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Evaluation of the pilot program on the real-time drug utilization review system in South Korea
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Evaluation of the pilot program on the real-time drug utilization review system in South Korea Ji Haeng Heo a , Dong Churl Suh b , Sukil Kim c , Eui-Kyung Lee a,∗ a b c
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea College of Pharmacy, Chung-Ang University, Seoul, South Korea School of Medicine, Catholic University, Seoul, South Korea
a r t i c l e
i n f o
a b s t r a c t
Article history:
Purpose: A pilot drug utilization review (DUR) program was initiated by the Korean gov-
Received 20 January 2013
ernment, which provided safety information in real-time at the stage of prescribing and
Received in revised form
dispensing. This study aimed to compare the “physician/pharmacist Co-DUR” system and
30 June 2013
the traditional “pharmacist-only DUR” system.
Accepted 1 July 2013
Methods: Data collected during a DUR pilot program from July 1 to October 31 of 2009 were obtained from the Health Insurance Review & Assessment Service. Descriptive analyses
Keywords:
were conducted to investigate DUR-pop up alert rates, categories of alerts, the reasons for
Drug utilization review
dispensing without prescription change after an alert, and changes in drug expenditures
Inappropriate prescribing
associated with the DUR.
Real-time system
Results: DUR pop-up alert rates were 8.55% at clinics and 1.90% at pharmacies in the physi-
Expenditures
cian/pharmacist Co-DUR, whereas the rate was 2.22% in the pharmacist-only DUR. Rates of pop-up alerts were high for between-prescription ingredient duplication at pharmacies, whereas for clinics, the rate for drug-pregnancy contraindications was high. A greater reduction in drug expenditure was estimated in the physician/pharmacist Co-DUR compared to the pharmacist-only DUR. Conclusions: The physician/pharmacist Co-DUR has better sensitivity at detecting potential adverse drug events than the pharmacist-only DUR. Pharmacists also have opportunities to double-check prescribed drugs when doctors do not voluntarily modify pop-up alerts. Further comprehensive study will be needed to confirm the results of pilot program that favored the physician/pharmacist Co-DUR. © 2013 Published by Elsevier Ireland Ltd.
1.
Introduction
Drug utilization review (DUR) is a quality assurance and improvement activity to ensure appropriate drug therapy. It is carried out with the aim of preventing potential adverse drug events arising from medication errors or the inappropriate use
of drugs [1,2]. Since 2008, several attempts have been made in South Korea to develop the nation’s DUR model through the operation of pilot programs. It intended to balance the quality of care and cost-containment in health care system. The need for a DUR system in Korea is closely related to the characteristics of the health care system, including lack of family doctors role as a gate-keeper and a high
∗ Corresponding author at: School of Pharmacy, Sungkyunkwan University, 300 Cheonchoen-dong, Jangan-gu, Suwon, Gyeonggi-do 440746, South Korea. Tel.: +82 31 290 7786; fax: +82 31 299 4379. E-mail address: [email protected] (E.-K. Lee). 1386-5056/$ – see front matter © 2013 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.ijmedinf.2013.07.001
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percentage of medical specialists among Korean primary care doctors [3]. In Korea, patients tend to visit different clinics depending on their symptoms, as most do not have their own family doctor. Frequently, several different medications are often prescribed to patients upon each visit to a doctor’s office. The average number of drugs in a single prescription was 4.05 in 2009, which is considerably higher than the mean number prescribed (2.86) in the USA [4,5]. Furthermore, 17.6% of all prescriptions had more than 6 drugs. One of the concerns is the frequent use of digestive medicines which were prescribed to 43% of the outpatients without any distinct diagnosis of digestive diseases [6]. When a patient visits more than one clinic, however, it is not possible to perform a comprehensive medication review among all clinics that the patient has visited. Consequently, this poly-pharmacy has resulted in duplicated prescriptions of drugs and increased concern over potential interactions between drugs [7–9]. Also of concern is drug expenditure waste. Accordingly, there is a need for improvement of the current system in order to assure appropriate prescription practices. In response, the Health Insurance Review & Assessment Service (HIRA), which is responsible for the review and assessment of medical treatment benefits in the Korean national health insurance system, has promoted a pilot program of real-time DUR in incremental stages. The first pilot program of DUR (phase 1), known as the “within-prescription review”, was initiated in April of 2008. This program encouraged clinics and pharmacies to monitor whether a given prescription has drugs with potential interaction contained within a specific prescription. The second pilot program of DUR (phase 2) included a “between-prescriptions review” in addition to the “within-prescription review” of the phase 1 DUR [10]. With the phase 2 DUR, newly prescribed drugs were compared with drugs previously prescribed for patients at the same or different medical institutions in order to monitor ingredient duplication and check for potential interactions between drugs in real-time [11]. When compared to Pharmacy Benefit Manager (PBM) in the USA and other systems adopted in many developed countries [12,13], the Korean DUR program is unique and differs in several ways. First, in addition to the traditional “pharmacist-only DUR (RPh-DUR)” approach, a “physician/pharmacist Co-DUR (Co-DUR)” approach was employed in the pilot program of DUR [10]. When developing the plan for phase 2 of the DUR program, the Korean Medical Association hoped to participate in the pilot program of DUR. Accordingly, two approaches, RPhDUR and Co-DUR, were comparatively evaluated during the pilot study. Second, a government agency, HIRA, has played a leading role in the development of the Korean DUR system, whereas PBMs, insurance organizations in the private sector, has operated the DUR system in the USA [14]. With the inclusion of HIRA, there was an advantage in that the prescription information of all people enrolled in the national health insurance program could be reviewed. Third, the phase 2 DUR included a “between-prescriptions review” in addition to “within-prescription review”, which most DUR systems use in general. HIRA used a comprehensive data set, which includes all national health insurants’ past prescription records, to perform between-prescriptions review, allowing the HIRA to
conduct more accurate between-prescriptions and withinprescription reviews. This study aimed to evaluate the two types of real-time DUR programs, the ‘physician/pharmacist Co-DUR (Co-DUR)’ vs. the traditional ‘pharmacist-only DUR (RPh-DUR)’, which were carried out under the national health insurance system in South Korea. The impact of pharmacist DUR within the CoDUR program was also compared with that of RPh-DUR. DUR pilot programs were compared based on the pop-up alert rates and changes in drug expenditure. More specifically the differences among DUR programs were analyzed regarding the pop-up alert rates for each DUR criteria, and reasons for dispensing without a change after a pop-up alerts.
2.
Methods
2.1.
Phase 2 DUR pilot program
Phase 2 DUR pilot program was implemented as a quasiexperimental design at Goyang City, Gyeonggi province, in South Korea for six months from May to October of 2009. Participation in this pilot program was voluntary. Co-DUR was employed only in one district with the participation of 78.5% clinics (102 of 130 clinics) and 97.2% pharmacies (103 of 130 pharmacies). RPh-DUR was tested in three districts, and 97% of pharmacies (321 of 332 pharmacies) chose to participate in this pilot project. The procedural flow of Co-DUR is summarized in Fig. 1. When a doctor issues a prescription to an outpatient, detailed information on the prescribed drugs is simultaneously sent to HIRA. The HIRA retrieves detailed information regarding the drugs previously prescribed at the same or different medical institutions for the patient from the accumulated claims database and reviews the newly prescribed drugs for ingredient duplication, drug–drug interaction, and others. If there are any safety concerns, pop-up alerts are displayed on computers in the clinic to request a re-evaluation of the prescribed drugs. In the same manner, when a pharmacy sends the information of prescribed drugs to HIRA prior to dispensing, HIRA carries out a DUR to compare them with previously prescribed drugs. When a pop-up alert is displayed at the pharmacy, the pharmacist must consult with the prescribing doctor to modify the prescription. However, for cases when original prescription cannot be changed after an alert, reasons for dispensing without prescription changes should be entered at the pharmacy, as directed by HIRA. The pilot program was designed to enter the reasons for dispensing only by pharmacies, not by clinics. In summary, Co-DUR is a double-monitoring system, with the first check performed by doctors at the point of prescribing at clinics, and the second check done by pharmacists at the point of dispensing at pharmacies. On the other hand, in RPhDUR, a review is carried out only at the time when drugs are dispensed at pharmacies.
2.2.
