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Data Analysis and Knowledge Discovery  2022, Vol. 6 Issue (7): 70-86    DOI: 10.11925/infotech.2096-3467.2021.1263
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Detecting Signals of Adverse Drug Reactions with Data from Online Health Community
Guo Jinjing1,Xia Guanghui2(),Huang Qi1,He Liyun3,Zhang Huabing3
1School of Information Management, Nanjing University, Nanjing 210023, China
2Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing 100020, China
3Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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Abstract  

[Objective] Online health communities provide new information for detecting adverse drug reaction (ADR) signals. This study identifies ADR signals from patients’ reviews and generates early warnings for potential side-effects of antidiabetic drugs. [Methods] First, we retrieved patients’ reviews (adverse reactions) on antidiabetic drugs from Ask a Patient website. Then, we combined natural language processing techniques and lexicons (UMLS and MedDRA) to normalize and map these reviews. Third, we constructed a drug-ADR co-occurrence matrix and used the PRR method to identify drug-ADR pairs meeting the signal detection threshold. Finally, we invited expert to interpret the extracted results, which were evaluated with Drugs.com standards. [Results] A total of 539 drug-ADR pairs were identified, with an overall identification accuracy of 85% and recall of 82%. [Limitations] The accuracy of identifying ADR terms was affected by the inclusion of non-ADR terms, such as examination, surgical operation, and social environment from MedDRA. [Conclusions] The proposed model enriches the data sources and methods of ADR signal detection.
Key words： Online Health Community      Knowledge Discovery      Proportional Reporting Ratio      Adverse Drug Reaction     
Received: 04 November 2021      Published: 24 August 2022
ZTFLH:  G250  
Fund:National Natural Science Foundation of China(91846106);Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019XK320029)
Corresponding Authors: Xia Guanghui,ORCID:0000-0003-4587-0344     E-mail: xiagh@imicams.ac.cn
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Jinjing Guo
Guanghui Xia
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Cite this article:

Guo Jinjing, Xia Guanghui, Huang Qi, He Liyun, Zhang Huabing. Detecting Signals of Adverse Drug Reactions with Data from Online Health Community. Data Analysis and Knowledge Discovery, 2022, 6(7): 70-86.

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https://manu44.magtech.com.cn/Jwk_infotech_wk3/EN/10.11925/infotech.2096-3467.2021.1263     OR     https://manu44.magtech.com.cn/Jwk_infotech_wk3/EN/Y2022/V6/I7/70

Detection Process of ADR Signals Based on Online Health Community
Process and Results of ADR Signals Detection for Antidiabetic Drugs
序号 中文通用名 英文名 商品名 药品种类 评论数
1 阿托伐他汀 atorvastatin LIPITOR 降脂药 1 244
2 阿仑膦酸钠 alendronate sodium FOSAMAX 抗甲状旁腺药、钙磷代谢调节药及抗骨质疏松药 1 208
3 瑞舒伐他汀 rosuvastatin CRESTOR 降脂药 1 208
4 辛伐他汀 simvastatin ZOCOR 降脂药 891
5 左甲状腺素钠 levothyroxine sodium SYNTHROID 甲状腺激素及其抗甲状腺药物 887
6 二甲双胍 metformin GLUCOPHAGE 胰岛素及口服降糖药 582
7 依折麦布 ezetimibe ZETIA 降脂药 537
8 吡格列酮 pioglitazone ACTOS 胰岛素及口服降糖药 360
9 非诺贝特 fenofibrate TRICOR 降脂药 325
10 利拉鲁肽 liraglutide VICTOZA 胰岛素及口服降糖药 244
11 普伐他汀 pravastatin PRAVACHOL 降脂药 225
12 艾塞那肽 exenatide BYETTA 胰岛素及口服降糖药 206
13 唑来膦酸 zoledronic acid RECLAST 抗甲状旁腺药、钙磷代谢调节药及抗骨质疏松药 184
14 罗格列酮 rosiglitazone AVANDIA 胰岛素及口服降糖药 99
15 西格列汀 sitagliptin JANUVIA 胰岛素及口服降糖药 98
16 胰岛素 insulin LANTUS 胰岛素及口服降糖药 94
17 度拉糖肽 dulaglutide TRULICITY 胰岛素及口服降糖药 56
18 溴隐亭 bromocriptine PARLODEL 下丘脑垂体疾病及其用药 53
List of the Selected Antidiabetic Drugs
处理参数 值
Knowledge Source 2020AB
Data Version NLM
Data Model Relaxed Model
Show CUIs yes
Use Word Sense Disambiguation yes
Restrict to Sources COSTAR, MDR, WHO
Data Processing Parameters of MetaMap

ADRi

ADDj		 1-阿托伐他汀-LIPITOR 2-阿仑膦酸钠-FOSA
MAX		 3-瑞舒伐他汀-CREST
OR		 … 18-溴隐亭-PAR
LODEL
Abdominal bloating 21 61 34 … 1
Abdominal cramps 4 5 1 … 1
Abdominal discomfort 0 0 2 …… 0
… … … … … …
Yeast
infection		 0 1 0 … 0
Co-occurrence Matrix of ADR and ADD
特定ADD 数据集中所有其他ADD
特定ADR a c
所有其他ADR b d
Four-grid Table Method Using by PRR
序号 1-阿托伐他汀-LIPITOR 2-阿仑膦酸钠-FOSAMAX 3-瑞舒伐他汀-CRESTOR
ADRs PRR ADRs PRR ADRs PRR
1 Parkinson’s disease 34.46 Osteonecrosis of jaw 28.67 Feeling of despair 15.89
2 Cataract 22.97 Osteopenia 22.94 Tietze’s Syndrome 15.89
3 Nerve injury 20.10 Pain in thumb 22.94 Tenderness muscle 15.89
4 Shoulder operation 17.23 Root canal procedure 17.20 Electric shock 15.89
5 Fatty liver 14.36 Bone necrosis 17.20 Renal function test 7.95
6 Biopsy 11.49 Pelvic pain female 17.20 Interventional procedure 7.95
7 Clumsiness 11.49 Angiogram NOS 17.20 Mixed anxiety and depressive disorder 7.06
8 Neck cramps 9.57 Osteoporosis 14.75 Radiating pain 5.30
9 Depression suicidal 8.62 Eye pain 13.93 Aggressive behavior 4.64
10 Hypersomnia 8.62 Bone scan NOS 13.76 Lipids NOS 4.54
序号 4-辛伐他汀-ZOCOR 5-左甲状腺素钠-SYNTHROID 6-二甲双胍-GLUCOPHAGE
ADRs PRR ADRs PRR ADRs PRR
1 Nodule 15.20 Hypothyroidism 69.46 Acidosis lactic 99.72
2 Oliguria 15.20 Graves’ disease 57.89 Gastrointestinal symptom NOS 79.78
3 Muscle mass 15.20 Goiter 48.24 Fecal Incontinence 59.83
4 Shooting pain 12.16 Behavior hyperactive 45.02 Polycystic ovary 49.86
