A system for reporting and evaluating adverse drug reactions of herbal medicine in Taiwan from 1998 to 2016.

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan's herbal medicines adverse reaction database and facilitate epidemiological analysis.

Assessment of adverse reactions to α-lipoic acid containing dietary supplements through spontaneous reporting systems.

BACKGROUND & AIMS: Alpha-lipoic acid (ALA)-containing dietary supplements are widely used in clinical practice, although their safety assessment is under-investigated. We characterize the safety profile of ALA-containing products by analysing spontaneous reports of suspected adverse reactions (ARs). METHODS: Suspected ARs to ALA-containing products were extracted from the Italian Phytovigilance System (IPS), and scrutinized in terms of seriousness and causality (through WHO UMC system), with a specific focus on important (IMEs) and designated medical events (DMEs). To characterize the reporting profile from an international perspective, the WHO-VigiBase was also queried. RESULTS: From March 2002 to February 2020, out of 2147 total reports, 116 reports concerning 212 ARs to ALA-containing products were collected. Women were involved in 68.1% of cases. Skin (44.9%) and gastrointestinal disorders (10.8%) were the most frequently represented ARs. Causality assessment resulted as definite (15), probable (35), possible (24), unlikely (5), and unclassifiable (37). In 70% of cases, events occurred within 30 days of ALA use. Forty-five reports were serious (38.8%), being insulin autoimmune syndrome the most frequently reported (N = 10). IMEs were recorded in 20 cases, including four DMEs (3 angioedema and one anaphylactic shock). Similar distribution emerged from the 5641 reports in the WHO-VigiBase. CONCLUSIONS: The remarkable reporting of unpredictable skin, immune and hepatic ARs, coupled with seriousness, strong causality and early onset, calls for a) careful risk-benefit assessment of ALA-containing products by regulators; b) awareness and monitoring by clinicians and c) continuous vigilance of their safety profile through valuable spontaneous reporting systems such as IPS.

Comparison of Three Different Data Sources of Adverse Drug Reactions Using Adverse Drug Reaction Data of Fluorouracil for Gastric Cancer as an Example.

Various sources of information are available for identifying and evaluating adverse drug reactions (ADRs). However, some studies only used the ADR data from spontaneous reporting databases to evaluate the safety of post-marketing drugs. This study was performed to identify an appropriate method for evaluating the safety of post-marketing drugs by comparing the frequencies of ADRs among three datasets: randomized controlled trials, published case reports, and spontaneous reports. Taking ADR data for fluorouracil as an example, we collected the three types of data and extracted their ADR information. All listed ADRs were sorted by frequency from high to low, and the top five ADRs were chosen from each dataset. We assigned an index value of 1.0 to the frequency of one specific ADR (diarrhea) and then calculated the index values of the other ADRs relative to diarrhea. Ten different ADRs were mentioned in the top five ADRs of the three datasets, and only diarrhea and nausea/vomiting were included in all three datasets. The rank orders of the top five ADRs varied among the three datasets. Nausea and vomiting was the most frequent ADR in all three datasets; the remaining ADRs differed among the datasets. There were significant differences in the recording of ADRs and the frequency distributions among the three datasets. A comprehensive and reliable safety profile for post-marketing drugs should not be based on any one source. Spontaneous reports from monitoring institutions provided the most ADR data. Randomized controlled trials and case reports published in the literature can supplement the results from spontaneous reports.

Adverse Events Reported to the United States Food and Drug Administration Related to Caffeine-Containing Products.

OBJECTIVE: To examine differences in the frequency and severity of federally reported adverse events between caffeine-containing and non-caffeine-containing products while also identifying the category of caffeine-containing products associated with the highest frequency and severity of adverse events. PATIENTS AND METHODS: All adverse event reports that met specified eligibility criteria and were submitted to the Center for Food Safety and Applied Nutrition Adverse Event Reporting System between January 1, 2014, and June 29, 2018, were extracted. In this retrospective observational study, the most severe adverse event experienced, an ordinal variable, was categorized into death, life-threatening, hospitalization/disability, and emergency department visit. A nonproportional odds model was used to compare the odds of caffeine-containing products being associated with more severe adverse events relative to a noncaffeine group. The analysis is of data only from those reporting adverse events and may or may not be representative of the entire population exposed to these products, which is not known from the examined data. RESULTS: Energy and preworkout products saw a significant increase in the odds of the adverse event experienced being death rather than the other less severe outcomes relative to the noncaffeinated group. Those products, along with weight loss products, had greater odds of the adverse event being death or life-threatening vs the less severe outcomes relative to the noncaffeinated group. CONCLUSION: Caffeine-containing products have a greater association with severe adverse events compared with non-caffeine-containing products. Exposure to preworkout and weight loss products had greater odds of being associated with a more serious adverse event relative to noncaffeinated products. Health care practitioners should use these outcomes to better inform and educate patients about the many factors related to caffeine intake and adverse outcomes.

