Health Products Safety Research Articles

Organizational and budget impact model (OBIM) of same™ a new autotransfusion medical device

Objectives: This study aimed to assess the budget and organizational impact of progressively replacing the intraoperative cell salvage centrifugation-based systems currently installed in French hospitals with the same™ system, a new autotransfusion medical device. Methods: An Organizational and Budget Impact Model (OBIM) was developed based on two methodological guidelines issued by the French Health Authority (Haute Autorité de Santé, HAS). The OBIM was also developed based on a pragmatic literature review, hospital data and hospital pharmacists’ expertise. Results: Considering an average hospital cohort of 600 cardio-thoracic surgery patients, with 57% experiencing mild hemorrhages, 23% moderate hemorrhages, and 20% massive hemorrhages, and a same™ market share of 33% in Year 1, the implementation of same™ resulted in significant savings. With an average allogeneic transfusion of 4.19 packed red blood cells (RBC) and 0.62 platelet concentrate per patient based on National Hemovigilance Report of the ANSM (French National Agency for the Safety of Medicines and Health Products) and when using same™ system a reduction of 45% of RBC transfusion associated with a reduction of 60% and 90% of platelet use for moderate and massive hemorrhages respectively, the first year annual saving amounted to €44,601 and the cumulated saving over 5 years to €535,206. Discussion: This model structure was developed based on overall hospitals’ needs and acknowledged guidelines, with inputs based on French literatures and hospital data, so findings were specifics to a context. Among the inputs, the number of annual same™ procedure is not based on device capability but rather on hospital capability with the number of operating rooms used for cardio-thoracic surgery equipped with the device. Conclusions: The results of this OBIM demonstrated the economic and organizational benefits of same™ for hospitals. This benefit results mainly of a reduction in the use of allogeneic blood products (RBCs, platelets).

Effectiveness of a pain neuroscience education programme on the physical activity of patients with chronic low back pain compared with a standard back school programme: protocol for a randomised controlled study (END-LC)

IntroductionEducation is recognised as an effective and necessary approach in chronic low back pain. Nevertheless, data regarding the effectiveness of education in promoting physical activity in the medium term or...

Real-world experience of larotrectinib in children, adolescents and young adults with TRK fusion solid tumors in France.

10056 Background: Larotrectinib is an FDA and EMA approved TRK inhibitor for TRK fusion solid tumors in patients with locally advanced or metastatic disease, or where surgical resection is likely to result in severe morbidity. Here we report the real-world activity and safety data on compassionate use and post-marketing authorization of larotrectinib collected in the SACHA-France study (NCT04477681), following the French Health Technology Assessment institution (HAS) request. Methods: All larotrectinib prescriptions made in France outside clinical trials since April 2019 for patients’ < 25 years-old were registered in the SACHA-France study. Safety and activity data were collected, with data cut-off of 23/01/2024. SACHA-France is open in all 31 French Society of Pediatric Oncology (SFCE) centers, it is approved as a real-world data source by the HAS and supported by the French National Agency for the Safety of Medicines and Health Products (ANSM). Results: 21 patients were included (4 compassionate use, 17 post-marketing authorization). Main cancer types were soft-tissue sarcomas (n=13, of them 7 infantile fibrosarcoma), followed by central nervous system (CNS) tumors (n= 7), and other solid extra-CNS tumors (n=1). All patients except one had a TRK fusion tumor: NTRK3 (n=10), NTRK2 (n=6, all CNS tumor) and NTRK1 (n=4). Median age at start of larotrectinib was 2.8 years (range: 0.2 -21.1). Ten patients had received no prior systemic therapy. Main reasons to start larotrectinib were to avoid mutilating surgery (n=9) and disease progression (n=9). Best objective response was reported as partial response in 13 out of 19 patients with evaluable disease (10/12 patients with soft tissue sarcomas, 2/6 patients with CNS tumors), with median time to response of 57 days. Of them, five patients with soft tissue sarcomas achieved a complete response after non mutilating surgery. Median treatment duration was 219 days (range: 10-1368, 5 patients still on therapy). Seven patients with soft tissue sarcomas stopped larotrectinib, after a median duration of 242 days (range: 122-1190), three of them after tumor surgery; none presented with tumor recurrence (follow-up: 350 days; range 40-636). At data cut-off, 8 patients had disease progression on-therapy (5/7 CNS tumors, 3/13 soft tissue sarcomas), with a NTRK resistance mutation identified in 2 out 3 patients with tumor biopsy. Adverse drug reaction (ADR) were reported in 2/21 patients (9%), including a grade 2 weight gain and a grade 3 neutrophil count decreased (1 patient each). Both ADRs were expected and required neither corrective treatment nor action on larotrectinib. Conclusions: Our real-world data confirm the favorable safety profile of larotrectinib with rapid and durable tumor-agnostic efficacy.

