Review of drug utilization research based on real-world data / 药学实践与服务

In recent years, the rapid development of medical information technology has made it critical to analyze large-scale diagnosis and therapeutic data and extract rules based on real medical environment. This has become an essential approach for marketing evaluation and regulatory decision-making of drugs and devices both domestically and internationally. Real world study （RWS）, as a novel methodology for clinical evaluation of drugs in the field of drug utilization research （DUR）, have presented opportunities and challenges for observational studies in assessing actual efficacy or effectiveness. However, despite being a popular methodological approach among scholars in the field, there are still limitations and deficiencies when analyzing population medication characteristics in RWS. Systematic evaluation research methods have not yet been established, leading to inadequate generation of real-world evidence （RWE）. The research design, methodological pathways, evaluation indicators, confounding factors, and bias management involved in DUR based on real-world data （RWD） were reviewed in this artical with the intention of providing guidance for further exploration into DUR.

A Method for Identifying Pregnant Women by Linking Mothers and Newborns in the JMDC Database and Its Generalizability Study / 薬剤疫学

Objective：To show that it is possible to capture pregnant women by identifying newborns and their mothers using JMDC database and examine a generalizability to Japan.Methods：We identified a newborn who was born between 2016 and 2020 and his/her mother using health insurance association's registry owned by JMDC Inc. First, we identified a newborn whose relationship to the insured was “child” and who joined the health insurance association at birth month. And we linked a woman member aged 18 to 49 who belongs to the same family at the newborn's birth month to the newborn as a mother. We assessed a generalizability of these mothers and newborns obtained from this method by an age distribution of mother at birth month and proportion of newborn against women aged between 18 and 49 using Vital Statistics, National Census, and Population Estimates in Japan as index.Results：We identified 194,036 mother-newborn pairs in JMDC database from 2016 to 2020. The mean mother's age at newborn's birth was 31.9. On the other hand, the number of births in Japan during the same period was 4,538,786, and the mean mothers' age was 31.5. Number of newborns per 1,000 women in JMDC database in 2020 was 19.0, and that in Japan was 37.0.Conclusion：We concluded that our method of identifying pregnant women and newborns is useful for study of pregnant women and newborns.

Real World Data Use in Pharmaceutical Companies in Japan： Current Status and Issues from Survey of Japan Pharmaceutical Manufacturers Association / 薬剤疫学

Objective：To investigate the purposes, reasons, and issues of Real World Data (RWD) utilization by data source among pharmaceutical companies in Japan. In this study, we focus on RWDs such as Electronic Medical Records (EMR), Personal Health Records, and registries, which are expected to be utilized in the future. Design：Web based-questionnaire surveyMethods：This questionnaire survey was conducted on 68 companies affiliated with Clinical Evaluation Expert Committee in Japan Pharmaceutical Manufacturers Association from January 18th to February 14th in 2022. In principle, the survey covered four divisions (Clinical development, Pharmacovigilance, Medical Affairs, Health Economics & Outcomes Research) of each company, and other cross-functional divisions were also acceptable to answer. Results：［Background］ Of 40 companies out of 68 companies, 102 respondents were responded to this survey. Overall, 75 respondents (73.5％) have “experienced in utilization of RWD”, and 12 (11.8％) have “experienced in considering utilization of RWD”. ［Utilization by RWD Type］ By data source, hospital-based claim data was the most frequently used (65 cases, 63.7％), followed by insurance-based claim data (61 cases, 59.8％), surveys (38 cases, 37.3％), and EMR (36 cases, 35.3％) in experienced RWD utilization. Conclusion：This study revealed the current status and issues related to the utilization of each type of RWDs in Japan. It is expected that data linkage among multiple RWDs and data standardization enable further utilization of RWDs in future.

