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PHARMACOEPIDEMIOLOGY AND PRESCRIPTION

Adherence to hospital drug formularies and cost of drugs

in hospitals in Denmark 

Hanne T. Plet   &  Jesper Hallas   &  Lene J. Kjeldsen

Received: 30 January 2013 /Accepted: 21 May 2013 /Published online: 14 June 2013# Springer-Verlag Berlin Heidelberg 2013

Abstract

 Purpose   To investigate adherence rates to hospital drug

formularies (HDFs) and cost of drugs in hospitals.

 Methods  Data on drugs used during 2010 were analyzed for ten hospitals (two hospitals from each of the five regions),

constituting 30 % of hospitals and 45 % of hospital beds in

Denmark. Drug use data from individual hospitals were

retrieved from the hospital pharmacies. Adherence to the

HDFs was analyzed for selected substances characterised by

extensive use both in primary and secondary sectors (ATC

codes A10, B03, C03, C07, C08, C09, C10, J01, N02, N05

and R03). Within each group, we also identified the drugs

constituting 90 % of the volume (= DU90%) and the adher-

ence to the HDF in this segment (Index of Adherence).

 Results   Substances used by hospitals varied between 598

and 1,093. The proportion of used substances that were onthe HDF varied between 14 % and 44 %. University hospi-

tals used a significantly higher total number of substances

(median 165 vs. 139,  p  = 0.019) and cost/DDD [(median 5

vs. 2 Euros,  p  = 0.033),  p  = 0.033] in the DU90% segment 

than the regional hospitals. Index of adherence varied be-

tween 43 % and 91 %. For the selected ATC codes, the

index of adherence was between 76 % and 100 %.

Conclusions   Adherence to the selected ATC groups was

high, which means that the most commonly used substances

are included in the HDFs, even though a variation existed. A

large variation existed between the hospitals in the number 

of substances at HDFs.

Keywords   Drug utilization . DU90 % . Adherence  .

Hospital   . Hospital drug formulary

Introduction

Drug expenditure in hospitals in Denmark, as well as in

other countries is increasing [1 – 4]. To avoid excessive drug

costs and to ensure optimal quality of drug treatment, drug

formularies (DFs) may be used as a tool to promote rational

drug use [4, 5].

DFs contain lists of essential drugs specific for health

care, and are widely used to promote rational pharmacother-

apy, and are hence based on evidence, costs and safety [6].

DFs are developed and implemented as management tools

in primary health care as well as in hospitals [7 – 9]. The

quality of the prescribed drugs and adherence to guidelines

has been evaluated at different levels (cross-national, hospi-

tal, primary care) [10 – 15], demonstrating a large diversity in

how drugs are selected in the formulary and how the for-

mulary was developed and implemented [2, 16 – 19].

In Denmark, a DF is developed at the national level, and

each of the five regions develops their own DF aimed at 

 primary care based on the national DF; DFs aimed at the

hospitals – hospital drug formularies (HDFs) – are developed,

implemented and monitored at the regional or hospital level

[20]. Guidelines for the most expensive drugs used at the

hospitals are developed at the national level, and implemented

at the regional level [21]. The DFs for primary and secondary

care are harmonized for drugs that are extensively used in both

sectors.

 No standards for monitoring and evaluating use of HDFs

exist. Adherence to HDFs can be used to monitor and evaluate

the quality of prescribing, guideline implementation, and to

compare within or between hospitals and regions. Hence, the

 purpose of this study was to investigate adherence rates to

hospital drug formularies and cost of drugs in hospitals.

H. T. Plet (*) : J. Hallas

Department of Clinical Pharmacology, Faculty of Health Sciences,

University of Southern Denmark, J.B. Winsloews Vej 19,2,

5000 Odense, Denmark 

e-mail: hanne@bundgaarden.dk 

H. T. Plet : L. J. Kjeldsen

SAFE, Amgros I/S, 2100 Copenhagen, Denmark 

Eur J Clin Pharmacol (2013) 69:1837 – 1843

DOI 10.1007/s00228-013-1540-6

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Methods

Settings and study design

Denmark is divided into five administrative regions. The main

responsibility of each region is health care, secondary care

(hospital services, both somatic and psychiatric) and activities

related to primary care physicians. University hospitals arerepresented in four regions, and each region has a DTC that 

develops a hospital drug formulary. Nevertheless, the DTCs

are organized differently [20]. The hospitals for this study were

selected to represent one university and one regional hospital

from each region, and in the one region without university

hospitals, two regional hospitals were selected instead.

