2024 年 31 巻 10 号 p. 1341-1352
Aims: Although administrative claims databases have recently been used for clinical research in Japan, no detailed description of their utilization in stroke research is available. We reviewed stroke studies using the Diagnosis Procedure Combination (DPC), the National Database of Health Insurance Claims and Specific Health Checkups (NDB), and several commercial databases sourced from social health insurance associations, focusing on their applications and limitations.
Methods: Original articles on stroke published by April 2024 using the DPC, NDB, and commercial databases were identified in Ovid MEDLINE. The characteristics of each database were compared in terms of comprehensiveness, traceability, baseline information, and outcome assessment in stroke research.
Results: A total of 114 studies were included (83 for DPC, 6 for NDB, and 25 for commercial databases). The number of stroke studies using administrative databases in Japan is still approximately 10 per year, although there is a slowly increasing trend. The DPC database was utilized for short-term outcome studies because of its detailed baseline and outcome information, although the inability to track patients once they changed facilities limits their use in long-term studies. The NDB database is potentially useful for long-term studies because of its comprehensiveness and traceability, but difficulties in data access restrict its usage. The most commonly used commercial database utilizes baseline information on lifestyle and blood test data, although the lack of coverage for those over 75 years old may limit its generalizability.
Conclusions: Administrative claims databases are beginning to be used in stroke research in Japan but are not yet fully utilized. Researchers need to understand their applications and limitations.
Administrative claims databases include information routinely collected, primarily for medical and nursing care insurance billing. These databases automatically accumulate real-world data on diagnoses, procedures, and drug prescriptions on a nationwide basis1). In Japan, utilization of these data was initially approved for post-marketing safety monitoring under a 2018 legal amendment2). They have since begun to be utilized for drug regulation and clinical studies, as the administrative claims database has a large sample size, high generalizability, and a wide variety of variables3).
Stroke research encompasses a broad perspective, including comparative effectiveness of acute treatment, prediction of recurrence in the chronic phase, descriptive epidemiology of rare diseases, health-economic analysis, and policy effectiveness. Conventional registry-based surveys have not adequately addressed these research questions because they are time-consuming, costly, provide only predefined variables, and are not sufficiently representative of the target population. Claims databases may help address broader research questions and facilitate stroke research.
In Japan, several administrative claims databases can be used for research. The main databases that have been used in the past decade are the Diagnosis Procedure Combination (DPC) database, the National Database of Health Insurance Claims and Specific Health Checkups (NDB), and several commercial databases sourced from social health insurance associations4, 5). However, these claims databases were not initially created for research purposes and therefore have a particular data structure that limits the research design4). Researchers have to select the most suitable database for their research questions and must recognize that each database has limitations that cannot be overcome.
AimsWe investigated how administrative claims databases in Japan have been utilized for stroke research and provide information on their applications and limitations.
This narrative review identified original articles on stroke using the DPC, NDB, and several commercial databases sourced from social health insurance associations. We searched articles in English included in Ovid MEDLINE published until April 1, 2024. The search terms were assembled with the support of a librarian specializing in the systematic review (Supplementary Table 1). We excluded (1) non-English studies, (2) non-original studies, (3) studies that did not use predefined databases, and (4) studies that did not include stroke or cerebrovascular disease in any of the target populations, exposure, comparison, or outcome. Commercial databases were selected from the list of databases introduced by the Japanese Society for Pharmacoepidemiology (Supplementary Table 1)5). Studies based on commercial databases that were not insurer-based but hospital-based and mainly derived from DPC were classified as studies based on DPC databases for the purposes of this review.
