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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

iv

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

viii

3.1.3.1.b Time cost of health workers 85

3.2 Results of 2004 87


3.2.2 Pharmacoepidemiologic evaluation 92

3.2.2.1 Drug utilization pattern 92

3.2.2.2 Asthma treatment 95




3.2.2.6 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


3.2.3.1 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


ix

4.1.2 Pharmacoepidemiologic analysis 138

4.1.2.1 Drug utilization pattern analysis 138

4.1.2.2 Asthma treatment analysis 140




4.1.2.6 The DDD of antiasthma per prescription 151

4.1.2.7 Amount and dose of antiasthma drugs prescribed 152


4.2 Comparison between 2003 and 2004 Data 156


4.2.2 Comparison of drugs utilization analysis 156


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

xii

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

xvi

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)


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.


Intermittent-mild Step (1)

Daily medications: None needed


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:

pharmacoepidemiologic and cost … · pharmacoepidemiologic and cost evaluation of asthma...

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