The study was designed as a cross-sectional comparison

study and included drug sales data from 10 hospitals in

Denmark in 2010. In total, four university hospitals and six

regional hospitals are represented. This cohort constitutes of 

30 % of hospitals and 45 % of hospital-beds in Denmark.

Hospital drug formularies

DTCs are responsible for developing HDFs that mainly con-

sist of drugs used at most wards. Only one HDF contained

specialist drugs [20]. At the hospitals, each ward have a 

wardlist, defined as a list of drugs used routinely on the wards,

which comprises drugs from the HDF and specialty drugs

used specifically at that ward but are not on the HDF [ 22].

Information on each drug includes product name, dispensing

form, ATC code, generic name, and strength. Indications were

only available for a limited number of drugs, and prices were

not available. The physicians had access to the HDF electron-

ically. Four regions had a regional HDF aimed at all hospitals

in the region, and in one one region, each hospital developed

their own HDF.

Data 

HDFs from 2010 were collected from the drug and therapeu-

tics committees (DTCs) in Denmark. Numbers of beds and

 bed-days were retrieved from the Danish Health and Medi-

cines Authority. Data on drugs sold to the 10 hospitals in 2010

were retrieved from BiWeb, which is a database containing

data on all drugs delivered from hospital pharmacies in Den-

mark to hospital wards. ATC code, generic name, product 

name, strength, dispensing form, package size, DDDs, number 

of each products used, and costs were available for each drug.

The following products (substances) were included in the

analysis:

&   Substances with an assigned, official ATC code at fifth-

level according to the World Health Organization

(WHO) [23].

&   Substances with a non-official ad hoc ATC code at fifth-

level, assigned jointly by the hospital pharmacies for 

drugs manufactured specifically for hospital use, e.g.

A12C### Phosphat oral solution with blackcurrant taste;

 N02AG##_ Morfin – Atropin – Papaverin suppositories.

The following products (substances) were excluded from

the analysis:

&   Products that were assigned ATC code V (Various) and

sublevel. This group comprises many different types of 

drugs and other types of products. Very few DDDs were

assigned in this group, and they were considered to be of 

little relevance to the analysis. In total, 75 substances

from this group were excluded.

Data analyses

Data were analyzed at hospital level and the Anatomical – 

Therapeutic – Chemical (ATC) classification system, and thedefined daily dose (DDD) technology recommended by the

WHO was used to classify drugs and to measure volume of 

drug use [23].

The drugs sold for each hospital was compared with HDF

for the particular hospital, and drugs were marked as HDF-

drug if the ATC code were on the HDF. The ATC code was

used because generic substitution was practiced during the

year.

The total number of substances, DDDs and cost (in Euros)

for all drugs and for HDF-drugs used were calculated for each

hospital. The percentages of HDF substances used of total

number of substances at the 10 hospitals were calculated.

Adherence to the HDFs was analyzed at substance level

using the drug utilization 90 % (DU90 %). The DU % segment 

is the drugs constituting 90 % of the volume as measured in

DDD and the adherence to the HDFs in this segment is termed

the Index of Adherence [24]. First, substances that had an

assigned DDD were identified, then the number of substances

that account for 90 % of the total volume of DDDs (=DU %)

were calculated, and at last the index of adherence were

calculated (number of DDDs for substances in HDF divided

 by the total number of DDDs within the DU %-segment).

In order to compare the drug costs between the hospitals,

cost/DDD was calculated for the DU % segment and for the

remaining 10 %. Cost expressed as % of total costs were

calculated for DU % segment, remaining 10 % and where

DDD=0.

To presents the variations in percentage of substances

used of the total number of drugs, median and interquartile

range was calculated for the hospitals.

Drugs prescribed in primary care have an impact on

drugs used in hospitals, and as a consequence used widely

in hospitals. We thus found it of particular interest to analyse

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adherence for drugs that were extensively used in both

sectors, i.e., ATC groups A10, B03, C03, C07, C08, C09,

C10, J01, N02, N05 and R03).