Real World Data Use in Pharmaceutical Companies in Japan： Current Status and Issues from Survey of Japan Pharmaceutical Manufacturers Association / 薬剤疫学

Objective：To investigate the purposes, reasons, and issues of Real World Data (RWD) utilization by data source among pharmaceutical companies in Japan. In this study, we focus on RWDs such as Electronic Medical Records (EMR), Personal Health Records, and registries, which are expected to be utilized in the future. Design：Web based-questionnaire surveyMethods：This questionnaire survey was conducted on 68 companies affiliated with Clinical Evaluation Expert Committee in Japan Pharmaceutical Manufacturers Association from January 18th to February 14th in 2022. In principle, the survey covered four divisions (Clinical development, Pharmacovigilance, Medical Affairs, Health Economics & Outcomes Research) of each company, and other cross-functional divisions were also acceptable to answer. Results：［Background］ Of 40 companies out of 68 companies, 102 respondents were responded to this survey. Overall, 75 respondents (73.5％) have “experienced in utilization of RWD”, and 12 (11.8％) have “experienced in considering utilization of RWD”. ［Utilization by RWD Type］ By data source, hospital-based claim data was the most frequently used (65 cases, 63.7％), followed by insurance-based claim data (61 cases, 59.8％), surveys (38 cases, 37.3％), and EMR (36 cases, 35.3％) in experienced RWD utilization. Conclusion：This study revealed the current status and issues related to the utilization of each type of RWDs in Japan. It is expected that data linkage among multiple RWDs and data standardization enable further utilization of RWDs in future.

A Method for Identifying Pregnant Women by Linking Mothers and Newborns in the JMDC Database and Its Generalizability Study / 薬剤疫学

Objective：To show that it is possible to capture pregnant women by identifying newborns and their mothers using JMDC database and examine a generalizability to Japan.Methods：We identified a newborn who was born between 2016 and 2020 and his/her mother using health insurance association's registry owned by JMDC Inc. First, we identified a newborn whose relationship to the insured was “child” and who joined the health insurance association at birth month. And we linked a woman member aged 18 to 49 who belongs to the same family at the newborn's birth month to the newborn as a mother. We assessed a generalizability of these mothers and newborns obtained from this method by an age distribution of mother at birth month and proportion of newborn against women aged between 18 and 49 using Vital Statistics, National Census, and Population Estimates in Japan as index.Results：We identified 194,036 mother-newborn pairs in JMDC database from 2016 to 2020. The mean mother's age at newborn's birth was 31.9. On the other hand, the number of births in Japan during the same period was 4,538,786, and the mean mothers' age was 31.5. Number of newborns per 1,000 women in JMDC database in 2020 was 19.0, and that in Japan was 37.0.Conclusion：We concluded that our method of identifying pregnant women and newborns is useful for study of pregnant women and newborns.

Discuss Application of Real-world Data from the Boao Lecheng Pilot Zone to Support Premarket Clinical Evaluation of Medical Device / 中国医疗器械杂志

The real-world data of Hainan Boao Lecheng International Tourism Pilot Zone has the advantage of supporting pre-market clinical evaluation of medical devices. Based on the relevant requirements of clinical evaluation of medical devices and based on the practical experience of pilot devices in the early stage, the application of Boao Lecheng real-world data in the pre-market clinical evaluation path of medical devices from the perspective of review is discussed. At the same time, the elements that should be considered in real-world study design and the way of data quality evaluation are proposed. Expect to provide a reference in order to allow registration applicants to use real world data wisely to help declare device registration for marketing.

Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm / 中国中药杂志

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Development and validation of ischemic heart disease and stroke prognostic models using large-scale real-world data from Japan

BACKGROUND@#Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data.@*METHODS@#IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013-December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan.@*RESULTS@#The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell's C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance.@*CONCLUSION@#Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.

