Policy-induced selection bias in pharmacoepidemiology: The example of coverage for Alzheimer's medications in British Columbia.

PURPOSES: To assess the impact of a government-sponsored reimbursement policy for cholinesterase inhibitors (ChEIs) on trends in physician visits with a diagnosis of Alzheimer's disease (AD). METHODS: Longitudinal population-based study using interrupted time series methods. British Columbia outpatient claims data for individuals aged 65 and older were used to compute monthly AD visit rates and examine the impact of the ChEI reimbursement policy on the coding of AD. We examined trends in the number of patients with AD visits, the number of AD visits per patient, and visits with "competing" diagnoses (mental, neurological, and cerebrovascular disorders and accidental falls). Finally, we described demographic and clinical features of diagnosed patients. RESULTS: We analyzed 1.9 million AD visits. Faster growth in recorded AD visits was observed after the policy was implemented, from monthly growth of 7.5 visits per 100 000 person-months before the policy (95% confidence interval [CI], 6.1-8.9) to monthly growth of 16.5 per 100 000 person-months after the policy (95% CI, 14.8-18.3). After the implementation of the policy, we observed increased growth in the number of patients with recorded AD visits and the number of AD visits per patient, as well as a shift in diagnoses away from mental diseases and accidental falls to AD (diagnosis substitution). CONCLUSIONS: British Columbia's reimbursement policy for ChEIs was associated with a significant acceleration in Alzheimer's visits. Evaluations of health services utilization and clinical outcomes following drug policy changes need to consider policy-induced influences on the reliability of the data used in the analysis.

The ENCePP Code of Conduct: A best practise for scientific independence and transparency in noninterventional postauthorisation studies.

PURPOSE: The ENCePP Code of Conduct provides a framework for scientifically independent and transparent pharmacoepidemiological research. Despite becoming a landmark reference, practical implementation of key provisions was still limited. The fourth revision defines scientific independence and clarifies uncertainties on the applicability to postauthorisation safety studies requested by regulators. To separate the influence of the funder from the investigator's scientific responsibility, the Code now requires that the lead investigator is not employed by the funding institution. METHOD: To assess how the revised Code fits the ecosystem of noninterventional pharmacoepidemiology research in Europe, we first mapped key recommendations of the revised Code against ISPE Good Pharmacoepidemiology Practices and the ADVANCE Code of Conduct. We surveyed stakeholders to understand perceptions on its value and practical applicability. Representatives from the different stakeholders' groups described their experience and expectations. RESULTS: Unmet needs in pharmacoepidemiological research are fulfilled by providing unique guidance on roles and responsibilities to support scientific independence. The principles of scientific independence and transparency are well understood and reinforce trust in study results; however, around 70% of survey respondents still found some provisions difficult to apply. Representatives from stakeholders' groups found the new version promising, although limitations still exist. CONCLUSION: By clarifying definitions and roles, the latest revision of the Code sets a new standard in the relationship between investigators and funders to support scientific independence of pharmacoepidemiological research. Disseminating and training on the provisions of the Code would help stakeholders to better understand its advantages and promote its adoption in noninterventional research.

A retrospective study on the utilization of and expenditure for immunosuppressants for organ transplant recipients in Taiwan--updated to 2006.

We sought to examine the utilization of and expenditure for immunosuppressants among transplant recipients under the Taiwan global budget system updated from 2004 to 2006, as provided by the Taiwan Longitudinal Health Insurance Database (2005). By using all ambulatory care orders (OO) of files from 2002 to 2006, we identified immunosuppressive agents by the Anatomic Therapeutic Chemical (ATC) code. We selected and analyzed all immunosuppressants classified into the L04 group. For the analytic work, a generalized linear model was developed to examine the effect of time and different ATC subgroup immunosuppressants on drug expenditures. Compared with the previous report covering 1999-2003, wherein the most frequently prescribed immunosuppressive agents were cyclosporine (43%), mycophenolate (30.8%), and tacrolimus (21.3%), the updated information showed cyclosporine 36.8%, tacrolimus 30.17%, and mycophenolate 21.46%. In 2005, the total drug expenditure for tacrolimus was higher than for cyclosporine which was the major immunosuppressive agent used previously. Wald chi-square tests on the effect of time from 2001 to 2006 with different immunosuppressive drug classes showed a significant result (P<.01), namely, increased drug expenditures over time owing to different ATC classes of immunosuppressants. Projecting drug expenditure using a pharmacoepidemiology approach could show the overall picture of cost utilization, including the complex determinants of price inflation, utilization, and physician behavior.

Variable access to clopidogrel in a harmonized EU market.

OBJECTIVES: This study focuses on the different national coverage and reimbursement strategies and their consequences for access to clopidogrel, a drug with a central European Union (EU) registration. Our objectives are 1) to assess whether changes in reimbursement policies in EU member states influenced clopidogrel prescribing; and 2) to determine whether clopidogrel-specific policy characteristics, general characteristics of the health system, or indicators for the amount of cardiovascular care delivered were associated with the level of clopidogrel prescribing. METHODS: Data were collected in Austria, Belgium, Denmark, Germany, Hungary, Portugal, Slovenia, The Netherlands, and the United Kingdom (England). Utilization rates were expressed as defined daily doses (DDDs)/1000 persons/day. To determine whether changes in reimbursement policies influenced clopidogrel utilization, a segmented linear regression approach was used. RESULTS: Clopidogrel prescribing varied widely in the studied countries, from 2.76 (The Netherlands) to 6.83 (Belgium) DDDs/1000 persons/day (March 2005). Six countries had therapeutic indication restrictions to clopidogrel use. Health system characteristics did not explain variation in clopidogrel prescribing. CONCLUSION: A disconnect will be indicated in this study between the concept of a harmonized EU pharmaceuticals market and the reality in an individual member state. Although clopidogrel was centrally registered in the EU, policy measures at the national level result in different roles in clinical practice for this drug.

Costos directos y aspectos clínicos de las reacciones adversas a medicamentos en pacientes hospitalizados en el servicio de medicina interna de una institución de tercer nivel de Bogotá / Direct costs and clinical aspects of adverse drug reactions in patients admitted to a level 3 hospital internal medicine ward

Introducción. Las reacciones adversas a medicamentos constituyen un problema clínico frecuente en el ámbito hospitalario y aumentan los costos de la atención en salud. En Colombia son pocos los estudios realizados para evaluarlas desde el punto de vista clínico y económico.Objetivo. Determinar los costos generados por las reacciones adversas a medicamentos en pacientes hospitalizados en el servicio de medicina interna de una institución de tercer nivel e identificar sus principales características clínicas. Materiales y métodos. Se hizo seguimiento intensivo de los pacientes del servicio de medicina interna durante un período de cinco meses para detectar reacciones adversas. La información se recolectó mediante un formulario basado en el formato de reporte del INVIMA. La probabilidad de causalidad se generó mediante el algoritmo de Naranjo. Se calcularon los costos directos desde la perspectiva del pagador teniendo en cuenta la estancia adicional, los medicamentos, los exámenes paraclínicos, los procedimientos, los traslados a la unidad de cuidado intermedio o intensivo y los insumos. Resultados. Se detectaron 268 reacciones adversas en 208 de los 836 pacientes que ingresaron en el servicio (proporción de incidencia, 25,1 por ciento; razón de presencia, 0,32). El 74,3 por ciento se clasificó como probable; el 92,5 por ciento fue tipo A; el 81,3 por ciento correspondió a reacciones moderadas. El sistema más frecuentemente afectado fue el hematológico (33,9 por ciento). Los medicamentos que actúan en sangre fueron los más frecuentemente relacionados (37,6 por ciento). El costo generado por la atención de las reacciones adversas fluctuó entre $93'633.422 y $122'155.406. Conclusiones. Dado el impacto negativo de las reacciones adversas en el bienestar de los pacientes, los recursos que se emplean en su atención y la proporción importante de reacciones adversas prevenibles, se requieren programas operativos de farmacovigilancia institucional.

Enhanced funding of pharmacoepidemiology through patenting the disclosure of adverse event information.

PURPOSE: Known drug adverse events have been estimated to be between the 4th and 6th leading cause of death in the US (1). There are currently insufficient funds to perform the quantity and quality of studies necessary to ensure all drug adverse events are discovered in a timely fashion. METHODS/RESULTS: One approach to attract capital for pharmacoepidemiology studies is to patent the discoveries from the studies. Potential investors, whether executives of branded pharmaceutical companies or not, will consider funding pharmacoepidemiology studies if they can expect to receive competitive returns on their investments. Pharmacoepidemiolists who desire to patent their discoveries should seek novel drug-drug and drug-food interactions or negative interactions between drugs and certain phenotypes, genotypes or preexisting comorbidities. CONCLUSION: These discoveries can lead to safer, and patentable, use of the drug by avoiding these interactions.

How do we best detect toxic effects of drugs taken during pregnancy? A EuroMap paper.

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 combines some of the available datasets in Europe. Using these sources as a starting point, one can develop a system that has sufficient power to detect even rare diseases like congenital malformations and sufficient diversity to detect several possible outcomes from spontaneous abortions to childhood disorders. We also suggest that case-crossover designs should be used in case-control monitoring systems that carry a high risk of recall bias. These considerations are based upon our results from a European Union-funded concerted action called EuroMaP (Medicine and Pregnancy).

Organizational context and taxonomy of health care databases.

An understanding of the organizational context and taxonomy of health care databases is essential to appropriately use these data sources for research purposes. Characteristics of the organizational structure of the specific health care setting, including the model type, financial arrangement, and provider access, have implications for accessing and using this data effectively. Additionally, the benefit coverage environment may affect the utility of health care databases to address specific research questions. Coverage considerations that affect pharmacoepidemiologic research include eligibility, the nature of the pharmacy benefit, and regulatory aspects of the treatment under consideration.