Clinical research and drug regulation in the challenging times of individualized therapies: A pivotal role of clinical pharmacology.

Since the 1980s, medical specialists in Clinical Pharmacology have been playing a crucial role in the development of drug regulation in Spain. In this article we report on the activities carried out and the prospects for development in three very relevant areas from the regulatory perspective: 1) the development of stable public infrastructures to facilitate non-commercial clinical research with medicines, 2) the regulatory aspects of individual access to medicines in special situations, beyond their regular access after marketing approval and funding by the National Health System, and 3) the challenges of development and access to advanced therapies, with special reference to the figure of the hospital exemption.

Implementing pharmacogenetics in clinical trials: considerations about current methodological, ethical, and regulatory challenges.

Introduction: The implementation of pharmacogenetic analysis within clinical trials faces methodological, ethical, and regulatory challenges, as well as tackling the difficulty in obtaining actionable information with a sufficient level of evidence to enable its integration into routine clinical practice.

Areas Covered: We discuss the current status of pharmacogenetics integration in clinical trials, underscore the associated challenges, and make some suggestions on the aspects to address in any clinical trial including a pharmacogenetic evaluation. We conducted a literature review, thoroughly reviewed the applicable regulations and available guidelines, and assessed the application dossiers submitted for evaluation to the Ethics committee of Hospital La Paz (Madrid, Spain) to extract information related to inclusion of pharmacogenetics evaluations.

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit.

Background: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network.

Objective: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public.

Acute Poisoning Readmissions to an Emergency Department of a Tertiary Hospital: Evaluation through an Active Toxicovigilance Program.

The aim of this study is to investigate hospital readmissions during 1 year after acute poisoning cases (APC), analyze the temporal behavior of early readmissions (ER) (in the month after the index episode) and predict possible ER. A descriptive analysis of the patients with APC assisted between 2011 and 2016 in the Emergency Department of Hospital La Paz is presented, and various methods of inferential statistics were applied and confirmed by Bayesian analysis in order to evaluate factors associated with total and early readmissions. Out of the 4693 cases of APC included, 968 (20.

Experience of a Strategy Including CYP2C19 Preemptive Genotyping Followed by Therapeutic Drug Monitoring of Voriconazole in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation.

Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype.

Health Care Workers' Reasons for Choosing Between Two Different COVID-19 Prophylaxis Trials in an Acute Pandemic Context: Single-Center Questionnaire Study.

Background: In April 2020, two independent clinical trials to assess SARS-CoV-2 prophylaxis strategies among health care workers were initiated at our hospital: MeCOVID (melatonin vs placebo) and EPICOS (tenofovir disoproxil/emtricitabine vs hydroxychloroquine vs combination therapy vs placebo).

Objective: This study aimed to evaluate the reasons why health care workers chose to participate in the MeCOVID and EPICOS trials, as well as why they chose one over the other.

Methods: Both trials were offered to health care workers through an internal news bulletin.

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments.

Study Objective: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe.

Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score ≥4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments.

Efficient diagnosis and treatment of acute paracetamol poisoning: cost-effectiveness analysis of approaches based on a hospital toxicovigilance program.

Objectives: To evaluate 5 diagnostic-therapeutic strategies for suspected acute paracetamol poisoning in terms of cost-effectiveness in a tertiary university hospital with an active, validated poisoning surveillance program (SAT-HULP).

Material And Methods: Cost-effectiveness analysis of the 5 diagnostic-therapeutic alternatives considered when attending patients with suspected paracetamol poisoning. The alternatives were chosen by means of a decision tree.

Limited sampling strategies for tacrolimus exposure (AUC0-24) prediction after Prograf(®) and Advagraf(®) administration in children and adolescents with liver or kidney transplants.

To develop limited sampling strategies (LSSs) to predict total tacrolimus exposure (AUC0-24 ) after the administration of Advagraf(®) and Prograf(®) (Astellas Pharma S.A, Madrid, Spain) to pediatric patients with stable liver or kidney transplants. Forty-one pharmacokinetic profiles were obtained after Prograf(®) and Advagraf(®) administration.

Conversion from Prograf to Advagraf in stable paediatric renal transplant patients and 1-year follow-up.

Background: The conversion from Prograf to Advagraf on a 1:1 (mg:mg) basis has been questioned in light of the publication of studies showing a decrease in tacrolimus blood concentrations after the administration of Advagraf.

Methods: The bioavailability of Prograf and Advagraf was evaluated in an open-label conversion study in 21 stable renal transplant paediatric patients. Serial blood samples for determining tacrolimus levels were collected during a 24-h period before (on Prograf) and after (on Advagraf) conversion.

Conversion from Prograf to Advagraf in adolescents with stable liver transplants: comparative pharmacokinetics and 1-year follow-up.

The recommended dose of Advagraf for conversion from Prograf is considered to be 1:1 on a milligram basis. However, the long-term equivalence of Prograf and Advagraf has been questioned. The relative bioavailability of Advagraf and Prograf was evaluated in a single-center, open-label study of Prograf-to-Advagraf conversion in 20 patients, ranging in age from 12 to 18 years, who had a stable liver transplant and were receiving Prograf.

Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection.

There is evidence showing the importance of reaching immunosuppressant target concentrations as soon as possible. The aim of this study was to evaluate the relationship between tacrolimus trough concentrations within the first week after transplantation and the rate of acute rejection. In this descriptive-analytic study, we included 57 renal transplant patients receiving tacrolimus as the primary immunosuppressive drug.

Outcome trials of COX-2 selective inhibitors: global safety evaluation does not promise benefits.

Background: Gastrointestinal toxicity is the most frequent adverse effect associated with nonsteroidal anti-inflammatory drug use. The most clinically relevant side effects of this toxicity are ulcer complications, including perforation, obstruction, or bleeding. Selective cyclooxygenase (COX-2) inhibitors (coxibs) have been proposed as a safer alternative to traditional, nonsteroidal anti-inflammatory drugs and they are currently widely used in clinical practice.