Standard and intensive lipid-lowering therapy with statins for the primary prevention of vascular diseases: a population-based study.

PURPOSE: To describe the clinical profile of the patients that initiate statin therapy for the primary prevention of vascular diseases and to investigate the extent to which clinicians use intensive vs. standard regimens. METHODS: A cross-sectional analysis of nationwide individual data regarding individuals ≥ 11 years with a first prescription of statin, recorded between 1 January 2007 and 31 December 2011. Subjects were defined as intensive therapy initiators if a statin dose superior to simvastatin 40 mg (or equivalent dose if different statin) was first prescribed. Multivariable logistic regression models were built for dependent summary variables to evaluate the strength of the association between them and the use of intensive therapy. RESULTS: Overall, 69,737 patients receiving a first prescription of statin for the primary prevention of vascular diseases were identified. Predictors for intensive therapy initiation were male gender (adjusted OR: 1.28; 95%CI: 1.10-1.48), history of hypothyroidism (1.47; 1.17-1.85), current treatment of diabetes (1.18; 1.00-1.41), proteinuria (1.87; 1.12-3.12), age, and year of statin prescription. Modifiable risk factors associated with intensive therapy were elevated tryglicerides (1.63; 1.39-1.91), elevated LDL-C (1.96; 1.69-2.28), obesity (1.25; 1.07-1.47), smoking (1.32; 1.14-1.55), comedication with ezetimibe (3.76; 1.87-7.55), fibrates (1.96; 1.43-2.70) and calcium antagonists in women (1.42; 1.02-1.98). CONCLUSIONS: The use of intensive therapy with statins in primary prevention was not very high in absolute terms, but is increasing considerably. The association between intensive therapy and previous hypothyroidism or its combination with fibrates may raise additional safety and tolerability concerns.

Adverse events associated with the use of recommended vaccines during pregnancy: an overview of systematic reviews

Introduction: Maternal immunization is aimed at reducing morbidity and mortality in pregnant women and their newborns. Updated evidence synthesis of maternal-fetal outcomes is constantly needed to ensure that the risk-benefit of vaccination during pregnancy remains positive. Methods: An overview of systematic reviews (OoSRs) was performed. We searched The Cochrane Library, MEDLINE and EMBASE for SRs including recommended vaccines for maternal immunization reporting the following: abortion, stillbirth, chorioamnionitis, congenital anomalies, microcephaly, neonatal death, neonatal infection, preterm birth (PTB), low birth weight (LBW), maternal death and small for gestational age (SGA) from 2010 to April 2019. Quality and overlap of SRs was assessed. Results: Seventeen SRs were identified, eight of them included meta-analysis; quality was high in three SRs, moderate in six SRs, low in two SRs, and critically low in six SRs. Stillbirth and PTB were the most frequently reported outcomes by 15 and 13 SRs, respectively, followed by abortion (9 SRs), congenital anomalies (9 SRs), SGA (8 SRs), neonatal death (8 SRs), LBW (4 SRs), chorioamnionitis (3 SRs), maternal death (1 SR). SRs included mainly observational evidence for influenza and Tdap vaccines (11 SRs and 4 SRs, respectively); limited evidence was found for hepatitis (1 SR), yellow fever (1 SR), and meningococcal (1 SR) vaccines. Most of the SRs found no effect. Eight SRs found benefit/protection of influenza vaccine (for stillbirth, neonatal death, preterm birth, LBW), or Tdap vaccine (for preterm birth and SGA); one found a probable risk (chorioamnionitis/Tdap). The SRs for Hepatitis B, meningococcal and yellow fever vaccines were inconclusive. Conclusions: Definite risks were not identified for any vaccine and outcome; however better evidence is needed for all outcomes and vaccines. The available evidence in the SRs to support vaccine safety was based mainly on observational data. More RCTs with adequate reporting of maternal-fetal outcomes and larger high-quality observational studies are needed. (AU)

[Ethical and methodological quality of non-interventional post-authorization studies promoted by Hospital Pharmacy Departments]. / Calidad ética y metodológica de los estudios posautorización de tipo observacional promovidos por Servicios de Farmacia Hospitalaria.

OBJECTIVES: To describe the ethical and methodological quality of non-interventional post-authorization studies promoted by Hospital Pharmacy Departments (HPD). METHODS: HPD promoted studies in the 2009-2011 period included in the Spanish Agency of Medicines and Medical Devices (AEMPS) registry and/or published in "Farmacia Hospitalaria" were identified. The most relevant ethical and methodological characteristics were analyzed. Studies promoted by HPD were also compared with studies not promoted by HPD. RESULTS: Twenty two studies promoted by HPD, and registered in the AEMPS were identified. Within the registered studies HPD promoted studies had lower sample size estimation (41,5% vs 80%) and international scope (0% vs 24%) compared to non HPD promoted studies with significant differences (p < 0,05). None of the published studies in the journal Farmacia Hospitalaria have been registered in the AEMPS and had lower methodological quality than the registered studies promoted by HPD in characteristics such as presence of control group (3,8% vs 27,3%) (p = 0,0072) and the sample size estimation of (19,2% vs 42,8%) (p < 0,05). CONCLUSION: The management and the methodological and ethical characteristics of the studies promoted by HPD should be improved according to the regulation. The registration in the AEMPS might have a positive impact on the quality of these research protocols.

Objetivos: Describir la calidad ética y metodológica de los estudios posautorización de tipo observacional con medicamentos de uso humano promovidos por los Servicios de Farmacia Hospitalaria (SFH). Métodos: Se identificaron los estudios promovidos por los SFH registrados en la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) durante 2009-2011 y/o publicados en la revista Farmacia Hospitalaria en el mismo período. Se analizaron los aspectos éticos y metodológicos más relevantes. Con el fin de conocer las diferencias de los estudios promovidos por los SFH respecto a estudios realizados por otros promotores, se compararon con los estudios registrados durante 2003-2007. Resultados: Se registraron en la AEMPS 22 estudios promovidos por SFH, que comparados con aquellos realizados por promotores diferentes, mostraron un menor cumplimiento de los aspectos éticos recogidos en la normativa, así como resultados más discretos y estadísticamente significativos (p < 0,05), respecto a justificación del tamaño muestral (41,5% vs 80%) o ámbito internacional (0% vs 24%). Respecto a los estudios publicados en la revista Farmacia Hospitalaria (n = 52), ninguno fue registrado en la AEMPS. En comparación con los estudios registrados promovidos por SFH, presentaron menor calidad metodológica, en aspectos tales como presencia de grupo control (3,8% vs 27,3%) (p = 0,0072) o justificación del tamaño muestral (19,2% vs 42,8%) (p < 0,05). Conclusión: Existen aspectos administrativos, metodológicos y éticos de los estudios promovidos por los SFH que deben ser mejorados según la normativa. El registro en la AEMPS, parece tener un efecto positivo en el rigor científico y ético de los protocolos de investigación.

[Regulatory procedures of non-interventional post-authorization studies in Spain]. / Normativa de los estudios posautorización de tipo observacional en España.

This article describes the administrative and legal requirements to carry out non-interventional post-authorization studies in Spain.

Este artículo describe los procedimientos administrativos y requerimientos legales para llevar a cabo estudios observacionales con medicamentos de uso humano en España.

Normativa de los estudios posautorización de tipo observacional en España / Regulatory procedures of non-interventional post-authorization studies in Spain

Este artículo describe los procedimientos administrativos y requerimientos legales para llevar a cabo estudios observacionales con medicamentos de uso humano en España (AU)

This article describes the administrative and legal requirements to carry out non-interventional post-authorization studies in Spain (AU)

Calidad ética y metodológica de los estudios posautorización de tipo observacional promovidos por Servicios de Farmacia Hospitalaria / Ethical and methodological quality of non-interventional post-authorization studies promoted by hospital pharmacy departments

Objetivos: Describir la calidad ética y metodológica de los estudios posautorización de tipo observacional con medicamentos de uso humano promovidos por los Servicios de Farmacia Hospitalaria (SFH). Métodos: Se identificaron los estudios promovidos por los SFH registrados en la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) durante 2009-2011 y/o publicados en la revista Farmacia Hospitalaria en el mismo período. Se analizaron los aspectos éticos y metodológicos más relevantes. Con el fin de conocer las diferencias de los estudios promovidos por los SFH respecto a estudios realizados por otros promotores, se compararon con los estudios registrados durante 2003-2007. Resultados: Se registraron en la AEMPS 22 estudios promovidos por SFH, que comparados con aquellos realizados por promotores diferentes, mostraron un menor cumplimiento de los aspectos éticos recogidos en la normativa, así como resultados más discretos y estadísticamente significativos (p < 0,05), respecto a justificación del tamaño muestral (41,5% vs 80%) o ámbito internacional (0% vs 24%). Respecto a los estudios publicados en la revista Farmacia Hospitalaria (n = 52), ninguno fue registrado en la AEMPS. En comparación con los estudios registrados promovidos por SFH, presentaron menor calidad metodológica, en aspectos tales como presencia de grupo control (3,8% vs 27,3%) (p = 0,0072) o justificación del tamaño muestral (19,2% vs 42,8%) (p < 0,05). Conclusión: Existen aspectos administrativos, metodológicos y éticos de los estudios promovidos por los SFH que deben ser mejorados según la normativa. El registro en la AEMPS, parece tener un efecto positivo en el rigor científico y ético de los protocolos de investigación (AU)

Objectives: To describe the ethical and methodological quality of non-interventional post-authorization studies promoted by Hospital Pharmacy Departments (HPD). Methods: HPD promoted studies in the 2009-2011 period included in the Spanish Agency of Medicines and Medical Devices (AEMPS) registry and/or published in "Farmacia Hospitalaria" were identified. The most relevant ethical and methodological characteristics were analyzed. Studies promoted by HPD were also compared with studies not promoted by HPD. Results: Twenty two studies promoted by HPD, and registered in the AEMPS were identified. Within the registered studies HPD promoted studies had lower sample size estimation (41,5% vs 80%) and international scope (0% vs 24%) compared to non HPD promoted studies with significant differences (p < 0,05). None of the published studies in the journal Farmacia Hospitalaria have been registered in the AEMPS and had lower methodological quality than the registered studies promoted by HPD in characteristics such as presence of control group (3,8% vs 27,3%) (p = 0,0072) and the sample size estimation of (19,2% vs 42,8%) (p < 0,05). Conclusion: The management and the methodological and ethical characteristics of the studies promoted by HPD should be improved according to the regulation. The registration in the AEMPS might have a positive impact on the quality of these research protocols (AU)