| Search terms | |
|---|---|
| Stroke | #1. cerebrovascular disorders/ or exp basal ganglia cerebrovascular disease/ or exp brain ischemia/ or exp carotid artery diseases/ or exp cerebral small vessel diseases/ or exp intracranial arterial diseases/ or exp “intracranial embolism and thrombosis”/ or exp intracranial hemorrhage/ or stroke/ or exp brain infarction/ or stroke, lacunar/ or vasospasm, intracranial/ or vertebral artery dissection/ or brain injuries/ or brain injury, chronic/ |
| #2. (stroke$ or poststroke or apoplex$ or cerebral vasc$ or brain vasc$ or cerebrovasc$ or cva$ or SAH).tw. | |
| #3. ((brain or cerebr$ or cerebell$ or vertebrobasil$ or hemispher$ or intracran$ or intracerebral or infratentorial or supratentorial or “middle cerebral artery” or MCA$ or “anterior circulation” or “posterior circulation” or “basilar artery” or “vertebral artery” or “space-occupying”) and (isch?emi$ or infarct$ or thrombo$ or emboli$ or occlus$ or hypoxi$)).tw. | |
| #4. ((brain$ or cerebr$ or cerebell$ or intracerebral or intracran$ or parenchymal or intraparenchymal or intraventricular or infratentorial or supratentorial or basal gangli$ or putaminal or putamen or posterior fossa or hemispher$ or subarachnoid) adj5 (h?emorrhag$ or h?ematoma$ or bleed$)).tw. | |
| #5. #1 or #2 or #3 or #4 | |
| DPC | ((“Diagnosis Procedure Combination database” OR “nationwide database” OR “administrative database” OR “inpatient database” OR “discharge database”) AND (Japan OR Japanese)).ti,ab. |
| NDB | ((“claims” AND “NDB”) OR “National Database of Health Insurance Claims” OR “National Database of Health Insurance Claim” OR “National Database of Japanese Health Insurance Claims” OR “nationwide administrative claims database”).ti,ab. |
| Commercial databases sourced from social health insurance associations | |
| JMDC | ((“JMDC”) OR (“jmdc database”) OR (“Japan Medical Data Center”)).ti,ab. |
| JammNet | ((“JammNet”) OR (“jammnet database”) OR (“Japan Medical Market Network”)).ti,ab. |
| MinaCare | ((“MinaCare”) OR (“minacare database”)).ti,ab. |
| Medi-Scope | ((“Medi-Scope”) OR (“medi-scope database”)).ti,ab. |
Abbreviations: DPC, Diagnosis Procedure Combination (DPC) database; NDB, National Database of Health Insurance Claims and Specific Health Checkups.
The search formulae were used in combination. For example, for stroke studies using the DPC database, the search formula for “Stroke” was combined with the search formula for “DPC” using AND. The studies based on the MDV database (medical.data.vision Inc.) were classified as studies based on the DPC database because they were not insurer-derived but hospital-derived and mainly based on DPC.
Owing to the nature of the narrative review, we did not assign two independent reviewers for screening; only one reviewer (SE) screened the titles and abstracts and determined the studies that would ultimately be included in the full-text review process. The lists of stroke studies were created using these databases, and the annual trends in the number of published articles were visualized. Representative studies using each database were explained. The characteristics of each database in stroke research were compared narratively from the perspective of comprehensiveness (whether patients with stroke are adequately covered as a target population), traceability (whether patients can be followed up for a long period to check outcomes), baseline information (how detailed baseline information can be assessed), and outcome assessments (how detailed outcome information can be assessed).
The DPC database is a nationwide repository of inpatient information from administrative data for acute-care hospitals in Japan6-8). This database collects claims and discharge data from 1763 nationwide hospitals in 2023. It is characterized by a wide variety of clinical information on patient backgrounds, including age, sex, height, and weight on admission; smoking status; drugs used; surgeries or diagnostic tests performed; the main diagnoses on admission; the diagnoses with the most medical resources invested at discharge; comorbidities; and complications differentiated from comorbidities recorded with Japanese text data and the International Classification of Diseases, Tenth Revision (ICD-10) codes; level of consciousness on admission and at discharge; hospital mortality; discharge destination; length of hospital stay; and readmission within 90 days. Drugs and procedures were recorded based on medical receipt data and the date of use or implementation. For patients with stroke, the onset date and modified Rankin Scale (mRS) before the onset and at discharge were also documented. The attending physicians were responsible for clinical data entry for each patient. However, because information is collected on a facility basis, it is often difficult to track patients when they change medical institutions.
The NDB database collects information on receipts and specified health checkups9, 10). Included in this database are the details of medical institutions’ claims to insurers other than those paid by patients, information that has been collected monthly since 2009 9). The NDB database can be said to be the most comprehensive administrative database in Japan because it collects electronic receipts from all types of insurers in Japan, and 99.9% of receipts from medical hospitals and pharmacies have been electronic since April 2011 11). While the other two databases collect data by the insurer or the medical institution, the NDB database collects electronic receipts, regardless of the source. Therefore, the NDB has the potential to track patients over time because it collects electronic receipts regardless of whether they are from the insurer or medical institution. These data include medical, dental, home, and nursing care receipts. However, there are also some difficulties associated with accessing the data, as they can only be provided by the Ministry of Health, Labor, and Welfare or by a limited number of on-site research centers9).
Commercial databases sourced from social health insurance associations accumulate inpatient, outpatient, prescription receipt, and health checkup data from several health insurance associations, although there are some differences among databases5, 12, 13). In general, they are easier to handle than other public databases because the data-acquiring company has standardized them. Because the data are collected from corporate insurers, unlike DPC, it is possible to track patients even if they are transferred from one hospital to another or visit multiple medical facilities. However, tracking patients can be impossible if they quit or change jobs and are excluded from insurance. It should also be noted that private social insurance associations generally do not cover the population over 75 years old, as all individuals ≥ 75 years old are covered by a special public medical insurance system for these individuals in Japan. The details of each database are described elsewhere8, 10, 13).
