Perspectives and Achievements
with Rational Pharmacotherapy
6. November 2002, Copenhagen
European drug statistics
What is the reason for the differences between
the various EU countries
Ulrich Schwabe
Pharmakologisches Institut
der Ruprecht-Karls-Universität Heidelberg
EU average
252 €
400
349
356
377
303
300
197
200
208
211
213
250
232
254
264
276
174
122
100
Ita
ly
Fi
nl
an
Sw d
Lu
e
x e de n
m
bo
ur
g
Au
st
ria
G
er
m
an
y
Fr
an
c
Be e
lg
iu
m
0
Ire
la
nd
G
re
ec
e
Po
Ne rtu
ga
th
l
er
la
nd
s
De
nm
ar
k
Sp
G
re
ai
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at
Br
ita
in
Sales per inhabitants per year in €
Drug expenditures in 15 EU countries in 1999
Rosian I. et al.: Drug expenditures, strategies for cost containement in the European Union. Austrian Federal Institute of Health Service (ÖBIG), Vienna 2001.
Drug markets in 15 EU countries in 1999
Country
Number
Reimbursed
of medicines
Austria
Belgium
Denmark
Finland
France
Germany
Great Britain
Greece
Ireland
Italy
Luxembourg
Netherlands
Portugal
Spain
Sweden
All EU countries
a
a
12,394
a
6,078
6,671
a
4,576
9,273
a
23,387
19,201
11,835
7,067
9,182
a
10,372
16,572
11,309
a
4,535
60%
58%
67%
81%
50%
87%
87%
64%
58%
48%
75%
90%
36%
68%
90%
Sales
Sales
Mio. €
per inhabitant, €
2,926
2,971
738
1,068
20,276
27,201
11,519
1,994
492
14,400
119
3,644
2,236
7,923
2,108
303
377
211
254
356
349
232 (1998)
174
122 (1997)
250
276 (1998)
208
197 (1998)
213
264 (1997)
99,615
252
Drug lists
Drug list
Positive list
Positive list
Positive list
Positive list
Negative list
Positive list
Positive list
Negative list
Positive list
Negative list
Positive list
Positive list
Positive list
Positive list
without different package sizes
Rosian I. et al.: Drug expenditures, strategies for cost containement in the European Union. Austrian Federal Institute of Health Service (ÖBIG), Vienna 2001.
Sales (€) or DDD per inhabitant per year
Drug utilization as defined daily doses (DDD)
500
Sales in 1999 €
DDD in 1999
400
349
393
349 €
385
328 €
300
211 €
200
100
0
Denmark
Germany
Norway
Denmark: The Danish Medicines Agency: Medicinal product statistics Denmark 1995–1999 and 1997–2001
Germany: Schwabe U., Paffrath D. (eds.): Drug Prescription Report 2002. Springer-Verlag, Berlin Heidelberg New York
Norway: Norwegian Institute of Public Health: Drug consumption in Norway 1993–1997 and 1997–2001
The ATC/DDD System
Anatomical therapeutic chemical (ATC)
classification system
Classification by 14 main groups at 5 different levels
1. Level: A
2. Level: A10
Alimentary tract and metabolism
Drugs used in diabetes
Anatomical main group
Therapeutic main group
3. Level: A10B
Oral blood glucose lowering drugs Therapeutic subgroup
4. Level: A10B A
Biguanides
Pharmacological subgroup
5. Level: A10B A02 Metformin (INN)
Chemical substance subgroup
Definition of the defined daily dose (DDD)
The DDD is the assumed average maintenance dose per day
for a drug used for its main indication in adults.
DDD of metformin: 2000 mg
Presentation of data: DDDs per 1000 inhabitants per day
Drug utilization data in EU countries
Country
Austria
Belgium
Denmark
Finland
France
Germany
Great Britain
Greece
Ireland
Italy
Netherlands
Norway
Portugal
Spain
Sweden
Sales
million €
Utilization
data
Packages
DDD
2,926
2,971
738
1,068
20,276
27,201
11,519
1,994
492
14,400
3,644
1,459
2,236
7,923
2,108
IMS
+
+
+
+
+
+
0
0
+
+
+
IMS
+
+
IMS
+
+
0
+
+
+
0
0
+
+
0
+
+
+
0
+
+
+
0
+
0
0
0
+
+
+
0
0
+
EURO-MED-STAT Monitoring Expenditure and Utilization of Medicinal Products. A Public Approach. Summary of the drug registers.
