Relevant Safety Information Research Articles

Mutagenic and genotoxic in silico QSAR prediction of dimer impurity of gliflozins; canagliflozin, dapaglifozin, and emphagliflozin and in vitro evaluation by Ames and micronucleus test

Canagliflozin, Dapagliflozin, and Empagliflozin, glucagon-like peptide-1 receptor agonists, are indicated for managing type II diabetes. Although the genotoxicity profiles of these drugs are well-explored, limited information exists regarding the genotoxic potential of their impurities. In this investigation, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin underwent both in silico and in vitro assessments for mutagenic potential. Tester strains of Salmonella typhimurium and Escherichia coli were subjected to the Ames test, utilizing concentrations of up to 1 µg per plate, with and without the presence of metabolic activation. Evaluation of micronucleus induction in TK6 cells was conducted through a micronucleus test, exploring concentrations up to 500 µg/mL, with or without the presence of exogenous metabolic activation. Under the specific test conditions, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin showed no evidence of mutagenicity or clastrogenicity, establishing their in vitro classification as nonmutagenic. These findings align with negative in silico predictions from quantitative structure–activity relationship (QSAR) analyses for mutagenicity and genotoxicity of the dimer impurities. Collectively, these studies contribute clinically relevant safety information by confirming that the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin are nonmutagenic and nongenotoxic, emphasizing the consistency between in silico and in vitro data.

Evaluation of FDA Labeling Changes Related to PREA Safety-Waivers.

The Pediatric Research Equity Act (PREA) gives the US Food and Drug Administration (FDA) authority to require pediatric studies for drug and biologics products under certain circumstances and to waive this requirement in some, or all, pediatric ages. When studies are waived for safety, PREA stipulates the safety issue must be described in labeling. This study assessed the rate of including waiver-related safety information in labeling. FDA databases were reviewed to determine the number of safety-related pediatric study waivers and issued from December 2003 through August 2020, and corresponding labeling to establish when relevant safety information was included. Descriptive comparisons were conducted across Cohort 1: December 2003-2007, Cohort 2: 2008-2011, Cohort 3: 2012-2015, and Cohort 4: 2016-August 2020. One hundred sixteen safety waivers were issued [Cohort 1 (n = 1); Cohort 2 (n = 38), Cohort 3 (n = 37), and Cohort 4 (n = 40)] for 84 unique drugs or biologics. Most (106 of 116; 91%) waiver-related safety issues were described in labeling [Cohort 1 (1 of 1), Cohort 2 (33 of 38), Cohort 3 (33 of 37), and Cohort 4 (39 of 40)]. Safety waivers were most common in patients ≤ 17years (n = 40) and least common in patients ≤ 6months (n = 15). Products for infections (n = 32) were the most common group receiving safety waivers; 17 for non-antiviral anti-infective products including treatments for dermatologic infestations/infections, and 15 for antiviral products. The data confirm that FDA consistently describes waiver-related safety information in drug/biologic product labeling since the inception of PREA in December of 2003.

Development of a Website for a Living Network Meta-analysis of Atopic Dermatitis Treatments Using a User-Centered Design: Multimethod Study.