Included Articles and Annual Trends in PublicationThe initial search retrieved 174 studies (121 from DPC, 11 from NDB, and 42 from commercial databases sourced from social health insurance associations). Ultimately, 114 studies were included in our review (83 from DPC, 6 from NDB, and 24 from commercial databases). The screening process is described in Fig.1, and the included studies are listed in Supplementary Table 2. The number of published articles in the DPC, NDB, and commercial databases, as well as their annual trends, are shown in Fig.2.
Abbreviations: DPC, Diagnosis Procedure Combination (DPC) database; NDB, National Database of Health Insurance Claims and Specific Health Checkups. The commercial database included Japanese commercial databases sourced from social health insurance associations.
| No. | Title | Published year | First author |
|---|---|---|---|
| DPC database | |||
| 1 | Reconsidering the value of rehabilitation for patients with cerebrovascular disease in Japanese acute health care hospitals | 2011 | Kazuaki Kuwabara |
| 2 | Stroke care units versus general medical wards for acute management of stroke in Japan | 2013 | Takahiro Inoue |
| 3 | Association of early post-procedure hemodynamic management with the outcomes of subarachnoid hemorrhaging patients | 2013 | Kazuaki Kuwabara |
| 4 | Association between ambulance distance to hospitals and mortality from acute diseases in Japan: national database analysis | 2013 | Atsuhiko Murata |
| 5 | Ischemic stroke after cervical spine injury: analysis of 11,005 patients using the Japanese Diagnosis Procedure Combination database | 2014 | Hirotaka Chikuda |
| 6 | Impact of regional clinical pathways on the length of stay in hospital among stroke patients in Japan | 2014 | Yoshihisa Fujino |
| 7 | Factors affecting mortality following emergency admission for chronic obstructive pulmonary disease | 2014 | Wakae Hasegawa |
| 8 | Effects of comprehensive stroke care capabilities on in-hospital mortality of patients with ischemic and hemorrhagic stroke: J-ASPECT study | 2014 | Koji Iihara |
| 9 | Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan | 2014 | Toshiaki Isogai |
| 10 | Factors associated with the administration of tissue plasminogen activator for acute ischemic stroke | 2014 | Susumu Kunisawa |
| 11 | Effects of remifentanil on in-hospital mortality and length of stay following clipping of intracranial aneurysm: a propensity score-matched analysis | 2014 | Kanji Uchida |
| 12 | Effects of edaravone on early outcomes in acute ischemic stroke patients treated with recombinant tissue plasminogen activator | 2014 | Tomoki Wada |
| 13 | Geographical analysis of aneurysmal subarachnoid hemorrhage in Japan utilizing publically-accessible DPC database | 2015 | Toru Fukuhara |
| 14 | Effectiveness of Hospital Functions for Acute Ischemic Stroke Treatment on In-Hospital Mortality: Results From a Nationwide Survey in Japan | 2015 | Tetsuya Iwamoto |
| 15 | Variation in Risk-Standardized Mortality of Stroke among Hospitals in Japan | 2015 | Hiroki Matsui |
| 16 | Outcomes after early or late timing of surgery for infective endocarditis with ischaemic stroke: a retrospective cohort study | 2015 | Kojiro Morita |
| 17 | Risks of in-hospital death and complications after fusion surgery in patients with atlantoaxial subluxation: analysis of 1090 patients using the Japanese Diagnosis Procedure Combination database | 2015 | Junichi Ohya |
| 18 | Perioperative stroke in patients undergoing elective spinal surgery: a retrospective analysis using the Japanese diagnosis procedure combination database | 2015 | Junichi Ohya |
| 19 | Relationship between hospital volume and early outcomes in acute ischemic stroke patients treated with recombinant tissue plasminogen activator | 2015 | Tomoki Wada |
| 20 | Categorized diagnoses and procedure records in an administrative database improved mortality prediction | 2015 | Hayato Yamana |
| 21 | Very Early versus Delayed Rehabilitation for Acute Ischemic Stroke Patients with Intravenous Recombinant Tissue Plasminogen Activator: A Nationwide Retrospective Cohort Study | 2016 | Ryo Momosaki |
| 22 | Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists and Risk of Pneumonia in Patients with Acute Stroke | 2016 | Ryo Momosaki |
| 23 | Cerebral infarction after intraarterial and intravenous chemoradiotherapy for head and neck cancer: A retrospective analysis using a Japanese inpatient database | 2016 | Sayaka Suzuki |
| 24 | Ozagrel for Patients With Noncardioembolic Ischemic Stroke: A Propensity Score-Matched Analysis | 2016 | Tomoki Wada |
| 25 | Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke: Observational Nationwide Study in Japan | 2016 | Tomoki Wada |
| 26 | Association Between Colorectal Cancer and Atherosclerotic Diseases: A Study Using a National Inpatient Database in Japan | 2016 | Yutaka Yamaji |
| 27 | Factors affecting in-hospital mortality and likelihood of undergoing surgical resection in patients with primary cardiac tumors | 2017 | Toshiaki Isogai |
| 28 | Development and validation of a score for evaluating comprehensive stroke care capabilities: J-ASPECT Study | 2017 | Akiko Kada |
| 29 | Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study | 2017 | Keiko Kamei |
| 30 | Impact of Rehabilitation on Outcomes in Patients With Ischemic Stroke: A Nationwide Retrospective Cohort Study in Japan | 2017 | Maiko Yagi |
| 31 | Comparison of surgical and conservative treatment outcomes for type a aortic dissection in elderly patients | 2018 | Takeshi Aoyama |
| 32 | Effect of treatment modality on in-hospital outcome in patients with subarachnoid hemorrhage: a nationwide study in Japan (J-ASPECT Study) | 2018 | Ryota Kurogi |
| 33 | Comparing intracerebral hemorrhage associated with direct oral anticoagulants or warfarin | 2018 | Ryota Kurogi |
| 34 | Efficacy of Antimicrobial Catheters for Prevention of Catheter-Associated Urinary Tract Infection in Acute Cerebral Infarction | 2018 | Keiji Muramatsu |
| 35 | In-hospital complication rate following microendoscopic versus open lumbar laminectomy: a propensity score-matched analysis | 2018 | Nozomu Ohtomo |
| 36 | In-hospital mortality and morbidity of pediatric scoliosis surgery in Japan: Analysis using a national inpatient database | 2018 | Yuki Taniguchi |
| 37 | Trends in hospital standardized mortality ratios for stroke in Japan between 2012 and 2016: a retrospective observational study | 2019 | Rebeka Amin |
| 38 | Clinical Effects of Early Edaravone Use in Acute Ischemic Stroke Patients Treated by Endovascular Reperfusion Therapy | 2019 | Masaya Enomoto |
| 39 | Treatment Risk for Elderly Patients with Unruptured Cerebral Aneurysm from a Nationwide Database in Japan | 2019 | Fusao Ikawa |
| 40 | National trends in outcomes of ischemic stroke and prognostic influence of stroke center capability in Japan, 2010-2016 | 2019 | Akiko Kada |
| 41 | In-hospital Takotsubo syndrome versus in-hospital acute myocardial infarction among patients admitted for non-cardiac diseases: a nationwideinpatient database study | 2019 | Toshiaki Isogai |
| 42 | Patient characteristics and in-hospital complications of subcutaneous implantable cardioverter-defibrillator for Brugada syndrome in Japan | 2019 | Iwanari Kawamura |
| 43 | Association between Angiotensin-Converting Enzyme Inhibitors and Post-Stroke Aspiration Pneumonia | 2019 | Ryosuke Kumazawa |
| 44 | Can Elective Spine Surgery Be Performed Safely Among Nonagenarians?: Analysis of a National Inpatient Database in Japan | 2019 | Takeshi Oichi |
| 45 | Association of dialysis with in-hospital disability progression and mortality in community-onset stroke | 2019 | Tomoko Usui |
| 46 | Outcomes in Elderly Japanese Patients Treated for Aneurysmal Subarachnoid Hemorrhage: A Retrospective Nationwide Study | 2020 | Kohei Hironaka |
| 47 | Association between comprehensive geriatric assessment and short-term outcomes among older adult patients with stroke: A nationwide retrospective cohort study using propensity score and instrumental variable methods | 2020 | Tatsuya Hosoi |
| 48 | Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older | 2020 | Keisuke Ido |
| 49 | Propensity Score Matching Analysis for the Patients of Unruptured Cerebral Aneurysm from a Post Hoc Analysis of a Nationwide Database in Japan | 2020 | Fusao Ikawa |
| 50 | Risk Management of Aneurysmal Subarachnoid Hemorrhage by Age and Treatment Method from a Nationwide Database in Japan | 2020 | Fusao Ikawa |
| 51 | In-hospital mortality and poor outcome after surgical clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage using nationwide databases: a systematic review and meta-analysis | 2020 | Fusao Ikawa |
| 52 | Effects of case volume and comprehensive stroke center capabilities on patient outcomes of clipping and coiling for subarachnoid hemorrhage | 2020 | Ryota Kurogi |
| 53 | Validity of Claims Diagnosis Codes for Cardiovascular Diseases in Diabetes Patients in Japanese Administrative Database | 2020 | Yasuhisa Ono |
| 54 | Proportion and risk factors of cholesterol crystal embolization after cardiovascular procedures: a retrospective national database study | 2020 | Hiroyuki Tanaka |
| 55 | Surgical treatment for infective endocarditis in the ageing society: a nationwide retrospective study in Japan | 2021 | Hiroyuki Kiriyama |
| 56 | Hospitalization for urinary tract infections in Japan, 2010-2015: a retrospective study using a national inpatient database | 2021 | Akahito Sako |
| 57 | Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study | 2022 | Toshiki Fukasawa |
| 58 | Association between comprehensive geriatric assessment and polypharmacy at discharge in patients with ischaemic stroke: A nationwide, retrospective, cohort study | 2022 | Tatsuya Hosoi |