Evaluation of a Web-Based, 'Purchase Event' Intensive Monitoring Method for Pharmacovigilance of Natural Health Products: Lessons and Insights from Development Work in New Zealand.

INTRODUCTION: Intensive monitoring methods are used in pharmacovigilance for prescription medicines but have not yet been implemented for natural health products (NHPs). OBJECTIVES: Our objective was to assess feasibility issues with a new 'purchase event' intensive monitoring method for pharmacovigilance of NHPs, including pharmacy and NHP purchaser recruitment rates, collection of NHP purchaser key patient identifier information for data linkage and quality and completeness of data. METHODS: For the Ginkgo study, 213 community pharmacies in the Auckland (Aotearoa New Zealand) District Health Board area were invited to participate. Staff in participating pharmacies (n = 3 [1.4%]) recorded ginkgo product sales and gave purchasers a study invitation card (October 2015-January 2016). Ginkgo purchaser participants were emailed links to web-based baseline and follow-up questionnaires about adverse events occurring during/after taking ginkgo. Participating pharmacists and consumers were invited to provide qualitative feedback about the study. For the NHP-Lite study, all NHPs were included for monitoring. Community pharmacies in the Green Cross Health network were invited to participate. Participating pharmacy staff gave all NHP purchasers a study invitation card over a 2-week period (May 2016). NHP purchaser participants were emailed links to web-based baseline, follow-up and feedback questionnaires. RESULTS: Few community pharmacists (Ginkgo study, n = 3; NHP-Lite study, n = 18) and NHP purchasers (Ginkgo study, n = 0; NHP-Lite study, n = 4) participated. Pharmacists (Ginkgo study, 3/3; NHP-Lite study, 11/18) described several reasons for participating and suggested ways to increase consumer recruitment, including simplifying study procedures. CONCLUSIONS: These web-based, purchase event, intensive monitoring studies, with cohorts built through NHP purchases in pharmacies, identified substantial issues with recruiting pharmacists/pharmacies and NHP purchasers that, at present, render such studies unfeasible. Future studies need to consider other methods of recruiting NHP purchasers and develop a simple method for recording NHP purchases.

Post Marketing Safety of Plus CBD™ Products, a Full Spectrum Hemp Extract: A 2-Year Experience.

The market for products featuring hemp extracts is large and growing larger. However, safety concerns have been raised by medical and regulatory agencies. Post marketing surveillance of full spectrum hemp extract (FSHE) products manufactured and distributed by CV Sciences (CVSI) and traded under the brand PlusCBD™ was conducted over a 2-year period (2018-2019). The safety of these products was assessed by analyzing adverse events reports. From a total of approximately five million product units sold during the 2-year period, 1,429 (0.03%) adverse events (AE) were reported in 1,151 unique customers. Of those, only two were classified as serious AEs. For orally ingested products, the most common types of AEs reported were gastrointestinal (e.g. abdominal discomfort), while for topically applied products, the most reports mentioned dermatological symptoms (e.g. rashes). There has been no evidence of liver toxicity associated with CVSI products. Based on this longitudinal dataset, the products manufactured using CVSI's proprietary processes are safe and well tolerated at the recommended doses.

Biological therapy-associated adverse reactions in asthma: analysis of reporting to the Portuguese pharmacovigilance system.

Objectives: Biological drugs have been successfully tested in asthma, especially in the most severe forms of the disease. The goal of this study was to characterize the safety profile of biologicals used in asthma.Methods: Retrospective and descriptive analysis of spontaneous reports (SRs) involving omalizumab and mepolizumab, sent to the Portuguese Pharmacovigilance System, since market launch until October 2018.Results: A total of 127 SRs for omalizumab and 10 SRs mepolizumab were found. Most patients were female (75.6% omalizumab and 90.0% mepolizumab), and aged 18-64 years (61.4% and 50.0%, respectively). 71.7% of the reports for omalizumab were serious, with 2 cases of anaphylaxis, 12 malignant neoplasms and 2 abortions. Only 20.0% of the reports for mepolizumab were considered serious. A total of 391 adverse drug reactions (ADRs) for omalizumab and 20 ADRs for mepolizumab were found. Most reported ADRs belonged to System organ class (SOC) groups: 'respiratory, thoracic and mediastinal disorders' and 'investigations', for omalizumab; 'musculoskeletal and connective tissue disorders' and 'general disorders and administration site conditions' for mepolizumab.Conclusion: Over the years, there was an increasing trend of SRs with these biological drugs. However, it is necessary to continue to develop educational programs in order to get a better reporting system.