Design Diagram：A Framework for Visualizing Study Designs Using Real-world Data and Improving Study Reproducibility / 薬剤疫学

There is growing interest in generating evidence from routinely collected real-world data to support medical and regulatory decision-making. However, longitudinal study designs using real-world data are often complex, and text-only descriptions make it difficult for most readers to understand their designs. To address this issue, in 2019, experts from industry, government, and academia developed the “design diagram,” a framework for visualizing longitudinal study designs. The design diagram uses standardized terminology and a graphical structure to communicate study design details to readers, thereby improving reproducibility. Based on previous work by a joint task force between the International Society for Pharmacoepidemiology (ISPE) and the Professional Society for Health Economics and Outcomes Research (ISPOR), the diagram includes a comprehensive set of key study parameters related to reproducibility. It successfully presents study designs in an unambiguous and intuitive manner. Diagrams have been proposed for various study designs, including cohort, nested case-control, and self-controlled designs. Recently, a new diagram was developed that adds at-a-glance elements to show the observability of the source data used in the study. The use of design diagrams is recommended in both the ISPE/ISPOR-endorsed harmonized protocol template (HARPER) and in reporting guidelines for pharmacoepidemiological research, and its widespread use is expected. This paper describes the structure of the design diagram and provides examples of its use. Effective use of design diagrams is expected to improve the reproducibility and reliability of database studies.

Study on Clinical Application and Supervision of LC-MS in in Vitro Diagnosis Test / 中国医疗器械杂志

From the perspective of technical evaluation, this study reviewed the current situation of application and clinical application of medical device products were detected by liquid chromatography-tandem mass spectrometry in the market in recent years. The regulatory requirements of these products in China, USA, EU and Japan were compared and analyzed, and the monitoring situation of adverse events after listing, the standards for reference and the domestic and foreign regulatory documents were combined, the clinical application and regulatory risks of the product were analyzed. The problems such as pre-treatment, system matching, adequacy of performance index requirements, inter-room consistency, reference interval and registration unit were discussed and suggestions for supervision were given, with a view to the field of product R&D and production, review and approval of supervision to provide technical reference.

Study on clinical application evaluation of patient monitor based on real world data / 医疗卫生装备

Objective To establish a comprehensive evaluation system for the patient monitor clinical application based on real world data(RWD)to provide references for levels of medical institutions to purchase patient monitors.Methods RWD method was used to collect clinical application data of the monitors from 14 medical institutions in Guangxi Zhuang Autonomous Region,and a Chinese brand X(including X1 series for mid-end products and X2 series for high-end products)and a foreign brand Y(including Y1 series for mid-end products and Y2 series for high-end products)with the highest market share were selected to construct a monitor clinical application evaluation system involving in five indicators such as clinical efficacy,applicability,reliability,instrument function and service system.Data processing was carried out with Mantel-Haenszel analysis,propensity score analysis and pairwise comparison method to calculate the clinical application evaluation scores of X and Y brands of monitors.Results In the mid-end products,X series gained advantages over Y series in clinical efficacy,reliability and applicability(P＜0.05),while the differences between the service systems were not statistically signifi-cantly(P＞0.05);in the high-end products,there were no significant differences between the clinical efficacy,applicability,reliability and service systems(P＞0.05).Brand X and Y monitors were equipped with similar basic and advanced functions.Conchision The evaluation system established based on real-world data can be able to effectively evaluate the clinical appli-cation of the monitor,which provides references for clinical application evaluation of medical devices in China.[Chinese Medical Equipment Journal,2023,44(11):71-78]

Evaluation of Screening Model for Advanced Colorectal Adenoma and Traditional Chinese Medicine Tongue Image Analysis Based on Real World Data / 中医杂志

