine Arts Commission, brings the project of the Association to the attention of Congress and includes its building site in the great monumental thor0ughfare from the Capitol to the Lincoln Memorial. Certainly this will stimulate the interest of many who have not heretofore realized what this Institute of American Pharmacy means to Pharmacy. It means among other things that the Headquarters of Pharmacy will stand in one of the most interesting groups of buildings in Washington .... "The letter which follows is from Chairman Moore, communicating information to Hon. Henry W. Keyes, Chairman of the Committee on Public Buildings and Grounds, U.S. Senate, relative to the developments in this section ... : '''It is contemplated to occupy the whole area between Seventeenth Street and Twenty-Third Street with a series of buildings of the general character of the Corcoran Gallery, the Red Cross, the [Daughters of the American Revolution] Building and the Pan American Building; that is to say, comparatively small, low buildings with ample space for gardens in front of them. The idea is to make a frame for the Lincoln Memorial. The type of building contemplated is shown in the National Academy of Sciences Building, which was designed as the first unit along B Street [now Constitution Avenue]. "'There are five possible units. The National Academy of Sciences Building is one. The American Pharmaceutical Association Building, to be built adjacent to it, a building designed in accordance with the idea above adverted to, is the second; the Pan American would be the third; leaving two squares to be taken care of in the future .... This scheme provides a suitable termination for B Street, which is now being developed as the great monumental thoroughfare from the Capitol to the Lincoln Memorial .... When these considerations were taken up with Doctor Rowe he brought them to the attention of Secretary of State Kellogg and President Coolidge, and received from them their unqualified indorsement of the proposed change. ' "Pharmacists now have the greatest opportunity for placing the profession of phannacy where it rightly belongs for rendering the best service for the pUblic. It requires the united efforts of all engaged in pharmaceutical activities-let everyone do his part and have a deserved share in the accomplishment of the project which has made progress far beyond early expectation ." Eberle EG. The headquarters building of the American Pharmaceutical A ociation-a unit in Washington improvement plans [editorial]. JAm PharmAssoc. 1929;18:544-5 .
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Journal of the American Pharmaceutical Association
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Improving Drug Therapy for Patients with Asthma-Part 2: Use' of Antiasthma Medications Hanne Herborg. Birthe Soendergaard. Tove .Jorgenaen. Lotte Fonneabaek, Charlea D. Hepler. Helle Holat. and Bente Froekjaer
Objectiva: To describe the use of antiasthma drugs among the study patients and to evaluate whether therapeutic outcomes monitoring (TOM) is associated with improved quality of drug therapy, o..ign: Prospective, controlled, multicenter study, Consumption of antiasthma medications was measured as the number of defined daily doses (DDDs) purchased. Data were collected from the pharmacies' computer systems for a period beginning 6 months before the start of the study (period 1) and during its first and second halfyears (periods 2 and 3). Treatment changes for TOM patients were classified on the basis of drug regimens at periods 1 and 3. Setting: Community pharmacies in Denmark (16 intervention, 15 control). Pati8lJts: Five hundred patients with asthma aged 16to 60 years who were being treated in primary health care; this study used data from 350 patients from this sample. Intervention: TOM. Main
Outcome Measures: Changes in the use of individual drugs and changes in therapeutic patterns-distribution of purchased drugs; proportion of corticosteroid users; frequency of drug regimens used; treatment changes for TOM patients. Raub: TOM patients' consumption of ~2-agonists decreased by 12% overall from period 1 through period 3, while control patients' consumption of these medications decreased by only 1%. TOM patients' use of inhaled corticosteroids increased by more than 50% compared with 9% among controls. In both groups, about one-half of all purchased DDDs were for inhaled ~2-agonists. The proportion of inhaled corticosteroids increased from 27% to 42% of total ODDs for the TOM group and remained constant for controls. Of patients using ~2-agonists, 68% also used inhaled steroids initially in both the TOM and control groups. The proportion of inhaled steroid users in the TOM group increased to 84%, and to 70% among controls. The most common regimen was inhaled short-acting ~2-agonists and corticosteroids in combination, and the second most common regimen was monotherapy with short-acting
~2-agonists.
With time, the regimens changed
more toward consensus guidelines among TOM patients. Changes in drug therapy totaled 451, averaging 2.4 changes per TOM patient. The largest number of changes (49%) involved inhaled corticosteroids. Conclusion: Changes in medication use among TOM patients were toward improved asthma treatment. Our results show that community pharmacists, physicians, and patients, working together, can improve prescribing, solve drug therapy problems, and improve outcomes for patients with moderate-to-severe asthma.