Adverse drug effect in the context of drug shortage: the CIRUPT prospective study from the French pharmacovigilance network

ObjectivesDrug shortages are of increasing concern to worldwide public health. The consequences of drug shortages for patient safety have been little studied, especially from a pharmacovigilance point of view. In...

Évaluation de la pratique pharmaceutique en établissement de santé : une étude exploratoire comparant les processus en France et au Québec

To ensure compliance with the legal and normative framework, the professional orders, which supervise the practice of pharmacy have established a professional inspection process. In addition to this process, other external organizations also require an accreditation, authorization, certification or validation process for professional practices. The main objective is to identify and compare the methods of evaluating pharmaceutical practice in hospitals in France and Quebec. In order to identify and compare the methods of evaluating pharmaceutical practice in hospitals in France and Quebec, our approach allowed us to identify more organizations in France (i.e., High Authority of Health, Regional Health Agencies, the National Order of Pharmacists, the Nuclear Safety Agency, the Biomedicine Agency and the National Agency for the Safety of Medicines and Health Products) than in Quebec (i.e., Accreditation Canada, Ordre des pharmaciens du Québec and Health Canada). The study highlights the legal framework and applicable standards, the surveyors, the evaluation methods and the particularities for the evaluation of the hospital, the pharmacy department and the members of the department. This study highlights the evaluation processes of pharmaceutical practice in hospitals. In France, as in Quebec, we recognize the importance of the drug circuit in the hospital, the development and operation of a pharmacy department and the practice of pharmacy. While there are more similarities for the assessment of the drug circuit in hospitals and pharmacy department, important differences are observed for the assessment of individuals. We believe that the publication of a comparative analysis can contribute to discussions and exchanges to benefit from the best practices of each country.

Impact of the withdrawal of macrotextured implant on reconstruction practices

On 22 November 2018, the French Society for Plastic, Reconstructive and Aesthetic Surgery recommended that Allergan® macrotextured breast implants be recalled, a decision endorsed by the French national health products safety agency (ANSM) on 2nd April 2019. At the Georges-François Leclerc Cancer Center (CGFL) in Dijon, we decided to stop using macrotextured implants as of November 2018 in favor of smooth implants. The purpose of this study is to evaluate the impact of the recall of macrotextured implants on breast reconstruction surgical practices and their complications. This is a single-centre, retrospective study performed at the CGFL in Dijon, France. Reconstruction techniques and complications were compared between two periods, i.e. before the recall of macrotextured breast implants (period 1: 1st September 2017-November 22, 2018) and after the recall (period 2: 23 November 2018-31st March 2020). All patients who underwent breast reconstruction for the first time were included. Data were collected from 168 reconstructions in period 2, and 159 in period 2. The rate of use of breast implants during reconstructions decreased significantly in period 2 (53.6% vs. 23.9%; P<0.001). The rate of autologous reconstructions increased significantly for muscle sparing latissimus dorsi (2.4% vs. 12.6%; P<0.001) and exclusive fat grafting (9.5% vs. 21.5%; P<0.01). Clavien-Dindo Stage IIIb complications decreased in period 2 (10% vs. 18.4%; P=0.04). Since the recall of macrotextured breast implants, the reconstruction rate has decreased in our centre in favor of autologous techniques with lower complication rates.

