pharmacoepidemiologic and cost evaluation of asthma
TRANSCRIPT
PHARMACOEPIDEMIOLOGIC AND COST EVALUATION OF ASTHMA MANAGEMENT IN
UNIVERSITI SAINS MALAYSIA HEALTH CENTER
ABDALLA GORASHI BASHIR AHMED
UNIVERSITI SAINS MALAYSIA 2007
PHARMACOEPIDEMIOLOGIC AND COST EVALUATION OF ASTHMA MANAGEMENT IN
UNIVERSITI SAINS MALAYSIA HEALTH CENTER
by
ABDALLA GORASHI BASHIR AHMED
Thesis submitted in fulfillment of the requirements for the degree of
Master of Science
June 2007
ii
DEDICATION
TO
My beloved late father, mother Fatima, brothers, and sisters.
My darling wife Amani,
my lovely sons Mohamed, Abdul Rehman, Asaad and
my pretty daughters, Eieman and Fatima
Who constantly give me moral support, faith, love, and joy
that energises me to pursue and
accomplish my goals.
Abdalla 13.07.2006
iii
ACKNOWLEDGMENTS
I am grateful to Allah the Almighty for bestowing me health and availing
me the strength and patience to complete this research.
I would like to express my thanks and deep appreciations to my
supervisor, Associate Prof. Dr. Mohamed Izham Mohamed Ibrahim for his
invaluable help, advice, guidance, and discussion throughout this study.
I am thankful to the Centre for Knowledge, Communication, and
Technology (Pusat Pengetahuan, Komunikasi dan Teknologi) for facilitating the
collection of data for my research and for their cooperation during the data
collection process. Special thanks to Mr. Zulham Hamdan (Acting, Chief
Information Officer), Mr. Mazlifendirizan Bin Md Rejab (Information System
Officer), Miss Nur Razeany Razlan (Information System Officer), Md Syahril Bin
Saad (Information System Officer), and Rizman Suzaidi Bin Zafri Ali (Assistant
Information System Officer).
I would like to express my sincere appreciations to Universiti Sains
Malaysia and special thanks to the School of Pharmaceutical Sciences for
affording me the opportunity to further my postgraduate studies in this
esteemed institution. In addition, I wish to thank the staff of the Institute of Post-
graduate Studies (IPS), librarians at the USM Main Library for their invaluable
help. Specifically, I shall never forget the assistance that I received from Mrs.
Arinawati Ayob, a librarian in the library’s reference section.
I am greatly indebted and thankful to Ministry of Defense of Sudan for
offering me a scholarship to pursue my postgraduate studies. My thanks also
extend to the Sudan Medical Corps, Department of Training and Planning in
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Medical Corps, and my friends and colleagues in the Medical Corp for their
sincere support.
Special thanks to my Sudanese friends and colleagues in Malaysia for
their assistance and moral support. I also wish to record my thanks to the IPS
students from all countries, especially from the Islamic nations, for their moral
support and encouragement.
Finally, I am eternally indebted to my parents who brought me up,
successfully educated me to be what I am now, and for sacrificing their lives for
their children’s happiness. Many thanks are due to my wife and children for their
patience and fortitude during my extended leave away from them. My profound
appreciations also extend to my brothers, my sisters, and my extended family
for their encouragement and moral support, which enabled me to successfully
conduct and complete this study. May Allah bless them all.
v
TABLE OF CONTENTS
Page
DEDICATION ii
ACKNOWLEDGEMENTS iii
TABLE OF CONTENTS v
LIST OF TABLES xi
LIST OF FIGURES xvi
LIST OF ABBREVIATIONS xviii
ABSTRAK xx
ABSTRACT xxiii
CHAPTER 1: INTRODUCTION
1.1 Background 1
1.2 Asthma 4
1.2.1 Classification of asthma 4
1.2.2 Approach of asthma management 6
1.2.3 Asthma treatment 6
1.2.3.1 Quick relief medications 7
1.2.3.2 Anti-inflammatory drugs 9
1.2.3.3 Other drugs 10
1.2.3.4 Step approach to therapy and asthma guidelines 11
1.3 Asthma in Malaysia 15
1.4 Asthma in the USM Health Center 15
vi
1.5 Pharmacoepidemiology 16
1.6 Drug Utilization 17
1.6.1 Units of measurement in drug utilization studies 18
1.6.1.1 Cost 18
1.6.1.2 Volume 19
1.6.1.3 Prescribed daily dose 20
1.6.1.4 Defined daily dose 20
1.6.2 Anatomical Therapeutic Chemical Index 21
1.7 Pharmacoeconomics 23
1.7.1 Cost minimization analysis 25
1.7.2 Cost effectiveness analysis 25
1.7.3 Cost benefit analysis 25
1.7.4 Cost utility analysis 26
1.7.5 Cost of illness analysis 26
1.7.5.1 Direct cost 26
1.7.5.2 Indirect cost 27
1.7.5.3 Intangible cost 27
1.7.6 Perspectives in a pharmacoeconomical study 27
1.8 Literature Review 28
1.9 Problem Statements 40
1.10 Rational of the Study 40
1.11 Study Objectives 41
1.11.1 General aims 41
1.11.2 Specific objectives 41
1.12 Significant of the Study 42
vii
CHAPTER 2: METHODOLOGY
2.1 Study Approval 44
2.2 Study Design 44
2.3 Study Location and Time 47
2.4 Study Population and Sample Size 48
2.5 Data Collection Procedure 48
2.6 Variables 49
2.7 Data Analysis 50
CHAPTER 3: RESULTS
3.1 Results of 2003 52
3.1.1 Demographic analysis 52
3.1.2 Pharmacoepidemiologic evaluation 57
3.1.2.1 Drug utilization pattern 57
3.1.2.2 Asthma treatment 59
3.1.2.3 Prescribing pattern among prescribers 63
3.1.2.4 Cost of prescriptions 68
3.1.2.5 The total cost of each antiasthma classes 74
3.1.2.6 The DDD of antiasthma drugs per prescription 76
3.1.2.7 Amount per DID and dose of antiasthma drugs prescribed in 2003
79
3.1.2.8 Comparison between prescribed daily dose (PDD) and defined daily dose (DDD) of antiasthma drugs
81
3.1.3 Pharmacoeconomics analysis 84
3.1.3.1 Direct medical cost 84
3.1.3.1.a Cost of drug treatment 84
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3.1.3.1.b Time cost of health workers 85
3.2 Results of 2004 87
3.2.1 Demographic analysis 87
3.2.2 Pharmacoepidemiologic evaluation 92
3.2.2.1 Drug utilization pattern 92
3.2.2.2 Asthma treatment 95
3.2.2.3 Prescribing pattern among prescribers 99
3.2.2.4 Cost of prescriptions 104
3.2.2.5 The total cost of each antiasthma classes 110
3.2.2.6 The DDD of antiasthma drugs per prescription 112
3.2.2.7 Amount per DDD and dose of antiasthma drugs prescribed in 2004
115
3.2.2.8 Comparison between prescribed daily dose (PPD) and defined daily dose (DDD) of antiasthma drugs
117
3.2.3 Pharmacoeconomics analysis 120
3.2.3.1 Direct medical cost 120
3.2.3.1.a Cost of drug treatment 120
3.2.3.1.b Time cost of health worker 121
3.3 Comparison between Data of 2003 and 2004 123
3.3.1 Comparison in terms of demographic data 123
3.3.2 Comparison in terms of drug utilization 125
3.3.3 Comparison in terms of direct medical costs 134
CHAPTER 4: DISCUSSION
4.1 Analysis of 2003 and 2004 Data 136
4.1.1 Demographic analysis 136
ix
4.1.2 Pharmacoepidemiologic analysis 138
4.1.2.1 Drug utilization pattern analysis 138
4.1.2.2 Asthma treatment analysis 140
4.1.2.3 Prescribing pattern among prescribers 145
4.1.2.4 Cost of prescriptions 147
4.1.2.5 The total cost of each antiasthma classes 150
4.1.2.6 The DDD of antiasthma per prescription 151
4.1.2.7 Amount and dose of antiasthma drugs prescribed 152
4.1.3 Pharmacoeconomics analysis 154
4.2 Comparison between 2003 and 2004 Data 156
4.2.1 Demographic analysis 156
4.2.2 Comparison of drugs utilization analysis 156
4.2.3 Pharmacoeconomics analysis 158
CHAPTER 5: CONCLUSION AND RECOMMENDATION
5.1 Study Summary 159
5.2 Limitation of the Study 161
5.3 Recommendations 161
5.3.1 Patients and families 161
5.3.2 Health care providers 162
5.3.3 Policy makers 162
BIBLIOGRAPHY 166
APPENDICES
Appendix A Figures from results of 2003 and 2004 174
x
Appendix B Tables from results of 2003 and 2004 178
Appendix C Drugs price list according to drug class and sub class 184
Appendix D Number of population of main campus 188
Appendix E-1 The calculation of DDD for antiasthma drugs in 2003 190
Appendix E-2 The calculation of DDD for antiasthma drugs in 2004 192
Appendix F The calculation of professional’s time in asthma management
194
Appendix G-1 Data Collection Form for demographic and clinical data 195
Appendix G-2 Data Collection Form for drug regimen and cost per prescription
196
Appendix H Approval letter for the study 197
xi
LIST OF TABLES
Table No. Title
Page
Table 1.1 Classification of asthma severity according to frequency symptoms, and pulmonary function measurement as adapted from NAEPP (1997)