JAm Pharm Assoc. 2001;41:551-9. Received June 16, 2000, and in revised form November 13, 2000. Accepted for publication November 17, 2000. Hanne Herborg, MSc, is head, Division of Research and Development; Birthe Soendergaard, PhD, is project coordinator; Tove Jorgensen, MSc, PhD, is pharmacist; Lotte Fonnesbaek, MSc, is pharmacist, Pharmakon, Danish College of Pharmacy Practice, Hilleroed, Denmark. Charles D. Hepler, PhD, is distinguished professor, pharmacy health care administration, University of Fla., Gainesville, Fla. Helle Holst, MSc, PhD, is associate professor, Department of Mathematical Modelling, Technical University of Denmark, Lyngby, Denmark. Bente Froekjaer, MSc, is project coordinator, Division of Research and Development, Danish College of Pharmacy Practice, Hilleroed, Denmark. Correspondence: Hanne Herborg, Pharmakon, Danish College of Pharmacy Practice, Milnersvej 42, DK-3400 Hilleroed, Denmark. Fax: 01145-4820-6062. E-mail: [email protected]. See related articles on pages 514 and 539.
VoL 41, No 4
July/August 1001
Efforts to improve drug therapy often focus on single components, for example, adherence or prescribing. In pharmaceutical care, the individual patient is the focus, and the goal is to achieve definite outcomes of drug therapy (e.g., improved quality of life) by identifying, resolving, and preventing drug-related problems (DRPs) . Thus, pharmaceutical care shifts the focus of quality management of the medication use process from single process components to outcomes and from use of drug products to care for the patient as a whole. We hypothesized that, for patients with moderate-to-severe asthma, a pharmaceutical care program would cost-effectively improve health status, clinical and psychosocial outcomes, and quality of drug therapy. Patients with asthma were chosen because the disease is associated with a high frequency of drug-related morbidity,l-3 despite the availability of improved treatments.
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Danish TOM Project-Part 2
To test this hypothesis, we evaluated a therapeutic outcomes monitoring (TOM) program in a 12-month controlled trial involving 31 community pharmacies (16 intervention, 15 control) in Denmark. In cooperation with physicians and patients, TOM pharmacists identified and resolved (or referred) DRPs that, if not addressed, might have resulted in therapeutic failure or' adverse effects. The TOM program has been previously described.4 The Danish TOM project, including processes and patient outcomes in the present study, is described in Part 1,5 also in this issue of JAPhA. The present article, Part 2, reports the effects of TOM on patients' use of antiasthma drugs. The results of the outcomes study demonstrate that the strategy used in the Danish TOM project was effective in improving the quality of drug therapy for asthma patients in primary care. Drug therapy outcomes-symptom status, quality of life (health-related and asthma-specific) and days of sicknesstended to improve for intervention patients. Beneficial effects were also found for the following intermediate outcome and process measures: knowledge of asthma and the medications used to treat it, inhalation errors, drug use, and drug therapy problems. Also, as reported elsewhere, the program was costeffective. 6 Appropriate medication use can significantly improve outcomes for many patients with asthma. Therefore, demonstrated improvements in medication use would provide an important explanatory link between the provision of TOM services by pharmacists and the improved outcomes of care described in Part 1.
Objectives Our objectives in this article are to describe the consumption of antiasthma drugs by the study patients and to evaluate whether TOM was associated with improved quality of drug therapy, i.e.,
with drug consumption that is more consistent with consensus treatment guidelines.
Methods The general methods of the controlled, prospective study carried out from August 1994 and through July 1995 are described in Part 1. The specific measures used in this study are described in Table P A total of 500 patients participated in the study. To ensure reliability of data, however, we included data on drug use only for patients purchasing more than 90% of their drugs in a study pharmacy (n =350).
Measures and Sampling We analyzed data on drug consumption (purchased drugs) for three periods: period I-beginning 6 months prior to the start of the study (February 1994 through July 1994); period 2-the frrst half-year of the study (August 1994 through January 1995); and period 3-the second half-year of the study (February 1995 through July 1995). Drug consumption was measured as use of defmed daily doses (DDDs).7 It was possible to identify and quantify the medications patients were purchasing because pharmacies in Denmark use Anatomical and Therapeutic Classification (ATC) codes to identify and track drugs 8 and DDDs to identify the amount of drug consumed. ATC codes and DDDs have been defined by the World Health Organization as a classification standard and a standard for daily drug doses for the purpose of assembling national and international statistics on drug consumption. Consumption of the following categories of antiasthma drugs was measured: inhaled P2-agonists (ATC code R03AC), inhaled adrenergic agonists (R03AK), inhaled cortico-steroids (R03BA), inhaled anticholinergics
Table 1. Indicators and Number of Pharmacies and Patients Studied
Analysis Use of individual drugs Oral corticosteroid use Mean drug consumption Mean individual difference in drug consumption Therapeutic pattern Pattern of purchased drugs Distribution of users Drug treatment regimens Changes in drug therapy for TOM patients
Indicator
No. Pharmacies
No. Patients (TOM/Control) (241/228) (181/169) (181/169) (181/169)
Result
Number of courses per patient Purchased (ODDS/user/day) x 100 a) MID in (ODDS/user/day) x 100 b) MID x 100%/group mean (period 1)
31 298 29 8 298
469 350 350 350
Total ODDs of each drug group as percentage of total ODDs purchased Percentage of inhaled corticosteroid users among users of inhaled f}2-agonists Drug regimens for individual patients (as purchased) Number and type of therapy changes
29
350 (181/169)
Figure 1
29
350 (181/169)
Figure 2
26
302 (133/169)
Figure 3
14
184
Table 3
Text Table 2 (column 1) Table 2 (column 2) Table 2 (column 3)
DOD = defined daily dose; MID = mean individual difference; TOM = therapeutic outcomes monitoring. "The subanalysis for inhaled short- and long-acting f}i-agonists involved 26 pharmacies and 302 patients.