Prevention and management of health products shortages by the French national agency (ANSM), 10 years of experience.

Shortages of drugs and medical devices have tended to increase in France and worldwide, with consequences for patients and healthcare professionals. Preventing shortages of health products has become a priority for regulatory authorities, including the French National Agency for Medicines and Health Products Safety (ANSM). To highlight perspectives for a better prevention, we described and analyzed the management of shortages in the availability of health products in France over the last 10 years. The supply chain was mapped to identify the main causes of shortages and stakeholders involved in managing shortages throughout the supply chain. National and European initiatives and regulatory measures were reviewed. A retrospective nationwide data analysis from the French reporting system of health product shortage reports was conducted over 10 years for drugs (2013-2022) and over an 18-month period for medical devices, from 1st March 2022 to 31st August 2023. An increase in drug shortage reports was observed, rising from 404 in 2013 to 3,761 in 2022 for drugs, with a relatively constant distribution of affected therapeutic classes. In 2022, the main reported causes of drug shortage risk were insufficient production capacity (27.1%), increased sales volume (21.5%), or lack of supply (13.6%). Over half of the reports on medical devices (55.4%) were objectified as indispensable, and their causes were mainly due to a lack of supply (48.2%), discontinuation of marketing (14.9%), increased sales volume (13.2%), and regulatory reasons (9.6%). ANSM and French authorities have engaged a public health policy for prevention and management of health product shortages including financial penalties, minimum safety stocks for Major Therapeutic Interest drugs, and a shortage management plan. Based on 10 years of experience, four priority measures have been identified to anticipate the risk of heath products shortages based: the importance of a national coordination from raw materials to local market, the implementation of new prevention and management actions in the supply chain, strengthening European cooperation and regulation including the establishment of a list of critical drugs, and promoting transparency and information.

Constructs for Safe-use of Natural Health Products Among Malaysian Consumers

Since the outbreak of Covid-19 in 2020, people have become more health-conscious and thus felt responsible for taking care of their own health for long-term well-being. The public is more aware to seek extra health measures with alternative therapies as awareness of sustainable lifestyles was promoted before the vaccine was introduced. The term “natural” brings a positive attitude towards the product since most consumers perceive natural as safe even though it does not necessarily mean safer or better. There are many reports on natural health products that are adulterated with harmful substances, and many still do not have data on their efficacy, hence it is pivotal that consumers know the safe-use elements of natural health products. It is important for consumers to know and have the right knowledge regarding the safety of natural health products to prevent any adverse effects in the future. The objective of this study is to identify the safe-use elements perceived by consumers for natural health products. A qualitative approach of Focus-Group Discussion (FGD) is employed to elucidate the safe-use elements, and thematic analysis is being done on the qualitative data to explore the objective. There are 11 safe-use elements of natural health products mentioned by consumers. However, there is only 1 safe use element that is in line with the current regulation in Malaysia. A complete guideline on the safe use of natural herbal products for consumers is pivotal to maintain their general health and well-being.

Real life experience of compassionate use of 177Lu-PSMA-1 for metastatic castration-resistant prostate cancer patients in Leon Berard Cancer Centre