5
Table 1.2 Stepwise and approach for managing asthma in adults and children over 5 years of age (Adapted from NAEPP,1997)
14
Table 1.3 Number of patients visiting USM Health Center during the 2001 and 2002 with different chronic diseases
16
Table 1.4 Defined daily doses (DDD) of commonly used antiasthma drugs
23
Table 3.1 Demographic profile of asthmatic patients in 2003 56
Table 3.2 The frequency of drugs prescribed at the USM Health center for asthmatic patients in 2003
58
Table 3.3 The frequency of antiasthma drugs prescribed during 2003 from the USM Pharmacy
59
Table 3.4 Prescribing frequency of combination and non-combination antiasthma medications in the USM Health Center (n=438)
60
Table 3.5 Cross tabulation between age groups and combination and non-combination of drugs per prescription (n=474)
62
Table 3.6 Cross tabulation between age groups and the most frequent drugs and drug combination per prescription
63
Table 3.7 Cross tabulation between prescribers, combination, and non-combination of drugs per prescriptions in 2003
65
Table 3.8 Cross tabulation between prescribers and the most frequent combinations of drugs per prescriptions at the USM Health Center in 2003
66
Table 3.9 The relationship between prescribers and the frequency of prescriptions for different age groups of patients (n=474) in 2003
67
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Table 3.10 The relationship between prescribers and the frequency of prescriptions for different age groups of patients (n=460)
68
Table 3.11 The average and median cost of prescriptions associated with category of patients in the USM Health Center in 2003
70
Table 3.12 The total cost of drugs per year for asthmatic patient for each category of patients and average cost per year for each patients in 2003 (n=205)
70
Table 3.13 Total cost of drugs for each age group patients and average and median cost of prescriptions associated with each group in 2003
72
Table 3.14 Percentage of total cost of drugs for each age group of patients and average cost per year for each patient in year 2003 (n=205)
72
Table 3.15 The average and median cost of prescriptions associated with prescribers in the USM Health Center in 2003
73
Table 3.16 The total quantity and cost of each antiasthma medication issued during 2003 at the USM Health Center
75
Table 3.17 The mean and median DDD of antiasthma drugs per prescription associated with gender in 2003
76
Table 3.18 The average and median DDD of antiasthma drugs per prescriptions associated with prescribers in the USM Health Center in 2003
77
Table 3.19 Total DDD of antiasthma drugs for each age group of patients, mean and median DDD of antiasthma drugs per prescriptions associated with each age group in 2003
78
Table 3.20 The percentage consumption of antiasthma drugs in the USM Health Center in 2003
79
Table 3.21 The average daily dose for inhaled corticosteroids in 2003 80
Table 3.22 The average prescribed daily dose and defined daily dose (DDD) for antiasthma medications in 2003
82
Table 3.23 Summary and profile of antiasthma drug utilization in 2003 83
Table 3.24 Cost of medications for asthmatic patients in 2003 84
Table 3.25 Total health personnel’s time cost per visit per year, and cost of drugs dispensing per visit per year in 2003
85
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Table 3.26 Total direct medical cost of asthma management in the USM Health Center in 2003
86
Table 3.27 Demographic profile of asthmatic patients in 2004 91
Table 3.28 The frequency of drugs prescribed at the USM Health Center for asthmatic patients in 2004
94
Table 3.29 The frequency of antiasthma drugs prescribed during 2004 from the USM Pharmacy
95
Table 3.30 Prescribing frequency of combination and non-combination of antiasthma medications in the USM Health Center
96
Table 3.31 Cross tabulation between age groups and combination and non-combination of drugs per prescription (n=574)
98
Table 3.32 Cross tabulation between age groups and combination of drugs per prescription (n=570)
99
Table 3.33 Cross tabulation between prescribers and combination and non-combination of the drugs per prescription in 2004
101
Table 3.34 Cross tabulation between prescribers and the most frequent combination of antiasthma drugs per prescription at the USM Health Center in 2004
102
Table 3.35 The relationship between prescribers and frequency of prescriptions for the various age groups of patients (n=574) in 2004
103
Table 3.36 The relationship between prescribers and frequency of prescriptions for different age group of patients (n=557) in 2004
104
Table 3.37 The average and median cost of prescriptions associated with category of patients in the USM Health Center in 2004
106
Table 3.38 The total cost of drugs per year for asthmatic patients for each category of patients and average cost per year for each patient in 2004 (n=237)
107
Table 3.39 Total cost of drugs for each age group of patients and average and median cost of prescriptions associated with each age group in 2004
108
Table 3.40 Percentage of total cost of drugs for each age group of patients and average cost per year for each patient in year 2004 (n=237)
108
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Table 3.41 The average and median cost of prescriptions associated with prescribers in the USM Health Center in 2004
109
Table 3.42 The total quantity and cost of each antiasthma medication issued during 2004 at the USM Health Center
111
Table 3.43 The mean and median DDD of antiasthma per prescription associated with gender in 2004
112
Table 3.44 The average and median DDD of antiasthma per prescriptions associated with prescribers in the USM Health Center in 2004
113
Table 3.45 Total DDD of antiasthma drugs for each age group of patients, mean and median DDD of antiasthma drugs per prescriptions associated with each group in 2004
114
Table 3.46 Percentage consumption of antiasthma drugs in the USM Health Center in 2004
115
Table 3.47 The average daily dose for inhaled corticosteroids in 2004 116
Table 3.48 The average prescribed daily dose and defined daily dose (DDD) for antiasthma medications in 2004
118
Table 3.49 Summary and profile of antiasthma drug utilization in 2004 119
Table 3.50 Cost of medications for asthmatic patients in 2004 120
Table 3.51 The total heath personnel’s time cost per visit per year, and the drugs dispensing cost per visit per year in 2004
121
Table 3.52 Total direct medical cost of asthma management in the USM Health Center in 2004
122
Table 3.53 Comparison between the demographic data of asthmatic patients in 2003 and 2004 at the USM Health Center
124
Table 3.54 Comparison between the total number of visits, prescriptions, and the average number of drugs per prescription in 2003 and 2004 for asthmatic patients at the USM Health Center
125
Table 3.55
Comparison of prescription frequencies of different drugs classes prescribed for asthmatic patients in 2003 and 2004
126
Table 3.56
Comparison of prescription frequencies of different antiasthma classes prescribed in 2003 and 2004
127
xv
Table 3.57 Frequencies of combination and non-combination of the antiasthma drugs per prescription in 2003 and 2004
128
Table 3.58 Comparison of total DDDs, mean, and median of antiasthma per prescription in 2003 and 2004
129
Table 3.59 Comparison of the mean PDD of antiasthma drugs prescribed in 2003 and 2004 for adults (> 17 years old) and children (≤ 17 years old)
130
Table 3.60 Comparison between the DID of antiasthma drugs in 2003 and 2004
131
Table 3.61 Comparison of different costs (RM) of prescriptions in 2003 and 2004 at the USM Health Center
132
Table 3.62 Comparison of costs of prescription and costs of total prescriptions per patient in 2003 and 2004 at the USM Health Center
133
Table 3.63 Comparison of different costs of antiasthma drugs in 2003 and 2004 at the USM Health Center
133
Table 3.64 The comparison of total direct medical cost, cost of drugs, cost of health personnel, and cost of treatment of an asthmatic patient per year in 2003 and 2004
134
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LIST OF FIGURES
Figure No.