A rapid expansion of systemic immunological treatment options for atopic dermatitis (AD) has created a need for clinically relevant and understandable comparative efficacy and safety information for patients and clinicians. Given the scarcity of head-to-head trials, network meta-analysis (NMA) is an alternative way to enable robust comparisons among treatment options; however, NMA results are often complex and difficult to directly implement in shared decision-making. The aim of this study is to develop a website that effectively presents the results of a living systematic review and NMA on AD treatments to patient and clinician users. We conducted a multimethod study using iterative feedback from adults with AD, adult caregivers of children with AD, dermatologists, and allergists within a user-centered design framework. We used questionnaires followed by workshops among patients and clinicians to develop and improve the website interface. Usability testing was done with a caregiver of a patient with eczema. Questionnaires were completed by 31 adults with AD or caregivers and 94 clinicians. Patients and caregivers felt it was very important to know about new treatments (20/31, 65%). Clinicians felt the lack of evidence-based comparisons between treatments was a barrier to care (55/93, 59%). "Avoiding dangerous side effects" was ranked as the most important priority for patients (weighted ranking 5.2/7, with higher ranking being more important), and "improving patients' overall symptoms" was the most important priority for clinicians (weighted ranking 5.0/6). A total of 4 patients and 7 clinicians participated in workshops; they appreciated visualizations of the NMA results and found the website valuable for comparing different treatments. The patients suggested changes to simplify the interface and clarify terminology related to comparative efficacy. The user in the usability testing found the website intuitive to navigate. We developed a website, "eczematherapies.com," with a user-centered design approach. Visualizations of NMA results enable users to compare treatments as part of their shared decision-making process.

Workplace Learning in China: Transferring Training Into Practice to Improve Performance

Purpose: The present study seeks to examine the efficacy of different training modalities on increasing workplace learning, representatives' intent to transfer what they learned into their work, and importantly how training impacts actual work performance. These relationships are tested in the context of a Chinese division of a multinational pharmaceutical company, where pharmaceutical representatives are tasked with relaying relevant efficacy and safety information on pharmaceutical products to health care professionals who prescribe them to patients. Methods: The present study employed a three-group between-subjects experimental design. Representatives received varying forms of training (instruction only, instruction plus reflection, and instruction, reflection, plus direct feedback) based on experimental conditions. After three training sessions over the course of six weeks, representatives were assessed on how much they learned in the training and their actual work performance through observer assessment of meetings with health care professionals, facilitated by the representatives. Findings: In this study, it was found that the process of actively reflecting on what was learned in training led to increased learning, as well as increased performance, compared to simply studying the material. However, receiving direct feedback on training performance, combined with active reflection training, did not provide any further benefits in terms of learning or work performance. Notably, there were no differences in intent to transfer learned material to work, as all conditions reported high levels of transfer intention. Conclusion: The finding provides insightful evidence to support the benefits of fostering trainees' active reflections for work-based learning in the Chinese industry training scenario. In contrast, receiving direct comments on how students performed from a manager or trainer, as well as advise on how do better in the future, had no effect on increasing learning or performance. Although the effect of direct feedback is not statistically significant in this context, further research should be done in understanding individuals' thoughts and behaviors when received direct feedbacks received in workplace training. Relatively little workplace research has assessed both workplace learning and performance in the same study, specifically in the Chinese context. While training efficacy likely varies across cultures to begin with, compensation structures in China do not provide the same monetary incentives for workplace learning (i.e. chance to increase income) as Western culture. This means that any way to increase workplace learning should be of extra value, as employees otherwise may not engage in it at all.

Adverse events in the digital age and where to find them.

Exponential growth of health-related data collected by digital tools is a reality within pharmaceutical and medical device research and development. Data generated through digital tools may be categorized as relevant to efficacy and/or safety. The enormity of these data requires the adoption of new approaches for processing and evaluation. Recognition of patterns within the safety data is vital for sponsors seeking regulatory approval for their new products. Nontraditional data sources may contain relevant safety information; early evaluation of these data will help to determine the product safety profile. Advanced technologies have allowed the development of digital tools to screen these data, which in some situations are classified as software as a medical devices and subject to clinical evaluation and post-marketing surveillance. Artificial intelligence may help to reduce or even eliminate noise from within these data, allowing safety experts to focus on the most pertinent evidence. We propose a data typology and provide considerations on how to define adverse events within different types of data, even where no human reporter exists. Proposals are made for the automation of screening processes. We consider validation aspects to support solutions that are proven to produce reliable results, and to deliver trusted outputs to stakeholders.