Kratom Use and Toxicities in the United States.

BACKGROUND: Kratom is an herbal supplement containing alkaloids with opioid properties. This review was conducted to determine toxicities associated with kratom use in the United States in order to provide insight into its safety as a dietary supplement. METHODS: We conducted a retrospective review of kratom exposures reported to the National Poison Data System to determine the toxicities associated with kratom use. We also reviewed records from a county medical examiner's office in New York State to identify kratom-associated fatalities. RESULTS: A total of 2312 kratom exposures were reported, with 935 cases involving kratom as the only substance. Kratom most commonly caused agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), and confusion (8.1%). Serious effects of seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%) were also reported. Kratom was listed as a cause or contributing factor in the death of four decedents identified by the county medical examiner's office. CONCLUSIONS: Kratom use is increasing and is associated with significant toxicities. Our findings suggest kratom is not reasonably expected to be safe and poses a public health threat due to its availability as an herbal supplement.

The effect of community dialogues and sensitization on patient reporting of adverse events in rural Uganda: Uncontrolled before-after study.

BACKGROUND: Patients experiencing adverse drug events (ADE) in many developing countries are in the best position to report these events to the authorities but need to be empowered to do so. Systematic evaluation of community engagement and patient support especially in rural areas would provide evidence for a program to monitor potential harm from medicines. The aim of this study was to assess the effects of a community dialogue and sensitization (CDS) program on the knowledge, attitude and practises of community members for reporting ADE. METHODS: This an uncontrolled before-after study was conducted in two eastern Ugandan districts between September 2016 and August 2017. RESULTS: After implementation of the community dialogue and sensitization (CDS) program, there was an overall 20% (95% CI:16% to 25%) increase in knowledge about ADE in the community compared to before the program began. Awareness levels increased by 50% (95% CI: 37% to 63%) among those with little or no education and by41% (95% CI: 31% to 52%) among young people (15-24 years). Furthermore, 5% (95% CI: 3% to 7%) more respondents recognized the need for reporting ADEs compared to before the program. Finally, there was a significant increase of 115% (95% CI:137% to 217%) in respondent recognition and reporting of ADEs compared to the beginning of the CDS program. Overall, this community found the CDS program acceptable and proposed aspects that could be improved for future use. CONCLUSION: Our evaluation showed that the CDS program increased knowledge and improved attitudes by catalyzing discussions among community members and healthcare professionals on health issues and monitoring safety of medicines compared to before the program. Successful implementation of the program depends on holistic health systems strengthening and adaptation to the community's way of life.

Adverse event reporting patterns of concomitant botanical dietary supplements with CYP3A4 interactive & CYP3A4 non-interactive anticancer drugs in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

BACKGROUND: To examine the adverse event (AE) reporting patterns for concomitant Botanical Dietary Supplements (BDS) and anticancer drugs. RESEARCH DESIGN AND METHODS: Using the 2004-2015 U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, AEs involving commonly used BDS and anticancer drugs (categorized into CYP3A4 interactive and CYP3A4 non-interactive) were examined. Disproportionality analyses using reporting odds ratios (RORs) assessed the relative reporting rates of 1) serious AEs (i.e., mortality and morbidity) with concomitant use of BDS (overall and by type) and anticancer drugs compared to anticancer drugs only; and 2) AEs by specific System Organ Classes (SOCs). RESULTS: A total of 3,264 AEs were reported involving concomitant BDS and CYP3A4 interactives, and 3,885 involving concomitant BDS and non-interactive anticancer drugs. ROR of serious AEs with concomitant all BDS and anticancer drugs compared to anticancer drugs alone showed a potential protective signal (ROR = 0.65, 95% CI = 0.62,0.68), but ROR for açaí and non-interactive anticancer drugs indicated potential risk (ROR = 1.70, 95% CI = 1.01,2.86). Heterogeneity of reporting patterns of AEs related to certain SOCs was observed for use of BDS along with anticancer drugs. CONCLUSION: This study identified potential protective and risk signals for AEs with concomitant use of BDS and anticancer drugs.

The safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age: A Vaccine Safety Datalink study.

PURPOSE: To evaluate the safety of live attenuated influenza vaccine (LAIV) in children 2 through 17 years of age. METHODS: The study was conducted in 6 large integrated health care organizations participating in the Vaccine Safety Datalink (VSD). Trivalent LAIV safety was assessed in children who received LAIV between September 1, 2003 and March 31, 2013. Eighteen pre-specified adverse event groups were studied, including allergic, autoimmune, neurologic, respiratory, and infectious conditions. Incident rate ratios (IRRs) were calculated for each adverse event, using self-controlled case series analyses. For adverse events with a statistically significant increase in risk, or an IRR > 2.0 regardless of statistical significance, manual medical record review was performed to confirm case status. RESULTS: During the study period, 396 173 children received 590 018 doses of LAIV. For 13 adverse event groups, there was no significant increased risk of adverse events following LAIV. Five adverse event groups (anaphylaxis, syncope, Stevens-Johnson syndrome, adverse effect of drug, and respiratory failure) met criteria for manual medical record review. After review to confirm cases, 2 adverse event groups remained significantly associated with LAIV: anaphylaxis and syncope. One confirmed case of anaphylaxis was observed following LAIV, a rate of 1.7 per million LAIV doses. Five confirmed cases of syncope were observed, a rate of 8.5 per million doses. CONCLUSIONS: In a study of trivalent LAIV safety in a large cohort of children, few serious adverse events were detected. Anaphylaxis and syncope occurred following LAIV, although rarely. These data provide reassurance regarding continued LAIV use.

Identifying natural health product and dietary supplement information within adverse event reporting systems.

Data on safety and efficacy issues associated with natural health products and dietary supplements (NHP&S) remains largely cloistered within domain specific databases or embedded within general biomedical data sources. A major challenge in leveraging analytic approaches on such data is due to the inefficient ability to retrieve relevant data, which includes a general lack of interoperability among related sources. This study developed a thesaurus of NHP&S ingredient terms that can be used by existing biomedical natural language processing (NLP) tools for extracting information of interest. This process was evaluated relative to intervention name strings sampled from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). A use case was used to demonstrate the potential to utilize FAERS for monitoring NHP&S adverse events. The results from this study provide insights on approaches for identifying additional knowledge from extant repositories of knowledge, and potentially as information that can be included into larger curation efforts.

Knowledge, Attitude, and Practices regarding Pharmacovigilance and Adverse Drug Reaction reporting among Dental Students in a Teaching Hospital, Jodhpur, India: A Cross-sectional Study.

INTRODUCTION: This is a cross-sectional knowledge, attitude, and practices (KAPs) study on pharmacovigilance (PV) and adverse drug reaction (ADR) reporting among dental students in a teaching hospital in India. AIM: The aim of this study was to assess the KAP of dental students regarding PV, ADR reporting, and barriers toward the same. MATERIALS AND METHODS: A cross-sectional survey using a self-administered, investigator-developed, close-ended questionnaire was conducted in an academic dental hospital in India. All prescribers including third year students, final year students, and house surgeons of the same institute were included for assessment of KAP regarding PV using 16, 8, and 8 items respectively. Data regarding barriers toward ADR reporting and demographics were also collected. Mann-Whitney U-test and Kruskal-Wallis test were applied followed by post hoc test. RESULTS: A total of 241 of 275 respondents participated in the study with a response rate of 87.5%. Overall, 64% reported that they had no idea about the term PV. Age was significantly associated with knowledge (p = 0.045) and attitude (p = 0.016). Barriers contributing to underreporting were difficulty in deciding whether or not an ADR has occurred (52.0%), concerns that the report may be wrong (37%), lack of confidence to discuss ADR with colleagues (29%), and almost no financial benefits (24%). CONCLUSION: Participants had a comparatively favorable attitude toward PV, but their knowledge and practice need considerable improvements. This study highlights the need for appropriate dental curriculum changes and further multicentric studies to shed more light on important issues of PV among dentists in India. CLINICAL SIGNIFICANCE: This study explores dentists' knowledge, attitude, and behavior regarding PV, which could help to improve patient's safety and care. The favorable attitude of dentists is an indication that PV could be added in depth in the curriculum and in general practice. Information on barriers for reporting the ADRs could help to find possible solutions for removing the barriers precisely.