PurposeWe present a retrospective feedback of PSMA-targeted radioligands therapy (PRLT) using onsite radiolabeled 177Lu-PSMA-1 to treat metastatic castration-resistant prostate cancer patients (mCRPC) progressing after conventional treatments. MethodsOnsite radiolabeling of the PSMA-1 with 177Lu was authorized by the National Agency for the Safety of Medicines and Health Products (ANSM) after IMPD (Investigational Medicinal Product Dossier) approval allowing to treat patients before 177Lu-PSMA-617 national agreement. Patients were screened on 68Ga-PSMA and 18F-FDG PET-CTs and would be included in case of significant PSMA uptake in the majority of known lesions without mismatch between FDG and PSMA especially in liver metastases, following the THERAP trial procedure. Treatments would consist in 6 injections of 7.4GBq of 177Lu-PSMA-1 every 6 weeks following the VISION phase III trial. A clinical, biological and radiological follow-up during the treatment allowed the detection of possible adverse effects or tumor progression that should lead to treatment discontinuation, and the monitoring and characterization of the expected benefits, according to PCWG3 criteria. Whole-body SPECT-CT was performed in all patients 24hours after injection at each cycle using the VERITON® - Spectrum Dynamics to monitor lesions 177Lu-PSMA-1 uptake. ResultsBetween April 2021 and July 2022, 21 of the 24 patients screened could be included after clinical, biological and imaging screening. Ten received at least 4 injections, and 6 received all 6 injections. Three patients demonstrated a 50% reduction in PSA (PSA50), and 3 others any significant PSA evolution. The safety profile was favorable, with however grade 3 toxicities leading to permanent discontinuation of the treatment. ConclusionOn-site radiolabeled 177Lu-PSMA-1 appeared safe and lead to clinical benefit in most patients. The benefit-risk balance seems to be favorable for these multitreated mCRPC progressive patients in the absence of therapeutic alternatives. It requires a close multidisciplinary and multiprofessional collaboration within the nuclear medicine department. Further studies are necessary to specify the modalities of scans analysis, the impact of post-therapy scans, the length of the benefits observed, and the position of PRLT in the management of prostate cancers.

Role of Supply Chain Management in Quality of Healthcare Services

Healthcare organizations in Haryana (Kurukshetra) face many supply chain management challenges that can be addressed through effective operational and management decisions. The aim of this paper is to examine the supply chain management of healthcare quality in developing countries, particularly in rural healthcare in Haryana (Kurukshetra), and to consider demographic variables such as gender, age, education level and healthcare experience. Design and Hypothesis Testing Approach Distributed 500 questionnaires to determine the impact of aspects of supply chain management on the quality of health services. 27 of his seven procurement officers and administrative staff in Kurukshetra Haryana. The primary method was to collect data from 73 rural health managers and procurement managers to identify the quality and size of health services. The results of our study show that a combination of timely delivery of health products, specifications, level of health product providers and safety in the rural health sector of Haryana (Kurukshetra) is related to the quality of health services. The scope of this article focuses on employing appropriate human resources and highly trained professionals in supply chain departments to improve the quality of health services in the supply chain. As a practical contribution, this article can help healthcare supply chain managers and organizations do their jobs better or create a competitive advantage by addressing the issues and challenges facing individual healthcare managers, organizations and their partners.

National reflection on organs-on-chip for drug development: New regulatory challenges

Organs-on-chip (OoC) are innovative and promising in vitro models, particularly in the process of developing new drugs, to improve predictivity of preclinical studies in humans. However, a lack of regulatory consensus on acceptance criteria and standards around these technologies currently hinders their adoption and implementation by end-users. A reflection has been conducted at the National Agency for Medicines and Health products safety (ANSM) in order to address this issue, which has gained momentum at the international level in recent years. If the subject of OoC is of international interest, France is also in the process of structuring an OoC network, in order to best support the emergence of this new technological innovation. Focusing on liver-on-a-chip, the authors drafted a first list of regulatory requirements to help standardize these devices and their use. Technological and biological relevance of liver-on-a-chip was also evaluated, in comparison with current in vitro and in vivo models, based on the available literature. The authors offer an analysis of the current scientific and regulatory situation, highlighting the key regulatory issues for the future.

Clinical Trial Authorisation: A Final Look Back to Better Appraise the New European Regulation.

The implementation of the new European Clinical Trial Regulation on 31 January 2022, is a major step to promote clinical research in Europe. The French National Agency for Medicines and Health Products Safety (ANSM) proposes to share some key aspects of the preparation for the application of the Regulation initiated in 2017 and to discuss shared indicators that should be considered to monitor clinical trials opportunities on a territory with regards to access to innovation for patients and attractiveness for sponsors. New criteria based on the time from the first request for authorisation to the first inclusion could be of particular interest to appraise the implementation of the European Clinical Trial Regulation.

