CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response ...against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).
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•Higher NT50 titers was observed in mRNA-1273 arm against Delta and BA.1 at day 28•Higher NT50 titers was observed in mRNA-1273 arm against G614 variant at day 90•Suboptimal neutralization against recent Omicron variants was observed at day 180•Asymptomatic breakthrough infections do not ensure XBB.1.5 and JN.1 neutralization
Immunology; Immune response
There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the ...clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug‐evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double‐blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value.
Objetivos: Análisis de la investigación no comercial en ensayos clínicos con medicamentos realizada en el Hospital Universitari Vall d’Hebron (HUVH) tras la aplicación de la Directiva europea ...2001/20/CE, y de las principales diferencias entre este tipo de investigación y la promovida por la industria farmacéutica.
Método: Estudio descriptivo observacional retrospectivo, que analiza todos los ensayos clínicos con medicamentos presentados al Comité Ético de Investigación Clínica (CEIC) del HUVH desde mayo de 2004 (fecha de entrada en vigor del RD 223/2004 que regula los ensayos clínicos con medicamentos que suponía la trasposición de la Directiva europea) hasta mayo de 2009. Se recogen y analizan de forma descriptiva variables de las características de los ensayos clínicos, así como datos sobre las etapas de puesta en marcha, ejecución, finalización y difusión de sus resultados.
Resultados: Del total de ensayos clínicos con medicamentos presentados al CEIC del HUVH (832), tan sólo el 16,3% fueron de promotor no comercial. El porcentaje de ensayos que obtuvieron un dictamen desfavorable fue del 3,8%, sin observarse diferencias en función del tipo de promotor. Se aprobaron un total de 778 ensayos. La mediana del tiempo desde la solicitud de evaluación al CEIC del HUVH hasta su aprobación cumplió con el tiempo establecido en la Directiva europea (inferior a 60 días), sin diferencias según el tipo de promotor. El tiempo desde la obtención del dictamen favorable del CEIC de referencia hasta la aprobación de la AEMPS fue superior para los ensayos clínicos de promotor no comercial respecto a los de promotor comercial. Los ensayos clínicos aprobados por el CEIC del HUVH de promotor no comercial en el período de estudio fueron principalmente de fase IV, ámbito multicéntrico nacional, diseño controlado paralelo y no enmascarados, en comparación con los ensayos de promotor comercial que fueron principalmente de fase III, de ámbito multicéntrico internacional, diseño controlado paralelo y enmascarados a doble ciego. Los ensayos clínicos realizados exclusivamente en población pediátrica fueron una minoría (menos del 5%), independientemente del tipo de promotor, y el uso de placebo como control del ensayo fue menos frecuente en los ensayos de promotor no comercial. En el 90% de los ensayos de promotor no comercial se evaluaron medicamentos comercializados, en comparación con los de promotor comercial, en los cuales se evaluaron en menos de una tercera parte. En cuanto a la etapa de ejecución, el tiempo desde la aprobación de la AEMPS hasta el inicio del ensayo y desde el inicio hasta la finalización fue superior en los ensayos de promotor no comercial. Los ensayos de promotor comercial fueron registrados con mayor frecuencia en el registro público ClinicalTrials.gov, y la actualización de la información sobre el seguimiento y el estado de los ensayos en los diferentes registros públicos fue inferior para los ensayos de promotor no comercial. De los ensayos aprobados por el CEIC del HUVH en el periodo del estudio, se han publicado en revistas científicas de revisión por pares el 60% de los ensayos que se encontraban finalizados, finalizados anticipadamente o en activo (63,8% de los ensayos de promotor comercial y 39,4% de los de promotor no comercial). En el 54,5% de los resúmenes de los ensayos clínicos controlados publicados se mostraron resultados positivos y en el 45,5% resultados negativos o no concluyentes, sin mostrarse diferencias según el tipo de promotor.
Objectives: Analysis of non-commercial research in clinical trials with drugs conducted in Vall d'Hebron University Hospital (HUVH) following the implementation of European Directive 2001/20/EC, and the main differences between this research and the pharmaceutical industry sponsored research.
Methods: Retrospective observational descriptive study, that has analysed all clinical trials with drugs submitted to the Ethics Committee of the HUVH (CEIC) from May 2004 (date of entry into force of the RD 223/2004 which regulates clinical trials and with it the transposition of the EU Directive) to May 2009. Descriptive variables of the characteristics of clinical trials were collected and analysed, as well as data on the stages of start-up, implementation, conclusion and dissemination of results.
Results: Of all the clinical trials with drugs submitted to the CEIC of HUVH (832), only 16.3% were from a non-commercial sponsor. The percentage of the trials that obtained an unfavourable opinion was 3.8%, and there were no differences regarding the sponsor. A total of 778 trials were approved. The median time from the submission until the CEIC approval was within the time limit established in European Directive (less than 60 days), and there were no differences regarding the sponsor. The time from the reference CEIC approval until the Competent Authority approval was higher for non-commercial clinical trials than for commercial clinical trials. The non-commercial clinical trials approved by the CEIC of HUVH in the study period were mainly in phase IV, multicenter national level, parallel controlled design, and non masked, compared to commercial clinical trials that were mainly in phase III, multicenter international, parallel design, and double blind masked. Clinical trials in paediatric population were only a minority (less than 5%), regardless of the sponsor, and the use of placebo control was less common in non-commercial clinical trials. In 90% of non-commercial clinical trials marketed drugs were evaluated, compared to commercial clinical trials, where marketed drugs were evaluated in less than one third of them. In the implementation phase, the time from the approval of the Competent Authority until start-up, and from the start-up to the end was higher in non-commercial clinical trials. Commercial clinical trials were registered more often in the public registry ClinicalTrials.gov, and the update of the follow-up information and the state of the clinical trials in the different public registers was lower for the non-commercial clinical trials. Of the approved clinical trials by the CEIC HUVH in the study period taking into account those completed, prematurely ended and ongoing clinical trials, 60% have been published in peer-review scientific journals (63.8% of commercial clinical trials and 39.4% of non-commercial clinical trials). In 54.5% of the abstracts of published controlled clinical trials positive results can be observed and in 45.5% of them there were negative or inconclusive results. Differences were not observed regardless of the type of sponsor.
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