5 Angina pectoris 11.40 Dry skin 35.62 Soft stools 39.89
6 Chest X-ray 10.13 Racing thoughts 28.94 Explosive diarrhoea 34.19
7 Lack of libido 8.26 Irregular menstruation 28.94 Taste metallic 32.64
8 Faeces clay-coloured 7.60 Infertility 28.94 Loose stools 31.53
9 Lymphadenopathy 7.60 Cold intolerance 28.94 Gastrointestinal irritation 29.92
10 Back surgery 7.60 Overactive 28.94 Diarrhea 15.27
序号 7-依折麦布-ZETIA 8-吡格列酮-ACTOS 9-非诺贝特-TRICOR
ADRs PRR ADRs PRR ADRs PRR
1 Nasal sinus congestion 30.56 Leg edema 95.61 Biliary colic 82.26
2 Pulmonary congestion 19.65 Dry cough 28.68 Fish-eye disease 20.56
3 Diverticulitis 13.10 Ankle edema 27.52 Prurigo 15.67
4 Weird feeling 9.82 Body fluid retention 22.31 Slurred speech 7.48
5 Inflammation mucous membrane 7.86 Anemia 21.73 Pain in joint involving hand 7.22
6 Upper GI series 7.86 Swelling of legs 21.51 Skin greasy 5.96
7 Chest pressure 7.49 Congestive heart failure 18.59 CAT scan 4.99
8 Constriction throat 6.55 Water retention 17.93 Pain in elbow 4.99
9 Cardiac flutter 6.55 Swelling of tongue 17.93 Influenza-like symptoms 3.10
10 Gas pain 5.95 Severe pre-eclampsia 14.71 Blood test NOS 2.81
序号 10-利拉鲁肽-VICTOZA 11-普伐他汀-PRAVACHOL 12-艾塞那肽-BYETTA
ADRs PRR ADRs PRR ADRs PRR
1 Nausea and vomiting 73.65 Cardiac pain 16.04 Injection site bruising 275.61
2 Pancreatitis 49.10 Pain dull 6.80 Injection 24.65
3 Bad taste 23.01 Nephritis 6.07 Bite 18.37
4 Eructation 22.25 Hepatic enzyme 4.88 Anorexia 13.78
5 Vomiting 9.99 Forgetfulness 4.32 Vomiting 10.71
6 Dehydration 7.01 Libido decreased 4.28 Gas pain 10.60
7 Rhinorrhea 6.90 Confusion 3.51 Redness 9.19
8 Irritable bowel syndrome 6.50 Tinnitus 3.12 Nausea 9.10
9 Nausea 6.02 Muscle weakness 2.93 Weight decreased 8.52
10 Stomach cramps 5.71 Memory loss 2.67 Contusion 8.35
序号 13-唑来膦酸-RECLAST 14-罗格列酮-AVANDIA 15-西格列汀-JANUVIA
ADRs PRR ADRs PRR ADRs PRR
1 Infusion 772.22 Infection 90.96 Rhinorrhea 21.04
2 Exostosis 119.83 Congestive heart failure 41.35 Poor weight gain 15.30
3 Femur fracture 59.91 Water retention 36.39 Upper respiratory infection 13.60
4 Kidney failure 23.97 Sluggishness 30.32 No adverse effect 9.05
5 Fever 15.32 Heart fluttering 27.29 Pharyngitis 8.77
6 Paronychia 11.41 Electrocardiogram 24.81 Coughing 5.26
7 Breathing abnormally deep 9.99 Foot edema 24.64 Tachycardia 4.43
8 Flu symptoms 9.99 Hypoglycemia 22.74 Anxiety 3.21
9 Fracture 9.59 Heart rate irregular 21.40
10 Bone pain 9.44 Edema 14.08
序号 16-胰岛素-LANTUS 17-度拉糖肽-TRULICITY 18-溴隐亭-PARLODEL
ADRs PRR ADRs PRR ADRs PRR
1 Fire accident 38.75 Explosive diarrhoea 34.37 Hallucinations 217.27
2 Burn 31.00 Injection 18.74 Nose congestion 81.48
3 Hypoglycemia 22.15 Dehydration 17.57 Hypotension 59.26