Statistics

Standard descriptive statistical measures were used. Differ-

ences were tested by Mann – Whitney   U -test. A value of  p<0.05 was considered significant. Analyses were carried

out using STATA/IC 12.0 (StataCorp, College Station, Texas

77845, USA, Copyright 1985 – 2011).

Results

The hospitals had used 1,587 different substances, of which

149 substances were excluded from the analysis according

to the criteria given above. Consequently, 1,438 substances

were included in the analysis, and of these, 134 substances

had no assigned DDD. Total drug costs for the 10 hospitalswere 481 million Euros, and HDF-drugs accounted for 76

million Euros (16 %). Cost of drugs with DDD=0 were 44

million Euros (9 %), and of these drugs, substances from

ATC code L (antineoplastic and immunomodulating agents)

accounted for 40 million Euros (91 %).

Regarding the individual hospitals, the median number of 

substances used was 851, and the median percentage of used

substances also found on the HDF was 24 % (n=185)

(Table   1). The median number of substances on the HDFswas 193, with a university hospital having the highest number 

of substances of 528 (Table   1). This hospital also had the

highest use of HDF-substances 448 (44 %) (Table   1). The

number of substances used by the university hospitals tended

to be higher than for regional hospitals (median 969 vs. 794,

 p=0.055). The costs per 100 bed days were significantly

higher for drugs used at university hospital than for regional

hospitals (median 36,104 vs. 9,429 Euros,   p=0.011). The

median number of substances on the HDF was 193 for both

university and regional hospitals.

The median index of adherence was 52 % (range 43 – 91).

The outlier with a high adherence rate of 91 % also had thehighest number of substances (n=528) on the HDFs and the

Table 1   Information on hospitals, hospital drug formularies (HDFs), number of substances used and costs

Hospital

type

Region Hospital HDF

typea  Number of beds Substances Cost 

On

HDF b

(n)

Total

used

(n)

HDF

used

(n)

Used on

HDF

(%)

Per hospital

(EUR)

Per 100

 bed days

% of cost 

on HDF

substances

University 1 1 R 808 183 910 181 20 45,209,682 19,556 8

2 3 R 847 203 849 200 24 72,410,323 54,192 4

3 5 H 946 528 1,028 448 44 75,664,423 24,842 65

5 9 R 908 155 1,093 152 14 162,054,356 47,367 4

Median 878 193 969 191 22 74,037,373 36,104 6

Min 808 155 849 152 14 45,209,682 19,556 4

Max 946 528 1,093 273 44 162,054,356 54,192 65

Regional 1 2 R 386 183 598 177 30 5,378,529 5,048 14

2 4 R 560 203 776 189 24 15,310,876 10,272 6

3 6 H 431 179 791 175 22 15,275,331 10,927 10

4 7 R 1,113 282 853 269 32 28,938,020 9,555 15

4 8 R 982 282 926 273 29 43,945,765 9,304 12

5 10 R 576 155 796 149 19 17,153,329 6,660 10

Median 568 193 794 183 27 16,232,103 9,429 11

Min 386 155 598 149 19 5,378,529 5,048 6

Max 1,113 282 926 273 32 43,945,765 10,927 15

Total

Median 828 193 851 185 24 36,441,893 10,600 10

Minimum 386 155 598 149 14 5,378,529 5,048 4

Maximum 1,113 528 1,093 448 44 162,054,356 54,192 65

a The hospital drug formulary (HDF) is developed; at the regional level (R), and is the same for all the hospitals in the region; or at the hospital level (H) b Number of substances on the hospital drug formulary

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highest DU90 % (n=195) (Table 2). The percentage of total

costs in the DU90 % segment was not significantly higher 

for university hospitals than for regional hospitals (median

50 % vs. 58 %,   p=0.09). The total number of substances

used in the DU90 % segment were significantly higher for 

university hospitals than for regional hospitals (median 165

vs. 139, p=0.019) and cost/DDD in DU90 % segment were

significantly higher for university hospitals than for regionalhospitals (median 5 Euros vs. 2 Euros,  p=0.033).