| 59 | Predictive Factors for Oral Intake Recovery After Acute Stroke: Analysis of a Japanese Nationwide Inpatient Database | 2022 | Yasuhiro Inooka |
| 60 | Short-Term Prognostic Factors in Hospitalized Herpes Zoster Patients and Its Associated Cerebro-Cardiovascular Events: A Nationwide Retrospective Cohort in Japan | 2022 | Yuichi Ishikawa |
| 61 | Comparison of short-term clinical outcomes between low-dose prasugrel and clopidogrel as part of triple antithrombotic therapy in patients requiring oral anticoagulant therapy and percutaneous coronary intervention | 2022 | Hideki Kitahara |
| 62 | Direct oral anticoagulants versus warfarin for secondary prevention of cerebral infarction and bleeding in older adults with atrial fibrillation | 2022 | Ryosuke Kumazawa |
| 63 | Postoperative cerebral infarction risk is related to lobectomy site in lung cancer: a retrospective cohort study of nationwide data in Japan | 2022 | Natsumasa Nishizawa |
| 64 | Oral Management by a Full-Time Resident Dentist in the Hospital Ward Reduces the Incidence of Pneumonia in Patients with Acute Stroke | 2022 | Kenichiro Ozaki |
| 65 | Trends in surgical procedures for spontaneous intracerebral hemorrhage in Japan | 2022 | Shigeyuki Tahara |
| 66 | Rehabilitation of Patients With Acute Ischemic Stroke Who Required Assistance Before Hospitalization Contributes to Improvement in Activities of Daily Living: A Nationwide Database Cohort Study | 2022 | Takuaki Tani |
| 67 | Validity of identification algorithms combining diagnostic codes with other measures for acute ischemic stroke in MID- NET | 2022 | Masatoshi Tanigawa |
| 68 | Nationwide Database Analysis of Risk Factors Associated with Decreased Activities of Daily Living in Patients with Alzheimer’s Disease | 2023 | Keishi Akada |
| 69 | Effect of admission in the stroke care unit versus intensive care unit on in-hospital mortality in patients with acute ischemic stroke | 2023 | Masato Kanda |
| 70 | Comparison of bleeding following gastrointestinal endoscopic biopsy in patients treated with and without direct oral anticoagulants | 2023 | Takaaki Konishi |
| 71 | Postoperative mortality analysis on nationwide data from diagnosis procedure combination database in Japan | 2023 | Susumu Kunisawa |
| 72 | National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study | 2023 | Ryota Kurogi |
| 73 | Dementia and acute care of ischemic stroke in Japan: A retrospective observational study using the Japanese Diagnosis Procedure Combination database | 2023 | Ryutaro Matsugaki |
| 74 | Association between use of transdermal tulobuterol and short-term outcomes in patients with stroke and underlying chronic obstructive pulmonary disease: A retrospective cohort study | 2023 | Yuichiro Matsuo |
| 75 | Physical Rehabilitation and Post-Stroke Pneumonia: A Retrospective Observational Study Using the Japanese Diagnosis Procedure Combination Database | 2023 | Takehiro Nishimura |
| 76 | Mortality Prediction of COVID-19 in Hospitalized Patients Using the 2020 Diagnosis Procedure Combination Administrative Database of Japan | 2023 | Shuko Nojiri |
| 77 | Artificial cerebrospinal fluid use during burr-hole surgery and reoperation rate in patients with chronic subdural hematoma: an analysis using a nationwide inpatient database | 2023 | Keita Shibahashi |
| 78 | Adjuvant oral tranexamic acid and reoperation after burr hole surgery in patients with chronic subdural hematoma: propensity score-matched analysis using a nationwide inpatient database | 2023 | Keita Shibahashi |
| 79 | Outcomes After Endoscopic Evacuation Versus Evacuation Using Craniotomy or Stereotactic Aspiration for Spontaneous Intracerebral Hemorrhage: Analysis Using a Japanese Nationwide Database | 2023 | Shigeyuki Tahara |
| 80 | Association between Care-need Level after Discharge and Long-term Outcomes in 7491 Patients Requiring Rehabilitation for Stroke | 2024 | Takaaki Konishi |
| 81 | Cilostazol versus Aspirin or Clopidogrel for Reducing Post-Stroke Aspiration Pneumonia: A Nationwide Retrospective Cohort Study | 2024 | So Sato |
| 82 | Real-World Clinical Profile of Patients Prescribed Evolocumab in Japan | 2024 | Feng Sheng |
| 83 | Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism Receiving Edoxaban in the Real World | 2024 | Yugo Ymahir |
| NDB database | |||
| 1 | Comorbidity status in hospitalized elderly in Japan: Analysis from National Database of Health Insurance Claims and Specific Health Checkups | 2019 | Shuko Nojiri |
| 2 | Maternal near-miss attributable to haemorrhagic stroke in patients with hypertensive disorders of pregnancy in Japan: A national cohort study | 2021 | Akihiko Ueda |
| 3 | Trends in outpatient rehabilitation practices in Japan: analysis using the National Database of Health Insurance Claims Open Data | 2022 | Shinsuke Hori |