Title
Page
Figure 3.1 Gender of asthmatic patients at the USM Health Center (n=205)
52
Figure 3.2 Age groups of asthmatic patients at the USM Health Center in 2003 (n=205)
53
Figure 3.3 Ethnic groups of asthmatic patients at the USM Health Center in 2003 (n=205)
54
Figure 3.4 Distribution of asthma among the different category of patients in 2003 (n=205)
55
Figure 3.5 The number of drugs per prescription and frequency (n=474) 57
Figure 3.6 Prescription groups according to the cost of prescription in 2003 (n=474)
69
Figure 3.7 Inhaled corticosteroid dose category in 2003 81
Figure 3.8 Gender of asthmatic patients at the USM Health Center (n=237)
87
Figure 3.9 Age groups of asthmatic patients at the USM Health Center in 2004 (n=237)
88
Figure 3.10 Ethnicity of asthmatic patients at the USM Health Center in 2004 (n=237)
89
Figure 3.11 Distribution of asthma among different category of patients in 2004 (n=237)
90
Figure 3.12 The number of drugs per prescription and frequency 93
Figure 3.13 Prescription groups according to the cost of prescription in 2004 (n=574)
105
Figure 3.14 Inhaled corticosteroid dose category in 2004 117
Figure A.1 Frequency of visits per year by asthmatic patients (n=205) to the USM Health Center in 2003
174
xvii
Figure A.2 Frequency of visits by asthmatic patients (n=237) to the USM Health Center in 2004
175
Figure A.3 Frequency of inhaled short β2-agonists in 2003 used by asthmatic patients (n=205)
176
Figure A.4 Frequency of inhaled short β2-agonists in 2004 used by asthmatic patients (n=237)
177
xviii
LIST OF ABBREVIATIONS
ATC Anatomical Therapeutic Chemical
BA β2-agonist
CBA Cost-Benefit Analysis
CEA Cost-Effective Analysis
CMA Cost-Minimization Analysis
COI Cost of Illness
CUA Cost Utility Analysis
DDD Defined daily dose
DID
DDD/1000/ day
DDD/1000/day
Defined daily dose per 1000 inhabitants
DU Drug Utilization
FEV1 Forced expiratory volume in one second
GINA Global Initiative for Asthma
GPs General practitioners
ICS Inhaled corticosteroid
KE Ketotifen
NAEPP National Asthma Education and Prevention Program
NHLBI National Heart, Lung, and Blood Institute
PDD Prescribed daily dose
PEFR Peak expiratory flow rate
PRN As needed
Ph E
Pharmacoeconomics
RM Malaysian Ringgit
xix
SD Standard deviation
SPSS Statistical Package for Social Sciences
TH Theophylline
USM Universiti Sains Malaysia
UK United Kingdom
US United States
US$
United States’ dollar
WHO World Health Organization
xx
PENILAIAN FARMAKOEPIDEMIOLOGI DAN KOS PENGURUSAN
PENYAKIT ASMA DI PUSAT KESIHATAN UNIVERSITI SAINS MALAYSIA
ABSTRAK
Asma adalah satu penyakit kronik yang memberi kesan kepada lebih
kurang 5 hingga 20% penduduk dunia. Ia menyebabkan morbiditi dan mortaliti
yang signifikan, mempengaruhi kualiti hidup dan menyebabkan bebanan
ekonomi yang tinggi. Objektif pertama kajian ini adalah untuk menilai aspek
farmakoepidemiologi pengurusan penyakit asma dengan menilai corak
penggunaan ubat penyakit asma dan keduanya, untuk menganggar kos
perubatan langsung penyakit asma di Kampus Induk Universiti Sains Malaysia
(USM). Data pesakit luar bagi tahun 2003 dan 2004 dengan preskripsi-
preskripsi mereka dikumpulkan secara retrospektif dari rekod perubatan
elektronik. Kaedah kajian penggunaan ubat dan kos penyakit digunakan dalam
kajian ini. Prosedur statistik inferensial yang digunakan termasuklah ujian-ujian
Khi Kuasa Dua, Kruskal-Wallis, Mann-Whitney, Wilcoxon dan Student-t. Paras
signifikan yang digunakan adalah 0.05 dengan selang keyakinan 95%.
Terdapat seramai 205 orang pesakit asma pada tahun 2003 manakala 237
orang pada tahun 2004. Dapatan kajian menunjukkan kebanyakan pesakit
adalah berbangsa Melayu, staf USM dan tangunggan. Kebanyakan pesakit
adalah di dalam linkungan umur 1-12 serta 26-45 tahun. Dari segi penggunaan
ubat, purata bilangan ubat per preskripsi adalah 2.1 bagi tahun 2003 dan 2.2
bagi tahun 2004. Kajian ini menunjukkan agonis-β2, yang penggunannya
meningkat secara langsung dengan umur pesakit, adalah ubat yang paling
xxi
banyak dipreskripsikan dan digunakan bagi tahun 2003 dan 2004. Ubat
kortikosteroid inhalasi (ICS) adalah ubat kedua yang paling kerap
dipreskripsikan. Seramai 23% dan 26.6% pesakit asma pada tahun 2003 dan
2004 setiap satu mengambil ICS. Kombinasi ubat yang paling biasa
dipreskripsikan adalah agonis-β2 + ICS. Kos min dan median preskripsi pada
tahun 2003 ialah RM20.44±12.85 dan RM18.29, manakala pada tahun 2004
kos min ialah RM20.13±13.63 dan median sebanyak RM16.89. Kos preskripsi
dan kos ubat-ubatan per pesakit per tahun meningkat dengan umur pesakit.
Terdapat perbezaan dalam kos preskripsi berdasarkan kategori pekerjaan dan
pegawai perubatan. Kajian ini mendapati penggunaan ubat asma meningkat
daripada 1.305 DID pada tahun 2003 kepada 1.514 DID pada tahun 2004. Dari
segi kos perubatan langsung, 75% daripada kos tersebut bagi kedua-dua tahun
2003 dan 2004 adalah untuk ubat, manakala peratus kos untuk personel
kesihatan adalah 25% daripada jumlah keseluruhan kos perubatan langsung.
Ubat asma memakan belanja 90% daripada kos total ubat-ubatan bagi tahun
2003 dan 2004. Merujuk kepada ubat-ubat penyakit asma, agonis-β2 inhalasi
terdiri daripada 61% manakala ICS terdiri 23% daripada kos total ubat-ubat bagi
penyakit asma. Jumlah keseluruhan kos perubatan langsung bagi pengurusan
asma bagi tahun 2003 adalah RM12,929.17 dan kos per pesakit per tahun
adalah RM 63.07. Dalam tahun 2004, jumlah keseluruhan kos perubatan
langsung meningkat kepada RM15,475.00 dan kos per pesakit per tahun
meningkat kepada RM65.30. Perbandingan data bagi tahun 2003 dan 2004
menjelaskan bahawa tiada perbezaan yang signifikan dari segi profil
demografik, corak mempreskripsi, kos purata preskripsi, purata lawatan per
pesakit, purata bilangan ubat per perpreskripsi, penggunaan drug per
xxii
preskripsi, preskripsi ubat-ubatan per pesakit dan kos langsung per pesakit per
tahun.
Kata Kunci: Asma, penggunaan ubat, penilaian kos, Pusat Kesihatan, pesakit
luar, farmakoepidemiologi, Universiti Sains Malaysia, universiti.
xxiii
PHARMACOEPIDEMIOLOGIC AND COST EVALUATION OF ASTHMA
MANAGEMENT IN UNIVERSITI SAINS MALAYSIA HEALTH CENTER
ABSTRACT
Asthma is a chronic disease that affects about 5% to 20% of the world’s
population causing significant morbidity and mortality, affecting the quality of
life, and resulting in considerable economic burden. The first objective of the
study is to evaluate the pharmacoepidemiology of asthma management by
evaluating the pattern of anti-asthma drugs utilization and secondly, to estimate
the direct medical costs of asthma in the main campus of Universiti Sains
Malaysia. Data of outpatients in 2003 and 2004 with their prescription records
were collected retrospectively from electronic medical records. The drug
utilization research and cost of illness methods were used in this study. The
appropriate inferential statistics used include the Chi-square test, the Kruskal-
Wallis test, the Mann-Whitney test, Wilcoxon test, and the student t-test. The
significance level was 0.05 with a confidence interval of 95%. There were 205
and 237 asthmatic patients in 2003 and 2004, respectively. The findings from
this study showed that the majority of patients were Malays, USM’s staff
members and dependants. Most of the patients were in the 1-12 and 26-45 age
groups. In terms of drugs utilization, the mean drug per prescription was 2.1 in
2003 and 2.2 in 2004. The study showed that β2-agonists, the use of which
increased with age, were the most prescribed and consumed drug in 2003 and
2004. The inhaled corticosteroid (ICS) was the second most frequently
prescribed drug. 23.0% and 26.6 % of asthmatic patients in 2003 and 2004
xxiv
respectively took ICS. The most commonly anti-asthma combination prescribed
was β2-agonist + ICS. The mean and median cost of prescription in 2003 was
RM20.44±12.85 and RM18.29, while in 2004, the mean cost was
RM20.13±13.63 with a median of RM16.89. The cost of prescriptions and the
cost of drugs per patient per year increased with age. There were variations in
the cost of prescription with regard to category of patients and prescribers. The
study found that the consumption of anti-asthma drugs increased from 1.305
DID in 2003 to 1.514 DID in 2004. In terms of direct medical cost, drugs
constituted about 75% of total direct medical costs in 2003 and 2004, while the
cost of health personnel constituted 25% of total direct medical costs. Anti-
asthma medications accounted for 90% of total drug costs in 2003 and 2004.
With regard to anti-asthma drugs, inhaled β2-agonist accounted for 63% of total
anti-asthma drugs cost in 2003 followed by ICS (18%). In 2004, inhaled β2-
agonist accounted for 61% while ICS accounted for 23% of total anti-asthma
drug costs. The total direct medical cost of asthma management in 2003 was
RM12,929.17 and the cost per patient per year was RM 63.07. In 2004, the total
direct medical cost increased to RM15,475.00 and the cost per patient per year
increased to RM65.30. A comparison of the data for 2003 and 2004 revealed
that there was no significant difference in terms of demographic profile,
prescribing patterns, the average cost of prescriptions, the average visit per
patient, the average number of drugs per prescription, the consumption of drugs
per prescription, the prescription of drugs per patient, and direct cost per patient
per year.
Keywords: Asthma, cost evaluation, drug utilization, Health Center, outpatient,
pharmacoepidemiology, Universiti Sains Malaysia, university.
1
CHAPTER 1
INTRODUCTION
1.1 Background
According to Evans (1998) and the National Heart, Lung and Blood
Institute (NHLBI) and World Health Organization (WHO) (1995) reports, asthma
is a chronic respiratory disease that affects 5-20% of the world population and
can cause significant morbidity and mortality. People of all ages especially
children are affected by asthma. It can be a severe and sometimes fatal disease
(NHLBI and WHO, 1995). Asthma affects the quality of life and leads to
considerable restrictions on physical, emotional and social activities. Asthma
can be significant burden not only in terms of health care costs, but also in
terms of lost productivity and reduced participation in family life (Ungar et al.,
2000; NHLBI and WHO, 1995). Asthma also interferes with schooling and work,
as it can lead to absenteeism among children and lost workdays among adults
as well as premature retirement (Clark, 1998).
Evidence suggests that the prevalence of asthma around the world is
increasing. This ranges from a 50% increase in New Zealand to a 150%
increase in Scotland (Palatine and Sly, 1999). The prevalence of asthma among
Malaysian children has been reported to be around 4.9-13.8% (Azizi, 1990;
Quah et al., 1997). The national prevalence of asthma symptoms in children
range widely from 1.6% in Indonesia to 36.8% in UK (Beasley et al., 1998).
However, in Saudi Arabia, it has been found to be 7% to 10% among school
children (AL-Frayh, 1990; AL-Rayes et al., 1997). A National Health Interview
survey conducted in 1995 in the United States indicated that 15 million
2
individuals identified themselves as asthmatic, with approximately 5 million
being under the age of 20 (Benson and Marrano, 1998). In the United States,
asthma was the most common chronic illness in children (Kelly and Kamada,
1998).
