Difference analysis of ADE signal for irinotecan in adults and children / 中国药房

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Difference analysis of ADE signal for irinotecan in adults and children / 中国药房

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Off label, compassionate and irrational use of medicines in Covid-19 pandemic, health consequences and ethical issues / Uso off label, compassivo e irracional de medicamentos na pandemia de Covid-19, consequências para a saúde e questões éticas

Abstract When Covid-19 emerged in December last year, there was no vaccine nor was there specific effective treatment for this fast-spreading and life-threatening viral respiratory infection. Clinical trials were planned and are in progress to investigate whether drugs used for influenza, HIV and other viruses, and also anthelmintics (ivermectin, nitazoxanide, niclosamide), and antimalarials (chloroquine, hydroxychloroquine) showing antiviral activity in in vitro assays, are effective and safe for Covid-19. So far there is no convincing evidence that these antiviral and antiparasitic drugs are of any benefit for Covid-19. Notwithsanding the absence of evidence of clinical efficacy, these drugs are widely used outside of clinical trials (off label) for prophylaxis and treatment of this viral infection. The rationale behind the prescription of macrolide antibiotics (azithromycin) for Covid-19 is obscure as well. The widespread prescription and use of drugs of unproven efficacy and safety for Covid-19 is at odds with the rational use of medicines, a cornerstone principle of pharmacotherapy advanced by WHO in 1985. This irrational use of drugs is cause for concern because some of them are associated with serious heart disorders and deaths.

Resumo Quando a Covid-19 surgiu em dezembro do ano passado, não havia vacina nem tratamento eficaz específico para esta infecção respiratória viral de rápida disseminação e risco de vida. Ensaios clínicos foram planejados e estão em andamento para investigar se os medicamentos usados para influenza, HIV e outros vírus e também anti-helmínticos (ivermectina, nitazoxanida, niclosamida) e antimaláricos (cloroquina, hidroxicloroquina) mostrando atividade antiviral em ensaios in vitro são eficazes e seguros para Covid-19. Até o momento, não há evidências convincentes de que esses medicamentos antivirais e antiparasitários sejam benéficos para a Covid-19. Não obstante a ausência de evidência de eficácia clínica, esses medicamentos são amplamente utilizados fora dos ensaios clínicos (off label) para profilaxia e tratamento dessa infecção viral. A lógica por trás da prescrição de antibióticos macrolídeos (azitromicina) para a Covid-19 também é obscura. A ampla prescrição e uso de medicamentos de eficácia e segurança não comprovadas para a Covid-19 está em desacordo com o uso racional de medicamentos, um princípio fundamental da farmacoterapia promovido pela OMS em 1985. Esse uso irracional de medicamentos é motivo de preocupação, porque alguns deles estão associados a graves doenças cardíacas e mortes.

Application Status of Global Trigger Tool / 医药导报

Objective To understand the current application status of global trigger tool ( GTT) in China and abroad, and to provide reference for application and improvement of GTT in medical institutes in China. Methods The databases of Pubmed and CNKI were searched, and the relevant literatures were reviewed and collected, and the application of GTT for measuring adverse events ( AE ) were analyzed and evaluated. Results Fifty-eight valid articles from 15 countries were included.The studies involve several aspects of GTT applications. Articles about GTT used for measuring the incidence of AE accounted for 62.07%, the researches on the object category of AE accounted for 36.21%, those evaluating the effectiveness of GTT as an AE measurement tool accounted for 27.59%, those about improvement and exploration of GTT application performance accounted for 23. 41%, and those about comparison between GTT and other AE detection methods accounted for 15. 52%. In 18.97% of the studies, the number of reviewers and criteria were accordant with the GTT White Paper, but 32.76% of the studies did not clearly describe the reviewers and criteria. The most common method for reporting the AE rate was the proportion of patients with AE.The research object includes 11 categories:common hospital patients, children, patients in intensive care unit ( ICU) , etc.; AE ratio of common hospital patients was 3. 4% to 43. 3%, the preventable proportion was between 32. 2% and 72.4%.The most common types of AE were drug related adverse events, infection/hospital acquired infections, surgery-related complications, abnormal blood potassium, pressure ulcer and so on. Evaluation performed in the United States, Republic ofKorea, Spain, China and other countries and regions' showed GTT had higher efficiency and other advantages as compared with the other AE detection methods including voluntary reporting system, HMPS, QPSIQ DLCR.The exploration of GTT performance improvement involves many factors influencing the detection effectiveness such as different reviewers, review experience, sampling method, sample size, trigger etc. Conclusion GTT has been applied to AE detection of hospital patients in various countries, and it has shown some advantages. GTT is an effective tool for AE measuring, which could be widely used in AE monitoring of hospitalized patients in medical institutions of China.