| 4 | Effectiveness and Safety of Reduced and Standard Daily Doses of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: A Cohort Study Using National Database Representing the Japanese Population | 2022 | Kiyoshi Kubota |
| 5 | Cardiovascular risk of urate-lowering drugs: A study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan | 2023 | Sono Sawada |
| 6 | Aggressive End-of-Life Treatments Among Inpatients With Cancer and Non-cancer Diseases Using a Japanese National Claims Database | 2023 | Shintaro Togashi |
| Commercial databases sourced from social health insurance associations | |||
| 1 | A retrospective, cross-sectional study of real-world values of cardiovascular risk factors using a healthcare database in Japan | 2014 | Daisuke Shima |
| 2 | High-Risk Atherosclerotic Cardiovascular Disease in a Real-World Employed Japanese Population: Prevalence, Cardiovascular Event Rates, and Costs | 2015 | Keith L Davis |
| 3 | High prevalence of cardiovascular comorbidities in patients with rheumatoid arthritis from a population-based cross- sectional study of a Japanese health insurance database | 2016 | Ryoko Sakai |
| 4 | Bleeding Risk of Warfarin and Direct Oral Anticoagulants in Younger Population: A Historical Cohort Study Using a Japanese Claims Database | 2018 | Satoshi Yokoyama |
| 5 | Adherence and persistence to hyperlipidemia medications in patients with atherosclerotic cardiovascular disease and those with diabetes mellitus based on administrative claims data in Japan | 2019 | Mayumi Wake |
| 6 | Restfulness from sleep and subsequent cardiovascular disease in the general population | 2020 | Hidehiro Kaneko |
| 7 | Association of Isolated Diastolic Hypertension Based on the Cutoff Value in the 2017 American College of Cardiology/ American Heart Association Blood Pressure Guidelines With Subsequent Cardiovascular Events in the General Population | 2020 | Hidehiro Kaneko |
| 8 | Impact of pre-existing hypertension and control status before atrial fibrillation onset on cardiovascular prognosis in patients with non-valvular atrial fibrillation: A real-world database analysis in Japan | 2020 | Kazuomi Kario |
| 9 | Predictive factors associated with bleeding in atrial fibrillation patients treated with anticoagulant drugs using a large claims database | 2020 | Kenji Momo |
| 10 | Comparison of the Safety and Effectiveness of Four Direct Oral Anticoagulants in Japanese Patients with Nonvalvular Atrial Fibrillation Using Real-World Data | 2021 | Aya Enomoto |
| 11 | Metabolically Healthy Obesity and the Risk of Cardiovascular Disease in the General Population - Analysis of a Nationwide Epidemiological Database | 2021 | Hidetaka Itoh |
| 12 | Possible association between eating behaviors and cardiovascular disease in the general population: Analysis of a nationwide epidemiological database | 2021 | Hidehiro Kaneko |
| 13 | Fasting plasma glucose and subsequent cardiovascular disease among young adults: Analysis of a nationwide epidemiological database | 2021 | Hidehiro Kaneko |
| 14 | Lipid Profile and Subsequent Cardiovascular Disease among Young Adults Aged ＜50 Years | 2021 | Hidehiro Kaneko |
| 15 | Association of Body Mass Index with Ischemic and Hemorrhagic Stroke | 2021 | Masahiro Shiozawa |
| 16 | Association of Life’s Simple 7 with incident cardiovascular disease in 53 974 patients with cancer | 2022 | Hidehiro Kaneko |
| 17 | Impact of Medication Adherence on the Association Between Oral Anticoagulant Use and Risk of Dementia: A Retrospective Cohort Study using the Japanese Claims Database | 2022 | Yuika Komatsu |
| 18 | Comparison of the effects on cardiovascular events between use of metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycaemic agents in Japanese patients with type 2 diabetes mellitus: a claims database analysis | 2022 | Rimei Nishimura |
| 19 | Estimating the causal effect of transient anemia status on renal and cardiovascular outcomes in community-dwelling patients in Japan at the beginning of impaired renal function using marginal structural modeling | 2022 | Satoshi Onozawa |
| 20 | Association between urate-lowering therapy and cardiovascular events in patients with asymptomatic hyperuricemia | 2023 | Hiroyuki Hashimoto |
| 21 | Risk factors for heart, cerebrovascular, and kidney diseases: evaluation of potential side effects of medications to control hypertension, hyperglycemia, and hypercholesterolemia | 2023 | Kazumitsu Nawata |
| 22 | Characteristics and short-term outcomes of outpatient and inpatient cardiac catheterizations: A descriptive study using a nationwide claim database in Japan | 2023 | Nao Setogawa |
| 23 | Gait Speed and Cardiovascular Disease by Glycemic Status | 2023 | Kensuke Ueno |
| 24 | Unawareness of being prescribed medications for diabetes and incident cardiovascular disease | 2024 | Jin Komuro |
DPC, the Diagnosis Procedure Combination database; NDB, the National Database of Health Insurance Claims and Specific Health Checkups.