The increasing of frequency of the asthma coupled with its under
diagnosis, its inadequate, inappropriate treatment and the non-adherence to
asthma medication prescriptions are considered to be the major factors for
deaths and morbidity among asthmatic patients. In addition, asthma consumes
high medical care resources (Ganse et al., 2002; Eason and Markowe, 1987;
Suissa et al., 2002; Suissa et al., 2000; Halterman et al., 2000; Barnes, 1994;
British Thoracic Association, 1982). Asthma can lead to an increase in the
socioeconomic burden of individuals suffering from it, as well as that of their
families who share the cost. Society as a whole also bears the burden through
the loss of economic productivity when patients are unable to work (de Marco et
al., 2003; Clark, 1998).
Asthma can be alleviated through appropriate asthma management and
prevention. The main approach towards the management of asthma is the use
of effective treatments (pharmacologic managements), and avoidance of
exposure to allergens and other triggers (non-pharmacologic management)
(Busse, 1993; Svedmyr, 1997). In addition, education of both patients and
health professionals is the key to the success of every asthma management
and prevention efforts (Clark, 1998). Furthermore, an improved adherence to
prescriptions of long-term control medications (such as inhaled corticosteroids)
can lead to reduced morbidity, mortality, and consumption of health care
resources (Neffen et al. 2006; Goldman et al., 2000; Momile et al., 1996; Schatz
3
et al., 2003). Additionally, it can also reduce the overuse of quick relief, or PRN
(as needed) medications (Gottlieb et al, 1995). A study of parent-reported
pediatric asthma medications use, noted an excessive reliance on PRN
medications coupled with non-adherence to control drug prescriptions (Lozano
et al., 2003).
Although the superiority of inhaled corticosteroids (ICS) for asthma
control has been well established, these drugs used irregularly and underused
(Staa, et al., 2003; de Marco et al., 2005; Anis et al., 2001). Prescribers often
hesitate to prescribe ICS due to a fear of systemic side effects. In contrast,
patients usually discontinued the use of ICS due to expectations of immediate
symptom relief (Anzueto and Angel, 2000). Under treatment of asthma has
been reported as a problem in several European countries and in the United
States (Kuar et al., 1998; Bousquet et al., 1996; Adams et al., 2002).
The economic impact of asthma is increasing, particularly in the second
half of the 20th century in some countries, and represents a substantial burden
on health care resources in these countries. Health care costs are under
pressure in all countries, and decisions about the use of new medicines are not
only concerned with safety and tolerability assessments, but also value for
money (Barnes et al., 1996). Hence, it is important for professionals, health
economists, and planners to work as a team to understand the costs of asthma
in order to identify where the burden occurs, to assess the effectiveness of
current asthma medications, and to know how to achieve optimal cost
effectiveness.
When the economic burden of asthma is considered, the assessment of
both direct costs (i.e., cost of providing health services) and indirect costs (i.e.,
4
the value of the resources lost as a result of illness such as absenteeism from
work and other daily activities) must be considered (Stempel, 2003; Barnes et
al., 1996).
For effective asthma management and rational use of antiasthma
drugs, it is important to have information on the previous pattern of the use of
these drugs, whether health care professionals and public health officials are
acting according to national asthma guidelines in asthma management, how
much money was spent on asthma management, and where high expenditure
occurs.
1.2 Asthma
Asthma is a chronic inflammatory disease of airways, which causes
significant morbidity and mortality if not managed optimally. The disease is
associated with a range of symptoms, including cough particularly at night,
wheezing, breathing difficulty and chest tightness. These episodes were
reversible, either spontaneously or with treatment (NHLBI and WHO, 1995).
1.2.1 Classification of asthma
Asthma is highly variable. It can be intermittent, mild persistent,
moderate persistent, and severe persistent. The severity of asthma is
determined by an assessment of symptoms, its clinical signs, and through
measurements of respiratory function using tests such as peak expiratory flow
rate (PEFR) or forced expiratory volume in 1 second (FEV1). The determination
of asthma severity is very important in asthma treatment, as drug dosage can
be determined based on the nature of the disease. In other words, therapy is
5
increased (step-up) as the severity of asthma increases and is reduced (step-
down) as asthma control is achieved (Global Initiative for Asthma (GINA) and
NHLBI, 2005; Bennett and Brown, 2003).
Table 1.1 below shows the classification of asthma severity according
to the frequency of its symptoms, and pulmonary function measurement as
adapted from National Asthma Education and Prevention Program (NAEPP)
(1997).
Table 1.1: Classification of asthma severity according to frequency symptoms, and pulmonary function measurement as adapted from NAEPP (1997). Asthma severity
Symptoms Nighttime symptoms
Lung function
Step 4 Severe persistent
*Continual symptoms *Limited physical activity*Frequent exacerbation
Frequent *FEV1 or PEF ≤ 60% predicted *PEF variability ≥ 30%
Step 3 Moderate persistent
*Daily symptom *Daily use of inhaled short acting β2-agonist *Exacerbations affect activity *Exacerbations ≥ 2 times a week
≥ 2 times a month
*FEV1 or PEF > 60%- <80% predicted *PEF variability > 30%
Step 2 Mild persistent
*Symptoms > 2 times a week But <1 time a day *Exacerbations may affect activity
> 2 times a month
*FEV1 or PEF ≥ 80% predicted *PEF variability < 20%
Step 1 Intermittent
*Symptoms ≤ 2 times a week *Asymptomatic and normal PEF between exacerbations *Exacerbations brief (from a few hours to a few days); intensity may vary
≤ 2 times a month
*FEV1 or PEF ≥ 80% predicted *PEF variability < 20%
6
1.2.2 Approach of asthma management
There are a few approaches utilized in the management of asthma. In
the following subsections, each of these approaches will be explained in detail.
They are:
• Patient and family members education: Patients must be
knowledgeable about asthma and its treatments. Patients must learn
how to take the prescribed medications correctly, to differentiate between
quick relief and long-term preventive medications, to avoid the triggers of
asthma, to be aware of the steps to follow if symptoms occur, to follow an
asthma management plan, and to seek for medical care in order to
prevent serious attacks (Gibson et al., 2003).
• Avoidance of exposure to allergens and precipitating factors; a critical
component of asthma control is the identification and management of
allergens or “triggers” of asthma. This approach is appropriate for
extrinsic asthma and may be feasible when it is related to some specific
situation, e.g. occupational asthma, but it is less feasible if, it is
widespread, e.g. house-dust mites (NHLBI and WHO, 1995).
• Use effective medications; this measure includes the use of
medications to reduce bronchial inflammation and hyperactivity, and
dilatation of narrowed bronchi (GINA and NHLBI, 2005).
1.2.3 Asthma treatment
An assessment of the disease’s severity is crucial in determining the
optimal treatment. A wide range of different classes of medication are available
for treatment of asthma and the selection of optimal treatment or combinations
7
of antiasthma medication is essential to ensure that the disease is well
controlled. It has been suggested that the current trends toward increased
morbidity and mortality associated with asthma may be due to under diagnosis,
and under treatment of the disease (Barnes, 1994). In general, the treatment
regimens should consist of quick relief medications for all patients, and long-
term control medications (anti-inflammatory drugs) for all patients with
persistent symptoms i.e., steps 2 through 4 severities (GINA and NHLBI, 2005).
1.2.3.1 Quick relief medications
These medications are used by all asthmatic patients. They are
bronchodilator drugs, which relieve bronchospams and improve the symptoms
of asthma. They should be used as required rather than regularly. The most
common quick relief medications used are the short acting β2-agonists. In some
cases, anticholinergic agents are used. They should be taken as required rather
than regularly. They consist of three main groups: β2-agonists, anticholinergics
and theophylline.
1- β2-agonists
These are the most effective bronchodilators with few side effects when
taken by inhalation (NHLBI and WHO, 1995; Bennett and Brown, 2003; Tierney
et al., 2005). Their main side effects are tremor and tachycardia. The short
acting formulations β2-agonists (inhaled salbutamol and terbutaline) are used
for acute exacerbations of asthma in addition to short β2-agonists tablet or
syrup. In contrast, long acting inhaled formulations (salmeterol, and formoterol)
are indicated for asthma prevention in combination with corticosteroids.
8
Sustained release oral formulations β2-agonists (salbutamol) are also available
and may be used by patients who cannot use long acting inhaled β2-agonists
(Tierney et al., 2005).
2- Anticholinergics drugs
Inhaled anticholinergics have a slower onset but a longer duration of
action. They are frequently combined with β2-agonists in an urgent care setting.
They have very few side effects, as they are poorly absorbed from the lung. The
common side effects associated with inhaled anticholinergics are dry mouth,
blurred vision, and urinary retention. An example of an inhaled anticholinergic is
ipratropium bromide (Kelly and Sorkness, 2005; Walker and Edward, 2003)
3- Methylaxnthines (Theophylline)
The short acting theophylline may be used to treat moderate to severe
attacks when high doses of inhaled β2-agonists, the preferred treatment, are not
available (NHLBI and WHO, 1995; Kelly and Sorkness, 2005). The addition of
short acting theophylline to inhaled β2-agonists does not provide any additional
bronchodilator effect. On the other hands, long acting (sustained release)
theophylline is indicated for asthma maintenance therapy in order to control
asthma symptoms and to improve lung function. When inhaled corticosteroids
and sodium cromoglycate are not available or are too costly, theophylline can
be used as a long-term medication (Aracangello and Peterson, 2006; Tierney et
al., 2005)
Theophylline appears to exert a weak bronchodilator and/ or an anti-
inflammatory effect. These drugs are found in oral and parenteral form and they
9
have a narrow therapeutic window (Kelly and Sorkness, 2005; Walker and
Edward, 2003). At therapeutic serum level, theophylline can cause a variety of
cardiac and central nervous system effects including palpitations, tachycardia,
tremor, insomnia, headache, and irritability (Tierney et al., 2005). Because of its
potentially serious side effects, theophylline is usually considered as only a third
line agent for asthma management. Its sustained release form is useful in
nocturnal asthma (Weinberger and Hendeles, 1983), (e.g. Nuelin SR, Theodur,
and Euphylline.)
1.2.3.2 Anti-inflammatory drugs
These drugs are used for patients with persistent asthma and they act
by reversing and preventing inflammation caused by an asthma attack. These
drugs include:
1- Corticosteroids
Corticosteroids are the main prophylactic drugs in adult asthmatics. They
are indicated for both prevention and the treatment of asthma exacerbations.
They should be taken in inhalation in minimum doses to reduce their side
effects (Toogood, 1990). On the other hand, since an optimal response to ICS
requires 4 weeks of therapy, the oral or parenteral routes may be used for
severe chronic asthma exacerbation (Kelly and Kamada, 1998). Common oral
corticosteroids include prednisolone and methylprednisolone, while examples of
ICS include beclomethasone dipropionate, budesonide, and fluticasone. Study
estimates suggest that compliance with inhaled corticosteroids is only about 34
to 56% (Yuksel et al., 2000). ICS side effects are generally minor. The most
10
common side effects are dysphonia, cough, and oral candidiasis (Walker and
Edward, 2003). These side effects are attributed to oropharyngeal depositions
of the drug.
2- Sodium cromoglycate (Intal)
Sodium cromoglycate impairs the immediate response to allergen and
acts by inhibiting the release of mediators from the mast cells (Kelly and
Sorkness, 2005; Aracangello and Peterson, 2006). Cromoglycate is not
effective at terminating an existing attack, i.e. it prevents bronchoconstriction
rather than induces bronchodilation. It is administered by inhalation (well
absorbed from the lungs, but poorly absorbed from gastrointestinal tract) and is
very safe with no significant side effects. It is useful in extrinsic (allergic) and
exercise-induced asthma (Bennett and Brown, 2003).
Nedocromil sodium is structurally unrelated to cromoglycate but has a
similar profile of actions and can be used by metered aerosol in place of
cromoglycate (Bennett and Brown, 2003).
1.2.3.3 Other drugs
Antileukotrienes are bronchodilators that act by terminating the actions
of leukotrienes. The NAEPP recommends that the antileukotrienes (zileuton,
zafirlukast, and montelukast) should be considered as second or third line drugs
for asthma control following β2-agonists and corticosteroids. Adverse effects of
antileukotrienes are infrequent and mild including headache, dizziness, nausea,
and diarrhea (GINA and NHLBI, 2005; Tierney et al., 2005)
11
Ketotifen is a histamine H1-receptor blocker and also may have some
antiasthma effect, but it has been proven to be of limited efficacy and benefit in
many clinical trials. Similarly as with other antihistamines, it can cause
drowsiness (Bennett and Brown, 2003).
1.2.3.4 Stepwise approach to therapy and asthma guidelines
The appropriate management of asthma depends on an accurate
assessment of asthma severity and the appropriate prescription of medications.
In order to establish the proper management parameters, various sets of
asthma guidelines, both national and international guidelines such as Global
Initiative for Asthma (GINA), and the Malaysian consensus guidelines on the
management of asthma (Malaysian Thoracic Society, 1996) have been issued
over the last few years. These guidelines have been designed to help primary
care physicians, GPs, nurses, public health officials, and program planners in
the management of their patients, in order to reduce the personal, social, and
economic burden of asthma. Though these asthma guidelines were published
ten years ago and emphasize the use of ICS as the first line treatment for
persistent asthma, the results of various studies suggested that the health
professionals do not strictly adhere to them (Gourgoulianis et al., 1998;
Vermeire et al., 2002; Poluzzi et al., 2002; Verleden and Vuyst, 2002; Donahue
et al., 2000). Consequently, this problem leads to poor quality of life among
patients, and a heavy social burden (de Macro et al., 2003).
Despite improvements in understanding asthma pathophysiology and
the availability of effective drugs over the last decade, poor asthma control has
led to an increase in asthma frequency and severity in many countries, both
12
among children and adults. There are two major reasons for the lack of success
in the management of asthma. First, under prescribing of medications by
doctors (Rabe et al., 2004; Adams et al., 2002; Cydulka et al., 2005), and
second, the poor prescription compliance by patients (Cerveri et al., 1999). Poor
compliance of patients can be overcome by patient education, more frequent
patient contact, the development of a close patient-clinician partnership, and
simplification of treatment (Bender, 2002; Stempel et al., 2005).
Because of variations in asthma severity among different patients, and
within each patient over a period of time, a step approach to therapy is
recommended to control asthma with the least possible use of medications
(GINA and NHLBI, 2005; Tierney et al., 2005). The number and frequency of
medications increase (step-up) as asthma worsens and decrease (step-down)
when asthma is kept under control. After classifying the severity of a patient’s
asthma, the physician or GPs should judge the treatment stage. Once control is
sustained for about 3 months, a reduction in therapy or step-down can be
considered. This helps to reduce the risk of side effects and enhances
adherence to the treatment plan (NHLBI and WHO, 1995). The National Asthma
Education and Prevention Program (NAEPP, 1997) has developed treatment
recommendations specific to each severity level (please refer to Table 1.2).