ObjectiveTo evaluate the effectiveness and consistency of three commonly used early colorectal cancer screening models for advanced colorectal adenoma as a noninvasive means， and to assess the predictive value of traditional Chinese medicine （TCM） tongue images in the models. MethodsPatients diagnosed with colorectal adenoma who underwent colonoscopy and pathological examination were selected as the study participants. Basic clinical data and tongue image were collected. The prediction models of Asia-Pacific colorectal screening （APCS） model， its revision （M-APCS） and colorectal neoplasia predict （CNP） model were applied to compare the predictive effects of the three models on advanced stage adenomas of the colon， the differences in clinical data and traditional Chinese medicine tongue characteristics among patients with different degrees of adenomas， and the similarities and differences in tongue characteristics among the models. The discriminative ability of the three risk models was evaluated using the area under the curve （AUC） and receiver operating characteristic （ROC） curves. The calibration was assessed using the Kuder-Richardson coefficient and the Hosmer-Lemeshow test for consistency analysis. ResultsA total of 227 patients with adenoma were analyzed， including 104 patients （45.82%） with advanced adenoma. In the detection of advanced adenoma， those with greasy coating （70 cases， 67.3%） were higher than those without greasy coating （34 cases， 32.7%， P＜0.05）. After multivariate analysis， the odds ratio （OR） value of non-greasy coating was 0.371 （0.204~0.673， P＜0.01）， indicating that non-greasy coating was a protective factor for advanced adenomas. Among the three risk models， the detection rate of advanced adenoma in the high-risk group with APCS was the highest （63.3%）， which was 1.49 times and 2.04 times that of the medium-risk group （42.6%） and the low-risk group （31.1%， P＜0.01）. The detection rate of advanced adenomas in high-risk groups of M-APCS and CNP was slightly higher than that in moderate or low risk groups （P＞0.05）. The proportion of yellow and greasy coating in high-risk group was higher than that in the medium-risk or low-risk group （P＜0.05）. For the ability to distinguish advanced and non-advanced adenomas， the AUC of APCS was 0.629 （95% CI： 0.556~0.702） and was higher than that of M-APCS （0.591） and CNP （0.586）. In calibration evaluation， Cronbach's alpha was 0.919 （＞0.7）， which indicated that the three models were consistent. In the correlation matrix， the correlation coefficients between APCS model and M-APCS model， and CNP model were 0.794 and 0.717， respectively， and the correlation coefficients between M-APCS model and CNP model were 0.873， Hosmer-Lemeshow χ2 =2.552， P＞0.05， which suggested that the three models had good calibration ability. ConclusionAll three models demonstrate the efficiency to identify advanced colorectal adenoma， and their calibration ability is considered to be good. Among the three models， the APCS exhibits the highest recognition efficiency， however， the recognition accuracy of the APCS model needs improvement. The presence of a greasy coating is identified as one of the potential predictors of advanced adenoma. Consequently， it can be considered for inclusion in the risk model of advanced colorectal adenoma to enhance the accuracy.

Observaciones en el mundo real sobre la efectividad del sistema flash de monitorización de glucosa en la práctica clínica en Chile / Real-world observations of the effectiveness of the flash glucose monitoring in clinical practice in Chile