Access to innovation through clinical trials and the national early access program for patients with lung cancer in France: focus on atezolizumab and durvalumab.

Tumor genomic profiling and PD-L1 testing mean lung cancer management can be tackled through a personalized approach. Targeted therapies and immunotherapy are necessary to improve survival and preserve the patients' quality of life. Early access to innovation before marketing authorization (MA) is possible in France through clinical trials and an early-access program called a Temporary Authorization for Use (ATU), which is a unique regulatory system in Europe. This study aims to assess the impact of early access to innovation through clinical trials and ATUs in thoracic oncology. Data from clinical trials between 2018 and 2021 and ATUs between 2005 and 2019 were collected internally and assessed for drugs in thoracic oncology, with specific focus on 2 ATUs, respectively, atezolizumab and durvalumab. From 2018 to 2021, the National Agency for the Safety of Medicines and Health Products authorized 145 clinical trials in lung cancer. Between 2005 and 2019, 19 drugs obtained an EU MA or an MA extension for a therapeutic indication in lung cancer. During this period, 11 of these drugs were granted an ATU, corresponding to 6851 patients treated. Of this total number of patients, data were collected for 33.1% and 71.2%, who received durvalumab and atezolizumab, respectively. Real-life efficacy data were consistent with the clinical trial data. Over the past 15years, clinical trials and the French early access program have allowed considerable early access to therapeutic innovation in real life for patients, especially in thoracic oncology.

Prediction of residual disease using circulating DNA detection after potentiated radiotherapy for locally advanced head and neck cancer (NeckTAR): a study protocol for a prospective, multicentre trial

BackgroundSensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy.MethodsThis will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study.DiscussionThe decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival.Trial registrationClinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15th, 2022.

Profile of adverse drug reaction reports in South Africa: An analysis of VigiBase® for the year 2017.

The South African Health Products Regulatory Authority (SAHPRA) monitors the safety of health products by collecting and evaluating adverse drug reaction (ADR) reports submitted by healthcare professionals, patients and pharmaceutical companies. The reports are shared with the World Health Organization (WHO) Programme for International Drug Monitoring. A demographic and clinical profile of ADR reports will improve our understanding of ADR reporting in South Africa to enhance training of reporters at all levels. This study describes the demographic and clinical profile of spontaneous ADR reports received by the SAHPRA during the year 2017. A retrospective, cross-sectional study was conducted to describe all ADR reports submitted by South Africa to VigiBase®, the WHO global database of Individual Case Safety Reports (ICSRs), during 2017. The demographic profile included patient characteristics (age and sex), type of reporter and the vigiGrade™ completeness score for each ICSR. The clinical profile included characteristics of the case, medicine(s) and reaction(s). A total of 8 438 reports with a mean completeness score of 0.456 (SD = 0.221) were assessed. Females and males represented 61.96% and 33.05% of cases, respectively (if sex was reported). All age groups were represented; however, 76.28% involved adults (aged 19-64 years). Physicians submitted the most reports (39.66%). Consumers were the reporters in 29.39% of cases. Pharmacists submitted only 4.45% of the reports. Anti-infective medicines were the most reported Anatomical Therapeutic Class (20.08%), while Human Immunodeficiency Virus was the top indication reported (10.27%). The highest number of MedDRA preferred terms used to describe reactions belonged to the System Organ Class, general disorder and administration site conditions. In 55.87% of the reports, the cases were reported as serious and 12.47% fatal. Death was the most reported MedDRA preferred term used to describe a reaction (5.17%). This was the first study that described ADR reports received by SAHPRA and improves our understanding of reporting in the country. The core clinical elements that are important in signal detection were often not included in reports. The findings demonstrated that patients were more active contributors to the national pharmacovigilance database than pharmacists. Reporters should be trained in pharmacovigilance and ADR reporting processes to increase the quantity and completeness of reports.

