The INSPIRE doctoral network in safety pharmacology - Looking back and ahead.

内容摘要

The INSPIRE project, funded by the European Marie Skłodowska-Curie Action (MSCA) program, was a doctoral network designed to train early-stage researchers (ESRs) and stimulate exploratory research in cardiovascular safety pharmacology (SP). From 2020 until 2024, INSPIRE trained 15 doctoral candidates hosted by a consortium of academic and industrial partners. The current publication summarizes the outcomes of INSPIRE and reflects on the impact to the field. As part of INSPIRE, ESRs were engaged in individual research projects covering a range of topics, yet grounded in 4 thematic clusters to facilitate collaboration. The first cluster focused on human induced pluripotent stem cells-derived cardiomyocyte (hiPSC-CM) assays and explored additional readouts such as morphological profiling, miRNAs panels and artificial intelligence assisted analyses. The second cluster aimed to develop a new telemetry platform with integrated positioning system, but technical drawbacks required initiation of alternative plans still aligned with the mission to refine in vivo SP studies. A third cluster explored new concepts for hemodynamic assessment, such as arterial stiffness and in silico modelling. Finally, the fourth cluster involved mechanistic research in cardio-oncology. Some ESR projects, especially those hosted by industry partners, delivered tangible prototype products or services with potential for commercialization. Alternative outcomes included optimized experimental workflows, datasets with reference compounds and mechanistic insights. Overall, INSPIRE delivered on its mission to initiate explorative research in SP, although many results will require further development, standardization and establishment of their context of use. This highlights the difficulty of achieving regulatory relevance within PhD timelines. For the latter, sustained engagement from industry beyond the duration of the doctoral program seems essential. Educationally, 8 ESRs have successfully defended their PhD thesis and a few ESRs have transitioned into permanent roles in drug R&D. Mobility of ESRs was a crucial, mandatory element of the training resulting in 23 secondments. The close interaction with industrial partners significantly enhanced trainee awareness of regulatory thinking, experimental robustness, and translational constraints. A yearly summer school was organized to facilitate mutual learning and build group cohesion. Meanwhile, the INSPIRE summer school has become a legacy with close to 100 alumni and offers a mix of theoretical lectures and broader sessions on career development. Looking ahead, ongoing revisions of international SP guidance (ICH S7A) and increasing interest in new approach methodologies (NAMs) create opportunities for a next-generation training network. In this context, we propose a roadmap for initiating INSPIRE v2.0 and have launched a call for input and participation to help shaping the future of SP.