Abstract:
INTRODUCTION:The Bradford Hill criteria are a widely used, useful tool for the assessment of biomedical causation. We have examined their application to pharmacovigilance using the example of cisapride-induced QTc interval prolongation/arrhythmia. METHODS:A literature search was conducted using MEDLINE, EMBASE, Reactions Weekly and regulatory websites to identify evidence for the association between cisapride and QTc interval prolongation/arrhythmia that had been published in the English language. Two hundred and five publications were identified as being potentially suitable for the study. After excluding irrelevant articles, studies on high-risk populations and review articles, 70 publications were assessed using the Bradford Hill criteria. These included 24 case reports, case series or spontaneous report summaries; eight epidemiological studies; 22 clinical studies; and 16 experimental (in vivo and in vitro) publications. RESULTS:The most compelling evidence for an association between cisapride use and QTc interval prolongation/arrhythmia came from case/spontaneous reports and biological plausibility. Considering the rare incidence of serious cardiac events, these criteria formed the basis for the strength of the association. The number of reports from different populations showed consistency. Specificity was supported by clinical and cardiographic characterisation of the events. There were temporal relationships between the events and the initiation of cisapride treatment, increases in the dosage and the receipt of interacting medications. The relationships between the adverse events and the latter two factors exhibited biological gradients. Experimental evidence could be found from biological models, as well as reports of positive dechallenge and/or rechallenge found in individual patients. Cisapride was found to bind the human ether-a-go-go-related gene (HERG) potassium channel, which provides a plausible mechanism for QTc interval prolongation/arrhythmia. Other QTc interval-prolonging/arrhythmic drugs that also bind to HERG provided an analogy for cisapride causing QTc interval prolongation/arrhythmia via this mechanism. The evidence provided by clinical studies was inconsistent, and epidemiological studies failed to demonstrate an association. Nevertheless, this did not prevent the assessment of causation. DISCUSSION:This study showed how different types of evidence found in pharmacovigilance can be evaluated using the Bradford Hill criteria. Further work is required to examine how the criteria can be applied to different types of adverse events and how they may be applied to pharmacovigilance.
journal_name
Drug Safjournal_title
Drug safetyauthors
Perrio M,Voss S,Shakir SAdoi
10.2165/00002018-200730040-00006subject
Has Abstractpub_date
2007-01-01 00:00:00pages
333-46issue
4eissn
0114-5916issn
1179-1942pii
3046journal_volume
30pub_type
杂志文章,meta分析相关文献
DRUG SAFETY文献大全abstract::The term 'benefit-risk ratio' is often used as a general term linked to the use of a medicine. To balance risk and benefit is, however, a very complex exercise. For most medicines the benefits are limited to a few indications and for an individual patient there is usually only a single benefit sought but the potential...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/00002018-199615010-00001
更新日期:1996-07-01 00:00:00
abstract::It is a major clinical and public health problem that there is no clear strategy as to how we best make use of information obtained when pregnant women take drugs. For this reason, some pregnant women are not treated as they should be and some are given drugs they should not use. We suggest a monitoring system that co...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/00002018-200225010-00003
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. OBJECTIVE:The aim of the study was to characterize ADRs reported to the WHO-ADR database, ...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/BF03262002
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Problematic prescription drug use is reflected by or associated with drug-seeking aberrant behaviours. Research gaps include lack of post-marketing evidence and instruments. As part of the pharmacovigilance requirements, a risk management plan was developed for fentanyl buccal tablets (FEBT) by the manufactu...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-014-0193-4
更新日期:2014-08-01 00:00:00
abstract::This 'Erice Call for Change' is a report from a group of experts, patients and patient representatives who met in Erice in September 2019 following previous similar meetings after the original Erice Declaration (1996). The aim of the meeting was to discuss the challenge of causal complexity and individual variation in...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-020-00919-2
更新日期:2020-06-01 00:00:00
abstract::The aim of this review is to analyse and summarise the literature data about the incidence of weight gain in patients exposed to atypical antipsychotics during long-term (>or=1 year) treatment regimens. Despite the clinical relevance of the topic, the vast majority of reviewed studies showed methodological limitations...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200629040-00002
更新日期:2006-01-01 00:00:00
abstract::Cytokines are now commonly used in the treatment of many conditions, especially cancer, haematological malignancies and chronic viral hepatitis. With some of these cytokines, clinical induction and/or exacerbation of autoimmune manifestations have been observed. This has been the case with interferon-alpha and interfe...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199717020-00002
更新日期:1997-08-01 00:00:00
abstract::The introduction of MedDRA, the Medical Dictionary for Regulatory Activities, as a standardised terminology may have a major impact on the performance of risk management. Thus, MedDRA is likely to have an important effect on the analysis of clinical trial safety data. Review of the most commonly used terms in clinical...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200427080-00010
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:An association between oral contraceptive (OC) use and venous thromboembolism (VTE) has long been recognized. However, no summary estimates of the increase in VTE risk associated with OC use have been available since 1995, and no meta-analyses have evaluated the VTE risk of new preparations containing drospi...