OBJETIVO: Evaluar el tiempo en rango de glucosa y su asociación con otras medidas del control glicémico establecidas por el consenso internacional del tiempo en rango en usuarios de vida real del sistema flash de monitorización de glucosa FreeStyle LibreTM en Chile. MÉTODOS: Se analizaron los datos provenientes de la base de datos Freestyle Libre™ entre diciembre de 2014 y enero de 2022. Las lecturas se dividieron en 10 grupos (deciles) del mismo tamaño (cada decil contenía aproximadamente 498 usuarios) en función del tiempo en rango. Para cada decil se calculó la media de determinaciones diarias, el promedio de glucosa, la HbA1c, la desviación estándar de glucosa, el coeficiente de variación de la glucosa, el tiempo en rango, el tiempo de glucosa (porcentaje) por encima de 250 mg/dL (TA250), el tiempo de glucosa (porcentaje) por encima de 180 mg/dL (TA180), el tiempo por debajo (porcentaje) de 70 mg/dL (TB70) y el tiempo por debajo (porcentaje) de 54 mg/dL (TB54). RESULTADOS: Desde diciembre de 2014 hasta enero de 2022 hubo 4984 lectores. El grupo con el mayor tiempo en rango mostró significativamente una menor glucosa promedio que el grupo con el tiempo en rango más bajo (decil 1: media 248,3 mg/dL, decil 10: media 113,2 mg/L, diferencia ­135,1 mg/dL, p<0.05). Asimismo, el mayor tiempo en rango se asoció con una menor desviación estándar (decil 1: media 93,7mg/dL, decil 10: media 26,7mg/L, diferencia: -67,0 mg/ dL, p<0,05), menor coeficiente de variación (decil 1: media 37,8%, decil 10: media 23,3%, diferencia: -14,5%, p<0,05), menor TA250 (decil 1: media 46,5%, decil 10: media 0,2%, diferencia: -46,3%, p<0.05), menor TA180 (decil 1: media 73,9%, decil 10: media 3,8%, diferencia: -70,1%, p<0.05), menor TB70 (decil 5: mediana 6,13%, decil 10: mediana 1,70%, diferencia: -4,43%, p<0.05) y menor TB54 (decil 5: mediana 1,79%, decil 10: mediana 0,12%, diferencia: -1,67%, p<0.05). El mayor tiempo en rango se asoció también significativamente con más determinaciones diarias (decil 1: media 11,4, decil 10: media 16,6, diferencia: 5,2, p<0,05). La frecuencia media de las determinaciones entre todos los lectores fue de 14,7 determinaciones diarias. CONCLUSIONES: En los pacientes con diabetes en Chile, el empleo del sistema flash de monitorización demuestra la asociación entre el mayor tiempo en rango, la reducción de la variabilidad de la glucosa y un menor riesgo de hiperglucemias e hipoglicemias y también con un mayor compromiso.

OBJECTIVE: To evaluate glucose time in range and its association with other metrics of glucose control established by the International Consensus on TIR amongst real-life patients using the Flash Glucose Monitoring system FreeStyle LibreTM in Chile. METHODS: Data from the Freestyle Libre™ database between December 2014 and January 2022 were analyzed. Readers were divided into 10 groups (deciles) of the same size (each decile had approximately 498 users) according to time in range. For each decile of time in range, the mean of daily scans, average glucose, estimated HbA1c, glucose standard deviation, glucose coefficient of variation, time in range, glucose time (percentage) above 250 mg/dL (TA250), and glucose time (percentage) above 180 mg/dL (TA180), and the median of glucose time (percentage) below 70 mg/dL (TB70) and glucose time (percentage) below 54 mg/dL (TB54), were calculated. RESULTS: From December 2014 to January 2022, there were 4984 readers. The group with the highest TIR showed significantly lower average glucose than the group with the lowest TIR (decile 1: mean 248.3 mg/dL, decile 10: mean 113.2 mg/L, difference: ­135.1 mg/dL, p<0.05). In addition, more time in range was associated with a lower glucose standard deviation (decile 1: mean 93.7 mg/dL, decile 10: mean 26.7 mg/L, difference: -67.0 mg/dL, p<0.05), lower glucose coefficient of variation (decile 1: mean 37.8%, decile 10: mean 23.3%, difference: -14.5%, p<0.05), lower TA250 (decile 1: mean 46.5%, decile 10: mean 0.2%, difference: -46.3%, p<0.05),lower TA180 (decile 1: mean 73.9%, decile 10: mean 3.8%, difference: -70.1%, p<0.05), lower TB70 (decile 5: median 6.13%, decile 10: median 1.70%, difference: -4.43%, p<0.05) and lower TB54 (decile 5: median 1.79%, decile 10: median 0.12%, difference: -1.67%, p<0.05). Greater TIR was also associated with significantly more daily scans (decile 1: mean 11.4, decile 10: mean 16.6, difference: 5.2, p<0.05). Mean scan frequency amongst all readers was 14.7 daily scans. CONCLUSIONS: In patients with diabetes from Chile, the use of the flash glucose monitoring system demonstrates the association between greater TIR, reduced glucose variability, and reduced risk of hyperglycemia and hypoglycemia, and also its association with greater engagement.