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(R03BB), inhaled antiallergics (sodium cromoglycate, called cnr molyn sodium in the United States, and nedocromil sodium) (R03BC), oral ~2-agonists (R03CC), and theophylline (R03DA).
Use of Individual Drugs We collected drug consumption data, measured as number of DDDs purchased per patient, from the computer systems at 29 of the 31 participating phannacies (both intervention and control) for periods I through 3. Data from two pharmacies were excluded because of a software problem. Four vendors provided additional software tools and service to assist in recording and collecting data in the correct ATC and DDD fonnats. Printouts of pharmacy ftles on asthma drugs purchased each month were collected for all 500 patients. Only data for patients who reported obtaining more than 90% of their asthma drugs from a study pharmacy were entered into an SPSS database, resulting in the inclusion of 350
RESEARCH
patients in the analysis of drug consumption. More detailed information was needed to distinguish between short- and long-acting inhaled 132-agonists; because three TOM pharmacies were unable to provide this level of detail, data on use of inhaled ~2-agonists were collected from only 26 phannacies. . Except for oral corticosteroids, data on consumption of individual drugs were converted to an index of DDDs per user per day x 100. (Hence, if all users consume 1 DDD/day, the index is 100. If the index is below 100, the drug is prescribed or used less frequently or in smaller dosages.) A patient was considered a user of a given group of drugs if he or she purchased a drug in that group during any of the three time periods. . Pharmacists collected information on the number of courses of asthma-specific oral corticosteroids .during evaluation sessions at the ends of periods 1,2, and 3. Oral steroid use was analyzed as the number of courses of therapy used by each patient.
Table 2_ Consumption of Antiasthma Drugs
Mean Value in OOOs/User!Day x 100 (SEM) Period Period Period 1 2 3 Short-acting i32-agonists s.b TOM group (n = 111) Control group (n = 148)
87.1 (9.2) 94.0 (8.9)
Long-acting i32-agonists TOM group (n = 23) Control group (n = 23)
27.4 (7.2) 57.0 (12.1)
91 .4 (9.6) 111 .5 (9.8) 46.6 (9.6) 66.6 (11.8)
Mean Individual Difference (SEM) Period Period 2-1 3-1
PValues (tTest/Nested ANOVA) in Use Period Period Period 2- 1 3-1 3-1
% Change
64.7 (8.9) 90.4 (9.0)
4.3 (5.8) 17.5 (5.5)
-22.4 (6.4) - 3 .6 (8.1)
4.9 18.6
- 25.7 -3.8
.086 .169
72.1 (11 .0) 56.4 (10.8)
19.2 (10.0) 9 .7 (7.5)
44.7 (14.4) -{J.50 (11 .7)
70. 1 17.0
163.1 -{J.9
.019 .114
5 .2 (5.5) 4.4 (5.6)
- 10.0 (6.1) - 1.0 (7.8)
6 .1 4.2
- 11.7 -1 .0
.374 .238
3 .0 249.6
- 26.2 1,584.6
.099 .071
51 .5 24.7
52.5 9 .1
.018 .102
i32-agonists (total) TOM group (n = 162) Control group (n = 155)
85.2 (7.3) 103.6 (9.0)
90.4 (7.9) 108.1 (8.9)
75.4 (7.6) 102.5 (8.7)
Inhaled adrenergic agonists C TOM group (n = 12) Control group (n = 9)
148.0 (58.3) 12.3 (9.3)
152.5 (44.8) 43.0 (17 .8)
109.2 (32.0) 207.2 (140.2)
4.5 (28.3) 30.7 (9.7)
Inhaled corticosteroids TOM group (n = 167) Control group (n = 137)
49.3 (4.9) 62.3 (5.2)
74.7 (4.4) 77.6 (5.8)
75.2 (5.2) 68.0(5.0)
25.4 (4.4) 15.4 (5. 1)
25.9 (6.2) 5 .7 (5.6)
Inhaled anticholinergicsd.e TOM group (n = 7) Control group (n = 9)
196.8 (54.3) 28.4(12.1)
139.8 (28. 1) 29.2 (12.4)
71 .0 (28.8) 34.5 (13.9)
-57.1 (44.4) 0 .7 (8.0)
-125.8 (70.0) 6.0 (14.2)
- 29.0 2 .6
-53.9 21 . 1
. 111 . 101
Inhaled antiallergics TOM group (n = 3) Control group (n = 4)
97.3 (83.4) 65.3 (14.7)
0(0) 31.4 (17.8)
0(0) 35.4 (17.3)
- 97.3 (83.4) -34.0 (14.9)
- 97.3 (83.4) - 30.0 (16.8)
-100.0 - 52.1
- 100.0 -45.9
.507
Oral i32-agonists TOM group (n = 31) Control group (n = 37)
51.6 (10.6) 33.2 (6.9)
48.9 (8.8) 28.8 (6.2)
29.8 (7.4) 33.6 (6.5)
- 2 .7 (8. 1) -4.4 (5.5)
- 21 .8 (9.8) 0 .4(6.2)
-5.2 - 13.2
-42.2 1.2
.053 .079
Theophylline' TOM group (n = 40) Control group (n = 30)
77.9 (10.0) 84.6 (11 .9)
104.3 (10.9) 78.9 (11 .4)
67.3 (10.1) 78.6 (11.7)
26.3 (10.7) - 5.7 (10.8)
- 10.7 (10 .4) -5.0 (11 .0)
33.8
-13.7 -7.1
.763 .618
ANOVA = analysis of varianc e; DOD = defined daily d ose; SEM · Phys ic ian difference e ffect ( P = .0465). bPharmacy difference effect (P = .0001) . CPhysician difference effect (P = .0013) . dPharmacy difference effe ct (P = .0086), ephysician difference e ffe ct (P = .0076). ' Phys ician difference effect (P = .0451).