Allergy-Like Immediate Reactions with Herbal Medicines: A Retrospective Study Using Data from VigiBase®.

INTRODUCTION: Herbal medicines are used worldwide and with an increasing popularity in Western countries. Although often perceived as 'naturally safe', herbals may cause severe adverse drug reactions (ADRs), with immediate allergic reactions being particularly life threatening. OBJECTIVES: The aim of this study was to analyse immediate allergy-like ADRs to herbals documented in VigiBase®, the WHO international pharmacovigilance database. METHODS: The documentation of all suspected ADRs in association with herbal exposure reported to VigiBase® from 1969 to August 2014 was retrieved. Among all reports in which WHO-ART reaction terms were indicative of acute allergic reactions, those classified as 'suspect' with a documented causality assessment and latency time of ≤1 day were selected. For the most frequent specific herbal-ADR combinations, the information component (IC) as a measure of disproportionality based on Bayesian statistics was calculated. RESULTS: We identified 757 reports out of 1039 ADRs. Products with mixed herbals (36.0 %) as well as those administered orally (63.2 %) were predominant. The most frequent reactions were urticaria and rash (49.2 %). Anaphylactic reactions accounted for 9.5 %. Disproportionally frequent reporting of mouth edema (IC = 1.81) and anaphylactic reactions (IC = 1.24) to Phleum pretense were noted. CONCLUSION: Our findings indicate that herbal medicines for oral use carry a risk of causing immediate allergy-like ADRs. Studies using the Vigibase® database can identify specific combinations of particular herbs and adverse reactions. Healthcare professionals and patients should be aware of these risks and report any serious adverse experiences.

FINDING POTENTIALLY UNSAFE NUTRITIONAL SUPPLEMENTS FROM USER REVIEWS WITH TOPIC MODELING.

Although dietary supplements are widely used and generally are considered safe, some supplements have been identified as causative agents for adverse reactions, some of which may even be fatal. The Food and Drug Administration (FDA) is responsible for monitoring supplements and ensuring that supplements are safe. However, current surveillance protocols are not always effective. Leveraging user-generated textual data, in the form of Amazon.com reviews for nutritional supplements, we use natural language processing techniques to develop a system for the monitoring of dietary supplements. We use topic modeling techniques, specifically a variation of Latent Dirichlet Allocation (LDA), and background knowledge in the form of an adverse reaction dictionary to score products based on their potential danger to the public. Our approach generates topics that semantically capture adverse reactions from a document set consisting of reviews posted by users of specific products, and based on these topics, we propose a scoring mechanism to categorize products as "high potential danger", "average potential danger" and "low potential danger." We evaluate our system by comparing the system categorization with human annotators, and we find that the our system agrees with the annotators 69.4% of the time. With these results, we demonstrate that our methods show promise and that our system represents a proof of concept as a viable low-cost, active approach for dietary supplement monitoring.

[Adverse Event Trends Associated with Over-the-counter Drugs: Data Mining of the Japanese Adverse Drug Event Report Database].

Over-the-counter (OTC) drugs play an important role in self-medication. To ensure patient safety, pharmacists should ask patients to pay attention to possible adverse events (AE) associated with OTC drugs and educate patients about the symptoms related to those AEs. The aims of the present study were as follows: (1) to assess the tendency of AEs to occur with OTC drug use in Japan; (2) to detect a safety signal for OTC drugs using the reporting odds ratio (ROR); and (3) to evaluate clustery features, which include suspected drugs and therapeutic classifications, and safety signal indices (number of reports and the ROR), using cluster analysis. The number of reports of AEs following use of combination cold remedy, antipyretic and analgesic remedy, and herbal medicine was 1007, 566, and 221, respectively. We set the cluster number at five; clustery features obtained were as follows: (1) high reporting rate for skin and subcutaneous tissue disorder AEs was the largest group related to combination cold remedy; (2) high reporting rate for nervous system disorder AEs including dizziness was the second largest group. The same medicinal ingredient may demonstrate similar tendencies of the occurrence of AEs and similar clustery features in the Japanese Adverse Drug Event Report database. Our analysis of AEs associated with OTC drugs may be useful for pharmacists and patients alike. Further studies are required to draw better-informed conclusions.

A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications.

From adverse drug event detection to prevention. A novel clinical decision support framework for medication safety.