4 Injection 14.53 Eructation 17.06 Syncope 27.94
5 Hunger 8.21 Appetite absent 11.48 Vomiting 7.27
6 Burning sensation 6.64 Vomiting 8.37 Vertigo 5.95
7 Edema 5.00 Illness 7.81 Dizziness 5.24
8 Constipation 3.42 Sweating 5.02 Palpitations 5.17
9 Pruritus 3.32 Abdominal pain 4.77 Drowsiness 4.71
10 Weight 3.29 Nausea 4.73 Nausea 3.94
ADRs Corresponding to the 18 Kinds of ADDs and PRR Values（Top-10）
序号 1-阿托伐他汀-LIPITOR 2-阿仑膦酸钠-FOSAMAX 3-瑞舒伐他汀-CRESTOR
ADR PRR ADR PRR ADR PRR
1 Parkinson’s disease 34.46 Osteonecrosis of jaw* 28.67 Feeling of despair* 15.89
2 Cataract 22.97 Osteopenia 22.94 Tietze’s Syndrome 15.89
3 Nerve injury* 20.10 Pain in thumb* 22.94 Tenderness muscle* 15.89
4 Fatty liver 14.36 Bone necrosis* 17.20 Electric shock 15.89
5 Clumsiness 11.49 Pelvic pain female 17.20 Mixed anxiety and depressive disorder* 7.06
6 Neck cramps* 9.57 Osteoporosis* 14.75 Radiating pain 5.30
7 Depression suicidal* 8.62 Eye pain* 13.93 Aggressive behavior* 4.64
8 Hypersomnia* 8.62 Jaw pain* 11.72 Bad dreams* 4.54
9 Atrophy NOS 8.62 Gastric ulcer* 11.47 Sore feet* 4.33
10 Unspecified visual loss* 8.62 Stiffness hip* 10.04 Sleep disturbances* 3.97
Recall 0.50 0.80 0.70
序号 4-辛伐他汀-ZOCOR 5-左甲状腺素钠-SYNTHROID 6-二甲双胍-GLUCOPHAGE
ADR PRR ADR PRR ADR PRR
1 Nodule* 15.20 Graves’ disease* 57.89 Acidosis lactic* 99.72
2 Oliguria 15.20 Goiter* 48.24 Gastrointestinal symptom NOS* 79.78
3 Shooting pain* 12.16 Behavior hyperactive* 45.02 Fecal Incontinence* 59.83
4 Angina pectoris* 11.40 Dry skin 35.62 Soft stools* 39.89
5 Lack of libido* 8.26 Racing thoughts 28.94 Explosive diarrhoea* 34.19
6 Faeces clay-coloured* 7.60 Irregular menstruation* 28.94 TASTE METALLIC 32.64
7 Lymphadenopathy 7.60 Infertility* 28.94 Loose stools* 31.53
8 Neuralgia* 7.60 Cold intolerance* 28.94 Gastrointestinal irritation* 29.92
9 Frozen shoulder* 5.70 Overactive* 28.94 Diarrhea* 15.27
10 Muscle tightness* 5.07 Premenstrual syndrome 24.12 Thirst 13.30
Recall 0.80 0.70 0.80
序号 7-依折麦布-ZETIA 8-吡格列酮-ACTOS 9-非诺贝特-TRICOR
ADR PRR ADR PRR ADR PRR
1 Nasal sinus congestion* 30.56 Leg edema* 95.61 Biliary colic* 82.26
2 Pulmonary congestion 19.65 Dry cough* 28.68 Fish-eye disease* 20.56
3 Diverticulitis 13.10 Ankle edema* 27.52 Prurigo* 15.67
4 Weird feeling* 9.82 Body fluid retention* 22.31 Slurred speech 7.48
5 Inflammation mucous membrane 7.86 Anemia* 21.73 Pain in joint involving hand* 7.22
6 Constriction throat* 6.55 Swelling of legs* 21.51 Skin greasy 5.96
7 Cardiac flutter 6.55 Congestive heart failure* 18.59 Pain in elbow* 4.99
8 Gas pain* 5.95 Water retention* 17.93 Influenza-like symptoms* 3.10
9 Pain-left side* 5.24 Swelling of tongue* 17.93 Vertigo* 2.76
10 Increased frequency of defecation* 4.91 Severe pre-eclampsia 14.71 Exanthema* 2.49
Recall 0.60 0.90 0.80
序号 10-利拉鲁肽-VICTOZA 11-普伐他汀-PRAVACHOL 12-艾塞那肽-BYETTA
ADR PRR ADR PRR ADR PRR
1 Nausea and vomiting* 73.65 Cardiac pain* 16.04 Injection site bruising* 275.61
2 Pancreatitis* 49.10 Pain dull* 6.80 Anorexia 13.78
3 Bad taste* 23.01 Nephritis 6.07 Vomiting* 10.71
序号 10-利拉鲁肽-VICTOZA 11-普伐他汀-PRAVACHOL 12-艾塞那肽-BYETTA
ADR PRR ADR PRR ADR PRR
4 Eructation* 22.25 Forgetfulness* 4.32 Gas pain* 10.60
5 Vomiting* 9.99 Libido decreased* 4.28 Redness* 9.19
6 Dehydration* 7.01 Confusion* 3.51 Nausea* 9.10
7 Rhinorrhea 6.90 Tinnitus* 3.12 Weight decreased* 8.52
8 Irritable bowel syndrome* 6.50 Muscle weakness* 2.93 Feeling jittery* 8.11
9 Nausea* 6.02 Memory loss* 2.67 Ataxia Telangiectasia 7.07
10 Stomach cramps* 5.71 Hypoglycemia* 6.26
Recall 0.90 0.89 0.80
序号 13-唑来膦酸-RECLAST 14-罗格列酮-AVANDIA 15-西格列汀-JANUVIA
ADR PRR ADR PRR ADR PRR
1 Exostosis 119.83 Infection* 90.96 Rhinorrhea 21.04
2 Femur fracture* 59.91 Congestive heart failure* 41.35 Poor weight gain 15.30
3 Kidney failure* 23.97 Water retention* 36.39 Upper respiratory infection* 13.60
4 Fever* 15.32 Sluggishness 30.32 Pharyngitis* 8.77
5 Paronychia 11.41 Heart fluttering 27.29 Coughing* 5.26
6 Breathing abnormally deep* 9.99 Foot edema* 24.64 Tachycardia* 4.43
7 Flu symptoms* 9.99 Hypoglycemia* 22.74 Anxiety* 3.21
8 Fracture* 9.59 Heart rate irregular* 21.40
9 Bone pain* 9.44 Edema* 14.08
10 Inguinal pain 8.56 Ankle edema* 8.40
Recall 0.70 0.80 0.71
序号 16-胰岛素-LANTUS 17-度拉糖肽-TRULICITY 18-溴隐亭-PARLODEL
ADR PRR ADR PRR ADR PRR
1 Hypoglycemia* 22.15 Explosive diarrhoea* 34.37 Hallucinations* 217.27
2 Hunger* 8.21 Dehydration* 17.57 Nose congestion* 81.48
3 Burning sensation* 6.64 Eructation* 17.06 Hypotension* 59.26
4 Edema* 5.00 Appetite absent* 11.48 Syncope* 27.94
5 Constipation* 3.42 Vomiting* 8.37 Vomiting* 7.27
6 Pruritus* 3.32 Illness* 7.81 Vertigo* 5.95
7 Weight gain* 3.06 Sweating* 5.02 Dizziness* 5.24
8 Abdominal pain* 4.77 Palpitations* 5.17
9 Nausea* 4.73 Drowsiness* 4.71
10 Diarrhea* 4.34 Nausea* 3.94
Recall 1.00 1.00 1.00
Reviewed ADRs and PRR Values Corresponding to the 18 Kinds of ADDs（Top-10）
序号 中文通用名 评论数 符合初筛条件
的ADR		 专家判定后
的ADR		 覆盖金
标准数		 ADR术语识别
准确率		 Recall
（Top-10）		 Reall
（all）
1 阿托伐他汀 1 244 45 38 28 0.84 0.50 0.74
2 阿仑膦酸钠 1 208 62 48 34 0.77 0.80 0.71
3 瑞舒伐他汀 1 208 34 29 25 0.85 0.70 0.86
4 辛伐他汀 891 42 34 28 0.81 0.80 0.82
5 左甲状腺素钠 887 78 72 57 0.92 0.70 0.79
6 二甲双胍 582 40 34 30 0.85 0.80 0.88
7 依折麦布 537 28 24 16 0.86 0.60 0.67
8 吡格列酮 360 35 32 26 0.91 0.90 0.81
9 非诺贝特 325 15 12 10 0.80 0.80 0.83
10 利拉鲁肽 244 29 27 24 0.93 0.90 0.89
11 普伐他汀 225 10 9 8 0.90 0.89 0.89
