Table of content 1. INTRODUCTION

Table of content

1. INTRODUCTION... 18

1.1 P HARMACEUTICAL CARE , DRUG - RELATED PROBLEMS AND TOOLS 19 1.1.1 Pharmaceutical care and drug-related problems: history and definitions 19 1.1.1.1 Pharmaceutical care development...19

1.1.1.2 Pharmaceutical care in Europe...22

1.1.2 Drug-related problems characteristics, identification and tools 26 1.1.2.1 Drug-related problems: Terms and definitions...26

1.1.2.2 Drug-related problems: Classifications...34

Strand et al. classification...34

Westerlund classification system...35

PI-Doc: Problem-Intervention-Documentation...36

ABC of DRP...38

PCNE Classification Tool...39

GSASA...41

PharmDISC: Pharmacists' Documentation of Interventions in Seamless Care...42

1.2 D RUG - RELATED PROBLEMS IMPACT 44 1.2.1 Drug-related problems impact 44 1.3 D RUG - RELATED PROBLEMS AND CANCER 46 1.3.1 Cancer patients and treatments 46 1.3.1.1 Cancer burden in Belgium...46

1.3.1.2 Cancer treatment...48

Breast cancer treatment...48

Lung cancer treatment...50

Colorectal cancer treatment...51

1.3.1.3 Anti-cancer drugs...52

Covalent liaison with DNA...52

1.3.1.3.1.1 Platinum derivatives...52

1.3.1.3.1.2 Nitrogen mustard and derivatives...53

Microtubule inhibitors...54

1.3.1.3.1.3 Taxanes...54

1.3.1.3.1.4 Vinca alkaloids...55

Topoisomerases I and II inhibitors...56

1.3.1.3.1.5 Topoisomerase I inhibitors...56

1.3.1.3.1.6 Topoisomerase II inhibitors...57

Anthracyclines...57

Antimetabolites...58

1.3.1.3.1.7 Pyrimidine analogues...58

1.3.1.3.1.8 Methotrexate...59

Others...59

1.3.1.3.1.9 Endocrine therapy...59

1.3.1.3.1.9.1 Tamoxifen...59

1.3.1.3.1.9.2 Aromatase inhibitors...59

1.3.1.3.1.10 Monoclonal antibodies...60

1.3.1.3.1.11 Protein kinase inhibitors...60

1.3.1.4 DRP in the cancer population...61

1.4 D RUG - RELATED PROBLEMS COST 62 2. OBJECTIVES... 65

3. METHOD... 66 3.1 D RUG - RELATED PROBLEM IN COMMUNITY PHARMACIES 67

3.1.1 Adaptation and validation of PCNE drug-related problem classification v6.2 in French-speaking Belgian community pharmacies 67

 Translation and adaptation of the PCNE V6.2 classification 67

3.1.2 Pain DRP in Belgium Pharmacies 67 3.2 D RUG - RELATED PROBLEM IN HOSPITAL 69

3.2.1 Evaluation and analysis of drug-related problems in cancer patients readmitted to two Belgian care facilities within 30 days after discharge 69

3.2.1.1 Data Collection: Epi Info™ 7.2...69

3.2.1.2 DRP detection and causality...70

WHO-UMC Causality System...70

Lexicomp...71

3.2.1.3 Statistical analysis...71

Charlson Index...71

Logistic Regression...72

3.2.2 Drug Related Problems readmission cost in two Belgian hospitals: Is it avoidable ? 73 3.2.3 Drug-Drug interactions in Cancer Patients Readmitted 30 days after discharge 73 3.2.3.1 Interaction Assessment...74

Lexicomp

...74

Epocrates...74

Stockley’s...74

3.2.3.2 Statistical Analysis...75

4. RESULTS... 76

4.1 D RUG - RELATED PROBLEM IN COMMUNITY PHARMACIES 77 4.1.1 Adaptation and validation of PCNE drug-related problem classification v6.2 in French-speaking Belgian community pharmacies 77 4.1.1.1 Introduction...78

4.1.1.2 Objectives...79

4.1.1.3 Method...79

Translation and adaptation of the PCNE V6.2 classification...79

Content validity...80

Daily use of registration form...81

Inter-rater reliability...81

4.1.1.4 Results...82

Translation and adaptation of PCNE drug-related problem classification v6.2"...82

Content validity...84

Daily use of registration form...86

Inter-rater reliability...86

4.1.1.5 Discussion...88

4.1.1.6 Conclusion...90

4.1.2 Pilot Study of PCNE v6.2 daily use: Focus on Pain DRP in Belgium Pharmacies 91 4.2 D RUG - RELATED PROBLEM IN HOSPITAL 94 4.2.1 Evaluation and analysis of drug-related problems in cancer patients readmitted to two Belgian care facilities within 30 days after discharge 94 4.2.1.1 Introduction...95

4.2.1.2 Objectives...96

4.2.1.3 Methods...96

Study design...96

Patients...96

Data collection...97

DRP detection and causality...98

Statistical analyses...99

4.2.1.4 Results...100

Patient characteristics...100

DRP data...104

Statistical analyses...105

4.2.1.5 Discussion...107

4.2.1.6 Conclusion...110

4.2.2 Drug-related problems readmission cost in two Belgian care facilities: Is it avoidable? 111

4.2.2.1 Introduction...112

4.2.2.2 Objectives...113

4.2.2.3 Methods...114

Study design...114

Patients...114

DRP detection and causality...114

Costs database...115

DRP preventability...116

Statistical analyses...116

4.2.2.4 Results...116

Patients...116

DRP detection and causality...117

Costs data...118

DRP preventability...119

4.2.2.5 Discussion...120

4.2.2.6 Conclusion...124

4.2.3 Drug-drug interactions in cancer patients readmitted 30 days after discharge 124 4.2.3.1 Introduction...125

4.2.3.2 Objectives...126

4.2.3.3 Method...127

Study design...127

Patients...127

Data collection...127

DDI assessment...128

Interaction sources comparison...129

4.2.3.4 Results...130

Study population...130

Interaction sources comparison...136

Survival analysis...137

4.2.3.5 Discussion...140

4.2.3.6 Conclusion...143

5. DISCUSSION... 144

5.1 D RUG - RELATED PROBLEM IN COMMUNITY PHARMACIES 145 5.1.1 Summary of major results and literature comparison 145 5.1.2 Strengths and limitations 148 5.2 D RUG - RELATED PROBLEM IN HOSPITAL 149 5.2.1 Summary of major results and literature comparison 149 5.2.1.1 Evaluation and analysis of drug-related problems in cancer patients readmitted to two Belgian care facilities within 30 days after discharge...149

5.2.1.2 Drug-related problems readmission cost in two Belgian hospitals: Is it avoidable?...152

5.2.1.3 Potential drug-drug interactions in cancer patients readmitted 30 days after discharge...153

5.2.2 Strengths and limitations 155 5.2.2.1 Evaluation and analysis of drug-related problems in cancer patients readmitted to two Belgian care facilities within 30 days after discharge...155

5.2.2.2 Drug-related problems readmission cost in two Belgian hospitals: Is it avoidable?...156

5.2.2.3 Potential drug-drug interactions in cancer patients readmitted 30 days after discharge...156

5.3 G ENERAL D ISCUSSION 157 6. CONCLUSION AND PERSPECTIVES... 161

7. BIBLIOGRAPHY... 165

8. Supplementary Material :... 184