The prediction capability of a cataract surgery risk stratification model based on a large electronic medical record dataset

Purpose: The aim of this study was to develop a risk stratification system that predicts visual outcomes (uncorrected corrected visual acuity at one week and five weeks postoperative) in patients undergoing cataract surgery. Methods: This was a retrospective analysis in a multitier ophthalmology network. Data from all patients who underwent phacoemulsification or manual small-incision cataract surgery between January 2018 and December 2019 were retrieved from an electronic medical record system. There were 122,911 records; 114,172 (92.9%) had complete data included. Logistic regression analyzed unsatisfactory postoperative outcomes using a main effects model only. The final model was cross-checked using forward stepwise selection. The Hosmer朙emeshow goodness of fit test, the Bayesian information criterion, and Nagelkerke抯 R2 assessed model fit. Dispersion was calculated from deviance and degrees of freedom and C-stat from receiving operating characteristics analysis. Results: The final phacoemulsification model (n = 48,169) had a dispersion of 1.08 with a Hosmer朙emeshow goodness of fit of 0.20, a Nagelkerke R2 of 0.19, and a C-stat of 0.72. The final manual small-incision cataract surgery model (n = 66,003) had a dispersion of 1.05 with a Hosmer朙emeshow goodness of fit of 0.00015, a Nagelkerke R2 of 0.14, and a C-stat of 0.68. Conclusion: The phacoemulsification model had reasonable model fit; the manual small-incision cataract surgery model had poor fit and was likely missing variables. The predictive capability of these models based on a large, real-world cataract surgical dataset was suboptimal to determine which patients could benefit most from sight-restoring surgery. Appropriate patient selection for cataract surgery in developing settings should still rely on clinician thought processes, intuition, and experience, with more complex cases allocated to more experienced surgeons

Índices de internações, de mortalidade e de custos associados à doença pulmonar obstrutiva crônica (DPOC) no Distrito Federal após mudança do Protocolo Estadual de 2018 ­ Dados do mundo real / Hospitalization, mortality rates and costs associated with chronic obstructive pulmonary disease (COPD) in Distrito Federal, Brazil, before and after the change in 2018 state COPD protocol version ­ Real-world data

Objetivo: Avaliar os índices de hospitalização, mortalidade e custos associados à doença pulmonar obstrutiva crônica (DPOC) após mudança do Protocolo de Atenção à Saúde da Secretaria do Distrito Federal (SES-DF) em 2018 por um medicamento da mesma classe terapêutica, porém em dispositivo inalatório diferente. Métodos: Foi realizado um estudo observacional, transversal, em uma coorte de pacientes adultos internados em dois períodos específicos: gosto/2017 a julho/2018 (MAT 1 ­ vigência do Protocolo antigo) e agosto/2018 a julho/2019 (MAT 2 ­ vigência do novo Protocolo). Foram avaliados pacientes internados com diagnóstico principal de DPOC de acordo com a Classificação Estatística Internacional de Doenças e Problemas Relacionados com a Saúde Versão 10 (CID-10) estabelecida pelo protocolo de atenção à saúde e registrada no Datasus. Os desfechos avaliados foram número de internações, mortalidade e custos totais associados à internação por DPOC. Resultados: Após análise dos dados relacionados à DPOC, a comparação entre MAT 1 (agosto/2017 a julho/2018) e MAT 2 (agosto/2018 a julho/2019) resultou no aumento na ocorrência de importantes desfechos: +131,3% no número de internações com passagens em unidade de terapia intensiva (UTI) (n = 16 no MAT 1 vs. n = 37 no MAT 2, p < 0,01), +101,0% na frequência de internações com passagem em UTI sobre o total de internações (2,4% no MAT 1 vs. 4,8% no MAT 2, p = 0,01), +566,7% nos óbitos de pacientes internados em UTI (n = 3 no MAT 1 vs. n = 20 no MAT 2, p < 0,01) e +52,9% nos custos totais de internação (R$ 828.761 no MAT 1 vs. R$ 1.267.318 no MAT 2, p = 0,03). Conclusão: Durante os períodos analisados, houve aumento no uso de UTI, na mortalidade em UTI e nos custos totais relacionados à DPOC. A atualização do protocolo alterou tanto o dispositivo inalatório (névoa suave para pó seco) quanto a molécula (tiotrópio para glicopirrônio) e poderia ser um dos fatores responsáveis por esses desfechos, no entanto as limitações desta análise observacional não podem determinar um impacto causal da mudança do protocolo, pois outras variáveis também podem ter levado às diferenças descritas.

