[Reform of early access program in France: Impact on workload in a pharmacy and risk identification]. / Réforme de l'accès dérogatoire : impact sur la gestion dans une PUI et identification des risques.

The reform of derogatory access authorisations (DAs) on 1st July 2021 has distorted the routine of the hospital pharmacists dealing with innovative medicines that are waiting for marketing authorization or approval. There are two distinct categories of DAs: Compassionate Access Authorisations (CAAs) are granted by the French National Agency for the Safety of Medicines (ANSM) while Early Access Authorisations (EAPs) are granted at the request of pharmaceutical companies by the French National Authority for Health (HAS). All AAPs and a majority of the AACs are supported by a Protocol for Therapeutic Use and Data Collection (PTU-DC). The aim of this study is to assess the impact of the reform on pharmacy process one year following its implementation, and to identify the risks related to the new circuits. The working group, composed of three pharmacists carried out an initial assessment of the effects first measured the impact of the reform on medicine processes in DAs. They performed a comparison of the changes in their management methods: 3 months prior to the reform (M0), and 3 (M3) and 12 months (M12) post-reform. Risks analysis was conducted using the Failure Modes, Effects and Criticality Analysis (FMEA) method. The analysis was limited to the process steps specific related to DAs drugs were analyzed. The critical severity of the risk situations identified was rated. A critical hierarchy matrix was used to establish priority actions. The priority actions to be taken were determined using the critical hierarchy matrix. Over the span of one year, the number of DAs in our establishment showed a 31.7% increase, from 41 at M0 to 54 at M12. At M0, the proportion of drugs needed inclusion via a drug-specific digital platform, specific to each drug, stood at 27% (11/41) of drugs at M0 while at M12, it rose to 52% (28/54). The percentage of PTU-DCs therefore increased by a factor of 1.7, rising from 29% (12/41) at M0 to 47% (21/45) at M3 and 60% (32/54) at M12. For orders, which are always nominative, approval depends on both the presence of the PTU-DC tracking sheet being present in 12% of PAAs, and the inclusion number in 26% of PAAs. The risk analysis shows 49 failure modes leading to risk situations. Among the failure modes, 36 have a consequence of acceptable or tolerable criticality under control, whilst 13 are deemed of unacceptable criticality. A suitable control method exists has been identifies for 5 of them. Finally, the ranking evaluation of criticalities has highlighted 4 situations which require immediate action as a priority: delivery times, obtaining completed tracking sheets and ordering procedures. The aim of the DAs reform is to simplify access to innovative medicines. However, the reform has significant and damaging repercussions on pharmaceutical activities. Corrective measures need to be taken in conjunction with all parties involved in the circuits including laboratories and service providers (CROs), authorities and healthcare professionals.

Rapid and long-lasting response to selpercatinib of paraneoplastic Cushing's syndrome in medullary thyroid carcinoma.

The endocrine secretions of carcinomas can be life-threatening. Medullary thyroid carcinoma (MTC) is a rare cancer that is often associated with cortisol secretion, leading to paraneoplastic Cushing's syndrome. Mutations of the proto-oncogene RET are driver molecular events in 70% of MTC cases. Here, we report a case of a woman, born in 1956, who was diagnosed with sporadic MTC in 2005, with subsequent relapses treated with focal treatments. In April 2019, she presented with severe and rapidly progressive paraneoplastic Cushing's syndrome associated with lymph node, lung, liver and bone metastases. A supraclavicular lymph node biopsy revealed a somatic p.M918T (c.2753T>C) mutation in exon 16 of the RET proto-oncogene. The patient began treatment with selpercatinib in September 2019. Clinical efficacy was immediate. Chronic diarrhea disappeared within a few days. Clinical hypercorticism quickly disappeared, with quick improvements in muscle and skin conditions and fatigue. Two months after treatment initiation, urinary free cortisol normalized to 42 µg/24 h. Levels of the tumor markers carcinoembryonic antigen (CEA) and calcitonin also greatly decreased from baseline. After 34 months of treatment, selpercatinib elicits sustained clinical, biological and morphological responses. In summary, this case report illustrates the rapid and long-lasting antisecretory effect of selpercatinib associated with tumor control. As Cushing's syndrome associated with medullary thyroid cancer is associated with poor prognosis, this case report is very encouraging. In addition, this suggests the potential benefit of molecular testing in all cases of medullary thyroid cancer.

Answering Hospital Caregivers' Questions at Any Time: Proof-of-Concept Study of an Artificial Intelligence-Based Chatbot in a French Hospital.

BACKGROUND: Access to accurate information in health care is a key point for caregivers to avoid medication errors, especially with the reorganization of staff and drug circuits during health crises such as the COVID­19 pandemic. It is, therefore, the role of the hospital pharmacy to answer caregivers' questions. Some may require the expertise of a pharmacist, some should be answered by pharmacy technicians, but others are simple and redundant, and automated responses may be provided. OBJECTIVE: We aimed at developing and implementing a chatbot to answer questions from hospital caregivers about drugs and pharmacy organization 24 hours a day and to evaluate this tool. METHODS: The ADDIE (Analysis, Design, Development, Implementation, and Evaluation) model was used by a multiprofessional team composed of 3 hospital pharmacists, 2 members of the Innovation and Transformation Department, and the IT service provider. Based on an analysis of the caregivers' needs about drugs and pharmacy organization, we designed and developed a chatbot. The tool was then evaluated before its implementation into the hospital intranet. Its relevance and conversations with testers were monitored via the IT provider's back office. RESULTS: Needs analysis with 5 hospital pharmacists and 33 caregivers from 5 health services allowed us to identify 7 themes about drugs and pharmacy organization (such as opening hours and specific prescriptions). After a year of chatbot design and development, the test version obtained good evaluation scores: its speed was rated 8.2 out of 10, usability 8.1 out of 10, and appearance 7.5 out of 10. Testers were generally satisfied (70%) and were hoping for the content to be enhanced. CONCLUSIONS: The chatbot seems to be a relevant tool for hospital caregivers, helping them obtain reliable and verified information they need on drugs and pharmacy organization. In the context of significant mobility of nursing staff during the health crisis due to the COVID-19 pandemic, the chatbot could be a suitable tool for transmitting relevant information related to drug circuits or specific procedures. To our knowledge, this is the first time that such a tool has been designed for caregivers. Its development further continued by means of tests conducted with other users such as pharmacy technicians and via the integration of additional data before the implementation on the 2 hospital sites.

The effect of partial patients' adherence to antihypertensive drugs: scope for pharmacists' role in hypertension care.

In many individuals, blood pressure varies between clinic visits conducted days, weeks, or months apart. This visit-to-visit variability (VVV) of blood pressure has been recently related with an increased risk of coronary heart disease, stroke, and mortality, independently of mean blood pressure. As for other chronical diseases, patients' adherence to hypertensive therapies remains low and partial adherence to antihypertensive treatment may constitute a source of VVV, as suggested by recent studies. This data should lead to a new clinical approach for hypertension care, based on patients' real adherence to treatment. Therapeutic strategies should include patients' adherence. In this context, the role of community pharmacists for patients' follow-up of hypertension should be reinforced, as they represent efficient and easily accessible health professionals.