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It is clinically important to evaluate the safety and efficacy of Kampo prescriptions in long-term treatment cases. One practical method for this issue is to evaluate the incidence rates of events in long-term treatment cases. This paper gives an outline of this method and describes a statistical approach for evaluating the incidence rates of events.
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Statistical tests are commonly reported in papers published in the journal. The interpretation of the statistical results, however, is not necessarily proper, which may invalidate the conclusions. This paper describes the issues regarding the interpretation of the results of statistical tests in the journal, and refers to the proper use of statistical test and estimation.
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Objective : To know how to conduct good pharmacoepidemiology studies using hospital-based database in Japan.<BR>Methods : Medical records during 15 months January 1996 and March 1997 in the University of Tokyo Hospital Information System (HIS) are examined know whether it is possible to conduct pharmacoepidemiology studies similar to previous studies on asthma drugs (Spitzer et al, 1992) and calcium antagonists (Psaty et al, 1995). To know the stability of population covered by HIS, the following two intervals are calculated for ambulatory patients with asthma and hypertension ; 1) average intervals of successive two outpatient visits and 2) intervals between the last day of outpatient visit and the last day of observation.<BR>Results : The size of possible pharmacoepidemiology studies attainable using HIS is judged to be more than 5% of previous studies in Canada and America. Average intervals of successive two outpatient visits are estimated to be 30 days or less for 59% of 693 asthmatics and 77% of 2842 hypertensives. For 48% of asthmatics and 71% of hypertensives, intervals between the last day of outpatient visit and the last day of observation are estimated to be 30 days or less.<BR>Discussion : To attain a size appropriate for pharmacoepidemiology study, researchers must cooperate across hospitals. Although a patient can visit any hospital anywhere under Japanese comprehensive medical care plan, it seems that patients tend to become to visit one particular hospital. However, additional information on medical care in other hospitals is needed for each study subject.<BR>Conclusion : Japanese hospital-based database is suitable for pharmacoepidemiology studies as a record during a long time period is usually available for a large fraction of patients with a particular disease. The study may be free from some of biases closely associated with referral processes known to occur in hospital case-control studies. A design of case-control study selecting patients with long medical records across 5-10 hospitals is probably the most promising when using Japanese hospital-based databases.
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Background : In Japan most (>85%) voluntary reports on suspected drug reactions are collected by drug companies.<BR>Objective : To know various aspects of case reports on suspected drug reactions collected by Japanese drug companies.<BR>Methods : Questionnaires were designed by our department and mailed to 96 major drug companies in late March 1997. They were reminded in mid-May and mid-June when not having responded.<BR>Results and Conclusion : Of 96 drug companies, 3 were found to be not eligible (e. g., selling only the OTC drugs) and excluded. Of the remaining 93 companies, 91 (98%) responded. Of all the case reports collected by drug companies (approximately 27, 000/year), 36%of serious or important cases are duly reported to Ministry of Health and Welfare (MHW) within 15 days or 30 days of receipt. In Japan individual case reports collected by drug companies and reported to MHW have been closed. Eleven companies are opposed to disclosing individual case reports while 6 agree unconditionally. Seventy companies agree to disclosing individual case reports with various conditions such as protecting patients' privacy, not disclosing the reporter's identity, and making individual case reports available to medical personnel only. Finally, 20 of 91 drug companies complained that MHW does not let them know individual case reports associated with their own products sent to MHW directly from medical doctors or via other companies. To promote pharmacoepidemiology, disclosing voluntary reports is pivotal and MHW is going to adopt this policy in two years for which however reporters and drug companies must be prepared in advance.