Analysis of DUR pop-up alerts
Pop-up alert rate was defined as the percentage of prescriptions for which a DUR pop-up alert message is displayed
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Fig. 1 – Physician/pharmacist Co-DUR program flow. a DUR = drug utilization review.
among all prescriptions. HIRA categorized pop-up alerts into 7 types, as follows: drug–drug interaction; alert drugs causing changes in effect or safety by a co-administered drug, drug–age conflict; alert drugs that should not be given to certain age groups, drug–safety conflict; alert drugs considering safety problem, low dose duplication prescription; prohibit duplicated use of low dose drugs instead of lower-priced high dose drugs, between-prescriptions drug–drug interaction; alert interaction between newly prescribed drugs and already prescribed drug, between-prescriptions ingredient duplication; alert ingredient overlapping between two prescriptions, drug-pregnancy warning; alert drugs with possible risk for pregnant patients [10]. For a drug-pregnancy warning, the program was designed to verify the possibility of pregnancy for any female patients in childbearing age on the basis of the patient information, such as sex, age, and symptoms; this information is obtained when the doctor or pharmacist asks the patient detailed questions about her condition [15]. In this case, the pop-up alert rates for drug-pregnancy warning can vary depending on how extensively the doctor or pharmacist questions the woman about her condition. Therefore, an additional calculation was conducted without the inclusion of the pop-up alert rate for the category of drug-pregnancy warning. The proportion of therapeutic categories associated with pop-up alerts was analyzed. Therapeutic categories were based on rule No. 196 of the Korea Food and Drug Administration, which is a provision relating to the drug classification system. The reasons for dispensing without prescription
change after an alert was also evaluated relative to the total number of drug alerts at the level of individual drugs. Data collected during the pilot program of DUR were obtained from HIRA. Because the computer system was deemed unreliable in the early stages of the program (May and June, 2009), we concluded that the data collected during that time period were not appropriate for use in the analysis. Therefore, although the pilot DUR program was conducted for six months from May to October of 2009, only four months, from July to October, were used in the study analysis. Three distinct groups of patients who participated in the pilot programs (Co-DUR clinic patients, Co-DUR pharmacy patients, and RPh-DUR patients) were evaluated respect to demographic and clinical characteristics. In Co-DUR, the total number of patients for four months was 109,692 for clinics and 105,933 for pharmacies, whereas that for RPh-DUR was 643,960. Even though the participation rate of pharmacies was almost the same as 97.0% for both Co-DUR and RPh-DUR, the number of patient-claims was bigger for RPh-DUR because it was conducted at 3 districts. These 3 groups had similar demographics and clinical characteristics as gender (proportion of men = 42.37–44.56%), age (mean = 35.13–38.59), proportion of patients with health insurance (97–98%), and a number of drugs per one prescription (3.71–3.91) were not significantly different. These basic demographics and clinical characteristics were also found to be similar to those of the nation-wide patients. Means and standard deviations were calculated for continuous variables, and frequencies were tabulated for categorical
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variables. Continuous variables, such as age and number of drugs, were compared between groups using analysis of variance and t-tests. Pearson chi-square tests were used to compare categorical variables, including assessment of the differences between proportions of DUR events between CoDUR and RPh-DUR.
2.3.
Analysis of drug expenditure
Changes in drug expenditures related with DUR were calculated by subtracting the costs of drugs that were actually prescribed or dispensed from those of drugs which were initially entered by clinics or pharmacies when sending data to HIRA. If the prescription was changed after a review, this was reflected in the drug expenditure changes. Because the Ministry of Health & Welfare plans to implement the DUR system throughout the country, the nationwide change in annual drug expenditure was estimated using the results calculated from the four-month pilot program as follows. First, in order to estimate the number of yearly prescriptions at Goyang City, the actual number of prescriptions during the four months of the pilot test was multiplied by the ratio (3.2) of the number of yearly prescription on nationwide to the number of prescription from July to September. Second, the nationwide change in drug expenditure was estimated based on the ratio of the prescription numbers between the study city (Goyang City) and the entire nation. Given that 456,195,924 prescriptions overall were issued nationwide in 2009 in Korea, the change in drug expenditure associated with the pilot program was multiplied by 508 for Co-DUR and by 68 for RPh-DUR. All statistical analyses were performed using SAS 9.2 for Windows (SAS Institute, Cary, NC).
3.
Results
3.1.
DUR pop-up alert
In Co-DUR, clinics generated 24,584 pop-up alerts among 287,635 prescriptions during the 4-month pilot period. The pop-up alert rate was 8.55%. Subsequent to review at clinics, pharmacies experienced 4955 pop-up alerts among 260,487 prescriptions, (1.90%) under the Co-DUR. In contrast, RPh-DUR generated 47,424 pop-up alerts among 2,139,535 prescriptions (2.22%), which was significantly higher than that of experienced by pharmacies under the Co-DUR (p < 0.001) (Table 1). An evaluation of the reasons corresponding to pop-up alerts in clinics found that drug-pregnancy warnings occurred most frequently (78.68%), followed by ingredient duplication (20.95%) and low dose over prescription (0.12%). In pharmacies, however, ingredient duplication occurred most frequently (more than 95%), followed by drug-pregnancy warnings (4.14%) and between-prescriptions drug–drug interactions (0.13%) (p < 0.001). This pattern was also found within RPh-DUR (Table 2). With the increase in the number of pop-up alerts for ingredient duplication, evaluations of the phase 2 DUR with “between-prescriptions review” showed that a more extensive DUR was carried out as compared to the “withinprescription review” only, which was one part of phases 2 DUR.
DUR at clinics resulted in higher pop-up rates for drugpregnancy warnings than DUR at pharmacies. However, when drug-pregnancy warnings were excluded, the proportion of ingredient duplication alert increased to 98.27%. Without drug-pregnancy warnings, ingredient duplication was the main reason for pop-up alerts both at clinics and pharmacies (more than 98%). Anti-inflammatory analgesic drugs were the most frequent drugs among both Co-DUR and RPh-DUR pop-up alerts, followed by cough suppressants/expectorants, and drugs acting on digestive systems (>10%) at pharmacies (p < 0.001, Table 3). Reasons for dispensing without a change after a DUR popup alert are summarized in Table 4. Code A (when, owing to long-term business trip or travel, a prescription is required prior to the complete use of drugs) was entered for the majority of cases, followed by code C (loss of drugs) (p < 0.001). The rate of entering the code of reason for dispensing was 27.3% for Co-DUR, which is lower than 63.3% for RPh-DUR. It means pharmacists changed the prescription more under the Co-DUR than RPh-DUR.
3.2.
Change in drug expenditures
Reduction in drug expenditures that occurred during the fourmonth pilot program was KRW 2,502,047 (USD $2126.74) at clinics and KRW 289,573 (USD $246.14) at pharmacies under the Co-DUR in one district, whereas it was KRW 11,526,841 (USD $9797.81) at pharmacies under the RPh-DUR in three districts. For reference, KRW 1000 equals USD $0.85 (as of 1st November, 2009). Annual reduction was estimated as KRW 7,816,538 (USD $6644.06), KRW 904,643 (USD $768.95), and KRW 36,010,509 (USD $30,608.93), respectively (Table 5). The nationwide application of the DUR system would be expected to result in a reduction of KRW 4,427,575,453 (USD $3,763,439.14) under the Co-DUR (KRW 3,968,305,815 (USD $3,373,059.94) at clinics and KRW 459,269,638 (USD $390,379.19) at pharmacies). For RPh-DUR, the reduction in drug expenditures was estimated as KRW 2,457,776,050 (USD $2,089,109.64).
4.
Discussion
Results from the DUR pilot program showed that more DUR pop-up alerts were detected in Co-DUR system than in RPhDUR. For Co-DUR system, pop-up alert rates were 8.55% at clinics and 1.90% at pharmacies. In RPh-DUR, the pop-up alert rate was 2.22%. With the inclusion of the doctors’ review process under the Co-DUR system, the detection rate was higher than it was in RPh-DUR. However, DUR at pharmacies also generated 1.90% of pop-up alerts even after DUR was performed via Co-DUR at clinics. One possible explanation for this may be that although when pop-up alerts were generated at clinics, doctors did not voluntarily modify the prescriptions, resulting in additional DUR pop-up alerts at pharmacies. Although this rate was lower than the pop-up alert rate (2.22%) of RPh-DUR, significant numbers of pop-up alerts were generated at pharmacies again in Co-DUR. This suggests that Co-DUR would be better for assuring the safer use of drugs compared to RPhDUR.