BACKGROUND: Errors related to medication seriously affect patient safety and the quality of healthcare. It has been widely argued that various types of such errors may be prevented by introducing Clinical Decision Support Systems (CDSSs) at the point of care. OBJECTIVES: Although significant research has been conducted in the field, still medication safety is a crucial issue, while few research outcomes are mature enough to be considered for use in actual clinical settings. In this paper, we present a clinical decision support framework targeting medication safety with major focus on adverse drug event (ADE) prevention. METHODS: The novelty of the framework lies in its design that approaches the problem holistically, i.e., starting from knowledge discovery to provide reliable numbers about ADEs per hospital or medical unit to describe their consequences and probable causes, and next employing the acquired knowledge for decision support services development and deployment. Major design features of the framework's services are: a) their adaptation to the context of care (i.e. patient characteristics, place of care, and significance of ADEs), and b) their straightforward integration in the healthcare information technologies (IT) infrastructure thanks to the adoption of a service-oriented architecture (SOA) and relevant standards. RESULTS: Our results illustrate the successful interoperability of the framework with two commercially available IT products, i.e., a Computerized Physician Order Entry (CPOE) and an Electronic Health Record (EHR) system, respectively, along with a Web prototype that is independent of existing healthcare IT products. The conducted clinical validation with domain experts and test cases illustrates that the impact of the framework is expected to be major, with respect to patient safety, and towards introducing the CDSS functionality in practical use. CONCLUSIONS: This study illustrates an important potential for the applicability of the presented framework in delivering contextualized decision support services at the point of care and for making a substantial contribution towards ADE prevention. Nonetheless, further research is required in order to quantitatively and thoroughly assess its impact in medication safety.

Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review.

Assessment of treatment safety is 1 of the primary goals of clinical trials. Organizations and working groups have created reporting guidelines for adverse events (AEs). Previous research examining AE reporting for pharmacologic clinical trials of analgesics in major pain journals found many reporting inadequacies, suggesting that analgesic trials are not adhering to existing AE reporting guidelines. The present systematic review documented AE reporting in 3 main pain journals for nonpharmacologic, noninterventional (NP/NI) trials examining pain treatments. To broaden our pool of nonpharmacologic trials, we also included trials examining acupuncture, leech therapy, and noninvasive stimulation techniques (eg, transcutaneous electrical nerve stimulation). We documented AE reporting at 2 levels of specificity using coding manuals based on the Consolidated Standards of Reporting Trials (CONSORT) harms reporting standards and Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) AE reporting checklist. We identified a number of inadequacies in AE reporting across the 3 journals. For example, using the ACTTION coding manual, we found that less than one-half of the trials reported specific AE assessment methods; approximately one-third of the trials reported withdrawals due to AEs for each study arm; and about one-fourth of the trials reported all specific AEs. We also examined differences in AE reporting across several trial characteristics, finding that AE reporting was generally more detailed in trials with patients versus those using healthy volunteers undergoing experimentally evoked pain. These results suggest that investigators conducting and reporting NP/NI clinical trials are not adequately describing the assessment and occurrence of AEs.

Signal detection for Thai traditional medicine: examination of national pharmacovigilance data using reporting odds ratio and reported population attributable risk.

Herbal containing medicine consumption has increased while the awareness of adverse drug reaction (ADR) was less than conventional medicine. Early detection of unexpected numbers of ADRs from herbal medicines' reports which are abnormal from the whole database needs quantification. Disproportionality analysis has been performed for signal detection by using reporting odds ratio (ROR) as measurement. The impact of having medicine as exposures in each ADR should be measured by using reported population attributable risks (RPAR). This study aimed to quantify the contribution of Thai traditional medicine (TTM) to ADR reports and to assess the association between TTMs and serious adverse drug reactions. Data were retrieved from the adverse drug reaction surveillance database, Thai-Food and Drug Administration from 2002 to 2013. Crude and adjusted RORs for each drug-ADR pair and RPARs were computed. TTM contributed only 0.001% of all serious ADRs reported. Out of 4208 TTM-ADR pairs were examined, three had the statistically significant RORs, namely Andrographis paniculata and anaphylactic shock (ROR 2.32, 95% CI 1.03, 5.21); green traditional medicine and Stevens-Johnson syndrome (ROR 13.04, 95% CI 5.4-31.51) and Derris scandens Benth and angioedema (ROR 2.71, 95% CI 1.05-6.95). Their RPARs ranged from 0.05% to 0.16%. We conclude that TTMs need more intensive surveillance.