-Tosyl Hydrazone Benzopyran, a New Ligand of PPARα Obtained from Mapping the Conformational Space of Its Active Site.

We report here a new ligand for the peroxisome-proliferator-activated receptor type α (PPARα), an N-tosyl hydrazone benzopyran that was designed throughout the mapping of the polar zone of the binding site of PPARα; such a compound displays a strong activity on this receptor that is comparable to that of the reference compound WY-14643. For the design of the -tosyl hydrazone benzopyran, we have carried out an exhaustive conformational study of WY-14643 and a previously reported hydrazine benzopyran derivative using conformational potential energy surfaces (PES). This study allowed us to map in a systematic way the entire binding site of the PPARα.

Stakeholder Perspectives on Randomized Clinical Trials for Children With Poor-Prognosis Cancers.

Importance: In poor-prognosis children's cancers, new therapies may carry fresh hope for patients and parents. However, there is an absolute requirement for any new therapy to be properly evaluated to fulfill scientific, regulatory, and reimbursement requirements. Randomized clinical trials (RCTs) are considered the gold standard, but no consensus exists on how and when they should be deployed to best meet the needs of all stakeholders.

Navigating the path towards successful implementation of the EU HTA Regulation: key takeaways from the 2023 Spring Convention of the European Access Academy.

Background: The European Regulation on Health Technology Assessment (EU HTA R), effective since January 2022, aims to harmonize and improve the efficiency of common HTA across Member States (MS), with a phased implementation from January 2025. At "midterms" of the preparation phase for the implementation of the Regulation our aim was to identify and prioritize tangible action points to move forward.

Methods: During the 2023 Spring Convention of the European Access Academy (EAA), participants from different nationalities and stakeholder backgrounds discussed readiness and remaining challenges for the Regulation's implementation and identified and prioritized action points.

An Inclusive Civil Society Dialogue for Successful Implementation of the EU HTA Regulation: Call to Action to Ensure Appropriate Involvement of Stakeholders and Collaborators.

Objectives: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group.

Methods: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process.

Modified study designs to expand treatment options in personalised oncology: a multistakeholder view.

Personalised oncology, whereby patients are given therapies based on their molecular tumour profile, is rapidly becoming an essential part of optimal clinical care, at least partly facilitated by recent advances in next-generation sequencing-based technology using liquid- and tissue-based biopsies. Consequently, clinical trials have shifted in approach, from traditional studies evaluating cytotoxic chemotherapy in largely histology-based populations to modified, biomarker-driven studies (e.g.