Application of data mining techniques in pharmacovigilance

AIMS: To discuss the potential use of data mining and knowledge discovery in databases for detection of adverse drug events (ADE) in pharmacovigilance. METHODS: A literature search was conducted to identify articles, which contained details of data mining, signal generation or knowledge discovery in relation to adverse drug reactions or pharmacovigilance in medical databases. RESULTS: ADEs are common and result in significant mortality, and despite existing systems drugs have been withdrawn due to ADEs many years after licensing. Knowledge discovery in databases (KDD) is a technique which may be used to detect potential ADEs more efficiently. KDD involves the selection of data variables and databases, data preprocessing, data mining and data interpretation and utilization. Data mining encompasses a number of statistical techniques including cluster analysis, link analysis, deviation detection and disproportionality assessment which can be utilized to determine the presence of and to assess the strength of ADE signals. Currently the only data mining methods to be used in pharmacovigilance are those of disproportionality, such as the Proportional Reporting Ratio and Information Component, which have been used to analyse the UK Yellow Card Scheme spontaneous reporting database and the WHO Uppsala Monitoring Centre database. The association of pericarditis with practolol but not with other beta-blockers, the association of captopril and other angiotensin-converting enzymes with cough, and the association of terfenadine with heart rate and rhythm disorders could be identified by mining the WHO database. CONCLUSION: In view of the importance of ADEs and the development of massive data storage systems and powerful computer systems, the use of data mining techniques in knowledge discovery in medical databases is likely to be of increasing importance in the process of pharmacovigilance as they are likely to be able to detect signals earlier than using current methods.     

DIALOG医学类数据库资源概览

介绍国外有关医学药品类及与人类生命科学息息相关的数据库 ,着重介绍其包括的内容、收藏年限、更新周期等 ,通过这些数据库的概述 ,不仅可使从事医学方面的人士知道从哪可得到自己所需的信息 ,也可使情报工作者从中获得一些数据库建设的启迪     

Vulnerability among Vietnamese illicit drug users in Australia: challenges for change

A broad range of vulnerabilities, risk factors and challenges for change were examined in order to better understand why ethnic Vietnamese have the highest profile in Australia in relation to illicit drug use. A literature review of vulnerability and risk factors experienced by ethnic Vietnamese people in Australia was conducted. Emerging themes and concepts were tested against the 1996 Australian Census (Victoria), databases specific to illicit drug use, and the outcomes of key informant interviews and community consultations. Vietnam-born Australians are the third largest ethnic community in Australia. Due to high unemployment, poor English proficiency, experiences of racism, social and economic difficulties, inter-generational conflicts and acculturation, the ethnic Vietnamese community has become vulnerable to involvement with illicit drug use and distribution. Addressing drug problems among the ethnic Vietnamese community in Australia is hampered by a lack of structured, appropriate education and employment programs, biased media reporting and poor utilisation of drug treatment services. Socio-economic disadvantage and level of exclusion from the legitimate economy heighten involvement in illicit drug use and its associated harms.     

Review of procedures for protecting human subjects in recent clinical studies of pesticides

Arguments have been made for and against the regulatory use of data from human subjects on both scientific and ethical grounds. One argument against the use of data from human clinical studies involving pesticides asserts that such data are obtained from studies that do not follow the Common Rule (40 CFR 26), which provides procedures for protecting human subjects in studies funded by federal agencies, including the U.S. Environmental Protection Agency (U.S. EPA). Although privately conducted studies using human subjects are not legally subject to or required to comply with the Common Rule, the protections of the Declaration of Helsinki and the International Conference on Harmonisation (ICH) Good Clinical Practice are commonly followed. We sought to answer the question of whether recent human clinical studies with insecticides performed according to Good Clinical Practice provided volunteers with the same protections as the Common Rule. All three sets of guidance have in common the intent to protect volunteer human subjects by providing standards for the conduct of studies in which they participate. This analysis compares the elements of the Common Rule with comparable elements from the Declaration of Helsinki and Good Clinical Practice to evaluate similarities and differences in procedural requirements. It then evaluates the documentation from 15 recent human studies of twelve insecticides conducted at four clinical laboratories in order to determine whether the conduct of those studies is consistent with the protections of the Common Rule. There were some cases for which we could not verify compliance with certain Common Rule elements; however, based on our evaluation it is apparent that the studies we reviewed were conducted in a manner substantially consistent with the fundamental protections of the Common Rule-voluntary participation, informed consent, and review by an ethical committee or institutional review board.     

Using databases for studying and comparing health care costs and resource use

Data sources such as medical insurance claims are increasingly used in health outcomes research. We present opportunities and limitations associated with the use of such data for conducting studies of health care costs and resource use. We also provide examples on using databases for conducting research when the primary objective is to study costs or resource use. This information is intended to be helpful to experienced health services researchers and to those new to the field of either outcomes research or cost effectiveness research. We examine the reasons for using databases to study costs and resource use, desirable attributes of databases used for this purpose, potential pitfalls, other issues associated with conducting cost and resource use studies with databases, and appropriate methods for this research. Through examples and references, we examine issues to be considered in each of these areas, and make recommendations. Strengths and limitations of databases are indicated. Research using claims data to determine health care cost and resource use should be carried out responsibly. Limitations must be acknowledged for research using databases, and appropriate methods must be used. Still, databases represent a rich opportunity to conduct research in health care costs and resource use, and much can be learned using databases. Copyright © 2001 John Wiley & Sons, Ltd.     

4种用药方案治疗2型糖尿病的成本-效果分析

目的:评价4种用药方案治疗2型糖尿病的经济效果。方法:运用药物经济学原理对二甲双胍+格列吡嗪(A)、二甲双胍+吡格列酮(B)、二甲双胍+瑞格列奈(C)、二甲双胍+诺和灵30R(D)4种用药方案的成本-效果进行分析。结果:总有效率各组间无显著性差异,A、B、C、D组成本-效果比分别为2.21、3.21、2.63、6.54,B、C、D组相对于A组的增量成本-效果比分别为64.82、—6.41、51.25。结论:A方案为较佳选择。     

Pattern recognition in health insurance claims databases

Information in claims databases resides in data patterns rather than in data elements. Finding this information requires new terminology, a willingness to pose questions of form rather than specific hypotheses, and a quality control system that elevates the correctness of data relations above the validity of single facts. The language of claims data is a newspeak of CPT (Current Procedural Terminology), HCPCS (Health Care Financing Agency Common Procedure Coding System), ICD (International Classification of Disease), and NDC (National Drug Codes) for pharmaceutical codes. The techniques of pattern discovery are really ways of asking the data for classes of relations, and they vary in their reliance on external information. Sometimes, the question is entirely constrained by preceding factors. Other times we may recast the natural history of disease into a claims context and ask the data to give us the shape of disease evolution. We can use highly automated systems to evaluate the relations between prespecified factors, or empirical techniques to search out common relations that we have not specified in advance. Using massive data sets requires that quality control corresponds to the nature of the high‐level information that we derive from large databases. Copyright © 2001 John Wiley & Sons, Ltd.     

Substance Abuse Among Asian Indians in the United States: A Consideration of Cultural Factors in Etiology and Treatment

We explore cultural factors that contribute to substance use in the Asian Indian population in the United State and propose culturally sensitive treatment, with an emphasis on family issues. The 2000 U.S. Census figures show that Asian Indians residing in this country have grown to about 1.7 million from the 1990 U.S. Census figure of 815,000. On average, Asian Indians have a higher level of education and proficiency in English compared with many other new immigrant groups. The median family income for Asian Indians in the United State in 1999 was $70,708, compared with $53,356 for Whites. Based on these statistics, Asian Indians are erroneously labeled a “model minority.” However, a closer look shows that Asian Indians are paid lower than their White counterparts with comparable education. Also, many Asian Indians live in areas where the cost of living is higher, and high family income does not automatically translate into a higher standard of living. There is large within-group disparities in income, and Asian Indian families might fall at either end of the Socio-economic status (SES) pole.     

Substance abuse1 among Asian Indians in the United States: a consideration of cultural factors in etiology and treatment

We explore cultural factors that contribute to substance use in the Asian Indian population in the United State and propose culturally sensitive treatment, with an emphasis on family issues. The 2000 U.S. Census figures show that Asian Indians residing in this country have grown to about 1.7 million from the 1990 U.S. Census figure of 815,000. On average, Asian Indians have a higher level of education and proficiency in English compared with many other new immigrant groups. The median family income for Asian Indians in the United State in 1999 was 70,708 US dollars, compared with 53,356 US dollars for Whites. Based on these statistics, Asian Indians are erroneously labeled a "model minority." However, a closer look shows that Asian Indians are paid lower than their White counterparts with comparable education. Also, many Asian Indians live in areas where the cost of living is higher, and high family income does not automatically translate into a higher standard of living. There is large within-group disparities in income, and Asian Indian families might fall at either end of the Socio-economic status (SES) pole.     

Drugs and Youth: A Review of the Problem

Recent research concerning motives for alcohol and drug use is summarized and reviewed in the context of seeking common reasons for using alcohol and other drugs. Common motives were found which correlated with both drinking and other drug-taking behavior, and specific motives were also found which were related to use of alcohol, marijuana, and other drugs. The implication of these findings for both primary and secondary prevention efforts is discussed.     

Economics of institutional pharmacy services under national health insurance in Australia.

The development and effect of the National Health Scheme on institutional Health Scheme on institutional pharmaceutical services in Australia are discussed. Government control over drug costs and the provision of pharmacy services, with its effect on both community and institutional practice, is assessed. Methods of improving the present system of health insurance under the Pharmaceutical Benefits Scheme in Australia are suggested, including their relevance to health care in the United States.     

Multinational pharmaceutical companies gather in Berlin

The 39th Annual General Meeting of the Pharma Documentation Ring (PDR) was held in Berlin, Germany, on September 26, 1997. Common themes reported on included the impact and widespread use of intranet technology; expansion in end-user searching; experience with electronic journals; and programs for the development of electronic archiving and document management systems. Other sessions discussed aspects of chemistry systems; copyright; drug information systems on development products; information management, in-house management of databases; Intranet/Internet activities; and patents. The core topic presented at the meeting involved an overview on document delivery/electronic journals. There is considerable activity in this area by primary and secondary publishers with real momentum seen in the area of electronic document delivery services on the Internet. The 40th anniversary of the PDR will be celebrated at the upcoming AGM, to be held in Montpellier, France, September 30 October 2, 1998.     

Genome-wide evaluation of the public SNP databases

The public SNP databases are an important resource for groups performing genetic association and linkage studies. Both academic and commercial groups are developing large numbers of genotyping assays for SNPs in candidate genes or spread across the genome. These databases now contain in excess of 6 million SNPs that have been generated using a large number of methods and cohorts. Today, however, only a small fraction of these SNPs are well characterized and validated. The latest release of dbSNP contains approximately 3.7 million non-redundant entries, only 0.5 million of which are validated, and 0.2 million of which have frequency information. Users of these databases have several common questions. How many of the SNPs are real? What is the frequency spectrum of the SNPs in these databases? What is the distribution picture of these SNPs across different ethnic and geographical populations? What fraction of the total number of SNPs is already captured by these databases? In order to address these questions, we compared the public SNPs against a well-characterized collection of gene-centric SNPs that we have developed. From this comparison, we find that > 50% of high frequency SNPs in the genome (> 20% minor allele frequency) have already been captured by these databases. The coverage drops dramatically below frequencies of 10%. At high frequencies, there is no sampling bias with respect to ethnicity or to regions of the genome. Finally, a relatively large fraction (> 40%) of SNPs in these databases were not seen in our study, which means that they are either of very low frequency, mismapped, or not polymorphic at all.     

ADRIS--The Adverse Drug Reactions Information Scheme

Under the Adverse Drug Reactions Information Scheme (ADRIS) data and knowledge relevant to the etiology of adverse drug reactions (ADRs) such as chemical structure of parent compounds, metabolites, covalent adducts, nucleic acid and protein sequences, protein structures, pharmaco-, toxico- and enzyme kinetics, pharmaco- and toxicodynamics, protein interactions, molecular pathways and complexes, as well as toxicological and clinical outcomes, are collected and logically and semantically related. ADRIS reflects the ontological prerequisite for the creation of databases and knowledge discovery systems for the abstraction and visualization of theragenomic concepts. A final outcome is the prediction of ADRs based on a profound knowledge of drug function and the molecular basics for personalized drug safety and eventually, personalized medicine.     

How the literature can help in medical treatment

Experience from various hospitals has shown that the information received from journal literature, indexes and databases has a direct positive impact in improving patient care. Twenty percent of the doctors interviewed advised that the information supplied to them directly influenced their treatment of patients and altered their methods applied in patient care. Speed and precision is very important in supplying information to the medical doctors and health professionals in order to give them time to digest the information before the decision on treatment is made. Some of the indexes and databases are briefly described, which will give the necessary information with the minimum time and effort for use in medical treatment. Machinery of access to the databases and indexes is suggested with the accent on the microcomputer programs which will allow even the health professionals and librarians who might be unfamiliar with the search techniques to use the databases and indexes effectively.     

Perspectives on the use of data mining in pharmaco-vigilance.

In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.In this paper, we provide an overview of: (i) the statistical and operational attributes of several currently used methods and their strengths and limitations; (ii) information about the characteristics of various postmarketing safety databases with which these tools can be deployed; (iii) analytical considerations for using safety data-mining methods and interpreting the results; and (iv) points to consider in integration of safety data mining with traditional pharmaco-vigilance methods. Perspectives from both the FDA and the industry are provided.Data mining is a potentially useful adjunct to traditional pharmaco-vigilance methods. The results of data mining should be viewed as hypothesis generating and should be evaluated in the context of other relevant data. The availability of a publicly accessible global safety database, which is updated on a frequent basis, would further enhance detection and communication about safety issues.     

Evaluation of the Threshold of Toxicological Concern (TTC) – Challenges and approaches

Thresholds of Toxicological Concern (TTCs) have been used in the risk assessment of chemicals to which humans are exposed at very low levels. TTC values were developed using data from rodent cancer bioassays and from oral chronic and sub-chronic toxicity studies for non-cancer effects. The workshop assessed the adequacy and fitness for purpose of the TTC approach and the potential for future modifications of critical aspects. The current TTC value for cancer was considered adequate and fit for purpose because it is derived by linear extrapolation from the lowest TD₅₀ for each compound in the largest available rodent carcinogenicity database. The database on non-cancer endpoints was considered adequate and fit for purpose because the chemical domain, the distributions of NOAELs and the calculated TTC values are comparable across different databases. Application of the TTC approach gives conclusions compatible with the risk assessment approaches currently used by international advisory committees. The workshop recognised the desirability of developing better tools to assess the comparability of the chemical domain covered in different toxicological databases, and the need to develop an internationally acceptable framework and databases for updating the aspects critical to application of the TTC approach.