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-38.8 (49.2) 194.9 (142 .2)
-e..7
= standard error of mean ; TOM = therapeutic outcomes monitoring.
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Therapeutic Patterns We calculated the distribution of purchased drugs by therapeutic class for the TOM and control groups for each time period. The distribution was based on the total number of DDDs purchased in each drug group as percentage of the total DDDs purchased. The proportion of inhaled corticosteroid users among uS,ers of inhaled ~2-agonists was analyzed separately. The rationale for the indicator is that users of ~2-agonists constitute a target group likely to need additional steroid treatment.9 We compared proportion of steroid users between the TOM and control groups for each of the three time periods using the Fisher exact test. The most frequent drug regimens were identified among patients in both groups based on the drug groups purchased by each patient. The number of patients on each regimen was calculated, and a ranked list of regimens was produced. 10 Treatment changes for TOM patients were classified on the basis of TOM pharmacists' records of prescribed regimens at the beginning and end of the study. We collected data from 14 of the 16 TOM pharmacists using records for patients who completed the study (n = 184). We did not collect these data for control patients.
Statistical Analyses Changes (differences) in the drug use variables from period 1 to period 2 and from period 1 to period 3 were calculated for each patient. Group mean differences between periods 1 and 3 were then statistically compared between the TOM and control groups. These comparisons were performed by nested analysis of variance (ANOVA). The nested ANOVA included tests for betweenpharmacy and between-physician effects ("pharmacy" and "physician" effects). The ANOVA is, in theory, equivalent to the t test if both pharmacy and physician effects can be considered negligible. For all analyses, we also present results from ordinary Student t tests. After patients reach 45 years of age, asthma may be complicated by concomitant chronic obstructive pulmonary disease. Therefore, we carried out a preliminary analysis comparing drug use in patients older than 45 years with drug use in younger patients. All analyses were performed using SPSS or SAS statistical software. P values are reported in the article. Significance was set atP< .05.
Results Two preliminary analyses showed that use of some antiasthma drugs differed significantly between the TOM and control groups in period 1. However, these differences were in drug categories with small numbers of users '(inhaled long-acting ~2-agonists, inhaled adrenergic agonists, and inhaled anticholinergics). Also, antiasthma drug use did not differ between the two age groups
(younger or older than age 45), so no further distinction was made regarding age. The mean age for TOM patients included in this analysis was 38.7 years versus 42.5 for controls (P .004).
=
Use of Individual Drugs Reliable drug consumption data (see Table 2), defined as data from patients who reported obtaining more than 90% of their asthma drugs from a study phannacy, were obtained from 350 of the initial 500 patients in the study (181 in the TOM group, 169 in the control group, 70% of the total number of patients). A comparison of the 350 included patients and 121 excluded patients showed a lower number of DDDs purchased for most asthma drug groups among the excluded patients, which is consistent with our rationale for excluding them. In Table 2, the values for short- and long-acting inhaled ~2-agonists are based on data from the 26 pharmacies that could report these data, representing a total of 302 patients. The analysis of the overall use of inhaled P2-agonists, therefore, is a secondary analysis. Mean numbers of DDDs of antiasthma drugs (presented as DDDs/user/day x 100) are presented in Table 2 for TOM and control patients, together with the mean differences and P values. Percentage change in use is included as an aid to interpretation. Analyses with significant differences between pharmacies or between physicians are marked with footnotes. The use of short-acting ~2-agonists decreased by 25.7% in the TOM group compared with a 3.8% decrease among patients in the control group from period! to period 3. These differences were not statistically significant. Consumption of long-acting ~2agonists more than doubled from period 1 to period 3 for TOM patients; there was virtually no change for control patients. The result was significant at P .019 (t test). Consumption of total ~2agonists decreased by 11.7% overall from period 1 to period 3, compared with a 1.0% decrease in the control group. The use of inhaled corticosteroids increased by 51.5% in the TOM group; the increase took place in the first 6 months of the study and then leveled off. Use of inhaled steroids increased by a smaller percentage in the control group and was not sustained. The comparison for the 12 months was significant at P .018 (t test). Consumption of oral ~2-agonists decreased by 42.2% for TOM patients from period 1 to period 3, compared with a 1.2% increase in use among con'!Ol patients. This result was significant at P .053 (t test). During the first 6 months, theophylline use increased in the TOM group by 33.8%, while theophylline use decreased in the control group by 6.7%. ln the second half-year (not shown in the table), use of theophylline decreased by 35.6% in the TOM group compared with a decrease of 0.4% in controls. As a result, use of theophylline decreased in the TOM group from period 1 to period 3 by 13.7%, compared with a 7.1% decrease in the control group, but the overall difference was not significant. For all categories of asthma drugs, except adrenergic agonists, the percentage change in use from period 1 to period 3 was larger
=
=
=
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for TOM patien than contr 1 patient . In the 6 month preceding the tudy TOM patient u eel, on average, 0.15 cour e of oral cortico teroid ver us 0.24 cour e for control (P = .145). During the study, the mean for the TOM group wa unchanged (0.16 course per patient). In the control group the number of cour es per patient decrea ed to 0.21 (P = .402). The difference in average number of regimens between TOM and control group during the study year (period 3-period 1) was not significant (P = .32).
