Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity.

The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder its implementation in our healthcare environment. A retrospective analysis approach of anonymized data sourced from electronic health records was performed, encompassing a diverse patient population and evaluating key parameters such as prescribing patterns and test results, to assess the impact of pharmacogenetic testing. A head-to-head comparison with previously published activity results within the same pharmacogenetic laboratory was also conducted to contrast the progress made after 10 years. The analysis revealed significant utilization of pharmacogenetic testing in daily clinical practice, with 1,145 pharmacogenetic tests performed over a 1-year period and showing a 35% growth rate increase over time. Of the 17 different medical departments that sought PGx tests, the Oncology department accounted for the highest number, representing 58.47% of all genotyped patients. A total of 1,000 PGx tests were requested for individuals susceptible to receive a dose modification based on genotype, and 76 individuals received a genotype-guided dose adjustment. This study presents a comprehensive descriptive analysis of real-world data obtained from a public tertiary hospital laboratory specialized in pharmacogenetic testing, and presents data that strongly endorse the integration of pharmacogenetic testing into everyday clinical practice.

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. After an initial screening visit, all subjects were asked to respond to a web-based survey. RESULTS: In the first month, 206 health care workers were screened and 160 were randomized. The survey participation was high at 73.3%. Health care workers cited "to contribute to scientific knowledge" (n=80, 53.0%), followed by "to avoid SARS-CoV-2 infection" (n=33, 21.9%) and "the interest to be tested for SARS-CoV-2" (n=28, 18.5%), as their primary reasons to participate in the trials. We observed significant differences in the expected personal benefits across physicians and nurses (P=.01). The vast majority of volunteers (n=202, 98.0%) selected the MeCOVID trial, their primary reason being their concern regarding adverse reactions to treatments in the EPICOS trial (n=102, 69.4%). CONCLUSIONS: Health care workers' reasons to participate in prophylaxis trials in an acute pandemic context appear to be driven largely by their desire to contribute to science and to gain health benefits. Safety outweighed efficacy when choosing between the two clinical trials.

Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.

INTRODUCTION: Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism. MATERIALS AND METHODS: The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. CONCLUSION: This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. ETHICS AND DISSEMINATION: A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. TRIAL REGISTRATION NUMBER: Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.