Among them are, patients should take a rapid acting bronchodilator, such as a
short acting inhaled β2-agonist, for relieving asthma exacerbations regardless of
the disease’s severity. Patients with mild intermittent asthma (Step 1) do not
need daily maintenance medications since these patients have normal
pulmonary function between attacks. However, if these patients are using their
β2-agonists more than twice a week, a step-up in the treatment regimen is
13
needed. Patients with mild, moderate, and severe persistent asthma (Step 2, 3,
and 4, respectively) require daily use of maintenance medications. Maintenance
or “preventive” medications include ICS, oral steroids for severe asthma,
theophylline, long acting β2-agonists (salmeterol, formoterol), mast cell
stabilizers (cromolyn, nedocromil) and antileucotrienes ((GINA and NHLBI,
2005; Tierney et al., 2005; Kelly and Sorkness, 2005).
14
Table 1.2: Stepwise and approach for managing asthma in adults and children over 5 years of age (Adapted from NAEPP, 1997) Asthma severity
Long term management Quick-relief for exacerbation
Persistent-severe Step (4)
Daily medications: *Anti-inflammatory: High dose ICS (500-2000µg/ day or more, beclomethasone equivalent) + *Long acting bronchodilator-either long acting inhaled β2-agonist, theophylline SR or long acting β2-agonist + *Corticosteroid tablets or syrup (2mg/ kg/ day, not to exceed 60mg/ day).
Short acting inhaled β2-gonist on PRN basis
Persistent-moderate Step (3)
Daily medications: Anti-inflammatory: either *Medium dose ICS (500-800µg/day) beclomethasone equivalent or *Low medium dose ICS + *Long acting bronchodilator (long acting inhaled β2-agonist, theophylline SR or long acting β2-onist) If needed: *Medium high dose ICS (500-2000µg/day) or beclomethasone equivalent. + *Long acting bronchodilator, specially for night symptoms (long acting inhaled β2-agonist, theophylline SR or long acting β2-agonist)
Short acting inhaled β2-gonist on PRN basis
Persistent-mild Step (2)
Daily medications: Anti-inflammatory: either *Low dose ICS or *Cromolyn or nedocromil (usually chosen as the first line for children) Other alternatives: *Sustained –release theophylline (to serum level of 5 to 15µg/ ml; generally not preferred. *Antileukotrienes may be also considered for patents ≥12 years old; however, the exact place of antileukotrienes in therapy has not been firmly established.
Short acting inhaled β2-gonist on PRN basis
Intermittent-mild Step (1)
Daily medications: None needed
Short acting inhaled β2-gonist on PRN basis
15
1.3 Asthma in Malaysia A National Health and Morbidity Survey in 1996 indicated that the
prevalence of asthma in Malaysia was 4.2%. The survey also shows that the
prevalence of asthma varied according to the socioeconomic status of the
patients, and the geographical area. The study found that asthma was high
among lower socioeconomic groups (low education and income levels), and in
rural areas. By ethnicity, Chinese have a lower prevalence of asthma than the
other races. In terms of age, the study found that the prevalence of asthma
decreased by age but increased again after 40 years and above. The survey
finding also revealed that the majority of asthma cases was categorized as mild
(87.3%), followed by moderate (9.9%). Only 2.7% of the asthma patients
surveyed had severe asthma. The study also found that the majority of mild
asthma (65%) and moderate asthma cases (52%) were on non-inhaler
treatment. The similar survey revealed that there was inadequate treatment and
monitoring of asthmatic patients especially those with severe cases of asthma.
This eventually leads to high expenditure in health care costs (Rugayah et al.,
1999).
1.4 Asthma in the USM Health Center Data obtained from USM’s Health-Care Report indicates that, asthma
ranked second after hypertension among chronic diseases in USM’s Main
Campus in 2001 and 2002 (Izham, 2003). There were 238 asthmatic patients in
2001 and 237 in 2002. Table 1.3 shows the number of patients with different
chronic diseases.
16
Table 1.3: Number of patients visiting the USM Health Center during 2001 and 2002 with different chronic diseases* Disease Patients
number (2001)
Patients number (2002)
Increase rate (%)
Hypertension 374 449 20.1
Asthma 238 237 -0.4
Diabetes 175 208 18.9
Other (circulatory problem)
39 18 -53.8
Ischemic heart disease 27 40 48.1
TB 7 3 -57.1
Total 860 955 11.0
*Source: USM’s Health-Care Report (Izham, 2003)
1.5 Pharmacoepidemiology
In order to choose an appropriate disease management regime and to
obtain the rational use of drugs, it is important to have information on the past
and present use of drugs. This information must be concerned with types of
drugs prescribed, to which patient they were prescribed and indications on their
use. In addition, it is important to know the therapeutic cost/ benefit of drug use.
This is because without knowledge of how a drug is actually used, it is
impossible to discuss what correct or incorrect therapy is, or suggests
measures to improve prescribing habits, or initiate a discussion on rational drug
use. This information must be made available in drug utilization statistics for the
ultimate result. This information will help to assess whether the drug is being
rationally used or not (Nordic Council on Medicines, 1990; WHO, 2003). This
17
can be achieved by applying pharmacoepidemiology methods. WHO defined it
as “the study of the clinical use of drugs in populations or the study of the use
and effects/ side-effects of drugs in large numbers of people with the purpose of
supporting the rational and cost-effective use of drugs in the population, thereby
improving health outcomes” (WHO, 2003).
1.6 Drug Utilization
Drug utilization (DU) is essential part of pharmacoepidemiology and
they are some times used interchangeably (WHO, 2003). DU was defined by
WHO as “the studies of marketing, distribution, prescribing, and use of drugs in
society, with special emphasis on resulting medical, social and economic
consequences”. DU can be divided into descriptive and analytical studies. The
descriptive studies describe the patterns of drug utilization and identify
problems that need more studies, while analytical studies try to link data on
drug utilization and figure on morbidity with the outcome of treatments and the
quality of care with aims of assessing whether drug therapy is rational or not.
The WHO defines the rational use of drug as each patient receiving medication
appropriate for their clinical needs, at an optimal dose, for an adequate period,
with minimum costs to them and the community.
Drug utilization data provide indispensable information on drug
prescription and can be used to:
• describe patterns of the drug’s use
• look at the development of therapeutic profiles
• estimate the number of patients exposed to various drugs
18
• measure the effects of educational, informative, regulatory efforts,
price policies, and reimbursement schemes, etc.
• define areas for further investigations on the efficacy and safety of
. drug therapy.
• indicate over-use, under-use, misuse, and abuse of drugs.
• estimate drug need in a society (related to morbidity pattern) to be
used as a bases for the planning of drug selection, supply, and
distribution.
1.6.1 Units of measurement in drug utilization studies
In order to measure drugs use, it is important to have both a
classification system and a unit measurement. To study drug use over time, it is
important to have a stable and consistent method, which makes it possible to
compare drug statistics both nationally and internationally (WHO Collaborating
Centre for Drug Statistics Methodology, 2005). There are many different ways
of expressing drug consumption (cost, volume measures, prescribed daily dose
(PDD), and defined daily dose). None of these measures alone gives a
complete picture of drug utilization, but if used in combination, they may serve
as data for monitoring purposes.
1.6.1.1 Cost
Drug use can be expressed in terms of costs (e.g. national currency).
Cost figures are suitable for an overall cost analysis of drug expenditure. Cost
analysis is also applicable for prescription studies of only one substance.
