Edward Chia Cheng Lai

The asian pharmacoepidemiology network (AsPEN): Promoting multi-national collaboration for pharmacoepidemiologic research in Asia

Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden Medical Research Collaborating Center, Seoul National University Hospital/Seoul National University College of Medicine, Seoul, South Korea Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA Department of Medicine, Division of Pharmacoepidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA Department of Medical Informatics, School of Medicine, Hamamatsu University, Shizuoka, Japan Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Institute of Clinical Pharmacy and Pharmaceutical Sciences, and Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan Department of Preventative Medicine, College of Medicine, Seoul National University, Seoul, South Korea Korea Institute of Drug Safety and Risk Management, Seoul, South Korea Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia Duke Clinical Research Institute, Durham, NC, USA Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Karolinska University Hospital, Stockholm, Sweden Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, South Korea Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA

Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study.

To undertake a multi‐country study to investigate the risk of acute hyperglycaemia with antipsychotic use.

Comparative stroke risk of antiepileptic drugs in patients with epilepsy

Purpose:  Patients with epilepsy have higher stroke‐related morbidity and mortality, leading to the suspicion that the increased stroke events may be associated with antiepileptic drug (AED) exposure. We evaluated the comparative risk of stroke in adult patients with epilepsy receiving phenytoin (PHT), valproic acid (VPA), or carbamazepine (CBZ) to help determine the stroke risk for Asian patients with specific AED exposure.

Use of antiepileptic drugs and risk of hypothyroidism

This study aimed to investigate the risk of clinically significant hypothyroidism among all the currently available antiepileptic drugs (AED).

Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis

ABSTRACT Objective: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest. Results: 54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation. Conclusion: Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.

Prescription sequence symmetry analysis: assessing risk, temporality, and consistency for adverse drug reactions across datasets in five countries

Prescription sequence symmetry analysis (PSSA) is a signal detection method for adverse drug events. Its capacity to consistently detect adverse drug events across different settings has not been tested. We aimed to determine the consistency of PSSA results for detecting positive and negative control adverse drug events across different settings.

Effectiveness of Sulpiride in Adult Patients With Schizophrenia

The objective of this study is to compare the effectiveness among sulpiride, risperidone, olanzapine, and haloperidol by evaluating the persistence of drug use. A retrospective cohort study was conducted by analyzing the National Health Insurance Research Database of Taiwan. Patients with schizophrenia aged 18-65 years and newly prescribed with a single oral antipsychotic medication between years 2003 and 2008 were included. The primary outcome was the persistence of antipsychotic agents by calculating the treatment duration till treatment changed. All defined treatment changes were also analyzed separately, including discontinuation, switching, augmentation, and hospitalization. A total of 1324 eligible patients were included, with an average age of 36 years old and approximately 45% of them were female. The most prevalent antipsychotic use was risperidone (42.1%), followed by sulpiride (36.0%), haloperidol (14.2%), and olanzapine (7.7%). After adjusting for patient demographics, mental illness characteristics, and propensity score, the Cox regression models found that the risk of nonpersistence was significantly higher in patients receiving risperidone (hazard ratio [HR], 1.22; 95% CI, 1.06-1.40), haloperidol (HR, 1.98; 95% CI, 1.63-2.40), and olanzapine (HR, 1.34; 95% CI, 1.07-1.68), as compared with sulpiride, suggesting the effectiveness of sulpiride was better than the other 3 antipsychotics. Therefore, this study would provide strong grounds for a properly conducted randomized controlled trial of the clinical- and cost-effectiveness of sulpiride vs atypical antipsychotics.

Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies

Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by utilizing computerized claims data. The method has been increasingly used to investigate safety concerns of medications and as a pharmacovigilance tool to identify unsuspected side effects. Validation studies have indicated that SSA has moderate sensitivity and high specificity and has robust performance. In this review we present the conceptual framework of SSA and discuss advantages and potential pitfalls of the method in practice. SSA is based on analyzing the sequences of medications; if one medication (drug B) is more often initiated after another medication (drug A) than before, it may be an indication of an adverse effect of drug A. The main advantage of the method is that it requires a minimal dataset and is computationally efficient. By design, SSA controls time-constant confounders. However, the validity of SSA may be affected by time-varying confounders, as well as by time trends in the occurrence of exposure or outcome events. Trend effects may be adjusted by modeling the expected sequence ratio in the absence of a true association. There is a potential for false positive or negative results and careful consideration should be given to potential sources of bias when interpreting the results of SSA studies.

Use of the landmark method to address immortal person‐time bias in comparative effectiveness research: a simulation study

Observational comparative effectiveness and safety studies are often subject to immortal person-time, a period of follow-up during which outcomes cannot occur because of the treatment definition. Common approaches, like excluding immortal time from the analysis or naïvely including immortal time in the analysis, are known to result in biased estimates of treatment effect. Other approaches, such as the Mantel-Byar and landmark methods, have been proposed to handle immortal time. Little is known about the performance of the landmark method in different scenarios. We conducted extensive Monte Carlo simulations to assess the performance of the landmark method compared with other methods in settings that reflect realistic scenarios. We considered four landmark times for the landmark method. We found that the Mantel-Byar method provided unbiased estimates in all scenarios, whereas the exclusion and naïve methods resulted in substantial bias when the hazard of the event was constant or decreased over time. The landmark method performed well in correcting immortal person-time bias in all scenarios when the treatment effect was small, and provided unbiased estimates when there was no treatment effect. The bias associated with the landmark method tended to be small when the treatment rate was higher in the early follow-up period than it was later. These findings were confirmed in a case study of chronic obstructive pulmonary disease. Copyright

Databases in the Asia-pacific region: The potential for a distributed network approach

Background: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. Methods: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. Results: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. Conclusions: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs.