Thalidomide and the derivatives, lenalidomide and pomalidomide, are the most potent teratogenic medicines. Thalidomide Education and Risk Management System （TERMS^®）and RevMate^® for lenalidomide and pomalidomide have been operated with a goal of no exposed embryo to the drugs. The TERMS^®and the RevMate^®, a centralized management system, were revised in 2016 according to a request by a patient group. After the revision, the patient self-check sheet on adherence to conception prevention is primarily confirmed by his/her doctor, and the content of the completed sheet is sent to the management center in the pharmaceutical company after dispensing of the drug. The points for evaluation of the revised system will be as follows. (1) Has an appropriate procedure in accordance with the revised system been established in respective hospitals? (2) The rate of non-compliance with the procedure by the doctors or pharmacists, (3) Effect on awareness and behavior of the patients. Questionnaire studies of the patients, doctors, and pharmacists have been performed by the third-party committees.

Some case-control studies have been conducted to study the relationship between a drug and adverse events in Japan. However, most such studies adopted hospital controls and rarely adopted community controls. Here, we describe the methodological issues of performing a case-control study using Japanese community controls to illustrate the association between upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs.
To ensure efficient and accurate case identification, all candidate patients admitted to the participating hospitals with target conditions (upper gastrointestinal bleeding etc.) were listed by doctors/research coordinators. Summary tables with the candidates information on eligibility and whether or not the patient gave informed consent were reported back to the study office weekly. Using the summary tables, the fraction eligible and the participation rate for cases were estimated as 24% and 76%, respectively.
To select controls, residents matched with each case according to age, gender and district of residence were randomly sampled from the population registries in the municipal office. To achieve a satisfactory participation rate for residents (47%), we used envelopes with prestigious university letterhead and made phone calls in a timely manner rather than waiting for their replies, both of which yielded favorable results.
By telephone interview, a large amount of information was obtained in approximately 30 minutes. To help subjects' recall, a brochure displaying pictures of analgesics and a calendar for recent 4 weeks were sent in advance, and in the interview, questions using 6 kinds of “prompts” that might enhance recall were employed.

Objective : To find methods to minimize ‘lost to follow-up’ in the long-term follow-up in a pilot study of Prescription-Event Monitoring in Japan (J-PEM) where hypertensive subjects who took losartan or a control drug and gave informed consent to the study were directly followed by researcher for years.
Design : Cohort Study
Methods : We conducted the follow-up survey twice, in which questionnaires were sent to hypertensive patients who had consented to being involved in the survey and returned it by mail. In the questionnaire, we asked about the use of the monitoring drug, change of medical institutions for the treatment of hypertension, significant health-related events. In the second survey, we reminded the non-responders by a letter of reminder and by telephone. When no information was obtained from the subject, we sent a letter, together with a copy of the informed consent given by the subject, to the municipal office where the subject's home was registered to inquire about the subject's current address and related information including the vital status. We calculated Standardized Mortality Ratio (SMR) using the information on death obtained from the mailed questionnaires, telephone and information in the municipal office.
Results : In a pilot study of J-PEM on losartan, 4344 and 3517 questionnaires were sent to pharmacists and doctors, respectively. The doctors handed the informed consent form to the patients and 422 patients agreed to participate the study and sent back the signed form to the study office. In the first and second surveys, a questionnaire was mailed to the subject approximately 1 and 5 years after the first prescription of losartan or a control drug, respectively. The response rate was 73 and 60% in the 1 st and 2 nd survey, respectively. In the manuscript, the results of the 2 nd survey were mainly presented. The reminders by mail and telephone increased the response rate from 60 to 81% and provided the information on the vital status for 86% of the subjects. The response rate was further increased to 84% and the vital status was known for 99% when the information in the municipal office was used. SMR was estimated to be 0.59 (95% CI : 0.34-1.01) before reminding subjects, 0.78 (0.52-1.17) after reminding subjects by a letter and telephone and 0.92 (0.65-1.31) after further addition of the information from the municipal office. During the 5 years of the observation, 21% of 343 subjects who sent back a filled questionnaire did and 70% did not change the clinic/hospital where they received the care for hypertension, while 9% did not answer the relevant question.
Conclusion : The method of the systematic survey may be useful in minimizing the ‘lost to follow-up’ subjects in the long-term pharmacoepidemiology studies in Japan where a patient can change the clinic/hospital for his/her own health care without any letter of reference. In the systematic survey, the researchers may try to follow the subjects by using several methods including reminders like a letter or telephone as well as the use of the information in the municipal office. To facilitate better follow-up, a careful design of the study including the proper design of the informed consent form is essential to maximize the amount and quality of the available information, particularly when the subject has a serious event or dies in a hospital or institution apart from that where the patient has been registered.

Thalidomide and the derivatives, lenalidomide and pomalidomide, are the most potent teratogenic medicines. Thalidomide Education and Risk Management System （TERMS®）and RevMate® for lenalidomide and pomalidomide have been operated with a goal of no exposed embryo to the drugs. The TERMS®and the RevMate®, a centralized management system, were revised in 2016 according to a request by a patient group. After the revision, the patient self-check sheet on adherence to conception prevention is primarily confirmed by his/her doctor, and the content of the completed sheet is sent to the management center in the pharmaceutical company after dispensing of the drug. The points for evaluation of the revised system will be as follows. (1) Has an appropriate procedure in accordance with the revised system been established in respective hospitals? (2) The rate of non-compliance with the procedure by the doctors or pharmacists, (3) Effect on awareness and behavior of the patients. Questionnaire studies of the patients, doctors, and pharmacists have been performed by the third-party committees.

Background :There have been only a few comparative observational studies on the safety and effectiveness of drugs in Japan. Comparative observational studies would provide important information to address these issues and thus we need to establish a means to facilitate such studies. In comparative studies, it is important to prevent the distortion of results due to selection bias. Though we do not yet have a claims database for use in pharmacoepidemiological studies, recently many hospitals and pharmacies have computerized prescription data which may be used to minimize selection bias. Good standardized procedures for the identification of patients prescribed one of two or more drugs to compare in a study using computerized prescription data would serve as a basis for a variety of pharmacoepidemiological studies in Japan.
Methods :We carried out a questionnaire survey in 2753 hospitals and 909 community pharmacies to estimate the fraction of hospitals where computerized data can be used to identify all eligible patients who used a specific drug.
Results :Questionnaires were returned by 1942 (71%) of 2753 hospitals and 632 (70%) of 909 pharmacies. From among those which responded, patients were identified, the patient list was printed, and the electronic file of the patient list was generated in 75%, 64% and 36% of the 1942 hospitals and in 100%, 93% and 49% of the 632 pharmacies respectively.
Conclusion :With procedures using computerized prescription data, the cohort for observational comparative studies may be identified with a minimal selection bias in a majority of hospitals and pharmacies.