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.

The French Pregnancy Cohort: Medication use during pregnancy in the French population.

PURPOSE: We described the medication use during pregnancy in the French population using the French Pregnancy Cohort (FPC). METHODS: The FPC was built with the sampling of all pregnant women included in the French Echantillon généraliste des bénéficiaires (EGB), which is a 1/97th representative sample of the population covered by the French health insurance. The EGB includes anonymized information on the socio-demographic and medical characteristics of beneficiaries, and the health care services they have received such as diagnoses and procedure codes as well as data on filled reimbursed medication; EGB also includes data on hospital stays in all public and private French health facilities. Each filled prescription record contains information on drug brand and generic names, date of prescription and date of dispensing, quantity dispensed, mode of administration, duration of prescription, dosage, and prescribing physician specialty. FPC includes data on all pregnancies of women in the EGB (2010-2013). Date of entry in the FPC is the first day of pregnancy regardless of pregnancy outcome (spontaneous abortions or planned abortions (with or without medical reasons), deliveries), and data on women are collected retrospectively for a period of one year before pregnancy, and prospectively during pregnancy, and up to one year after delivery. The prevalence of prescribed medications before, during and after pregnancy was compared; comparison was also done between trimesters. Pregnancy outcomes are described and include spontaneous and planned abortions, livebirths, and stillbirths. RESULTS: FPC includes data on 36,065 pregnancies. Among them, 27,253 (75.6%) resulted in a delivery including 201 stillbirths (0.7%). The total number of spontaneous abortions was 6,718 (18.6%), and planned abortions 2,094 (5.8%). The prevalence of filled medication use was 91.1%, 89.9%, and 95.6% before, during and after pregnancy, respectively. Although there was a statistically significant decrease in the proportion of use once the pregnancy was diagnosed (first trimester exposure, 76.4% vs. exposure in the year prior to pregnancy, 91.1% (p < .01)), post-pregnancy medication use was above the pre-pregnancy level (95.6%). Maternal depression was the most prevalent comorbidity during pregnancy (20%), and post-partum depression was higher in those who delivered a stillborn infant (38.8%) as well as in those with a spontaneous (19.5%) or planned abortion (22.4%) compared to those with a liveborn (12.0%). CONCLUSION: FPC is an excellent tool for the study of the risk and benefit of drug use during the perinatal period. FPC has the advantage of including a representative sample of French pregnant women, and study medications only available in France in addition to others available worldwide.

Treatment of Congenital Toxoplasmosis: Safety of the Sulfadoxine-Pyrimethamine Combination in Children Based on a Method of Causality Assessment.

BACKGROUND: The treatment of newborns and infants with congenital toxoplasmosis is standard practice. Some observational studies have examined safety in newborns, but most of these failed to provide sufficient details for a provisional assessment of causality. The aim of this study was to evaluate the clinical and biological adverse effects of the combination of sulfadoxine-pyrimethamine. METHODS: Sixty-five children treated for 1 year with a combination of sulfadoxine-pyrimethamine (1 dose every 10 days) for congenital toxoplasmosis were followed up to evaluate abnormal hematological values and potential adverse events using a standardized method of causality assessment. RESULTS: Nine patients (13.8%) presented at least 1 adverse clinical event that was nonspecific, such as diarrhea on the day of drug administration, vomiting and agitation. In 1 patient, erythema appeared at the end of the treatment and resolved within 10 days. None of these events was attributed to the treatment. Six patients (9.2%) developed an adverse hematological event (neutropenia, n = 3; eosinophilia, n = 2 and both anemia and eosinophilia, n = 1) that was considered to be possibly related to the sulfadoxine-pyrimethamine combination. Four treatments were temporarily interrupted, and toxicity was observed after readministration of treatment in 1 case only. However, none of these adverse events was life threatening. CONCLUSIONS: According to our results and previously published data, the combination of sulfadoxine-pyrimethamine seems to be well tolerated. However, the sample size of our study was too small to rule out the risk of less frequent, but nevertheless severe, reactions and, in particular, of hypersensitivity reactions.

Paclitaxel hypersensitivity reactions: assessment of the utility of a test-dose program.

UNLABELLED: Several studies have suggested the usefulness of a test dose of paclitaxel to reduce the incidence of hypersensitivity reactions and the resulting cost of drug wastage. The aim of this study was to assess the utility of implementing such a test dose. METHOD: We retrospectively reviewed the medical charts of patients who had received one or two courses of single-agent paclitaxel or a combination chemotherapy regimen to calculate hypersensitivity reaction incidence and the cost of drug wastage. Thereafter, a paclitaxel test-dose program was routinely implemented during the first and second cycles of paclitaxel treatment for all patients. Hypersensitivity reaction incidence and drug wastage cost were again assessed. RESULTS: Before the routine use of a test dose, 162 patients received one or two paclitaxel infusions alone or in combination therapy from January 1, 1997 to February 28, 2003. Ten (6.2%) patients experienced a hypersensitivity reaction; one of them was severe. After implementation of the test-dose program, 130 patients received 244 test doses (12 mg paclitaxel/10 mL normal saline) with an intensified premedication regimen at the first and second cycles of chemotherapy from June 28, 2003 to March 2, 2005. Three patients (2.3%) experienced a minor hypersensitivity reaction, one immediately after the test dose and two during infusion of the full dose despite a well-tolerated test dose. Thus, the negative predictive value of the test dose was 98.4%. The overall incidence of hypersensitivity reactions experienced during the first or second cycle of paclitaxel chemotherapy decreased about 63% compared with the incidence before implementation of the test dose (P < 0.20). The test-dose program resulted in a 29% increase in the cost of chemotherapy (approximately 6100 dollars for 130 patients). CONCLUSION: To our knowledge, this is the largest study ever reported to test the potential cost-saving benefit of the implementation of a paclitaxel test-dose program to prevent hypersensitivity reactions. The results suggest that the routine use of a test dose is not a cost-effective measure.