Changes in Therapeutic Patterns Figure 1 shows the distribution of purchased drugs for the three time periods. For both TOM and control patients, about one-half of all purchased DDDs were for inhaled ~2-agonists (45.3% versus 54.9%). However, the proportion of ~2-agonists decreased somewhat more for the TOM group from period 1 to period 3 (to 40.4% in the TOM group versus 51.0% in the control group). The second most common drug class was inhaled corticosteroids. The proportion of total DDDs represented by these drugs increased from 27.2% to 41.6% for the TOM group and remained approximately constant for controls, with a change from 30.2% to 29.9%. As Figure 1 indicates, in the TOM group overall, use of inhaled ~2-agonists declined while use of inhaled steroids increased. This pattern was not observed in the control group. Figure 2 summarizes data on proportion of inhaled corticosteroid users. In period 1, 68% of ~2-agonist users in both groups also used corticosteroids. This proportion increased in the TOM group during the study year, and in the last 6 months 84.3% of inhaled ~2-agonist users also used inhaled steroids, compared with 70.4% among controls. The differences in use between
RESEARCH
TOM and control patient were ignificant in periods 2 and 3 P = .01 ). There was no difference between the proportion of teroid u er among patients receiving high do age of ~2-agoni t compared with patient on lower do age . Analysis of the mo t frequently u ed drug regimen wa ba ed on data from 26 pharmacie and 302 patients. Figure 3 how the 10 most common regimens found in the study, which cover 83% of the treatments u ed by the patients in the tudy. In both group , the highest proportion of patients used inhaled hort-acting ~2agonists and inhaled corticosteroids in combination. For TOM patients, the second most common regimen in period 1 wa mono therapy with short-acting ~2-agonists; however, by period 3 the second most common therapy in the TOM group had changed to monotherapy with inhaled corticosteroids. Among controls, the second most CCimmon regimen in both periods was short-acting ~2-agonists. These three regimens were used by 62% of the asthma drug users. The other regimens were used relatively infrequently (by 6% or fewer patients) in both groups. A regimen that became more common among TOM patients was short- and long-acting ~2-agonists with inhaled corticosteroids, which increased from 1.7% at period 1 to 6.1 % at period 3. A corresponding decrease was seen for regimens 8, 9, and 10. For an analysis of treatment changes in TOM patients' drug therapy, we relied on data from 14 TOM pharmacists and 184 TOM patients. The number of treatment changes in the TOM group from the beginning to the end of the study totaled 451, averaging 2.4 changes per patient. Changes for each group of asthma drugs are shown in Table 3. The greatest number of changes involved inhaled corticosteroids.
Figure 1 . Changes in D i stribution of Purchased Antiasthma Drugs 100
D I
80
Theophylline
Oral
~2-agonists
D Inhaled antiallergics
60
I
Inhaled anticholinergics
40 Inhaled corticosteroids
D Inhaled adrenergic agonists
20
I
Inhaled
~2-agonists
o TOM (Period 1)
TOM (Period 2)
Control (Period 1)
TOM (Period 3)
Control (Period 2)
Control (Period 3)
Group
TOM = t herapeutic outcom e s monitoring .
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Figure 2. Changes in Proportion of Inhaled Steroid Users Among Inhaled ~2-agonist Users 100
80
(/)
Q) 60
(/)
:l
D
+'"
.~
c::
0
C'l
Nonusers of steroids
40
cp
•
N
C!l.
Users of steroids
'#. 20
0
TOM
TOM
Control (Period 1)
(Period 1)
Control (Period 2)
(Period 2)
TOM (Period 3)
Control (Period 3 )
Group
TOM = therapeutic outcomes monitoring.