journal_title:Drug safety
pub_type: 杂志文章,meta分析,评审
doi:10.2165/11598050-000000000-00000
更新日期:2012-03-01 00:00:00
abstract::In general, the selective estrogen receptor modulators (SERMs) currently indicated for the treatment and prevention of breast cancer, i.e. tamoxifen and toremifene, are fairly well tolerated. However, tamoxifen has been shown to induce hepatocellular carcinomas in rats, but not in humans, and can increase the risk of ...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200124140-00003
更新日期:2001-01-01 00:00:00
abstract:INTRODUCTION AND OBJECTIVE:Pharmacovigilance requirements for biologics mandate that EU Member States shall ensure that any biologic that is the subject of a suspected adverse drug reaction (ADR) is identifiable by brand name and batch number. Recent studies showed that brand name identification is well established, wh...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-015-0383-8
更新日期:2016-02-01 00:00:00
abstract::The clinician prescribing beta-blockers for his or her patients is faced with an often difficult situation. There are many beta-blockers, each with its own pharmacological profile. Patients are often taking multiple medications, thus increasing the risk of both anticipated and unexpected drug interactions. Reports of ...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199513060-00005
更新日期:1995-12-01 00:00:00
abstract::Since the introduction of the interferons in the 1990s, a multitude of different immunomodulatory and immunosuppressant disease-modifying therapies for multiple sclerosis (MS) have been developed. They have all shown positive effects on clinical endpoints such as relapse rate and disease progression and are a heteroge...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.1007/s40264-018-0782-8
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Researchers using observational data to understand drug effects must make a number of analytic design choices that suit the characteristics of the data and the subject of the study. Review of the published literature suggests that there is a lack of consistency even when addressing the same research question...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-013-0103-1
更新日期:2013-10-01 00:00:00
abstract::The development of antiretroviral therapy (ART) has dramatically increased the lifespan of HIV patients but treatment is complicated by numerous adverse effects and toxicities. ART complications include neuropsychiatric, metabolic, gastrointestinal, cardiac, and numerous other toxicities, and clinicians often have to ...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.1007/s40264-016-0440-y
更新日期:2016-10-01 00:00:00
abstract::Most antiviral drugs are nucleoside analogues with potential teratogenic, embryotoxic, carcinogenic and antiproliferative activities. They must be administered with caution during pregnancy, because some are known teratogens (e.g. amantadine) and a similar propensity cannot be entirely excluded for others (e.g. aciclo...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199410040-00002
更新日期:1994-04-01 00:00:00
abstract::The US FDA has issued safety alerts and required manufacturers of leukotriene-modifying agents (LTMAs), including montelukast, zafirlukast and zileuton, to include suicide and neuropsychiatric events as a precaution in the drug label. This paper reviews the existing evidence on the potential association between the LT...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/11587260-000000000-00000
更新日期:2011-07-01 00:00:00
abstract:INTRODUCTION:New pharmacovigilance legislation was adopted in the EU in 2010 and became operational in July 2012. The legislation placed an obligation on all national competent authorities (NCAs) and marketing authorisation holders (MAHs) to record and report cases of suspected adverse drug reactions (ADRs) received fr...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-017-0534-1
更新日期:2017-07-01 00:00:00
abstract::Narcolepsy is a life-long central nervous system (CNS) syndrome characterised by excessive sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed night-time sleep. Unsuccessfully treated narcolepsy confers increased risks on patients and on society due to the patient's increased chance of beco...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200225110-00004
更新日期:2002-01-01 00:00:00
abstract::Transdermal devices are now marketed for the delivery of systemic medication through the skin. Advantages associated with transdermal drug delivery include avoidance of first-pass metabolism and improved patient compliance. Drugs currently available by this route include scopolamine (hyoscine), nitroglycerin (glyceryl...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199410020-00004