Application Status of Global Trigger Tool / 医药导报

Objective To understand the current application status of global trigger tool ( GTT) in China and abroad, and to provide reference for application and improvement of GTT in medical institutes in China. Methods The databases of Pubmed and CNKI were searched, and the relevant literatures were reviewed and collected, and the application of GTT for measuring adverse events ( AE ) were analyzed and evaluated. Results Fifty-eight valid articles from 15 countries were included.The studies involve several aspects of GTT applications. Articles about GTT used for measuring the incidence of AE accounted for 62.07%, the researches on the object category of AE accounted for 36.21%, those evaluating the effectiveness of GTT as an AE measurement tool accounted for 27.59%, those about improvement and exploration of GTT application performance accounted for 23. 41%, and those about comparison between GTT and other AE detection methods accounted for 15. 52%. In 18.97% of the studies, the number of reviewers and criteria were accordant with the GTT White Paper, but 32.76% of the studies did not clearly describe the reviewers and criteria. The most common method for reporting the AE rate was the proportion of patients with AE.The research object includes 11 categories:common hospital patients, children, patients in intensive care unit ( ICU) , etc.; AE ratio of common hospital patients was 3. 4% to 43. 3%, the preventable proportion was between 32. 2% and 72.4%.The most common types of AE were drug related adverse events, infection/hospital acquired infections, surgery-related complications, abnormal blood potassium, pressure ulcer and so on. Evaluation performed in the United States, Republic ofKorea, Spain, China and other countries and regions' showed GTT had higher efficiency and other advantages as compared with the other AE detection methods including voluntary reporting system, HMPS, QPSIQ DLCR.The exploration of GTT performance improvement involves many factors influencing the detection effectiveness such as different reviewers, review experience, sampling method, sample size, trigger etc. Conclusion GTT has been applied to AE detection of hospital patients in various countries, and it has shown some advantages. GTT is an effective tool for AE measuring, which could be widely used in AE monitoring of hospitalized patients in medical institutions of China.

Data Mining Technique for Signal Detection of Drug Adverse Events Using Health Insurance Claims / 薬剤疫学

Objective : To detect signals of potential drug adverse events (DAEs) through data mining of health insurance claims.<BR>Design and Data : Retrospective observational study. The data used were the database of health insurance claims collected and maintained by the Japan Medical Data Center consisting of 312, 797 medical and pharmaceutical claims in one year (August 2003 through July 2004) linked uniquely for 35, 410 patients using an encryption technique to ensure privacy.<BR>Methods : We counted all combinations (cross product or Cartesian product) of drugs and diagnoses appearing in the same claims and counted the number of times a given drug was prescribed preceding the suspected diagnosis in all combinations of the drug and the diagnosis appearing in a claim, i.e., the prescription date precedes the diagnosing date (the preceding number). We calculated the expected preceding number from the overall prevalence of drugs and diagnoses, and then calculated the observed and expected ratio, which was used as the signal indices. We calculated the signal indices on the health insurance claims data to detect DAEs of psychiatric drugs.<BR>Results : Amoxapine and trazodone HCL showed high signal indices with paralytic ileus and convulsion (epilepsy) as documented in their package inserts. However, paroxetine HCL and etizolam showed high signal indices with these potential adverse events although no such DAEs are documented in their package inserts.<BR>Conclusions : The undocumented high signal indices observed between the drugs and diagnoses indicate the potential DAEs and warrant in-depth pharmacovigilance. Given the strength of health insurance claims with a well-defined source population and accurate drug exposure, the proposed signal index will likely prove to be an effective data mining technique when combined with nested case-control analysis and counter-matching.