Multicentre, interventional, single-arm study protocol of telemonitored circadian rhythms and patient-reported outcomes for improving mFOLFIRINOX safety in patients with pancreatic cancer (MultiDom, NCT04263948)

IntroductionCircadian clocks regulate cellular proliferation and drug effects. Tolerability and/or efficacy of anticancer therapies have been improved by their administration according to circadian rhythms, while being predicted by circadian robustness....

Comprehensive nationwide study on the prescription of experimental anticancer therapies for compassionate use in children and adolescents in France.

10019 Background: Compassionate use prescriptions of innovative anticancer therapies are common in pediatric oncology, although rarely reported and activity/safety information mainly based on single/limited institutional retrospective experiences. Methods: In France, early drug access before marketing authorization is granted by the French National Agency for the Safety of Medicines and Health Products (ANSM) in case on unmet need, positive benefit/risk balance of preliminary data and no access within clinical trials. All anticancer prescriptions approved by the ANSM from 01/01/2020 to 31/12/2022 for patients &lt; 18 years-old were analyzed. Patients safety and activity data were collected through the SACHA France study (NCT04477681) in the 2020-2021 period. 2022 data analysis is currently ongoing and will be included in the presentation at ASCO. Results: In the study period, 1022 anticancer compassionate use prescriptions were authorized by ANSM. The most frequently prescribed drug was methotrexate drinkable solution (n = 526) and 383 prescriptions were within the inclusion criteria of the SACHA study (anti-cancer innovative therapies not approved in Europe or new formulation of an already approved drug after 2007). In the 2020-2021 period, 28 different therapies were prescribed to 188 patients in a French Society of Pediatric Oncology (SFCE) center. Of them, 14 patients never received the prescribed drug, mainly due to early death. 107 of 174 (61%) eligible patients from 21 SFCE centers were included in the SACHA study (56% in 2020 and 67% in 2021). Median age at inclusion was 6.0 years (range: 0.3 -17.3). Main cancer types were central nervous system (CNS) tumors (69), followed by non-CNS tumors (24) and leukemia/lymphoma (14). Main prescribed therapies targeted MEK/BRAF (66), EZH2 (11), BLC2 (7) and ALK/ROS1/MET (5). In 40/107 patients (37%) at least a grade ≥2 clinical and/or grade ≥3 biological adverse drug reaction (ADR) was reported, leading to delayed therapy in 15 % of patients. Overall, 10 serious ADRs were reported in 10 patients. At last news, 53/107 patients had stopped their drug, mainly due to disease progression (33), followed by physician decision (11) and toxicity ± physician decision (8). 12-months PFS was 49% (95 IC: 38-60 %), with a median of 334 days of follow-up for patients on therapy. Conclusions: To our knowledge, this is the first comprehensive nation-wide study on compassionate use prescriptions of experimental anticancer therapies to children and adolescents with cancer with prospective safety/activity information in more than 60% of patients. This study underscores the importance, and feasibility, of the close collaboration between academia and regulatory authorities to ensure adequate real-life monitoring of these prescriptions. Supported by Imagine for Margo, Association Hubert Gouin, Fondation du LEEM and the SFCE.

Phase I/II study testing the combination of AGuIX nanoparticles with radiochemotherapy and concomitant temozolomide in patients with newly diagnosed glioblastoma (NANO-GBM trial protocol)