Figure 3. The 10 Most Frequently Used Regimens Among TOM and Control Patients 40
35
30
25
I D
(/)
Period 1
~
(/)
:::l
20
'#
Period 3
15
10
5
0 A (1)
B (1)
A (2)
8 (2)
A (3)
B (3)
A (4)
8 (4)
A (5)
B (5)
A (6)
8 (6)
A (7)
8 (7)
A (8)
B (8)
A (9)
8 (9) A (1 0) 8 (10)
A = intervention group; B = control group; TOM = therapeutic outcomes monitoring . (1) = Inhaled short-acting i32-agonists and inhaled steroids; (2) = Inhaled corticosteroids; (3) = Inhaled short-acting 13 2-agonists ; (4) = Inhaled shortand long-acting 132-agonists and inhaled corticosteroids ; (5) = Inhaled short-acting 132-agonists, inhaled steroids, and theophylline ; (6) = Inhaled short-acting and oral132-agonists and inhaled corticosteroids; (7) = Inhaled long-acting i32-agonists and inhaled steroids ; (8) = Inhaled short-acting and oral i32-agonists, inhaled steroids, and theophylline; (9) = Inhaled short-acting 13 2-agonists and theophyline ; (10) = Inhaled short-acting and oral 13 2-a gon ists.
We excluded data from two phannacies (one TOM and one control) because of a oftware problem. The 15 TOM patients excluded from this analysis for this reason were older than the other TOM patients included in the study; 60% of tho e excluded
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were 45 years of age or older, compared with 33% among those included. The 14 excluded control patients showed no demographic differences from the included control patients.
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Table 3. Changes in Drug Therapy for Individual TOM Patients Short-acting Inhaled 13 2-agonists (n = 146)
Long-acting Inhaled 132-agonists (n = 24)
4
13
Withdrawn
6
2
Self-regulation
17
60
Increased dosage
5
50
Initiated
Oral 13 2 agonists (n = 17)
Inhaled Corticosteroids (n = 220)
Oral Corticosteroids (n =
Anticholinergic and Antiallergic Agents
10)
34 15
2
(n =
2
10
Decreased dosage
34
2
15
2
23
3
17
2
Change of drug within drug group
15
22
2
As
dosage~As
needed~fixed
needed
32
dosage
10
Prescribed but not used
Theophylline (n =
24)
3 19
Changed formulation
Fixed
10)
20
~used
TOM = therapeutic outcomes monitoring .
Discussion
A Systems Approach
The quality of drug therapy among TOM patients improved during the study; medication use became more consistent with consensus guidelines for drug therapy of asthma. Drug consumption (in DDDs) changed for TOM patients toward relatively more use of long-acting P2-agonists, inhaled corticosteroids, and recommended combination therapies. The data on proportions of drugs used suggest that older therapies were relinquished and newer ones adopted. In the TOM group, changes in corticosteroid use were toward patient self-regulation of dosage, increased dosages, and initiation of new therapy. Changes in the use of P2-agonists showed decreased dosages and more as-needed use of short-acting agents, with initiation of long-acting P2-agonists. Nearly 80% of changes in theophylline use involved discontinuation of the drug. In an earlier Danish study of 20- to 44-year-old patients with asthma, users of corticosteroids in combination with inhaled P2agonists were analyzed as a proportion of all users of inhaled P2agonists. 9 The proportion did not exceed 75% for any group of P2-agonist users. In -our study (see Figure 2), the proportion increased among TOM patients from 68% at the 6-month baseline to almost 85% by the end of the study. The TOM program led to a more appropriate therapeutic pattern, considering that all patients had moderate-to-severe asthma. In another Danish study, this one performed in 1994,10 the most common regimen was inhaled P2-agonists, followed by inhaled P2-agonists in combination with inhaled corticosteroids. Monotherapy with inhaled corticosteroids was third. Our results from period 1 included the same regimens, except that the order of fIrst and second place was reversed, with steroid monotherapy in third place. Our patient sample was chosen from the whole of Denmark, while that of Gaist et al.IOwas from a single county.