The median cost for substances with no assigned DDD

was 247,348 Euros (range 10,100−20,046,182 Euros). Two

university hospitals had 22.7 % and 26.5 % of total cost for 

substances without a DDD value, which was considerable

higher than for the other hospitals (range 0.1 – 5.1 %) (Table 2).

Substances with assigned ATC code L (antineoplastic and

immunomodulating agents) resulted in the highest cost for 

drugs with no assigned DDD, the median cost for this ATC

group was 41,799 Euros (range 701 – 19,511,387 Euros), for the

same two university hospitals it was respectively 15,762,733

and 19,511,387 Euros.Figure 1  present adherence measured as the median per-

centage of HDF-substances used of the total number of 

substances, and the interquartile range for the 10 hospitals.

Most of the substances used at the hospitals are non-HDFs.

ATC group G (genitourinary system and sex hormones), L

(antineoplastic and immunomodulating agents), M (musculo-

skeletal system), P (antiparasitic products, insecticides and

repellents) and S (sensory organs) had the lowest median

adherence rate about or below 20 %. From ATC group L

examples of most expensive non-HDF substances used were:university hospitals — substances from ATC group L01XC

(monoclonal antibodies — L01XC03 traztuzumab, L01XC02

rituximab); regional hospitals — substances from L04AB (tu-

mor necrosis factor alpha (TNF-?) inhibitor  — L04AB04

adalimumab, L04AB02 infliximab).

The median index of adherence for substances within the

selected ATC codes used both in primary and secondary

care varied from 76 – 100 % (Table   3). ATC group N05

(psycholeptics) had the lowest index of adherence (median

76; range 57 – 91 %), and the DU90 % segment consisted of 

eight substances. This group also included the highest num-

 ber of substances used (median 37). The median DU90 %segment for ATC groups C03 (diuretics), C07 (beta-

 blocking agents), C08 (calcium channel blockers), C10

Table 2   Cost and adherence to hospital drug formulary presented by DU90 %

Hospital

type

Hospital No. of substances

(DDD>0)

Index of 

adherence bCost/DDD (EUR) Cost (% of total costs)

Total DU90 %a  DU90 %

segment 

Remaining

10 %

DU90 %

segment 

Remaining

10 %

DDD=0

University 1 872 160 55 3.0 24.1 50.3 44.6 5.1

3 760 156 50 6.0 29.5 49.9 27.4 22.7

5 931 195 91 3.5 15.8 48.9 24.6 26.5

9 1,017 169 47 6.3 40.5 56.4 40.6 3.0

Median 902 165 53 4.8 26.8 50.1 34.0 13.9

Minimum 760 156 47 3.0 15.8 48.9 24.6 3.0

Maximum 1,017 195 91 6.3 40.5 56.4 44.6 26.5

Regional 2 581 105 54 1.9 4.9 76.4 22.3 1.2

4 769 149 43 3.0 16.5 62.2 37.8 0.1

6 710 138 50 2.0 18.2 49.3 49.2 1.5

7 816 140 70 2.1 18.5 50.3 49.4 0.3

8 874 159 60 3.2 19.8 59.1 40.7 0.2

10 757 128 50 2.2 14.4 56.8 41.7 1.6

Median 763 139 52 2.2 17.3 58.0 41.2 0.8

Minimum 581 105 43 1.9 4.9 49.3 22.3 0.1

Maximum 874 159 70 3.2 19.8 76.4 49.4 1.6

Total

Median 793 153 52 3.03 18.36 53.3 40.7 1.5

Minimum 581 105 43 1.89 4.91 48.9 22.3 0.1

Maximum 1,017 195 91 6.28 40.49 76.4 49.4 26.5

a DU90 %: number of substances constituting 90 % of the volume in DDDs b Index of adherence: percentage adherence to guideline within the DU90 % segment 

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(lipid modifying agents) was low (1 to 3 substances),

even though the median of the total number of sub-

stances used was between 9 and 11. For ATC groups

B03 (antiaenemic preparations), and J01 (antibacterials

for systemic use), the median DU90 %’s were 3 and 14

substances, and the median index of adherence were

86 % and 93 %. The range for index of adherence

varied considerably (range 46 – 100 %), especially ATC

code C09 (agents acting on the renin – angiotensin

system) and J01. For university hospitals, the DU90 %

segment for ATC groups J01 and R03 (drugs for ob-

structive airway disease) consisted of a significantly

higher number of substances than for regional hospitals

(16 vs. 13,   p=0.030 and 8 vs. 6,   p=0.038, respective-

ly). Similarly, the total number of substances used from

ATC groups J01 (median 46 vs. 39,   p=0.014) and N02

(median 22 vs. 20,   p=0.015) were significantly higher 

for university hospitals than for regional hospitals.