Objective: Evaluate the rates of hospitalization, mortality and costs associated with chronic obstructive pulmonary disease (COPD) before and after the change in COPD Treatment Protocol of State Health Secretariat of Distrito Federal (SES-DF). Methods: An observational, cross-sectional study was conducted in a cohort of hospitalized adult patients in two specific periods: August/2017 to July/2018 (MAT 1 ­ old version of Protocol in place) and August/2018 to July/2019 (MAT 2 - after the new Protocol version). Hospitalized patients with COPD as primary diagnosis according to International Statistical Classification of Diseases and Related Health Problems Version 10 (ICD-10) established by COPD Treatment Protocol and registered in DATASUS database were evaluated. The outcomes assessed were the number of hospitalizations, mortality and total costs ssociated with COPD hospitalizations. Results: After analyzing the data related to COPD, the comparison between MAT 1 (August/2017 to July/2018) and MAT 2 (August/2018 to July/2019) periods resulted in an increase in the occurrence of relevant outcomes: +131.3% in the number of hospitalizations with intensive care unit (ICU) admissions (n = 16 in MAT 1 vs. n = 37 in MAT 2, p < 0.01), +101.0% in the frequency of hospitalizations with ICU admissions over total number of hospitalizations (2.4% in MAT 1 vs. 4.8% in MAT 2, p = 0.01), +566.7% in deaths of patients admitted in ICU (n = 3 in MAT 1 vs. n = 20 in MAT 2, p < 0.01), +52.9% in total costs associated with COPD hospitalizations (R$ 828,761 in MAT 1 vs. R$ 1,267,318 in MAT 2, p = 0.03). Conclusion: During the analyzed periods, an increase in ICU usage, mortality in ICU and total costs related to COPD was observed. The update in the protocol switched the inhaler device (from soft mist to dry powder) and also the molecule (tiotropium to glycopyrronium) and could be potentially one of the factors responsible for these endpoints, however the limitations of this observational analysis cannot determine a causal impact of the protocol change as other variables could also have led to the differences described.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

2 ． Overview of the DeSC Database and Utilization for Clinical Epidemiology and Pharmacoepidemiology Research / 薬剤疫学

Studies using real-world data are recently increasing worldwide. Various types of real-world data are available in Japan. Administrative claims databases include the National Database (NDB) and other types of databases including several commercially available databases. This article describes the DeSC database, newly constructed by DeSC Healthcare Co., Ltd. in 2020. One of the features of the DeSC database is that it includes data from the National Health Insurance, Health Insurance, and Advanced Elderly Medical Service System. In the present article, we referred to our previous study on population representativeness of the DeSC database and explained its overview. Estimated prevalence of some diseases were described for each type of insurance. Furthermore, we discussed the use of the DeSC database for clinical epidemiology and pharmacoepidemiology research.