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Table 1 – Characteristics of the patients who participated in the DUR Pilot Program. Physician/pharmacist Co-DUR Clinic (N = 102)b a
Korea nationwided
Pharmacist-only DUR (N = 321)
Pharmacy (N = 103)
No. of patients
109,692 (100%)
105,933 (100%)
643,960 (100%)
42,350,733 (100%)
Sex Men Women
63,215 (42.37%) 46,477 (57.63%)
45,597 (43.03%) 60,354 (56.97%)
286,966 (44.56%) 356,994 (55.44%)
18,371,748 (43.38%) 23,978,985 (56.62%)
Agec ∼20 21–40 41–60 61+
36,999 (33.73%) 26,995 (24.61%) 29,836 (27.20%) 15,862 (14.45%)
34,494 (32.55%) 27,317 (25.79%) 29,507 (27.85%) 14,615 (13.81%)
181,664 (28.21%) 147,787 (22.95%) 194,192 (30.16%) 120,317 (18.68%)
10,354,813 (24.45%) 12,462,387 (29.43%) 12,896,913 (30.45%) 6,636,620 (15.67%)
Insurance type General Medicaid
107,498 (98.0%) 2194 (2.00%)
102,861 (97.10%) 3072 (2.90%)
624,748 (97.02%) 19,212 (2.98%)
40,938,303 (96.66%) 1,412,430 (3.34%)
No. drug per prescriptionc 1 2 3 4 5 6+
3.91 ± 1.69 11,935 (10.88%) 11,660 (10.63%) 18,297 (16.68%) 26,578 (24.23%) 23,200 (21.15%) 18,022 (16.43%)
3.84 ± 1.57 10,265 (9.69%) 11,695 (11.04%) 17,934 (16.93%) 29,216 (27.58%) 23,316 (22.01%) 13,507 (12.75%)
3.71 ± 1.76 83,650 (12.99%) 88,416 (13.73%) 123,705 (19.21%) 133,364 (20.71%) 119,390 (18.54%) 95,435 (14.82%)
3.86 ± 1.51 4,332,480 (10.23%) 5,120,204 (12.09%) 8,398,150 (19.83%) 9,871,956 (23.31%) 8,241,453 (19.46%) 6,386,491 (15.08%)
a b c d
Data is the total number of patients who participated in the DUR pilot program during four months (July 2009–October 2009). The number of clinics or pharmacies by DUR system type. Mean ± SD. Source: National Health Insurance Statistical Yearbook, 2010 [19].
Excluding the drug-pregnancy warnings, more than 95% of the pop-up alerts were “between-prescriptions ingredient duplication” alerts. In other words, the number of pop-up alerts increased sharply after the introduction of phase 2
DUR, indicating that a more extensive DUR was carried out. This may be related to the absence of the role of a gatekeeper in the Korean health care system, where patients may visit several clinics and doctors who prescribe many drugs,
Table 2 – Comparison of DUR pop-up alerts in Co-DUR and RPh-DURs. DUR pop-up alerta
Physician/pharmacist Co-DUR Clinic
Pharmacy
Pharmacist-only DUR
p value
No. of total prescriptions No. of prescriptions alerted DUR pop-up alert rate
287,635 24,584 8.55%
260,487 4,955 1.90%
2,139,535 47,424 2.22%
<0.001
Total no. of drugs alerted, n (%) Within-prescription Drug–drug interaction Drug–age conflict Drug–safety conflict Low dose duplicated prescription Drug-pregnancy warning Between-prescriptions Drug–drug interaction Ingredient duplication
32,337 (100.0) 25,507 (78.88) 14 (0.04) 12 (0.04) 0 (0.00) 39 (0.12) 25,442(78.68) 6830 (21.12) 54 (0.17) 6776 (20.95)
12,599 (100.0) 564 (4.48) 3 (0.02) 12 (0.10) 0 (0.00) 28 (0.22) 521 (4.14) 12,035 (95.52) 17 (0.13) 12,018 (95.39)
106,184 (100.0) 2529 (2.38) 33 (0.03) 115 (0.11) 2 (0.01) 301 (0.28) 2078 (1.96) 103,655 (97.62) 566 (0.53) 103,089 (97.09)
<0.001
No. of drugs alerted without drug-pregnancy warning, n (%) Within-prescription Drug–drug interaction Drug–age conflict Drug–safety conflict Low dose duplicated prescription Between-prescriptions Drug–drug interaction Ingredient duplication
6895 (100.0) 65 (0.94) 14 (0.20) 12 (0.17) 0 (0.00) 39 (0.57) 6830 (99.06) 54 (0.78) 6776 (98.27)
12,078 (100.0) 43 (0.35) 3 (0.02) 12 (0.10) 0 (0.00) 28 (0.23) 12,035 (99.64) 17 (0.14) 12,018 (99.50)
104,106 (100.0) 451 (0.43) 33 (0.03) 115 (0.11) 2 (0.002) 301 (0.29) 103,655 (99.56) 566 (0.54) 103,089 (99.02)
<0.001
a
Total data collected during four months from July to October 2009.
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Table 3 – Proportion of major therapeutic categories for DUR pop-up alerts. Therapeutic categoryb
Physician/pharmacist Co-DUR Clinic
Anti-inflammatory/pain/fever reducers Cough suppressants/expectorants Drugs acting on digestive system Anti-histamines Peptic ulcer drugs Psychiatric drugs Drug for cardiovascular diseases Antihypertensive drugs Drug-resistant Gram +/− germs Arteriosclerosis drugs Probiotics Others Total (N)a a b
Pharmacist-only DUR
Pharmacy
42.39% 1.93% 3.86% 1.22% 3.39% 7.20% 4.41% 5.77% 3.98% 3.94% 0.97% 20.94% 100.0% (32,337)
12.64% 11.26% 10.56% 6.12% 5.91% 5.50% 4.43% 4.24% 3.51% 2.40% 2.37% 31.06% 100.0% (12,599)
13.37% 12.56% 4.69% 5.00% 5.51% 3.13% 5.80% 7.38% 3.88% 5.84% 4.18% 28.66% 100.0% (106,184)
No. of DUR pop-up alert drug collected from July to October 2009. Therapeutic category was classified according to the provisions relating to classification numbers medication, The Korea Food and Drug Administration established rule No. 196 (August 24, 2009 enactment).
leading to the duplication of drugs containing the same ingredients. Because most medical visits are captured under the national health insurance system, the impact of “betweenprescriptions review” is expected to be enormous relative to the “within-prescription review” once the two-phase DUR system is expanded to the national level. The pop-up alerts generated at clinics were mostly related to drug-pregnancy warnings. The percentage of drugpregnancy warnings was 78.68% at clinics, whereas it was only 4.14% at pharmacies in Co-DUR, and 1.96% in RPh-DUR. This significant difference may have occurred because doctors have more information on their patient’s health condition and because clinics provide a more suitable environment for posing questions about the possibility of pregnancy. Also doctors can deal with the pop-up alert more easily and make their final prescribing decision without bothersome administrative
efforts, but pharmacists must contact doctors for intervention. Therefore, doctors can actively detect potential pregnancies, which can be another advantage of Co-DUR. The Korea Food & Drug Administration categorizes drugs contraindicated for pregnant women into two grades: ‘grade 1’, when the risk to unborn babies is remarkably high compared to the expected benefit, and ‘grade 2’, when the use of the drug is unavoidable for the purpose of treatment but must be used on the basis of clear clinical evidence [16]. For instance some of the anti-inflammatory analgesic drugs (loxoprofen, diclofenac, ibuprofen) are grade 2 drugs, which explained the higher rate of pop-up alerts for this therapeutic category. Because all pop-up alerts for drug-pregnancy warnings during the pilot DUR program involved only grade 2 drugs, they were not regarded as serious issues. Although there were no pop-up alerts for ‘grade 1’, it is desirable to establish a
Table 4 – Reasons for dispensing without a change after a DUR pop-up alert. Reasons for dispensing without changeb
Physician/pharmacist Co-DUR, n (%)
Pharmacist-only DUR, n (%)
A (prescription is required prior to complete use of drugs) B (adverse events or dose adjustment) C (loss of drugs) P (PRN) X (hard to contact prescriber) Text (drug–age conflict, drug–drug interaction) Others
1087 (46.68) 189 (8.13) 504 (21.64) 106 (4.57) 7 (0.31) 11 (0.47) 424 (18.20)
33,567 (56.69) 2872 (4.85) 14,886 (25.14) 2493 (4.21) 213 (0.36) 397 (0.67) 4784 (8.08)
Total
2329 (100)
59,211 (100)
12,599 2329 18.49%
106,184 59,211 55.76%
a
No. of drugs alerted No. of drugs including reasons Rate of entering reasons for dispensing c a b
c
p value <0.001
<0.001
No. of DUR pop-up alerts for drug collected from July to October 2009. The codes for dispensing without a change were as follows: A (when, owing to long-term business trip or travel, a prescription is required prior to the complete use of drugs); B (when it is not possible to change the prescription owing to adverse events or dose adjustment); C (loss of drugs); E (when a patient wants a new prescription prior to the complete use of drugs at his/her own expense); X (when the prescribing doctor cannot be contacted); P (PRN: pro re nata, different administration date); and Text (drug–age conflict, drug–drug interaction). Rate of entering reasons for dispensing (%) = no. of drugs including reasons/no. of drugs alerted × 100.