Prescription of statins 1993–2001
DDD per 1000 inhabitants per day
80
Norway
60
Germany
40
20
Denmark
0
1993
1994
1995
1996
1997
1998
1999
2000
2001
Denmark: The Danish Medicines Agency: Medicinal product statistics Denmark 1995–1999 and 1997–2001
Germany: Schwabe U., Paffrath D. (eds.): Drug Prescription Report 2002. Springer-Verlag, Berlin Heidelberg New York
Norway: Norwegian Institute of Public Health: Drug consumption in Norway 1993–1997 and 1997–2001
Prescription of statins in 2000
DDD per 1000 inhabitants per day
70
Simvastatin
Lovastatin
60
59.6
Pravastatin
Fluvatatin
50
Atorvastatin
Cerivastatin
40
30
20
23.9
26.5
15.4
10
0
Denmark
England
Germany
Norway
Prescription of the two leading statins 2000
DDD per 1000 inhabitants per day
35
Simvastatin
30
29.8
Atorvastatin
25
21.0
20
15
11.5
9.7
10
9.4
7.5
5.5
4.6
5
0
Denmark
England
Germany
Norway
Evidence for statines from clinical trials
Study
Method
Secondary prevention
All-cause mortality
Placebo
Statin
p-value
Simvastatin
4S-Study (1994)
4444 CHD patients, 5.4 years
LDL-C 188  122 mg/dl
11.5%
8.2%
0,0003
Pravastatin
CARE (1996)
4159 CHD patients, 5 years
LDL-C 139  98 mg/dl
9.4%
8.6%
ns
Pravastatin
LIPID (1998)
9014 CHD patients, 6.1 years
LDL-C 150  113 mg/dl
14.1%
22%
<0,0001
Simvastatin
HPS-Study (2002)
20536 patients with CHD,
stroke, diabetes, 5 years,
LDL-C 131  92 mg/dl
14.7%
12.9%
0,0003
4.1%
3.2%
ns
0,051
2.3%
2.4%
ns
Primary prevention
Pravastatin
WOSCOP (1995)
6595 Men, 4.9 years
LDL-C 192  144 mg/dl
6605 low HDL-C patients,
Lovastatin
AFCAPS/TexCAPS 5.2 years,
LDL-C 150  112 mg/dl
(1998)
DDD costs of statins in several European countries
Treatment costs (€ per DDD)
2
Simvastatin
Atorvastatin
1.47
1.5
1.28
1.25
1.16
1.07
1.05
0.93
0.92
1
0.5
0
Denmark
England
Germany
Norway
Prescriptions of therapeutically disputed drugs
in Germany
800
700
600
5
4.8
4.3
4,5
3.7
3.6
500
3.6
Sales
2.9
400
3,5
3
2.8
2.4
300
200
4
3.8
Prescriptions
2,5
2.0
1.9
100
2
1,5
0
1
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Schwabe U., Paffrath D. (eds.): Arzneiverordnungs-Report 2002. Springer-Verlag, Berlin Heidelberg (2002), p. 816.
Sales of therapeutically disputed drugs
in Germany
2000
2001
250
Sales (million €)
200
–7.6%
–3.4%
150
–3.6%
100
–7.8%
+4.4%
50
–6.3%
0
Expectorants
Antidementia
drugs
Antineuropathic
drugs
Vasodilators
Topical
antirheumatic drugs
Antivaricose
therapy
Prescription of peripheral vasodilators 2001
in Germany
50
Sales in million €
42.6
40
30
27.6
20
10
4.9
0
4.0
2.1
Prescription of peripheral vasodilators 2001
DDD per 1000 inhabitants per day
in 3 European countries
3.0
2.58
2.5
2.0
1.5
1.0
0.53
0.5
0
0.1
Pentoxifylline trials in patients with
intermittent claudication
Study
Patients
Maximal walking distance (m)
Bollinger & Frei (1977)
Porter et al. (1982)
Völker (1983)
Di Perri et al. (1984)
Donaldson et al. (1984)
Strano et al. (1984)
Roekaerts & Deleers (1984)
Gallus et al. (1985)
Kiesewetter et al. (1987)
Reilly et al. (1987)
Rudofsky et al. (1989)
Dettori et al. (1989)
Lindgärde et al. (1989)
Ernst et al. (1992)
Scheffler et al. (1994)
Norwegian Trial Group (1996)
Mean increase (m)
19
82
51
24
80
18
16
38
30
25
154
59
150
40
30
114
Drug
Placebo
Difference
before/after
before/after
(m)
226/697
172/247
331/465
222/358
108/119
121/175
251/555
68/91
202/247
138/175
218/360
112/324
132/198
166/504
75/154
60/100
177/270
181/250
230/290
210/216
97/129
134/139
224/190
88/100
174/189
101/191
211/287
144/349
155/200
151/420
72/158
50/100