Representative studies are presented below. The characteristics of each database are listed in Table 1.
| DPC | NDB | Commercial databases sourced from social health insurance associations | |
|---|---|---|---|
| Comprehensiveness | Yes | Yes | Limited |
| (whether patients with stroke are adequately covered as a target population) | (mainly inpatient) | (without age ＞75 years) | |
| Traceability | Limited | Yes | Partially Yes |
| (Whether patients can be followed up for a long period to check the outcomes) | (untraceable between different facilities) | (unless withdrawing from insurance, e.g., due to job loss) | |
| Baseline information | Yes | Limited | Yes |
| (how detailed baseline information can be assessed) | (baseline mRS and disease severity, detailed information according to the diseases) | (basically with ICD-10 codes, but will be linked to other databases in the future) | (available lifestyle and blood test data) |
| Outcome assessment | Partially Yes | Partially Yes | |
| (how detailed outcome information can be assessed) | (mRS available at discharge, long- term outcomes cannot be assessed) | (detailed functional outcomes cannot be assessed, but cardiovascular events can be assessed using surrogate measures like hospitalization and ICD-10 codes) | |
Abbreviations: DPC, Diagnosis Procedure Combination (DPC) database; ICD-10, International Classification of Diseases, Tenth Revision; mRS, modified Rankin Scale; NDB, National Database of Health Insurance Claims and Specific Health Checkups.
Enomoto et al. estimated the clinical effect of early edaravone use in patients with acute ischemic stroke treated by endovascular reperfusion therapy14). They included 11,508 acute ischemic stroke patients treated by endovascular reperfusion therapy. They defined exposures as edaravone use within two days of admission and outcomes as functional independence at discharge (mRS score 0-2), in-hospital mortality, and intracranial hemorrhaging. The covariates included age, sex, year of admission, Japan Coma Scale, pre-stroke modified Rankin Scale, activities of daily living before admission, Charlson comorbidity index, presence of intensive-care unit admission, ventilation within two days, thrombolytic therapy, antihypertensive medication, anti-edema medication, and details of the procedure (assessed by the device used).
The study design is consistent with the Japanese healthcare system because the amount of payment for stroke patients varies depending on whether or not edaravone is used; therefore, the exposure is considered reliable. The advantages of the DPC database include access to various variables, including the mRS before onset and at discharge as covariates and functional outcomes, and the Japan Coma Scale for stroke severity. It should be noted that the commonly used three-month mRS is not available in the DPC database. Another important limitation compared to the other two databases is the lack of long-term outcomes, such as recurrent stroke, which cannot be precisely confirmed.
NDB DatabaseKubota et al. assessed the effectiveness and safety of reduced and standard daily doses of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF)15). They included 944,776 patients with NVAF who had started an oral anticoagulant after at least 1 year of non-use. They matched patients taking reduced or standard doses of DOACs in a 1:1 ratio with those taking warfarin. The outcomes of interest were admission due to stroke or systemic embolism as effectiveness, and admission due to bleeding. The covariates included age, sex, 28 diagnoses based on the International Classification of Diseases, Tenth Revision (ICD-10) codes, and 34 drugs potentially relevant to the use of anticoagulants or occurrence of outcomes.
The strength of this study is that the real-world effectiveness and safety of reduced and standard doses of DOACs were tested using large-scale data with comprehensiveness and traceability. The authors adjusted the CHA2DS2-VASc and HAS-BLED scores using the ICD-10 codes15). One of the characteristics of the NDB database is that it can be used to assess long-term pharmacoepidemiological effectiveness and safety, such as thrombotic and hemorrhagic events, with antithrombotic therapy, as patients can be followed over time. However, the validity of ICD-10 codes has not been sufficiently established; therefore, further research on code validation is also important. Unlike DPC data, detailed background information on individual patients, such as the mRS, Japan Coma Scale, or time from onset to admission, is unavailable; therefore, appropriate research questions must be selected.