12 艾塞那肽 206 27 21 19 0.78 0.80 0.90
13 唑来膦酸 184 29 23 18 0.79 0.70 0.78
14 罗格列酮 99 21 17 15 0.81 0.80 0.88
15 西格列汀 98 8 7 5 0.88 0.71 0.71
16 胰岛素 94 11 7 7 0.64 1.00 0.88
17 度拉糖肽 56 14 12 12 0.86 1.00 1.00
18 溴隐亭 53 11 11 11 1.00 1.00 1.00
总计 539 457 373 0.85 0.82
Calculation Results of the Coincidence of the ADRs Corresponding to the 18 Kinds of ADD with the Gold Standard
序号 ADD ADR PRR 共现频次
1 阿托伐他汀-LIPITOR Parkinson’s disease 34.46 6
Cataract 22.97 4
Fatty liver 14.36 5
Clumsiness 11.49 4
Atrophy NOS 8.62 3
Lupus erythematosus 8.62 4
Atrophy skeletal muscle 5.74 4
Cerebration impaired 3.38 10
Restless legs syndrome 3.06 8
Scheuermann’s disease 2.26 22
2 阿仑膦酸钠-FOSAMAX Osteopenia 22.94 40
Pelvic pain female 17.20 3
Drug reaction with eosinophilia and systemic symptoms 10.04 7
Bone spur 8.60 3
Dislocation 8.60 3
Gingival pain 7.17 5
Malignant breast neoplasm 5.73 4
Muscle stiffness 4.81 47
Sciatica 3.32 11
Stiffness 3.24 48
Decompression sickness 3.19 15
Atrial fibrillation 3.13 6
Joint stiffness 2.87 10
Laceration 2.37 12
3 瑞舒伐他汀-CRESTOR Tietze’s Syndrome 15.89 3
Electric shock 15.89 3
Radiating pain 5.30 4
Gout 3.71 7
4 辛伐他汀-ZOCOR Oliguria 15.20 4
Lymphadenopathy 7.60 4
Bursitis 4.84 7
Mg++ increased 3.80 5
Heterosexuality 3.62 10
Shock 2.80 7
5 左甲状腺素钠-SYNTHROID Dry skin 35.62 48
Racing thoughts 28.94 3
Premenstrual syndrome 24.12 5
Dry hair 16.08 5
Carpal tunnel syndrome 9.65 6
Endometriosis 9.65 5
Hashimoto’s disease 9.65 3
Photophobia 8.04 5
Suicide 6.43 4
Hypertrichosis 4.70 39
Drying 4.48 13
Dryness of eyes 4.29 12
Upper respiratory infection 3.57 10
Cerebration impaired 3.38 7
Libido decreased 2.89 9
6 二甲双胍-GLUCOPHAGE Taste metallic 32.64 18
Thirst 13.30 10
Arsenical keratosis 2.78 6
Hypertrichosis 2.45 13
7 依折麦布-ZETIA Pulmonary congestion 19.65 3
Diverticulitis 13.10 3
Inflammation mucous membrane 7.86 3
Cardiac flutter 6.55 5
Night sweats 4.37 11
Middle insomnia 4.37 6
Anxiety attack 4.09 5
Bursitis 3.74 4
8 吡格列酮-ACTOS Severe pre-eclampsia 14.71 8
Increased appetite 7.03 5
Dyspnea 6.66 44
Mg++ increased 5.98 3
Epistaxis 5.98 3
Renal pain 5.12 3
9 非诺贝特-TRICOR Slurred speech 7.48 3
Skin greasy 5.96 5
10 利拉鲁肽-VICTOZA Rhinorrhea 6.90 3
Ataxia Telangiectasia 5.67 4
Xerostomia 3.92 5
11 普伐他汀-PRAVACHOL Nephritis 6.07 6
12 艾塞那肽-BYETTA Anorexia 13.78 3
Ataxia Telangiectasia 7.07 4
13 唑来膦酸-RECLAST Exostosis 119.83 3
Paronychia 11.41 4
Inguinal pain 8.56 3
Death NOS 4.56 4
Heterosexuality 4.28 3
14 罗格列酮-AVANDIA Sluggishness 30.32 4
Heart fluttering 27.29 3
15 西格列汀-JANUVIA Rhinorrhea 21.04 3
Poor weight gain 15.30 3
Some ADR Warning Signals Need to be Paid Attention to
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