National and international comparisons based on cost parameters are often
19
misleading and are of limited value in the evaluation of drug use. Price
differences between alternative preparations and different national cost levels
often make evaluation difficult. Long-term studies are also difficult due to
fluctuations in currency and prices. When cost data are used, the cheaper drugs
may have little effect on the total levels, while the shift effect to more expensive
drugs is more readily noticeable (WHO Collaborating Centre for Drug Statistics
Methodology, 2005).
1.6.1.2 Volume
Common physical units (e.g. gram, kilos, and liter), number of packages
or tablets, and number of prescriptions are used in the calculation of the amount
of drugs consumed. If consumption is given in terms of grams of an active
ingredient, drugs with a lower potency will have a larger fraction of the total than
drugs with a higher potency.
Counting the numbers of tablets also has disadvantages because the
strength of the tablets may vary, resulting in outcomes that indicates low
strength preparations contribute more than high strength preparations (WHO,
2003). In contrast, the numbers of prescriptions do not give a good expression
of total use, unless the total amounts of drugs per prescription are being
considered. Counting prescriptions, however, is of great value in measuring the
frequency of prescriptions and evaluating the clinical use of drugs (e.g.
diagnosis and dosage used) (WHO Collaborating Centre for Drug Statistics
Methodology, 2005).
20
1.6.1.3 Prescribed daily dose
The prescribed daily dose (PDD) is the average daily amount of drugs
that are actually prescribed as obtained from a representative sample of
prescriptions (WHO Collaborating Centre for Drug Statistics Methodology,
2005). It can be calculated by getting information on the quantity dispensed, the
strength and the number of days of supply. PDD should interpreted together
with the diagnosis as the recommended dose may differ from one indication to
another, or due to the severity of the illness. Furthermore, the dose may differ
according to age, sex, as well as local and national therapy traditions. It should
be noted that PDDs may differ from one country to another and even between
regions or health facilities within the same country. So when making
international comparisons this must be in considerations. When there is a
substantial discrepancy between the PDD and the defined daily dose (DDD), it
is important to consider this discrepancy when evaluating and interpretating
drugs consumption figures.
1.6.1.4 Defined daily dose
The defined daily dose (DDD) is a technical unit of drug consumption
measurement as assigned by the WHO Collaborating Center for Drug Statistics
Methodology (1993). It was developed to work with the Anatomical Therapeutic
Chemical (ATC) Classification system in order to overcome objections against
traditional units of measurement of drug consumption. The DDD for a given
drug is the assumed average maintenance dose per day for a drug used for its
main indication in an adult (WHO Collaborating Centre for Drug Statistics
Methodology, 2005). DDD does not necessarily reflect the recommended, or
21
actual dose used, rather it is used as a measurement of drug utilization within,
and across drug classes. It is also used when comparing drug utilization studies
carried out at different locations and at different time periods. DDD is usually
used expressed in DDD per thousand persons per day (DDD/ 1000/ day), and
provides a rough estimate of consumption and not a real picture of actual use.
For drugs used continuously, the number of DDDs gives a rough estimate of the
numbers of its users. The DDD metric may not reflect the recommended or
actual used dose (PDDs). Many drugs are for instance used in different dosage
on different indications. The PDDs differ between countries, ethnic group and
even between area or health facilities within same country. Thus, it can be
surmised that prescription data presented in DDDs will only provide a rough
estimate of consumption and not a real picture of actual use. The other
limitation of the DDD metric is that the DDDs for certain drugs have not been
established. Examples of these drugs include preparations for topical use, IV
solutions, sera, antineoplastic drugs, general and local anesthetics, and X-ray
contrast media (WHO Collaborating Centre for Drug Statistics Methodology,
2005).
1.6.2 Anatomical Therapeutic Chemical Index
The Anatomical Therapeutic Chemical (ATC) Index is an Anatomical
Therapeutic Chemical classification system that assigns code letters and
numbers to all drugs on an ATC basis (WHO Collaborating Centre for Drug
Statistics Methodology, 2003). In the ATC system, the drugs are divided into 14
different groups according to the organ and system on which they act, and their
chemical, pharmacological, and main therapeutic use. There is only one ATC
22
Code for each pharmaceutical formulation and different ATC Codes are given
for substances available in two different strengths or for formulations with
clearly different uses. This system has been officially adopted by the Nordic
countries and the WHO Drug Utilization Research Group (DURG), which has
used it for a number of years (WHO, 2003).
No drug classification system is ideal from a combined epidemiological,
clinical pharmacological, pharmaceutical, and chemical point of view. A drug
may be used for a variety of clinical purposes and drugs of different structures
may be used more or less for the same disease or symptom. Accordingly,
pragmatic compromise solutions are to a certain extent necessary. Thus, when
drug data are related to a specific area of use, reclassification may be helpful
before interpretation. The ATC system is suitable for use in both manual and
computerized systems. Table 1.4 below shows the ATC Code and the DDD of
commonly used antiasthma drugs (Gislason et al., 1997).
23
Table 1.4: Defined daily doses (DDD) of commonly used antiasthma drugs
Drug
ATC code One DDD per mg
Notes
β2-agonists
Salbutamol inhaler R03AC02 0.8 Aerosol/ powder
Terbutaline inhaler R03AC03 2.0 Aerosol/ powder
Oral salbutamol R03CC02 12.0 Oral/ parenteral
Oral terbutaline R03CC03 15.0 Oral/ parenteral
Inhaled steroids
Beclomethasone inhaler R03BA01 0.8 Aerosol/ powder
Budesonide inhaler R03BA02 0.8 Aerosol/ powder
Anticholinergics
Ipratropium inhaler R03BB01 0.12 Aerosol/ powder
Oxitropium inhaler R03BB02 0.6 Aerosol
Theophylline R03DA04 400 Oral
Cromoglycate inhaler R03BC01 40.0 Aerosol/ powder
Ketotifen R06Ax17 2.0 Oral
1.7 Pharmacoeconomics
The rapid growth of health expenditure accompanied with limited
resources has led to an increased interest in the economic evaluation of health
care interventions. Most health care professionals especially pharmacists, are
constantly faced with doing “more with less.” At the same time, they need to
satisfy their patients health care demands based on their real needs and on
24
their wants. So pharmacoeconomics and outcome research must be a part of
the background and expertise of many health professionals and pharmacists to
enable them to allocate available resources according to priorities and to make
choices between different pharmaceutical interventions.
Pharmacoeconomics analysis is defined as a tool to identify, measure,
and compare cost and consequences (outcome) of pharmaceutical
interventions with the aim of allocating health care resources and of optimizing
patient outcomes for a given limited supply of resources (Bootman et al., 1991;
Drummond et al., 1997). Costs are broadly classified as direct, indirect, and
intangible costs. While outcomes are broadly categorized into economic,
clinical, and humanistic outcomes (Reeder, 1995).
The objectives of pharmacoeconomics are to:
• optimize the patient’s outcomes with limited resources.
• help in making critical decisions such as which drug should be in the
health care formulary.
• defining the best strategy for managing a particular disease through a
creation of clinical guidelines for diagnosis and treatment.
• help the policy maker and administrator to decide which services should
be implemented within their organization
• determine how health resources should be allocated
• identify which of the series of alternative therapies will achieve the best
cost effectiveness.
• provide valuable information for health care decision makers
The common types of pharmacoeconomics studies are outlined in the
following sections: