[New Royal Decree on clinical trials: main implications for emergency medicine physicians who do research]. / Principales implicaciones del nuevo Real Decreto de ensayos clínicos para los urgenciólogos investigadores.

OBJECTIVES: The new European Union directives affecting clinical trials of medicines introduced important changes for Spain, leading to the publication of a Royal Decree regulating the conduct of clinical trials that went into effect in January 2016. The decree sets out the principles for complying with the EU directives, regulates the work of institutional review boards (IRBs) or ethics committees that review research proposals, introduces means to facilitate clinical research, and clarifies the role of the Spanish register of clinical trials, among other topics. This paper discusses the main changes that have been introduced, especially those intended to facilitate research, such as the new concepts of low intervention trial and noncommercial clinical research. These concepts may be particularly useful for clinical trials designed by emergency medicine physicians. We also comment on changes affecting vulnerable populations and the documents that must be presented to both the researchers' IRB and the Spanish Agency for Medicines and Health Care Products.

OBJETIVO: La puesta en marcha de una nueva regulación europea para la realización de ensayos clínicos con medicamentos ha supuesto cambios importantes en España, que se han traducido en la publicación de un Real Decreto que regula la realización de ensayos clínicos y que entró en vigor en enero de 2016. El nuevo Real Decreto pretende sentar las bases para trabajar de acuerdo con la normativa europea, regula los comités de ética de investigación con medicamentos (CEIm) que deben evaluar los estudios, introduce medidas para facilitar la investigación clínica y clarifica el Registro Español de Estudios Clínicos, entre otras cosas. Se revisan las modificaciones más importantes, sobre todo las que van dirigidas a facilitar la investigación, como las nuevas figuras que se crean de "Ensayo clínico de bajo nivel de intervención" e "Investigación clínica sin ánimo comercial". Estas figuras pueden resultar especialmente positivas para la realización de ensayos clínicos por parte de los urgenciólogos. También se comentan los cambios que se establecen para la investigación en poblaciones vulnerables y las modificaciones en la documentación que hay que presentar tanto al CEIm como a la Agencia Española de Medicamentos y Productos Sanitarios.

Principales implicaciones del nuevo Real Decreto de ensayos clínicos para los urgenciólogos investigadores / New Royal Decree on clinical trials: main implications for emergency medicine physicians who do research

La puesta en marcha de una nueva regulación europea para la realización de ensayos clínicos con medicamentos ha supuesto cambios importantes en España, que se han traducido en la publicación de un Real Decreto que regula la realización de ensayos clínicos y que entró en vigor en enero de 2016. El nuevo Real Decreto pretende sentar las bases para trabajar de acuerdo con la normativa europea, regula los comités de ética de investigación con medicamentos (CEIm) que deben evaluar los estudios, introduce medidas para facilitar la investigación clínica y clarifica el Registro Español de Estudios Clínicos, entre otras cosas. Se revisan las modificaciones más importantes, sobre todo las que van dirigidas a facilitar la investigación, como las nuevas figuras que se crean de «Ensayo clínico de bajo nivel de intervención» e «Investigación clínica sin ánimo comercial». Estas figuras pueden resultar especialmente positivas para la realización de ensayos clínicos por parte de los urgenciólogos. También se comentan los cambios que se establecen para la investigación en poblaciones vulnerables y las modificaciones en la documentación que hay que presentar tanto al CEIm como a la Agencia Española de Medicamentos y Productos Sanitarios (AU)

The new European Union directives affecting clinical trials of medicines introduced important changes for Spain, leading to the publication of a Royal Decree regulating the conduct of clinical trials that went into effect in January 2016. The decree sets out the principles for complying with the EU directives, regulates the work of institutional review boards (IRBs) or ethics committees that review research proposals, introduces means to facilitate clinical research, and clarifies the role of the Spanish register of clinical trials, among other topics. This paper discusses the main changes that have been introduced, especially those intended to facilitate research, such as the new concepts of low intervention trial and noncommercial clinical research. These concepts may be particularly useful for clinical trials designed by emergency medicine physicians. We also comment on changes affecting vulnerable populations and the documents that must be presented to both the researchers’ IRB and the Spanish Agency for Medicines and Health Care Products (AU)

Bioequivalence study of two formulations of enalapril, at a single oral dose of 20 mg (tablets): A randomized, two-way, open-label, crossover study in healthy volunteers.

BACKGROUND: Enalapril maleate is the monoethyl ester prodrug of enalapril- at, an angiotensin-converting enzyme inhibitor indicated in the management of essential and renovascular hypertension, and in the treatment of congestive heart failure and in asymptomatic patients with left ventricular dysfunction and an ejection fraction of ≥35%. Enalapril has little pharmacologic activity until hydrolyzed in vivo to enalaprilat. OBJECTIVE: The aim of the present study was to compare the bioavailability and tolerability of 2 commercial brands (test and reference formulations) of enalapril tablets (20 mg), described as the rate and extent of absorption of the active moiety, to assess their bioequivalence. METHODS: This single-dose, randomized, 2-way, open-label, crossover study in healthy volunteers aged 18 to 40 years was conducted at the Clinical Pharmacology Study Unit, Hospital Clínico San Carlos (Madrid, Spain). Subjects were randomized to receive (under fasting conditions) either the test or reference formulation of enalapril (20-mg tablet) at study period 1 and the opposite formulation at study period 2. Study periods were separated by a washout period of at least 7 days. During each study period, 15 plasma extractions were made to determine enalapril and enalaprilat plasma concentrations and to calculate the pharmacokinetic (PK) properties (maximal plasma drug concentration [Cmax], time to Cmax [Tmax], area under the plasma concentration-time curve [AUC] to the last measurable concentration [AUCt], AUC from time 0 to infinity [AUC0-∞], mean residence time, and elimination half-life [tl2]) of both. Physical examination, subject interview, laboratory analyses, electrocardiogram, and blood pressure (BP) were used to assess tolerability. RESULTS: Twenty-four subjects were included in the study (12 men, 12 women; mean [SD] age, 22.8 [2.2] years [range, 19-30 years]). Of these, 1 subject (4.2%) withdrew from the study for personal reasons; thus, PK and statistical analyses included results from 23 subjects. No statistically significant sequence or period effect was found. Tmax was not statistically different between the 2 formulations, and the 90% CI calculated for Tmax for the difference of the medians was within the predefined range. The 90% CIs of the logarithmically transformed concentration-derived parameters (Cmax AUCt, and AUC0-∞) also were within the predefined range; thus, the 2 formulations are considered bioequivalent. For both formulations, systolic and diastolic BPs showed significant reductions compared with baseline values (P < 0.05). Seven adverse effects were recorded, all of them transient and none of severe intensity. CONCLUSIONS: In this study of 2 commercial brands (test and reference formulations) of enalapril in healthy subjects, designed and conducted under Good Clinical Practice guidelines, a similar rate and extent of absorption for both formulations were found to be bioequivalent. Both formulations produced a significant decrease in BP values and were generally well tolerated.