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Table 5 – Change of drug expenditure by DUR type. Type of DUR
Pilot study (Goyang City)
Nationwide
4 months
1 year
Physician/pharmacist Co-DUR No. patient (N)b No. prescription (N) Reduction of drug expenditure (KRW)a Clinic Pharmacy Reduction of drug expenditure per Prescription (KRW) Reduction of drug expenditure per patient (KRW)
109,692 287,635 2,791,620 2,502,047 289,573 9.71 25.45
– 898,588 8,721,180 7,816,538 904,643 – –
42,350,733 456,195,924 4,427,575,453 3,968,305,815 459,269,638 9.71 104.55
Pharmacist-only DUR No. patient (N) No. prescription (N) Reduction of drug expenditure (KRW) Reduction of Drug Expenditure per Prescription (KRW) Reduction of Drug Expenditure per Patient (KRW)
643,960 2,139,535 11,526,841 5.39 17.90
– 6,684,029 36,010,509 – –
42,350,733 456,195,924 2,457,776,050 5.39 58.03
a b
1 year
Unit: KRW 1000 = USD 0.85 (1 November 2009). The number of prescription and patient of pharmacy in Co-DUR was considered as same as clinics in Co-DUR.
mandatory checking system for grade 1 drugs, as pharmacists do not actively check for potential pregnancy. In addition, fewer checklist items for DUR were provided in the Korean pilot program, as compared to the US system. In the USA, pharmacy benefit managers (PBMs) typically have more comprehensive review lists, which usually include additional categories such as therapy duplications, high-dose warnings, and over use/excessive duration alerts. However, the Korean pilot program focused on ingredient duplication rather than therapeutic duplication. Further, the drug–drug interaction or drug–age conflict alerts were limited to some ingredients. For example, AdvancePCS, a PBM in the USA, conducted a large-scale drug interaction study with the University of Arizona Health Sciences Center in 2001 [17]. The study showed that DUR alerts were generated for high-dose warnings (21.9%), drug interactions (21.3%), for overuse/excessive duration (15.7%), and for therapeutic duplication (10.0%). Chui and Rupp observed 41 pharmacies in Indiana and presented that the prospective DUR alert rate for prescription drug claims was 10.3%. Drug–drug interactions, therapeutic duplications, high or low dosage alerts accounted for 56.7% of the alerts (760/1340) [18]. Considering that pop-up alerts were mainly ingredient duplication in Korea, it is necessary to develop more comprehensive checklist items for the DUR system in the future. The study results also suggested that the phase 2 DUR program can contribute to drug expenditure reduction by preventing ingredient duplications and drug interactions. When applying the estimated reduction in drug expenditure in the four-month pilot program to the entire country, the total reduction was estimated to be KRW 4.4 billion (USD $3.8 million) in a single year for Co-DUR. In RPh-DUR, the estimated reduction was KRW 2.5 billion (USD $2.1 million). In other words, Co-DUR will likely contribute more than RPh-DUR in reducing drug expenditures, as prescriptions can be canceled or modified at clinics and can be subsequently re-checked at pharmacies to assure their appropriateness.
Because the pilot program of Co-DUR was first introduced in Korea for a short period of six months, this study has several limitations: First, at the early stage of this pilot program, some clinics did not show an interest in participating. Moreover, the computer network system for the program was not fully implemented. Therefore, the data generated at the early stage in clinics was not representative of all the clinics in the DUR pilot test. As a result, only data collected during a period of four months after the full implementation of a working electronic network system was used in this analysis. Second, we did not have enough data on patient health conditions which could be the confounding factors in interpreting the outcomes of two DUR programs. Even though data showed the similar patterns in gender, age and number of drugs per prescription between two groups, there remains the possibility for the potential bias in the conclusion due to patients attributes. Third, evaluation of costs included only the estimation of changes in drug expenditure. To fully quantify the costs associated with the program, the costs of the implementation of computer systems used in the program should be included in the analysis. Given that the Korean DUR system was developed by implementing the DUR program into the existing national insurance billing system, implementation of the DUR system did not impose a heavy burden on clinics and pharmacies. However, careful consideration is necessary regarding additional expenses of implementing the DUR program. Meanwhile, drug interactions and other potential side effects may be prevented, leading to a reduction in medical expenses. In this study, however, the pilot program was evaluated with a focus on changes in drug expenditures owing to insufficient data for an extensive estimation of total medical expenditure. Fourth, we used the ratio of the prescription numbers between Goyang City and the entire nation to estimate the nationwide change in drug expenditure. The demographic characteristics of Goyang City patients showed quite similar to
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Summary points What was already known about the topic • Drug utilization review (DUR) has been conducted mainly as a form of “within prescription review” in the western countries. • DUR detected inappropriate prescriptions such as drug–drug interactions, therapeutic duplications, excessive duration and high dosage.
• The physician/pharmacist Co-DUR can detect the warnings of adverse drug events better than the traditional pharmacist-only DUR. • With the physician/pharmacist Co-DUR, doctors can readily reflect clinical information of patients in the DUR process, and pharmacists also have opportunities to double-check prescribed drugs when doctors do not voluntarily modify pop-up alerts. • A more extensive DUR has been carried out with “betweenprescriptions review” among different prescribers compared to “within- prescription review” only.
Acknowledgments the patients nationwide. But the estimation cannot be verified due to the lack of accurate data to show that the patient mix of Goyang City is representative for the whole nation. Furthermore, only four months of data were available for analysis, and we cannot be certain that the drug utilization during the time period studied is representative of the remainder of the calendar year, as it is possible that seasonal variation may affect drug utilization. Therefore, a comprehensive future study of the effects on expenses is necessary. This study compared the Co-DUR system with the RPhDUR system through a government-driven pilot program in South Korea. In the Co-DUR system, doctors experienced a higher pop-up alert rate than that observed in RPh-DUR since these warnings included clinical information of patients in the DUR process, especially for drug-pregnancy warnings. Pharmacists also have opportunities to double-check prescribed drugs when doctors do not voluntarily modify pop-up warnings. With an increase of pop-up alerts for ingredient duplication, phase 2 DUR with “between and within prescriptions review” showed that a more extensive DUR was carried out as compared to a “within-prescription review” only. Even though there remains the possibility for potential bias in interpreting the outcomes of DUR pilot programs, Co-DUR system was found to be a more effective model to detect inappropriate drug prescribed compared to the traditional RPh-DUR system under the real-time DUR pilot study. Further study will be needed to confirm the results of pilot program that favored the physician/pharmacist CoDUR.
Authors’ contributions All the authors of this article have been involved in analysis and interpretation of data, revising the article and giving final approval of the manuscript. Ji Haeng Heo, Dong Churl Suh, Sukil Kim and Eui-Kyung Lee were involved in the conception and design of the study. Ji Haeng Heo was involved in the acquisition of data and drafted the manuscript.
Conflict of interest The authors declare no conflicts of interest. What this study adds?
This study was funded by an unrestricted research grant from the Health Insurance Review & Assessment Service in South Korea.
references
[1] G.L. Hayward, A.J. Parnes, S.R. Simon, Using health information technology to improve drug monitoring: a systematic review, Pharmacoepidemiol. Drug Saf. 18 (December 12) (2009) 1232–1237. [2] R.P. Navarro, Managed Care Pharmacy Practice, Chapter 8. Drug Utilization Review Strategies, Jones and Bartlett publishers, 2009. [3] H.J. Cho, J.Y. Shim, H.R. Lee, et al., Factors associated with possession of regular doctor in Korea, J. Korean Acad. Fam. Med. 22 (2001) 1612–1621. [4] U.S. Department of Health and Human Services, Health, United States, 2009 with Special Feature on Medical Technology, 2009. [5] Health Insurance Review and Assessment Service, 2/4 Evaluation of drug reimbursement management results, 2009. Health Insurance Review & Assessment Service, 2011. [6] S.M. Jang, D.S. Kim, H.J. Kim, et al., The Study for Monitoring Prescription Behavior for Digestive Medicines in Korea, Health Insurance Review and Assessment Service, 2005. [7] M.A. Steinman, C.S. Landefeld, G.E. Rosenthal, et al., Polypharmacy and prescribing quality in older people, J. Am. Geriatr. Soc. 54 (October 10) (2006) 1516–1523. [8] B. Hovstadius, K. Hovstadius, B. Astrand, G. Petersson, Increasing polypharmacy – an individual-based study of the Swedish population 2005–2008, BMC Clin. Pharmacol. 10 (December) (2010) 16 (open access). [9] B. Hovstadius, B. Astrand, G. Petersson, Assessment of regional variation in polypharmacy, Pharmacoepidemiol. Drug Saf. 19 (April 4) (2010) 375–383. [10] Health Insurance Review and Assessment Service, Guidance for Ingredient Duplication Prescription in Same Medical Center, 2009. [11] Health Insurance Review and Assessment Service, Guidance for Phase 2 Drug Utilization Review, 2009. [12] T.R. Fulda, A. Lyles, M.C. Pugh, D.B. Christensen, Current status of prospective drug utilization review, J. Manag. Care Pharm. 10 (September–October 5) (2004) 433–441. [13] R.S. Chung, D.A. Taira, C. Noh, Alternate financial incentives in multi-tiered formulary systems to improve accountability for outcomes, J. Manag. Care Pharm. 9 (July–August 4) (2003) 360–365. [14] A.L. Pittenger, C.I. Starner, K. Thompson, P.P. Gleason, Pharmacy students’ views of managed care pharmacy and
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PBMS: should there be more exposure to managed care in the pharmacy curriculum? J. Manag. Care Pharm. 16 (June 5) (2010) 346–354. [15] Health Insurance Review and Assessment Service, Question and answer for drug-pregnancy warning, 2009. [16] Korea Food & Drug Administration, Handbook of Drug Proper Use for Pregnancy Women, 2010.