0 20 40 60

% HDF-substances

S-sensory organs

R-respiratory system

P-antiparasitic products, insecticides and repellents

N-nervous system

M-musculoskeletal system

L-antineoplastic and immunomodulating agents

J-antiinfectives for systemic use

H-systemic hormonal preparations, excl. sex hormones and insulins

G-genito urinary system and sex hormones

D-dermatologicals

C-cardiovascular system

B-blood and blood forming organs

A-alimentary tract and metabolism

excludes outside values

Fig. 1   Box-and-whiskers plot 

of percent of hospital drug

formulary substances used of 

total number of substances at 

the 10 hospitals. The graph

indicates the median,

interquartile range and total

range for all major drug classes

Table 3   Adherence to hospital drug formularies at 10 hospitals for selected ATC codes

ATC code 2nd level DU90 %a 

(n)

Index of adherence b

(n)

Substances totalc

(n)

Substances on

HDFd (%)

Median Range Median Range Median Range Median Range

A10 Drugs used in diabetes 6 (5 – 8) 100 (68 – 100) 23 (17 – 28) 33 (20 – 36)

B03 Antianemic preparations 3 (2 – 4) 86 (72 – 100) 11 (9 – 13) 44 (33 – 54)

C03 Diuretics 2 (1 – 3) 100 (91 – 100) 11 (8 – 13) 30 (23 – 55)

C07 Beta-blocking agents 3 (2 – 4) 97 (86 – 100) 11 (8 – 12) 32 (20 – 36)

C08 Calcium channel blockers 2 (2 – 4) 89 (70 – 100) 9 (7 – 11) 22 (11 – 45)

C09 Agents acting on rennin-angiotensin system 7 (3 – 8) 93 (46 – 100) 26 (21 – 31) 16 (8 – 24)

C10 Lipid modifying agents 1 (1 – 2) 100 (78 – 100) 10 (8 – 12) 15 (8 – 50)

J01 Antibacterials for systemic use 14 (12 – 19) 93 (57 – 100) 42 (33 – 49) 43 (35 – 58)

 N02 Analgesics 4 (3 – 5) 92 (85 – 100) 21 (17 – 26) 27 (18 – 38)

 N05 Psycholeptics 8 (7 – 14) 76 (57 – 91) 37 (34 – 44) 27 (22 – 39)

R03 Drugs for obstructive airway diseases 6 (5 – 8) 100 (85 – 100) 20 (17 – 23) 53 (45 – 75)

a DU90 %: number of substances constituting 90 % of the volume in DDDs b Index of adherence: percentage adherence to guideline within the DU90 %-segment c Substances total: total number of substances (DDD>0) within the ATC groupd Substances on HDF: % of substances (DDD>0) on hospital drug formulary

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Discussion

This study showed a large variation in adherence to HDFs,

the number of substances used, number of HDF-substances

used, and differences in costs. One of the reasons for vari-

ations in adherence and cost could be a consequence of 

differences in HDFs and formulary management in the re-

gions DTCs [20]. Another reason could be that many ther-apeutic equivalent drugs existed and therefore may pose a 

 problem in the interface management between primary care

and hospitals regarding number of non-HDF drug used. The

results can be used to prioritize main area of actions within

selected ATC groups where most used substances are non-

HDF (ATC group G, L, M, P and S).

The main strength of the study is that we were able to

collect data for a variety of hospitals across different regions,

different status regarding secondary or tertiary care and were

able to compare university and regional hospitals. Another 

strength is that the data source used, BiWeb, employs the ATC

and DDD coding system, which allowed us to aggregate data and compare costs and volumes on virtually any level of 

detail. A minor part of the products did not have official ATCs

or DDDs assigned from the WHO. These products could be

handled by use of the provisional ATC codes and DDDs

assigned by the Danish hospital pharmacies.