The medication use process is complex and influenced by many factors. Drug therapy outcomes may be influenced directly by the quality of at least fIve activities and the effectiveness with which they are coordinated into a system: response to medical problems, prescribing, dispensing, patient advice and education, and patient behavior and monitoring of results by patients and professionals. Furthermore, according to the theory of continuous quality improvement, one would predict that management of drug use as a system (e.g., with process and outcome indicators) would be necessary to achieve and sustain improvements. ll Pharmaceutical services and other programs aimed at optimizing drug therapy can be divided into two categories: external controls and treatment modifIers.1 2,13 Services in the fIrst category influence prescribing and availability of pharmaceuticals. Examples are drug use review, therapeutic substitution programs, drug target programs, and fonnularies. Treatment modifiers are factors that influence but do not control the choice of drugs. Example are patient and physician education, therapeutic monitoring with appropriate interventions, and methods that improve therapeutic information available for decision makers. The TOM project fIts into the latter group. According to the philosophy of pharmaceutical care, health care professional and patients should work in close cooperation to optimize therapeutic outcomes. Taking a systems view that focuses on all components of the drug use process, many DRPs that are not considered preventable in the more traditional biomedical paradigm become potentially preventable. i l Traditionally, community pharmacist have focu ed on dispensing and, to a Ie ser extent, on influencing prescribing. In thi study, pharmacists in 16 TOM pharmacies increased their efforts to monitor drug therapy outcomes, advise patients and foster cooperation among patients, physicians, and pharmacists. These
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activities were associated with improved outcomes among TOM patients compared with control patients, as shown in Part 1.5 In this article we have described how TOM services led to improvements in medication use, which is consistent with the improved patient processes and outcomes reported in our earlier article.5 Some of the changes in drug consumption--for example, the increase in long-acting inhaled ~2-agonist use-may reflect changes in prescribing. The increase in inhaled corticosteroid use might also reflect new prescriptions, perhaps in addition to increased patient adherence to long-term regimens for inhaled steroids. The decreases in use of oral ~2-agonists and theophylline could also have resulted from prescribing changes as well as better management of drug therapy on the part of clinicians and more informed self-care on the part of the patient. It is noteworthy that the TOM training program emphasized patient care and improved outcomes over direct improvement of prescribing. There was no ''TOM formulary." TOM pharmacists did not contact physicians to discuss asthma therapy in general, as in "academic detailing." When pharmacists approached physicians, it was to discuss patient care (drug therapy problems), and communications were focused on individual outcomes. The improved outcomes shown in this study are consistent with those described in other studies that used a similar strategy of changing the structure of the drug use process. I 4-16 Systems strategies stand in sharp contrast to direct prescribing interventions, which rarely lead to improved patient outcomes and may even worsen patient outcomes and increase total costs of care. 17-20
Limitations Some limitations of this nonrandomized control group design are described in Part 1. We noted few additional methodological issues in this part of the study. We chose to include patients who purchased most of their asthma medications at a TOM pharmacy, since this made the drug data more reliable. Comparing included patients with those who were excluded because of their purchasing practices, we found no evidence that the exclusion of these patients biased the results. The TOM patients excluded because of a computer problem were older compared with participating TOM patients. However, in terms of drug use, older patients (> 45 years) showed no differences from the sample as a whole; therefore, excluding these patients did not appear to affect the results to any large extent. The analyses of changes in drug therapy and regimens, and the separate analyses of short- and long-acting ~2-agonists, were done on subsamples of patients. Thus, the results may not represent the total sample, although we found no evidence that these subsamples biased the results. The alternative would have been to ignore some potentially interesting information about changes in medication use. We analyzed our data on the basis of drug purchases ("intention to treat"). We know the drugs were purchased by patients
with a diagnosis of asthma, but we cannot be certain how much medication was actually consumed. However, the purchase of drugs must be considered a better proximal measure of actual use than the prescribing of drugs. Some practically significant changes in drug consumption in the hypothesized direction did not achieve statistical significance at the .05 level. For example, the lack of statistical significance for the relatively large reduction in use of inhaled short-acting ~2-ago nists could be the result of a type II error. The power of the t test to detect the observed difference was less than 0.50. For some drug groups, the lack of significance was probably a result of small numbers, but this is not likely for short-acting ~2-agonists.
Conclusion The changes in drug consumption among TOM patients were toward better asthma treatment according to consensus guidelines; that is, toward increased use of inhaled corticosteroids and more conservative use of oral asthma medication. Our data suggest that most changes in drug therapy were initiated as a result of the collaborative nature of the TOM process. Our results show that community pharmacists, patients, and physicians, working together, can improve prescribing, solve drug therapy problems, and improve patient outcomes for patients with moderate-tosevere asthma. The project was funded by Apotekerfonden of 1991. The authors declare no conflicts of interest or financial interests in any product or service mentioned in the article, including grants, employment, gifts, stock holdings, and honoraria. Acknowledgments: We thank all the patients, pharmacists, and general practitioners who made this project possible. We are also very grateful to the scientific committee that supported us: Professor Ebba Holme Hansen; Dr. Jens Peter Kampmann; Peter Lund Nielsen, PhD; Dr. Poul A. Pedersen; and Mette Rasmussen, PhD.
References 1. International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health. Bethesda, Md. 20892. Publication No. 92-3091. March 1992. Eur Respir J. 1992:5:601-41. 2. Hallas J, Davidsen 0, Grodum E, et a!. Drug-related illness as a cause of admission to a department of respiratory medicine. Respiration. 1992;59:30-4. 3. Juel K, Pedersen PA Increasing asthma morbidity in Denmark 1969-88 not a result of a changed coding practice. Ann Allergy. 1992;68:180-2. 4. Grainger-Rousseau TJ, Miralles MA, Hepler CD, et a!. Therapeutic outcomes monitoring: application of pharmaceutical care guidelines to community pharmacy. JAm Pharm Assoc. 1997;NS37:647-61. 5. Herborg H, SI/lndergaard B, Froekjaer B, et al. Improving drug therapy for patients with asthma-Part 1: patient outcomes. JAm Pharm
Assoc. 2001; 41:~. 6. SI/lndergaard B, Thorleifsson S, Herberg H, et al. Kvalitetssikring af astmapatienters Imgemiddelbehandling. Sundhedsl/lkonomisk analyse [Quality improvement of drug therapy for asthma patients: health ec0nomic analysis). Ugeskr LtBger. 2000;162:480-6. 7. World Health Organization Collaborating Centre for Drug Statistics Methodology. Guidelines for DOD. Oslo, Norway: WHO; 1993.