Commercial Databases Sourced from Social Health Insurance AssociationsKaneko et al. assessed the association of Life’s Simple 7 with incident cardiovascular diseases (CVDs), including stroke, among cancer survivors16). They included 53,974 patients with a history of breast, colorectal, or stomach cancer. They defined exposures using the modified Life’s Simple 7 cardiovascular health metrics as follows: non-smoking, body mass index ＜25 kg/m2, physical activity at goal, optimal dietary habits, untreated fasting plasma glucose ＜100 mg/dL, untreated blood pressure ＜120/80 mmHg, and untreated total cholesterol ＜200 mg/dL. The outcome of interest was the incidence of incident CVD, identified using ICD-10 codes. The covariates included the age, sex, alcohol consumption, cancer site, and presence of active cancer treatment before and after six months.
Some commercial databases have available lifestyle and blood test information from national health checkups12, 13). This study successfully used these data to quantify CVD risk. It should be noted that included individuals could be traced for a long period but were unable to be traced further once they left their place of employment and were no longer covered by insurance. The main limitation from the perspective of stroke research is that it mainly covers young and middle-aged people, and those ＞75 years old12, 13). In Japan, the median ages of stroke onset are reported to be 74, 70, and 64 years old for cerebral infarction, cerebral hemorrhaging, and subarachnoid hemorrhaging, respectively17). Therefore, if we selected stroke patients only from the commercial database sourced from private social insurance associations, it would result in a selection bias towards younger age groups. This database is useful if the study population is restricted to young people; otherwise, stroke can only be used as an outcome.
This narrative review showed that the number of stroke studies using administrative claims databases in Japan is still approximately 10 per year, although there is a slowly increasing trend. Among the included articles, those based on DPC were the most common, and those based on NDB were the least common. We found considerable differences in generalizability, traceability, patient baseline characteristics, and outcome information among the three databases, and previous studies took advantage of the characteristics of each database.
Overall, the results suggest that the DPC database has an affinity for studies dealing with short-term outcomes, NDB has an affinity for studies dealing with long-term outcomes, and commercial databases have an affinity for studies using the specific items of each database, such as lifestyle or blood test results in younger populations in stroke research. The DPC database may be most suitable for acute care research because of the availability of functional outcomes at discharge and detailed baseline inforamtion8). The NDB database has the potential for a broad range of applications due to the traceability of patients and comprehensiveness. However, data access is often a problem. To use the NDB database, researchers currently require a sophisticated security system in their laboratories or can only use it in on-site research centers9). This difficulty in data access seems to be a barrier to using the NDB database in stroke research. In a previous report evaluating data availability for administrative claims data in the Asia-Pacific countries, one of the commercial databases received a higher rating than the DPC and the NDB18). In the commercial databases, the processed information may be easily manageable even for inexperienced researchers, but the biased population limits the applicable research questions.
As pointed out in other reviews, studies using administrative claims databases have inherent limitations; the validity of the disease codes and missing essential variables are the major ones4). Validation of the codes of stroke has been reported mainly in DPC databases, with Omama et al. reporting a sensitivity of 86.6% and specificity of 92.7%, and Tanigawa et al. reporting a positive predictive value of more than 0.8 for DPC disease names with additional information19, 20). However, the validations of the code of stroke are still limited, and further studies are needed. The NDB database is linked to the DPC database and other disease registry databases, and the problem of missing variables may be solved to some extent21). Access to the NDB database is also expected to improve thanks to cloud computing and increased efficiency of submission systems of documents21). Epidemiological studies using administrative claims data are thus expected to develop further. Researchers in the field of stroke are expected to follow these trends and make further use of these databases.
Several limitations associated with the present study warrant mention. First, although we covered the main databases used in the past decade, there are several other administrative claims databases, particularly hospital information-derived commercial databases in Japan. The Japanese Society for Pharmacoepidemiology has compiled information on different databases, and we recommend checking them if necessary5). Second, we only included original articles written in English and not articles written in Japanese. Limiting articles to those published in English in Ovid MEDLINE is considered useful for ensuring a certain level of quality; however, important articles written in Japanese may have been omitted. Third, despite the assistance of a librarian specializing in systematic reviews, the search formula may be incomplete. Finally, the characteristics of each database described in this review are summarized narratively only from the perspective of stroke research and not as an inclusive summary of the characteristics of each database in general. Researchers are expected to utilize these databases with appropriate designs, according to their research questions.
In conclusion, administrative claims databases are beginning to be used in stroke research in Japan but are not yet fully utilized. Researchers need to understand their applications and limitations.
The authors thank Ms. Takada, a librarian from The Medical Library, Kyoto University, for assisting in developing the search formulae.
The authors report no conflicts of interest.
None.