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[17] AdvancePCS. Health Improvement Report, 2003. [18] M.A. Chui, RMT, Evaluation of online prospective DUR programs in community pharmacy practice, J. Manag. Care Pharm. 6 (January–February 1) (2000) 27–32. [19] National Health Insurance Statistical Yearbook, National Health Insurance Corporation/Health Insurance Review & Assessment Service, 2010.
journal homepage: www.ijmijournal.com
Evaluation of the pilot program on the real-time drug utilization review system in South Korea Ji Haeng Heo a , Dong Churl Suh b , Sukil Kim c , Eui-Kyung Lee a,∗ a b c
School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea College of Pharmacy, Chung-Ang University, Seoul, South Korea School of Medicine, Catholic University, Seoul, South Korea
a r t i c l e
i n f o
a b s t r a c t
Article history:
Purpose: A pilot drug utilization review (DUR) program was initiated by the Korean gov-
Received 20 January 2013
ernment, which provided safety information in real-time at the stage of prescribing and
Received in revised form
dispensing. This study aimed to compare the “physician/pharmacist Co-DUR” system and
30 June 2013
the traditional “pharmacist-only DUR” system.
Accepted 1 July 2013
Methods: Data collected during a DUR pilot program from July 1 to October 31 of 2009 were obtained from the Health Insurance Review & Assessment Service. Descriptive analyses
Keywords:
were conducted to investigate DUR-pop up alert rates, categories of alerts, the reasons for
Drug utilization review
dispensing without prescription change after an alert, and changes in drug expenditures
Inappropriate prescribing
associated with the DUR.
Real-time system
Results: DUR pop-up alert rates were 8.55% at clinics and 1.90% at pharmacies in the physi-
Expenditures
cian/pharmacist Co-DUR, whereas the rate was 2.22% in the pharmacist-only DUR. Rates of pop-up alerts were high for between-prescription ingredient duplication at pharmacies, whereas for clinics, the rate for drug-pregnancy contraindications was high. A greater reduction in drug expenditure was estimated in the physician/pharmacist Co-DUR compared to the pharmacist-only DUR. Conclusions: The physician/pharmacist Co-DUR has better sensitivity at detecting potential adverse drug events than the pharmacist-only DUR. Pharmacists also have opportunities to double-check prescribed drugs when doctors do not voluntarily modify pop-up alerts. Further comprehensive study will be needed to confirm the results of pilot program that favored the physician/pharmacist Co-DUR. © 2013 Published by Elsevier Ireland Ltd.
1.
Introduction
Drug utilization review (DUR) is a quality assurance and improvement activity to ensure appropriate drug therapy. It is carried out with the aim of preventing potential adverse drug events arising from medication errors or the inappropriate use
of drugs [1,2]. Since 2008, several attempts have been made in South Korea to develop the nation’s DUR model through the operation of pilot programs. It intended to balance the quality of care and cost-containment in health care system. The need for a DUR system in Korea is closely related to the characteristics of the health care system, including lack of family doctors role as a gate-keeper and a high
∗ Corresponding author at: School of Pharmacy, Sungkyunkwan University, 300 Cheonchoen-dong, Jangan-gu, Suwon, Gyeonggi-do 440746, South Korea. Tel.: +82 31 290 7786; fax: +82 31 299 4379. E-mail address: [email protected] (E.-K. Lee). 1386-5056/$ – see front matter © 2013 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.ijmedinf.2013.07.001
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percentage of medical specialists among Korean primary care doctors [3]. In Korea, patients tend to visit different clinics depending on their symptoms, as most do not have their own family doctor. Frequently, several different medications are often prescribed to patients upon each visit to a doctor’s office. The average number of drugs in a single prescription was 4.05 in 2009, which is considerably higher than the mean number prescribed (2.86) in the USA [4,5]. Furthermore, 17.6% of all prescriptions had more than 6 drugs. One of the concerns is the frequent use of digestive medicines which were prescribed to 43% of the outpatients without any distinct diagnosis of digestive diseases [6]. When a patient visits more than one clinic, however, it is not possible to perform a comprehensive medication review among all clinics that the patient has visited. Consequently, this poly-pharmacy has resulted in duplicated prescriptions of drugs and increased concern over potential interactions between drugs [7–9]. Also of concern is drug expenditure waste. Accordingly, there is a need for improvement of the current system in order to assure appropriate prescription practices. In response, the Health Insurance Review & Assessment Service (HIRA), which is responsible for the review and assessment of medical treatment benefits in the Korean national health insurance system, has promoted a pilot program of real-time DUR in incremental stages. The first pilot program of DUR (phase 1), known as the “within-prescription review”, was initiated in April of 2008. This program encouraged clinics and pharmacies to monitor whether a given prescription has drugs with potential interaction contained within a specific prescription. The second pilot program of DUR (phase 2) included a “between-prescriptions review” in addition to the “within-prescription review” of the phase 1 DUR [10]. With the phase 2 DUR, newly prescribed drugs were compared with drugs previously prescribed for patients at the same or different medical institutions in order to monitor ingredient duplication and check for potential interactions between drugs in real-time [11]. When compared to Pharmacy Benefit Manager (PBM) in the USA and other systems adopted in many developed countries [12,13], the Korean DUR program is unique and differs in several ways. First, in addition to the traditional “pharmacist-only DUR (RPh-DUR)” approach, a “physician/pharmacist Co-DUR (Co-DUR)” approach was employed in the pilot program of DUR [10]. When developing the plan for phase 2 of the DUR program, the Korean Medical Association hoped to participate in the pilot program of DUR. Accordingly, two approaches, RPhDUR and Co-DUR, were comparatively evaluated during the pilot study. Second, a government agency, HIRA, has played a leading role in the development of the Korean DUR system, whereas PBMs, insurance organizations in the private sector, has operated the DUR system in the USA [14]. With the inclusion of HIRA, there was an advantage in that the prescription information of all people enrolled in the national health insurance program could be reviewed. Third, the phase 2 DUR included a “between-prescriptions review” in addition to “within-prescription review”, which most DUR systems use in general. HIRA used a comprehensive data set, which includes all national health insurants’ past prescription records, to perform between-prescriptions review, allowing the HIRA to
conduct more accurate between-prescriptions and withinprescription reviews. This study aimed to evaluate the two types of real-time DUR programs, the ‘physician/pharmacist Co-DUR (Co-DUR)’ vs. the traditional ‘pharmacist-only DUR (RPh-DUR)’, which were carried out under the national health insurance system in South Korea. The impact of pharmacist DUR within the CoDUR program was also compared with that of RPh-DUR. DUR pilot programs were compared based on the pop-up alert rates and changes in drug expenditure. More specifically the differences among DUR programs were analyzed regarding the pop-up alert rates for each DUR criteria, and reasons for dispensing without a change after a pop-up alerts.
2.
Methods
2.1.