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Danish TOM Project-Part 2 8. World Health Organization Collaborating Centre for Drug Statistics Methodology. Guidelines for A TC Classification; Oslo, Norway: WHO; 1993. 9. Hallas J, Hansen NC. Individual utilization of antiasthma medication by young adults: a prescription database analysis. J Intern Med. 1993;234:65-70.
10. Gaist 0, Hallas J, Hansen NC, Gram LF. Are young adults with asthma treated sufficiently with inhaled steroids? A population-based study of prescription data from 1991 and 1994. Br J Clin Pharmacol. 1996;41 :285-9. 11. Hepler CO, Grainger-Rousseau TJ. Pharmaceutical care versus traditional drug treatment. Is there a difference? Drugs. 1995;49: 1-1 O. 12. Holdfold OA, Smith S. Improving the quality of outcomes research involving pharmaceutical services. Am J Health Syst Pharm. 1997;54: 1434-42. 13. Kozma CM, Reeder CE, Schultz RM. Economic, clinical and humanistic outcomes: a planning model for pharmacoeconomic research. Clin Ther.1993;15:1121-32.
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15. Borgsdorf LR, Knapp KK, Miano JS. Pharmacist-managed medication review in a managed care system. Am J Hosp Pharm. 1994;51 :772-7. 16. Clapham CE, Hepler CD, Reinders TP, et al. Economic consequences of two drug-use control systems in a teaching hospital. Am J Hosp Pharm.1988;45:232~0.
17. Horn SO, Sharkey PO, Tracy OM, et al. Intended and unintended consequences of HMO cost-containment strategies: results from the Managed Care Outcomes Project. Am J Managed Care. 1996;2:25~. 18. Kozma CM, Schulz RM, Dye JT, et al. Economic impact of cost-containment strategies in third party programmes in the U.S. Part II. Pharmacoeconomics. 1993;4: 187-202. 19. Soumerai SB, Ross Degnan 0, Avorn J, et al. Effects of Medicaid drug-payment limits on admission to hospitals and nursing homes. N Engl J Med.1991;325:1072-7. 20. Hepler CD. Where is the evidence for formulary effectiveness? Am J Health Syst Pharm. 1997;54:95.
14. Wilt VM, Gums JG, Ahmed 01, Moore LM. Outcome analysis of a pharmacist-managed anticoagulation service. Pharmacotherapy. 1995;15:732-9.
APhA SESQUICENTENNIAL: VOICES FROM PAST ISSUES OF JAPbA
APhA's Headquarters: Dreams into Re ality "Members of the American Pharmaceutical Association, all who have given to the project of establishing the Headquarters Building in Washington, and pharmacists generally will be interested in the letter printed herewith. The Committee on Public Buildings and Grounds of the United States Senate and the Commission on Fine Arts pass on buildings to be erected and those who will occupy the area to be developed, improved and beautified in the section wherein the Headquarters Building of the American Phannaceutical Association will be a unit. The letter of Chairman Charles Moore, of the Fine Arts Commission, brings the project of the Association to the attention of Congress and includes its building site in the great monumental thor0ughfare from the Capitol to the Lincoln Memorial. Certainly this will stimulate the interest of many who have not heretofore realized what this Institute of American Pharmacy means to Pharmacy. It means among other things that the Headquarters of Pharmacy will stand in one of the most interesting groups of buildings in Washington .... "The letter which follows is from Chairman Moore, communicating information to Hon. Henry W. Keyes, Chairman of the Committee on Public Buildings and Grounds, U.S. Senate, relative to the developments in this section ... : '''It is contemplated to occupy the whole area between Seventeenth Street and Twenty-Third Street with a series of buildings of the general character of the Corcoran Gallery, the Red Cross, the [Daughters of the American Revolution] Building and the Pan American Building; that is to say, comparatively small, low buildings with ample space for gardens in front of them. The idea is to make a frame for the Lincoln Memorial. The type of building contemplated is shown in the National Academy of Sciences Building, which was designed as the first unit along B Street [now Constitution Avenue]. "'There are five possible units. The National Academy of Sciences Building is one. The American Pharmaceutical Association Building, to be built adjacent to it, a building designed in accordance with the idea above adverted to, is the second; the Pan American would be the third; leaving two squares to be taken care of in the future .... This scheme provides a suitable termination for B Street, which is now being developed as the great monumental thoroughfare from the Capitol to the Lincoln Memorial .... When these considerations were taken up with Doctor Rowe he brought them to the attention of Secretary of State Kellogg and President Coolidge, and received from them their unqualified indorsement of the proposed change. ' "Pharmacists now have the greatest opportunity for placing the profession of phannacy where it rightly belongs for rendering the best service for the pUblic. It requires the united efforts of all engaged in pharmaceutical activities-let everyone do his part and have a deserved share in the accomplishment of the project which has made progress far beyond early expectation ." Eberle EG. The headquarters building of the American Pharmaceutical A ociation-a unit in Washington improvement plans [editorial]. JAm PharmAssoc. 1929;18:544-5 .
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