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Objective : To find the effective means to detect adverse drug reactions (ADRs) from hospital information system, three data sources, i.e. diagnosis data (Dx), laboratory data (Lab), and prescription data (Rx), are compared in diuretics induced hyperuricemia and/or gout (H/G).<BR>Design : Retrospective cohort study.<BR>Methods : Cohort entry period was three months. Hypertensive outpatients who already had H/G prior to that period were excluded. Then, they were surveyed for 9 months. The patients using diuretics were separated into two groups, i.e. Thiazide-treated group, and Loop-treated group.<BR>Controls were randomly selected from non-diuretic-treated hypertensive outpatients matched to each diuretic group by age and sex. Signals of ADRs were the new prescription of drugs employed in the treatment of H/G from Rx, abnormal serum uric acid level from Lab, and diagnosis of H/G from Dx. The interrelationship of them were examined by the Venn diagram and scatter plot. Finally the incidence of ADRs detected by the above signals and relative risks were calculated and compared. Moreover, prevalence of renal disease in each group was surveyed to examine the possibility that renal disease caused H/G.<BR>Results : Eighteen patients in 240 outpatients treated with Thiazide diuretics and 70 patients in 523 outpatients treated with Loop diuretics were found having developed H/G from Dx, Lab, and/or Rx data sources. More than 90% of total patients were detected from Lab while, a few patients were identified from Dx and Rx. It was rare and coincidental that the three data sources agreed with one another.<BR>The risk of Loop diuretics is approximately twice that of Thiazide diuretics. The incidence and risk of H/G in diuretics estimated in the current study were compatible with the prior report. However, the prevalence of renal disease were high (though not statistically significant) in Loop-treated group so that we possibly overestimated the risk of it.<BR>Conclusion : The order of three data sources, arranged according to the number of ADR signals detected, was Lab, Rx, and Dx. It may be possible to assess the risk of ADR even by Lab only. If Lab is not available, Rx and Dx are useful provided that more subjects and longer research period are involved. However it is necessary to combine three data sources, Dx, Lab, and Rx to detect as many suspected adverse events as possible when using the present clinical database.
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The purpose of this paper is to propose a two dimensional power-normal transformation model to detect the circadian rhythm of blood pressure. Our model is an extension of that proposed by Uragari et al In the proposed model, we consider the correlation between systolic and diastolic blood pressures, and check the influence of the truncated data distribution after the Box-Cox transformation. An application is given to the data obtained from a clinical phase-one study of a Kampo formulation. We also discuss the necessity of evaluating the effects of Kampo formulations on the circadian rhythm of blood pressure.
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In Therapeutic Drug Monitoring (TDM), does and intervals of administration are adjusted according to the individual patient based on plasma concentrations predicted from one or two measurements of the patient. Such monitoring has been applied to many kinds of drugs and is necessary in the study of Kampo formulations too. In this kind of monitoring, the selection of measurement points is quite important in order to achieve accurate predictions. The purpose of this paper is to propose a Monte Carlo approach to the selection of the optimum measurement point to predict plasma concentrations of a drug. The proposed approach is applied to the data obtained in a clinical phase-one study of a Kampo formulation. The necessity of Therapeutic Drug Monitoring for Kampo formulations is also discussed.
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For the evaluation of the efficacy in a long-term treatment with a Kampo prescription, it is important to analyze repeated measurements based on their time course patterns.<br>In this paper, we analyze from the point of model selection with AIC the repeated measurements of platelet obtained from 24 Idiopathic Thrombocytopenic Purpura patients treated with a Kampo prescription (Sho-saiko-to) for 1 year. With the results, we analyze the repeated measurements obtained from another 6 patients of the same disease.
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In many clinical studies to evaluate the efficacy of Kampo prescriptions, subjects are selected because they have high or low values of the characteristics of interest, such as blood pressure or serum cholesterol, and the data obtained from the subjects before and after treatment are analyzed. In such analyses, we should take into account the possible changes in the observations due to regression toward the mean, otherwise the results of the analyses will be incorrect.<br>In this paper, we consider the effect of regression toward the mean in analyzing data and propose a method of analysis with Akaike Information Criterion (AIC) to avoid incorrect results.
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It is well known that there exist inter-individual variations in the pharmacokinetics of pharmaceutical components in Kampo prescriptions. In the area of Kampo medicine, however, there have so far been no reports on the analysis by introducing these variations.<br>In this paper, from the perspective of population pharmacokinetics, we analyze the data of plasma concentration of ephedrine obtained from 8 healthy male volunteers after single oral administration of Sho-seiryu-to (extract) by introducing the inter-individual variations.<br>On the results, we simulate the plasma concentration in multiple oral administrations.