Phase 2 DUR pilot program
Phase 2 DUR pilot program was implemented as a quasiexperimental design at Goyang City, Gyeonggi province, in South Korea for six months from May to October of 2009. Participation in this pilot program was voluntary. Co-DUR was employed only in one district with the participation of 78.5% clinics (102 of 130 clinics) and 97.2% pharmacies (103 of 130 pharmacies). RPh-DUR was tested in three districts, and 97% of pharmacies (321 of 332 pharmacies) chose to participate in this pilot project. The procedural flow of Co-DUR is summarized in Fig. 1. When a doctor issues a prescription to an outpatient, detailed information on the prescribed drugs is simultaneously sent to HIRA. The HIRA retrieves detailed information regarding the drugs previously prescribed at the same or different medical institutions for the patient from the accumulated claims database and reviews the newly prescribed drugs for ingredient duplication, drug–drug interaction, and others. If there are any safety concerns, pop-up alerts are displayed on computers in the clinic to request a re-evaluation of the prescribed drugs. In the same manner, when a pharmacy sends the information of prescribed drugs to HIRA prior to dispensing, HIRA carries out a DUR to compare them with previously prescribed drugs. When a pop-up alert is displayed at the pharmacy, the pharmacist must consult with the prescribing doctor to modify the prescription. However, for cases when original prescription cannot be changed after an alert, reasons for dispensing without prescription changes should be entered at the pharmacy, as directed by HIRA. The pilot program was designed to enter the reasons for dispensing only by pharmacies, not by clinics. In summary, Co-DUR is a double-monitoring system, with the first check performed by doctors at the point of prescribing at clinics, and the second check done by pharmacists at the point of dispensing at pharmacies. On the other hand, in RPhDUR, a review is carried out only at the time when drugs are dispensed at pharmacies.
2.2.
Analysis of DUR pop-up alerts
Pop-up alert rate was defined as the percentage of prescriptions for which a DUR pop-up alert message is displayed
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Fig. 1 – Physician/pharmacist Co-DUR program flow. a DUR = drug utilization review.
among all prescriptions. HIRA categorized pop-up alerts into 7 types, as follows: drug–drug interaction; alert drugs causing changes in effect or safety by a co-administered drug, drug–age conflict; alert drugs that should not be given to certain age groups, drug–safety conflict; alert drugs considering safety problem, low dose duplication prescription; prohibit duplicated use of low dose drugs instead of lower-priced high dose drugs, between-prescriptions drug–drug interaction; alert interaction between newly prescribed drugs and already prescribed drug, between-prescriptions ingredient duplication; alert ingredient overlapping between two prescriptions, drug-pregnancy warning; alert drugs with possible risk for pregnant patients [10]. For a drug-pregnancy warning, the program was designed to verify the possibility of pregnancy for any female patients in childbearing age on the basis of the patient information, such as sex, age, and symptoms; this information is obtained when the doctor or pharmacist asks the patient detailed questions about her condition [15]. In this case, the pop-up alert rates for drug-pregnancy warning can vary depending on how extensively the doctor or pharmacist questions the woman about her condition. Therefore, an additional calculation was conducted without the inclusion of the pop-up alert rate for the category of drug-pregnancy warning. The proportion of therapeutic categories associated with pop-up alerts was analyzed. Therapeutic categories were based on rule No. 196 of the Korea Food and Drug Administration, which is a provision relating to the drug classification system. The reasons for dispensing without prescription
change after an alert was also evaluated relative to the total number of drug alerts at the level of individual drugs. Data collected during the pilot program of DUR were obtained from HIRA. Because the computer system was deemed unreliable in the early stages of the program (May and June, 2009), we concluded that the data collected during that time period were not appropriate for use in the analysis. Therefore, although the pilot DUR program was conducted for six months from May to October of 2009, only four months, from July to October, were used in the study analysis. Three distinct groups of patients who participated in the pilot programs (Co-DUR clinic patients, Co-DUR pharmacy patients, and RPh-DUR patients) were evaluated respect to demographic and clinical characteristics. In Co-DUR, the total number of patients for four months was 109,692 for clinics and 105,933 for pharmacies, whereas that for RPh-DUR was 643,960. Even though the participation rate of pharmacies was almost the same as 97.0% for both Co-DUR and RPh-DUR, the number of patient-claims was bigger for RPh-DUR because it was conducted at 3 districts. These 3 groups had similar demographics and clinical characteristics as gender (proportion of men = 42.37–44.56%), age (mean = 35.13–38.59), proportion of patients with health insurance (97–98%), and a number of drugs per one prescription (3.71–3.91) were not significantly different. These basic demographics and clinical characteristics were also found to be similar to those of the nation-wide patients. Means and standard deviations were calculated for continuous variables, and frequencies were tabulated for categorical
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variables. Continuous variables, such as age and number of drugs, were compared between groups using analysis of variance and t-tests. Pearson chi-square tests were used to compare categorical variables, including assessment of the differences between proportions of DUR events between CoDUR and RPh-DUR.
2.3.
Analysis of drug expenditure
Changes in drug expenditures related with DUR were calculated by subtracting the costs of drugs that were actually prescribed or dispensed from those of drugs which were initially entered by clinics or pharmacies when sending data to HIRA. If the prescription was changed after a review, this was reflected in the drug expenditure changes. Because the Ministry of Health & Welfare plans to implement the DUR system throughout the country, the nationwide change in annual drug expenditure was estimated using the results calculated from the four-month pilot program as follows. First, in order to estimate the number of yearly prescriptions at Goyang City, the actual number of prescriptions during the four months of the pilot test was multiplied by the ratio (3.2) of the number of yearly prescription on nationwide to the number of prescription from July to September. Second, the nationwide change in drug expenditure was estimated based on the ratio of the prescription numbers between the study city (Goyang City) and the entire nation. Given that 456,195,924 prescriptions overall were issued nationwide in 2009 in Korea, the change in drug expenditure associated with the pilot program was multiplied by 508 for Co-DUR and by 68 for RPh-DUR. All statistical analyses were performed using SAS 9.2 for Windows (SAS Institute, Cary, NC).
3.
Results
3.1.
DUR pop-up alert
In Co-DUR, clinics generated 24,584 pop-up alerts among 287,635 prescriptions during the 4-month pilot period. The pop-up alert rate was 8.55%. Subsequent to review at clinics, pharmacies experienced 4955 pop-up alerts among 260,487 prescriptions, (1.90%) under the Co-DUR. In contrast, RPh-DUR generated 47,424 pop-up alerts among 2,139,535 prescriptions (2.22%), which was significantly higher than that of experienced by pharmacies under the Co-DUR (p < 0.001) (Table 1). An evaluation of the reasons corresponding to pop-up alerts in clinics found that drug-pregnancy warnings occurred most frequently (78.68%), followed by ingredient duplication (20.95%) and low dose over prescription (0.12%). In pharmacies, however, ingredient duplication occurred most frequently (more than 95%), followed by drug-pregnancy warnings (4.14%) and between-prescriptions drug–drug interactions (0.13%) (p < 0.001). This pattern was also found within RPh-DUR (Table 2). With the increase in the number of pop-up alerts for ingredient duplication, evaluations of the phase 2 DUR with “between-prescriptions review” showed that a more extensive DUR was carried out as compared to the “withinprescription review” only, which was one part of phases 2 DUR.
DUR at clinics resulted in higher pop-up rates for drugpregnancy warnings than DUR at pharmacies. However, when drug-pregnancy warnings were excluded, the proportion of ingredient duplication alert increased to 98.27%. Without drug-pregnancy warnings, ingredient duplication was the main reason for pop-up alerts both at clinics and pharmacies (more than 98%). Anti-inflammatory analgesic drugs were the most frequent drugs among both Co-DUR and RPh-DUR pop-up alerts, followed by cough suppressants/expectorants, and drugs acting on digestive systems (>10%) at pharmacies (p < 0.001, Table 3). Reasons for dispensing without a change after a DUR popup alert are summarized in Table 4. Code A (when, owing to long-term business trip or travel, a prescription is required prior to the complete use of drugs) was entered for the majority of cases, followed by code C (loss of drugs) (p < 0.001). The rate of entering the code of reason for dispensing was 27.3% for Co-DUR, which is lower than 63.3% for RPh-DUR. It means pharmacists changed the prescription more under the Co-DUR than RPh-DUR.
3.2.
Change in drug expenditures
Reduction in drug expenditures that occurred during the fourmonth pilot program was KRW 2,502,047 (USD $2126.74) at clinics and KRW 289,573 (USD $246.14) at pharmacies under the Co-DUR in one district, whereas it was KRW 11,526,841 (USD $9797.81) at pharmacies under the RPh-DUR in three districts. For reference, KRW 1000 equals USD $0.85 (as of 1st November, 2009). Annual reduction was estimated as KRW 7,816,538 (USD $6644.06), KRW 904,643 (USD $768.95), and KRW 36,010,509 (USD $30,608.93), respectively (Table 5). The nationwide application of the DUR system would be expected to result in a reduction of KRW 4,427,575,453 (USD $3,763,439.14) under the Co-DUR (KRW 3,968,305,815 (USD $3,373,059.94) at clinics and KRW 459,269,638 (USD $390,379.19) at pharmacies). For RPh-DUR, the reduction in drug expenditures was estimated as KRW 2,457,776,050 (USD $2,089,109.64).