378
27
74
130
ns –21
49
338
ns 11
30
ns –53
66
ns 7
ns 21
ns 69
ns –7
ns –10
135
67
68
Exercise training in claudicatio intermittens
Training for 3–6 month
Patients
Maximal walking distance (m)
Larsen & Lassen (1966)
Dahllöf et al. (1976)
Ekroth et al. (1978)
Jonason et al. (1979)
Clifford et al. (1980)
Lundgren et al. (1989)
Hiatt et al. (1989)
Creasy et al. (1990)
Mannarino et al. (1991)
Hiatt et al. (1994)
Mean increase (m)
16
34
129
25
21
42
19
36
20
18
Control
Training Difference
before/after
before/after
m
248/233
301/512
322/381
221/215
84/115
397/391
222/629
318/742
298/749
261/583
299/535
183/459
343/746
119/655
89/183
512/922
422
213
451
322
236
276
344
442
63
413
37
335
318
Comparison of treatment in claudicatio intermittens
Walking distance
400 m
318 m
300 m
200 m
100 m
0m
68 m
82 m
64 m
16
Studies
9
Studies
10
Studies
10
Studies
Pentoxifylline
Naftidrofuryl
Ginkgo biloba
Exercise
E. Housley
Clinic for Peripheral Vascular Diseases
Royal Infirmary of Edinburgh
Brit. Med. J. 296: 1483–1484 (1988)
DDD per 1000 inhabitants per day
Prescription of pentoxifylline
7
Germany
6
5
4
3
2
1
Norway
Denmark
0
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
Denmark: The Danish Medicines Agency: Medicinal product statistics Denmark 1995–1999 and 1997–2001
Germany: Schwabe U., Paffrath D. (eds.): Drug Presription Report 2002. Springer-Verlag, Berlin Heidelberg New York
Norway: Norwegian Institute of Public Health: Drug consumption in Norway 1993–1997 and 1997–2001
Drug utilization studies
as health care indicator
Secondary prevention of coronary heart disease in 1996
Retrospective survey of 3569 patients with CHD in 9 European countries 6–48 month after hospital discharge
100%
before
after
80%
71
58
60%
53
44
40%
35
25
20%
19
22
19
18
0%
Smoking
Obesity
Hypertension
BMI >30 kg/m2
>140/90 mm Hg
Hypercholesterolemia
>212 mg/dl
EUROASPIRE Study Group: Eur. Heart J. 18: 1569-1582 (1997)
Diabetes
Prescription of lipid lowering agents in Germany
DDD per 1000 inhabitants per day
40
Treatment for
2.4 mio. patients
32.8
32
Statins
24
16
Fibrates
8
0
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Schwabe U., Paffrath D. (eds.): Arzneiverordnungs-Report 2002. Springer-Verlag, Berlin Heidelberg (2002), p. 521
Prevalence of coronary heart disease
in Germany
Disease
Prevalence
Number of
patients
million
Postinfarction patients
in the total population (18–80 years)
sick fund-insured population (70.95 mio.)
2.45%
a
1.453
1.264
Coronary heart disease
in the total population (82,44 Mio.)
sick fund-insured population (70,95 Mio.)
a
b
b
4,0%
3.300
2.840
Wiesner G. et al.: Gesundheitswesen 61 (S1): S72–S78 (1999)
Selvyn A.P., Braunwald E.: Ischemic heart disease. In: Harrison‘s Principles of Internal Medicine,
15th ed., pp 1399–1410 (2001)
Treated patients according to DDD utilization (mio.)
Number of statin-treated patients in Germany
3,5
3,0
Total number of
coronary patients
83%
2,84
66%
2,36
2,5
1,89
2,0
1,59
1,5
22%
1,28
treated patients
0,86
1,0
0,48
0,62
0,5
0,0
1995
1996
1997
1998
1999
2000
2001
Objectives of drug utilization studies

Report on the volume and structure of
drug prescriptions by physisians

Annual information on drug utilization for
– physicians
– sick funds
– pharmacists

Transparency of the drug market
– market share of generic drugs
– role of "me-too" drugs
– drugs of disputed therapeutic efficacy

Evaluation of market changes
– introduction of new drugs
– withdrawal of drugs to due adverse effects