Formularies should be the basis for management of drug

use, and influence the drugs used in primary care and hospi-

tals. Variations in the number of substances on the HDFs

 between hospitals in this, and other studies have been reported

 previously [2, 19, 25]. The HDF of one hospital contained a 

much higher number of substances than the remaining nine

hospitals. The result from this study showed a low median

number of substances on the HDFs among the 10 hospitals.

The median number of substances on HDF was nearly the

same as the number of substances on the   “Wise List ”, a 

formulary developed by the Stockholm County Council

aimed at physicians both in primary care and hospitals, how-

ever, it only included few specialist drug used in hospitals [5].

When compared to Dutch HDFs the median number of sub-

stances on HDF was considerable lower both for regional and

university hospital [19]. Awide range of number of substances

on the HDFs existed, even though evidence methods were

used developing HDFs in Denmark [20]. Gallini et al. showed

variations in the number and nature of HDF drugs within

selected ATC codes, even though rather similar criteria for 

drug selection in the different hospital were used [2].

The costs of HDF-substances were low for nine hospitals,

while one hospital also had specialist drug on the HDF and

this hospital also had the highest cost on HDF-substances.

University hospitals had significantly higher costs and used

more substances than regional hospitals. Use of more sub-

stances at university hospital has also been reported in other 

studies [19,   25], and it is likely that this higher use of 

number of substances and higher costs can be explained

 by the fact that they have more special and expensive

treatments, particularly from ATC code L (antineoplastic and

immunomodulating agents).

In this study DU90 % and index of adherence was used,

even though this methodology were intendedfor primary care,

however it has been used in hospital settings, and shown to

suitable to access prescribing [11]. The median number of substances within the DU90 % were low, however, one hos-

 pital had nearly twice as high index of adherence as the other 

hospitals, and about 25 % more substances used in the

DU90 % segment. The cost of the DU90 % segment was

approximately 50 % for all hospitals. The cost/DDD within

the DU90 % was low compared with the cost/DDD in the

DU10 % segment for all hospitals. The adherence rates mea-

sured as the percentage of total use accounted for by HDF-

substances use were low. A variation in percentage of HDF-

substances used within ATC code first level by the 10 hospi-

tals also existed, and the percentage of non-HDF substances

used was relatively high. The selected drugs used in both primary and secondary care had a high adherence rate, com-

 pared to the adherence rate for all substances used. Hospital

 pharmacies contributed to adherence to HDF [20], which

 probably influenced favorably on the adherence rate for the

selected ATC codes. The collaboration between primary care

and hospitals to harmonize drugs used for basic treatment 

could also have influenced favorably. However, many non-

HDF substances were used, which can be explained by the

fact that pre-admission drug therapy have an impact on non-

HDF drug request [26]. Variations in adherence rates have

also been reported in other studies [10, 11]. It has been shown

that a multifaceted intervention can increase the level of 

adherence to the formulary on drugs used for basic treatment 

in primary care [5, 10].

Adherence to the selected ATC groups was high, which

means that the bulk of the used substances are at the HDFs,

even though a variation existed. Despite the fact that varia-

tions in the presentation of HDFs existed, a carefully selected

drug formulary should guide the clinicians in choosing the

safest and most effective agents for treating specific medical

 problems.

Conclusion

A large variation between the hospitals in the number of 

substances at HDFs existed, and results from this study indi-

cate differences in development and implementation. The low

adherence probably reflects the low number of substances at 

the HDFs for the hospitals; specialist drugs were mostly not at 

the HDFs. Treatment guidelines are now developed for drugs

with the highest cost at the hospital at the national level, they

are implemented at the regional level, and it is mandatory to

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follow these guidelines. DTCs can focus on quality of pre-

scribing of drugs that are not included in the treatment guide-

lines. Continuing the collaboration between primary care and

hospitals in developing a common formulary, could be the

way forward to optimize the interface management. Discus-

sion at the national level of new ways to develop, implement 

and evaluate HDFs may be needed to improve adherence.

Acknowledgments   The authors would like to thank the hospital

 pharmacies in Denmark and Amgros I/S for given access to BiWeb.

This made it possible to retrieve the data used for this study.

Conflict of interest   None declared.

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Sundhedsdata%20og%20it/NSF/Dataformidling/5%20aars%

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