4.
Discussion
Results from the DUR pilot program showed that more DUR pop-up alerts were detected in Co-DUR system than in RPhDUR. For Co-DUR system, pop-up alert rates were 8.55% at clinics and 1.90% at pharmacies. In RPh-DUR, the pop-up alert rate was 2.22%. With the inclusion of the doctors’ review process under the Co-DUR system, the detection rate was higher than it was in RPh-DUR. However, DUR at pharmacies also generated 1.90% of pop-up alerts even after DUR was performed via Co-DUR at clinics. One possible explanation for this may be that although when pop-up alerts were generated at clinics, doctors did not voluntarily modify the prescriptions, resulting in additional DUR pop-up alerts at pharmacies. Although this rate was lower than the pop-up alert rate (2.22%) of RPh-DUR, significant numbers of pop-up alerts were generated at pharmacies again in Co-DUR. This suggests that Co-DUR would be better for assuring the safer use of drugs compared to RPhDUR.
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Table 1 – Characteristics of the patients who participated in the DUR Pilot Program. Physician/pharmacist Co-DUR Clinic (N = 102)b a
Korea nationwided
Pharmacist-only DUR (N = 321)
Pharmacy (N = 103)
No. of patients
109,692 (100%)
105,933 (100%)
643,960 (100%)
42,350,733 (100%)
Sex Men Women
63,215 (42.37%) 46,477 (57.63%)
45,597 (43.03%) 60,354 (56.97%)
286,966 (44.56%) 356,994 (55.44%)
18,371,748 (43.38%) 23,978,985 (56.62%)
Agec ∼20 21–40 41–60 61+
36,999 (33.73%) 26,995 (24.61%) 29,836 (27.20%) 15,862 (14.45%)
34,494 (32.55%) 27,317 (25.79%) 29,507 (27.85%) 14,615 (13.81%)
181,664 (28.21%) 147,787 (22.95%) 194,192 (30.16%) 120,317 (18.68%)
10,354,813 (24.45%) 12,462,387 (29.43%) 12,896,913 (30.45%) 6,636,620 (15.67%)
Insurance type General Medicaid
107,498 (98.0%) 2194 (2.00%)
102,861 (97.10%) 3072 (2.90%)
624,748 (97.02%) 19,212 (2.98%)
40,938,303 (96.66%) 1,412,430 (3.34%)
No. drug per prescriptionc 1 2 3 4 5 6+
3.91 ± 1.69 11,935 (10.88%) 11,660 (10.63%) 18,297 (16.68%) 26,578 (24.23%) 23,200 (21.15%) 18,022 (16.43%)
3.84 ± 1.57 10,265 (9.69%) 11,695 (11.04%) 17,934 (16.93%) 29,216 (27.58%) 23,316 (22.01%) 13,507 (12.75%)
3.71 ± 1.76 83,650 (12.99%) 88,416 (13.73%) 123,705 (19.21%) 133,364 (20.71%) 119,390 (18.54%) 95,435 (14.82%)
3.86 ± 1.51 4,332,480 (10.23%) 5,120,204 (12.09%) 8,398,150 (19.83%) 9,871,956 (23.31%) 8,241,453 (19.46%) 6,386,491 (15.08%)
a b c d
Data is the total number of patients who participated in the DUR pilot program during four months (July 2009–October 2009). The number of clinics or pharmacies by DUR system type. Mean ± SD. Source: National Health Insurance Statistical Yearbook, 2010 [19].
Excluding the drug-pregnancy warnings, more than 95% of the pop-up alerts were “between-prescriptions ingredient duplication” alerts. In other words, the number of pop-up alerts increased sharply after the introduction of phase 2
DUR, indicating that a more extensive DUR was carried out. This may be related to the absence of the role of a gatekeeper in the Korean health care system, where patients may visit several clinics and doctors who prescribe many drugs,
Table 2 – Comparison of DUR pop-up alerts in Co-DUR and RPh-DURs. DUR pop-up alerta
Physician/pharmacist Co-DUR Clinic
Pharmacy
Pharmacist-only DUR
p value
No. of total prescriptions No. of prescriptions alerted DUR pop-up alert rate
287,635 24,584 8.55%
260,487 4,955 1.90%
2,139,535 47,424 2.22%
<0.001
Total no. of drugs alerted, n (%) Within-prescription Drug–drug interaction Drug–age conflict Drug–safety conflict Low dose duplicated prescription Drug-pregnancy warning Between-prescriptions Drug–drug interaction Ingredient duplication
32,337 (100.0) 25,507 (78.88) 14 (0.04) 12 (0.04) 0 (0.00) 39 (0.12) 25,442(78.68) 6830 (21.12) 54 (0.17) 6776 (20.95)
12,599 (100.0) 564 (4.48) 3 (0.02) 12 (0.10) 0 (0.00) 28 (0.22) 521 (4.14) 12,035 (95.52) 17 (0.13) 12,018 (95.39)
106,184 (100.0) 2529 (2.38) 33 (0.03) 115 (0.11) 2 (0.01) 301 (0.28) 2078 (1.96) 103,655 (97.62) 566 (0.53) 103,089 (97.09)
<0.001
No. of drugs alerted without drug-pregnancy warning, n (%) Within-prescription Drug–drug interaction Drug–age conflict Drug–safety conflict Low dose duplicated prescription Between-prescriptions Drug–drug interaction Ingredient duplication
6895 (100.0) 65 (0.94) 14 (0.20) 12 (0.17) 0 (0.00) 39 (0.57) 6830 (99.06) 54 (0.78) 6776 (98.27)
12,078 (100.0) 43 (0.35) 3 (0.02) 12 (0.10) 0 (0.00) 28 (0.23) 12,035 (99.64) 17 (0.14) 12,018 (99.50)
104,106 (100.0) 451 (0.43) 33 (0.03) 115 (0.11) 2 (0.002) 301 (0.29) 103,655 (99.56) 566 (0.54) 103,089 (99.02)
<0.001
a
Total data collected during four months from July to October 2009.
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Table 3 – Proportion of major therapeutic categories for DUR pop-up alerts. Therapeutic categoryb
Physician/pharmacist Co-DUR Clinic
Anti-inflammatory/pain/fever reducers Cough suppressants/expectorants Drugs acting on digestive system Anti-histamines Peptic ulcer drugs Psychiatric drugs Drug for cardiovascular diseases Antihypertensive drugs Drug-resistant Gram +/− germs Arteriosclerosis drugs Probiotics Others Total (N)a a b
Pharmacist-only DUR
Pharmacy
42.39% 1.93% 3.86% 1.22% 3.39% 7.20% 4.41% 5.77% 3.98% 3.94% 0.97% 20.94% 100.0% (32,337)
12.64% 11.26% 10.56% 6.12% 5.91% 5.50% 4.43% 4.24% 3.51% 2.40% 2.37% 31.06% 100.0% (12,599)
13.37% 12.56% 4.69% 5.00% 5.51% 3.13% 5.80% 7.38% 3.88% 5.84% 4.18% 28.66% 100.0% (106,184)
No. of DUR pop-up alert drug collected from July to October 2009. Therapeutic category was classified according to the provisions relating to classification numbers medication, The Korea Food and Drug Administration established rule No. 196 (August 24, 2009 enactment).