3 ．Utilization of the Tokushukai Medical Database / 薬剤疫学

The Tokushukai Group is one of the largest hospital groups in Japan. By connecting all the hospitals via a network, the group has been able to achieve centralized management of clinical information. The Tokushukai Group has been utilizing the data in various ways, such as participation in clinical trials, development of anticancer drug protocol systems, participation in BioBank Japan, and provision of data to MID‒NET®. These days, the Tokushukai Group has started to provide the data, named as the “Tokushukai Medical Database (TMD)”, to academia and industries for research purposes. The TMD mainly consists of inpatient and outpatient administrative claims data, Diagnosis Procedure Combination (DPC) data, electronic health records including blood test results and vital signs, and hospital-based cancer registry information. The strengths of the TMD include the availability of blood test results and vital signs in an standardized format, and the possibility to go back to each patient's electronic medical record from their claims data and DPC data, with the permission of headquarters and the ethics committee in the Tokushukai group. By taking advantage of these strengths, there have been increasing number of studies in the TMD, such as research on acute kidney injury defined as blood test results, hyperkalemia in dialysis patients, and validation study on rheumatoid arthritis. The issues newly raised during the utilization of data (e.g., echocardiography data not standardized) are expected to be resolved with the update of the network system for a wider range of research topics in the future.

Research Trends and Future Issues Related to Pre-analysis Data Preprocessing in Large-scale Real-World Data ―With the Goal of Using it in Clinical Research― / 薬剤疫学

In recent years, the utilization of health care databases has been increasing worldwide. It is expected that Real World Data (RWD) will soon be effectively used for clinical research in Japan. On the other hand, database studies that use accumulated existing data such as electronic medical records, Diagnosis Procedure Combinations (DPCs), and health insurance claims, require extremely high loads of data preprocessing before statistical analysis is possible. So far, there is insufficient literature that describes the challenges of RWD preprocessing from an academic point of view. In this review paper, the challenges of database study are classified into three categories：（1）data content,（2）data structure, and（3）large-volume data handling. We then investigated existing preprocessing research and systematically introduced them. Most data preprocessing research targeted the improvement and reliability of the database itself through supplementing data contents required for each clinical research. There is very little research with the primary purpose of solving problems related to data structures and large-volume data processing. As the use of RWD for clinical research increases, the importance of the data preprocessing field will be recognized. In the future, we expect to see more research focused on RWD, which can enable the growth of clinical researches using RWD.

Research on cost-benefit analysis of in-hospital falls: based on real world data / 中国实用护理杂志

Objective:Based on the real-world clinical data of hospital electronic medical records, to analyze the length of stay and healthcare costs associated with in-hospital falls and fall injuries in hospitals.Methods:Based on the electronic medical record system of the First Affiliated Hospital of Nanjing Medical University, a retrospective cohort study was conducted on patients admitted to these departments reported falls in nursing management information system from January 2017 to December 2019. A total of 38 481 patients from 74 units were enrolled in this study. The patients′ characteristics, falls, falls injury, and explore the length of hospital stay and bottom-up direct cost were analyzed.Results:A total of 243 cases (0.6%) fell and 154 cases (63.4%) were injured by falls from January 2017 to December 2019. Compared with non-fallers, the median length of stay of patients with falls was 19 days, which was significantly increased compared with 7 days of patients without falls ( Z=-15.18, P<0.05). The median hospitalization cost of patients with falls was 39 000 yuan, which was significantly higher than 16 300 yuan of patients without falls ( Z=-11.47, P<0.01). There was no statistical difference between non-injuried fallers and injuried fallers for length of stay and healthcare costs ( Z=-0.92, -0.64, P>0.05). Linear regression model analysis showed that gender, age, comorbidity, inpatient department unit, reason of hospitalization were significantly correlated with inpatient cost and length of stay ( F=280.05, 217.31, all P<0.05). Conclusions:Patients who have an in-hospital fall have significantly longer hospital stays and higher direct costs, mainly can be attributed to the fall itself, not the injury. Our findings have important financial implications for real world in light of optimal intervention strategies, resource allocation and economic evaluation of fall prevention.