BackgroundDespite standard treatments including chemoradiotherapy with temozolomide (TMZ) (STUPP protocol), the prognosis of glioblastoma patients remains poor. AGuIX nanoparticles have a high radiosensitizing potential, a selective and long-lasting accumulation in tumors and a rapid renal elimination. Their therapeutic effect has been proven in vivo on several tumor models, including glioblastoma with a potential synergetic effect when combined with TMZ based chemoradiotherapy, and they are currently evaluated in 4 ongoing Phase Ib and II clinical trials in 4 indications (brain metastases, lung, pancreatic and cervix cancers) (> 100 patients received AGuIX). Thus, they could offer new perspectives for patients with newly diagnosed glioblastoma. The aim of this study is to determine the recommended dose of AGuIX as a radiosensitizer in combination with radiotherapy and TMZ during the concurrent radio-chemotherapy period for phase II (RP2D) and to estimate the efficacy of the combination.MethodsNANO-GBM is a multicenter, phase I/II, randomized, open-label, non-comparative, therapeutic trial. According to a dose escalation scheme driven by a TITE-CRM design, 3 dose levels of AGuIX (50, 75 and 100 mg/kg) will be tested in phase I added to standard concomitant radio-chemotherapy. Patients with grade IV glioblastoma, not operated or partially operated, with a KPS ≥ 70% will be eligible for the study. The primary endpoints are i) for phase I, the RP2D of AGuIX, with DLT defined as any grade 3–4 NCI-CTCAE toxicity and ii) for phase II, the 6-month progression-free survival rate. The pharmacokinetics, distribution of nanoparticles, tolerance of the combination, neurological status, overall survival (median, 6-month and 12-month rates), response to treatment, and progression-free survival (median and 12-month rates) will be assessed as secondary objectives. Maximum sixty-six patients are expected to be recruited in the study from 6 sites.DiscussionThe use of AGuIX nanoparticles could allow to overpass the radioresistance to the reference treatment of newly diagnosed glioblastomas that have the poorest prognosis (incomplete resection or biopsy only).Trial registrationClinicaltrials.gov: NCT04881032, registered on April 30, 2021. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°Eudra CT 2020-004552-15. Protocol: version 3, 23 May 2022.

The Rationale for Robust Pharmacovigilance in Monitoring the Safety of Traditional Medicines and Natural Health Products : Joanne Barnes, editor. Adis: Hardcover ISBN 978-3-031-07273-4, eBook ISBN 978-3-031-07275-8, 2022.

The Rationale for Robust Pharmacovigilance in Monitoring the Safety of Traditional Medicines and Natural Health Products : Joanne Barnes, editor. Adis: Hardcover ISBN 978-3-031-07273-4, eBook ISBN 978-3-031-07275-8, 2022.

Development, transfer and validation of a HPLC-DAD method for analysis of six herbal medicines marketed in D.R. Congo: Fingerprinting and stability study

ContextPhytomedicines, also known as improved traditional medicines (ITMs), are increasingly used in the management of diseases throughout the world. While quality control widely known to be an essential tool that can ensure the efficacy and safety of health products, most ITMs lack appropriate analytical methods for their control. The aim of this study was to develop a reliable analytical method for the quality control of ITMs commonly used in the Democratic Republic of the Congo (D.R. Congo). For this purpose the method needs to be validated and transferred. ObjectivesThe objective of this research was to develop, transfer, and validate an affordable, rapid and easily implementable analytical method by HPLC-DAD for the quality control of herbal medicines marketed in the Democratic Republic of the Congo. Also, to determine these drugs fingerprint and their stability under accelerated conditions. MethodsChromatographic separation was achieved using two chromatographic columns, an XBridge C18 (250 × 4.6 mm i.d.; 5 μm particle size) and an XBridge C18 (100 × 4.6 mm i.d.; 3.5 μm particle size), column maintained at 30 °C. The mobile phase consisted of a gradient mixture of mobile phases A (acetonitrile) and B (aqueous solution of trifluoroacetic acid 0.05%) pumped at 1.0 mL/min. UV detection was performed at 280 nm. The method using the short column was validated using the total extracts as references. The strategy of total error was used to decide on the reliability of the method taking into account the acceptance limits fixed at ± 10%. ResultsThe validation results show that the developed HPLC-DAD method presented an adequate trueness, linearity, precision and accuracy. Two extra peaks found in the finish products did not interfere with phytomarkers, thus confirming the selectivity of the developed method as appropriate chromatographic profiles. The method was successfully used to determine the content of the phytomarkers in six ITMs. Furthermore, we could notice that the ITMs submitted to the accelerated degradation studies remained chemically stable over six months of harsh treatments. ConclusionA generic method of analysis of herbal medicines was developed using HPLC-DAD, and subsequently validated before being applied in a stability study of these drugs. The proposed method holds the promise of providing a new tool for quality product development in the field of traditional herbal medicines.