更新日期:1994-02-01 00:00:00
abstract:BACKGROUND:Spontaneous reporting of adverse drug reactions (ADRs) is fundamental to drug safety surveillance (pharmacovigilance); however, substantial under-reporting exists and is the main limitation of the system. Several factors could favour under-reporting. OBJECTIVE:The aim of this pilot study was to assess the e...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/11319170-000000000-00000
更新日期:2010-05-01 00:00:00
abstract::Highly publicized safety issues of medicinal products in recent years and the accompanying political pressure have forced both the US FDA and the European Medicines Agency (EMA) to implement stronger regulations concerning pharmacovigilance. These legislative changes demand more proactive risk management strategies of...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/11586350-000000000-00000
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:Spontaneous reports of suspected adverse drug reactions to regulatory bodies and market authorization holders are important in pharmacovigilance. Follow-up information, which can be difficult to obtain, is often required from reporters; therefore, we developed targeted follow-up letters that we hoped would m...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/11318940-000000000-00000
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:The detection of new drug safety signals is of growing importance with ever more new drugs becoming available and exposure to medicines increasing. The task of evaluating information relating to safety lies with national agencies and, for international data, with the World Health Organization Programme for I...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/00002018-200023060-00004
更新日期:2000-12-01 00:00:00
abstract::As the variety and range of pharmaceutical agents available to the medical profession continues to expand, one unavoidable effect will be an increase in drug-induced disease, including cardiovascular disorders. However, given the high rates of cardiovascular disease and prevalence of recognised cardiovascular risk fac...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-200730090-00005
更新日期:2007-01-01 00:00:00
abstract::The main goal of pharmacological research in the field of topical corticosteroids (TCs) is to dissociate efficacy and adverse effects as much as possible. The optimal use of TCs, i.e. the careful evaluation of the benefit/risk ratio, depends on: (i) the chemical structure of the TC; (ii) the type of vehicle; (iii) the...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/00002018-199410050-00005
更新日期:1994-05-01 00:00:00
abstract:INTRODUCTION:Adverse drug events (ADEs) may represent an important item of expenditure for healthcare systems and their prevention could be associated with a relevant cost saving. OBJECTIVE:The objective of this study was to simulate the annual economic burden for ADEs in Tuscany (Italy) and the potential cost savings...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-018-0737-0
更新日期:2019-03-01 00:00:00
abstract::The generation of autoantibodies and autoimmune diseases such as systemic lupus erythematosus has been associated with the use of certain drugs in humans. Early reports suggested that procainamide and hydralazine were associated with the highest risk of developing lupus, quinidine with a moderate risk and all other dr...
journal_title:Drug safety
pub_type: 杂志文章,评审
doi:10.2165/11588500-000000000-00000
更新日期:2011-05-01 00:00:00
abstract:INTRODUCTION:While medical chart review remains the gold standard to validate health conditions or events identified in administrative claims and electronic health record databases, it is time consuming, expensive and can involve subjective decisions. AIM:The aim of this study was to describe the landscape of technolo...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.1007/s40264-019-00838-x
更新日期:2019-09-01 00:00:00
abstract:OBJECTIVE:Minocycline is an antibacterial drug used in the treatment of acne. Concern has been expressed over the possibility of severe adverse reactions to minocycline, including hepatitis. This study set out to identify and characterise reported cases of hepatotoxicity associated with the use of minocycline. METHODS...
journal_title:Drug safety
pub_type: 杂志文章
doi:10.2165/00002018-200023040-00006
更新日期:2000-10-01 00:00:00