leading to the duplication of drugs containing the same ingredients. Because most medical visits are captured under the national health insurance system, the impact of “betweenprescriptions review” is expected to be enormous relative to the “within-prescription review” once the two-phase DUR system is expanded to the national level. The pop-up alerts generated at clinics were mostly related to drug-pregnancy warnings. The percentage of drugpregnancy warnings was 78.68% at clinics, whereas it was only 4.14% at pharmacies in Co-DUR, and 1.96% in RPh-DUR. This significant difference may have occurred because doctors have more information on their patient’s health condition and because clinics provide a more suitable environment for posing questions about the possibility of pregnancy. Also doctors can deal with the pop-up alert more easily and make their final prescribing decision without bothersome administrative
efforts, but pharmacists must contact doctors for intervention. Therefore, doctors can actively detect potential pregnancies, which can be another advantage of Co-DUR. The Korea Food & Drug Administration categorizes drugs contraindicated for pregnant women into two grades: ‘grade 1’, when the risk to unborn babies is remarkably high compared to the expected benefit, and ‘grade 2’, when the use of the drug is unavoidable for the purpose of treatment but must be used on the basis of clear clinical evidence [16]. For instance some of the anti-inflammatory analgesic drugs (loxoprofen, diclofenac, ibuprofen) are grade 2 drugs, which explained the higher rate of pop-up alerts for this therapeutic category. Because all pop-up alerts for drug-pregnancy warnings during the pilot DUR program involved only grade 2 drugs, they were not regarded as serious issues. Although there were no pop-up alerts for ‘grade 1’, it is desirable to establish a
Table 4 – Reasons for dispensing without a change after a DUR pop-up alert. Reasons for dispensing without changeb
Physician/pharmacist Co-DUR, n (%)
Pharmacist-only DUR, n (%)
A (prescription is required prior to complete use of drugs) B (adverse events or dose adjustment) C (loss of drugs) P (PRN) X (hard to contact prescriber) Text (drug–age conflict, drug–drug interaction) Others
1087 (46.68) 189 (8.13) 504 (21.64) 106 (4.57) 7 (0.31) 11 (0.47) 424 (18.20)
33,567 (56.69) 2872 (4.85) 14,886 (25.14) 2493 (4.21) 213 (0.36) 397 (0.67) 4784 (8.08)
Total
2329 (100)
59,211 (100)
12,599 2329 18.49%
106,184 59,211 55.76%
a
No. of drugs alerted No. of drugs including reasons Rate of entering reasons for dispensing c a b
c
p value <0.001
<0.001
No. of DUR pop-up alerts for drug collected from July to October 2009. The codes for dispensing without a change were as follows: A (when, owing to long-term business trip or travel, a prescription is required prior to the complete use of drugs); B (when it is not possible to change the prescription owing to adverse events or dose adjustment); C (loss of drugs); E (when a patient wants a new prescription prior to the complete use of drugs at his/her own expense); X (when the prescribing doctor cannot be contacted); P (PRN: pro re nata, different administration date); and Text (drug–age conflict, drug–drug interaction). Rate of entering reasons for dispensing (%) = no. of drugs including reasons/no. of drugs alerted × 100.
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Table 5 – Change of drug expenditure by DUR type. Type of DUR
Pilot study (Goyang City)
Nationwide
4 months
1 year
Physician/pharmacist Co-DUR No. patient (N)b No. prescription (N) Reduction of drug expenditure (KRW)a Clinic Pharmacy Reduction of drug expenditure per Prescription (KRW) Reduction of drug expenditure per patient (KRW)
109,692 287,635 2,791,620 2,502,047 289,573 9.71 25.45
– 898,588 8,721,180 7,816,538 904,643 – –
42,350,733 456,195,924 4,427,575,453 3,968,305,815 459,269,638 9.71 104.55
Pharmacist-only DUR No. patient (N) No. prescription (N) Reduction of drug expenditure (KRW) Reduction of Drug Expenditure per Prescription (KRW) Reduction of Drug Expenditure per Patient (KRW)
643,960 2,139,535 11,526,841 5.39 17.90
– 6,684,029 36,010,509 – –
42,350,733 456,195,924 2,457,776,050 5.39 58.03
a b
1 year
Unit: KRW 1000 = USD 0.85 (1 November 2009). The number of prescription and patient of pharmacy in Co-DUR was considered as same as clinics in Co-DUR.
mandatory checking system for grade 1 drugs, as pharmacists do not actively check for potential pregnancy. In addition, fewer checklist items for DUR were provided in the Korean pilot program, as compared to the US system. In the USA, pharmacy benefit managers (PBMs) typically have more comprehensive review lists, which usually include additional categories such as therapy duplications, high-dose warnings, and over use/excessive duration alerts. However, the Korean pilot program focused on ingredient duplication rather than therapeutic duplication. Further, the drug–drug interaction or drug–age conflict alerts were limited to some ingredients. For example, AdvancePCS, a PBM in the USA, conducted a large-scale drug interaction study with the University of Arizona Health Sciences Center in 2001 [17]. The study showed that DUR alerts were generated for high-dose warnings (21.9%), drug interactions (21.3%), for overuse/excessive duration (15.7%), and for therapeutic duplication (10.0%). Chui and Rupp observed 41 pharmacies in Indiana and presented that the prospective DUR alert rate for prescription drug claims was 10.3%. Drug–drug interactions, therapeutic duplications, high or low dosage alerts accounted for 56.7% of the alerts (760/1340) [18]. Considering that pop-up alerts were mainly ingredient duplication in Korea, it is necessary to develop more comprehensive checklist items for the DUR system in the future. The study results also suggested that the phase 2 DUR program can contribute to drug expenditure reduction by preventing ingredient duplications and drug interactions. When applying the estimated reduction in drug expenditure in the four-month pilot program to the entire country, the total reduction was estimated to be KRW 4.4 billion (USD $3.8 million) in a single year for Co-DUR. In RPh-DUR, the estimated reduction was KRW 2.5 billion (USD $2.1 million). In other words, Co-DUR will likely contribute more than RPh-DUR in reducing drug expenditures, as prescriptions can be canceled or modified at clinics and can be subsequently re-checked at pharmacies to assure their appropriateness.
Because the pilot program of Co-DUR was first introduced in Korea for a short period of six months, this study has several limitations: First, at the early stage of this pilot program, some clinics did not show an interest in participating. Moreover, the computer network system for the program was not fully implemented. Therefore, the data generated at the early stage in clinics was not representative of all the clinics in the DUR pilot test. As a result, only data collected during a period of four months after the full implementation of a working electronic network system was used in this analysis. Second, we did not have enough data on patient health conditions which could be the confounding factors in interpreting the outcomes of two DUR programs. Even though data showed the similar patterns in gender, age and number of drugs per prescription between two groups, there remains the possibility for the potential bias in the conclusion due to patients attributes. Third, evaluation of costs included only the estimation of changes in drug expenditure. To fully quantify the costs associated with the program, the costs of the implementation of computer systems used in the program should be included in the analysis. Given that the Korean DUR system was developed by implementing the DUR program into the existing national insurance billing system, implementation of the DUR system did not impose a heavy burden on clinics and pharmacies. However, careful consideration is necessary regarding additional expenses of implementing the DUR program. Meanwhile, drug interactions and other potential side effects may be prevented, leading to a reduction in medical expenses. In this study, however, the pilot program was evaluated with a focus on changes in drug expenditures owing to insufficient data for an extensive estimation of total medical expenditure. Fourth, we used the ratio of the prescription numbers between Goyang City and the entire nation to estimate the nationwide change in drug expenditure. The demographic characteristics of Goyang City patients showed quite similar to
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Summary points What was already known about the topic • Drug utilization review (DUR) has been conducted mainly as a form of “within prescription review” in the western countries. • DUR detected inappropriate prescriptions such as drug–drug interactions, therapeutic duplications, excessive duration and high dosage.
• The physician/pharmacist Co-DUR can detect the warnings of adverse drug events better than the traditional pharmacist-only DUR. • With the physician/pharmacist Co-DUR, doctors can readily reflect clinical information of patients in the DUR process, and pharmacists also have opportunities to double-check prescribed drugs when doctors do not voluntarily modify pop-up alerts. • A more extensive DUR has been carried out with “betweenprescriptions review” among different prescribers compared to “within- prescription review” only.
Acknowledgments the patients nationwide. But the estimation cannot be verified due to the lack of accurate data to show that the patient mix of Goyang City is representative for the whole nation. Furthermore, only four months of data were available for analysis, and we cannot be certain that the drug utilization during the time period studied is representative of the remainder of the calendar year, as it is possible that seasonal variation may affect drug utilization. Therefore, a comprehensive future study of the effects on expenses is necessary. This study compared the Co-DUR system with the RPhDUR system through a government-driven pilot program in South Korea. In the Co-DUR system, doctors experienced a higher pop-up alert rate than that observed in RPh-DUR since these warnings included clinical information of patients in the DUR process, especially for drug-pregnancy warnings. Pharmacists also have opportunities to double-check prescribed drugs when doctors do not voluntarily modify pop-up warnings. With an increase of pop-up alerts for ingredient duplication, phase 2 DUR with “between and within prescriptions review” showed that a more extensive DUR was carried out as compared to a “within-prescription review” only. Even though there remains the possibility for potential bias in interpreting the outcomes of DUR pilot programs, Co-DUR system was found to be a more effective model to detect inappropriate drug prescribed compared to the traditional RPh-DUR system under the real-time DUR pilot study. Further study will be needed to confirm the results of pilot program that favored the physician/pharmacist CoDUR.
Authors’ contributions All the authors of this article have been involved in analysis and interpretation of data, revising the article and giving final approval of the manuscript. Ji Haeng Heo, Dong Churl Suh, Sukil Kim and Eui-Kyung Lee were involved in the conception and design of the study. Ji Haeng Heo was involved in the acquisition of data and drafted the manuscript.
Conflict of interest The authors declare no conflicts of interest. What this study adds?
This study was funded by an unrestricted research grant from the Health Insurance Review & Assessment Service in South Korea.
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