Curtailing invisibility of health and safety risks

Risk control in many areas in society is based on known danger and avoidance of predicted accidents. Between accidents as predicted and accidents as they actually occur, there is a gap however. This gap hides a multitude of relevant safety information which might therefore not be considered in safety management systems, risk inventories and accident scenarios. Hence, it might help to pay attention to the gap of "invisible" phenomena and mechanisms and study the concept of "invisibility". Wondering about the role of invisibility in this respect, the authors explore literature using a scoping review approach, in search of invisibility concepts: ways in which full or partial invisibility exists in a variety of areas relevant to safety. Some 202 of such concepts are found. They can be grouped into 22 frequently found types of invisibility, each capable of hiding relevant safety information. Using a theoretical object-path-observer model, deconstruction of invisibility concepts into their constituting parts, and a proposed systematic combination process, an inventory with many more invisibility concepts can be generated than presently found in literature. This provides a new tool to search for currently hidden safety information and scenarios in the gap. Several examples of newly generated scenarios are discussed. The methodical limitations of this study make the current results indicative only. Both the 22 most frequently found invisibility types and the generation of new object, path and observer property combinations are recommended for use in safety management practice. Further research is recommended to gather more complete data for justification of an invisibility concepts classification.

Prevalence and Exposure to Ergonomic Risk Factors among Crop Farmers in Nigeria

This study examined the prevalence and exposure to ergonomic risks factors among crop farmers in selected states in Nigeria. We used cross-sectional data to provide this evidence. Data were collected with the aid of a standardized questionnaire administered to farmers. A total of 480 smallholder cassava farmers selected across 24 farming communities in Kogi and Kwara states, Nigeria, were engaged in the study. Descriptive statistics and binary regression were used for analysis. About 96% of the respondents reported shoulder pain, 85% reported lower back pain, 82% reported upper back pain, 64% reported neck pain, and 53% reported elbow pain during farming operations. We found that the age of farmers (OR = 2.01) and daily duration of daily chemical spray (OR = 1.17) were risk factors, while previous training on the safe use and application of farm chemicals was found to be a protective factor (α = 0.05). The study identified affordability of farm safety measures and poor access to relevant safety information as top constraints to farmers’ adoption of safe farm practices. We concluded there is a high prevalence of ergonomic risks during cassava operations among respondents. A crop-specific co-designed ergonomic intervention targeted at Nigerian farmers to reduce exposure to ergonomic risks is recommended.

Efficacy and safety of once-monthly Risperidone ISM\xae in schizophrenic patients with an acute exacerbation

To evaluate the efficacy and safety of Risperidone ISM® against placebo in patients with acute exacerbation of schizophrenia. A multicenter, randomized, double-blind, placebo-controlled study was conducted between June 2017 and December 2018 (NCT03160521). Eligible patients received once-monthly intramuscular injections of Risperidone ISM® (75 or 100 mg) or placebo for 12 weeks. The primary efficacy outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 12. The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Altogether, 438 patients were randomized (1:1:1) and 390 included in the modified ITT efficacy set. The PANSS total score (mean difference, 95% CI) improved significantly from baseline to day 85 with Risperidone ISM® 75 and 100 mg, with placebo-adjusted differences of −13.0 (95% CI, −17.3 to −8.8); (p < 0.0001), and −13.3 (−17.6 to −8.9); (p < 0.0001), respectively. Significantly improved mean changes were also obtained for CGI-S score from baseline to day 85 for both doses of Risperidone ISM® compared with placebo −0.7 (−1.0 to −0.5); p < 0.0001, for both doses. The statistically significant improvement for both efficacy outcomes were observed as early as 8 days after first injection. The most frequently reported treatment-emergent adverse events were increased blood prolactin (7.8%), headache (7.3%), hyperprolactinemia (5%), and weight increase (4.8%). Neither new nor unexpected relevant safety information was recorded. Risperidone ISM® provided rapid and progressive reduction of symptoms in patients with acutely exacerbated schizophrenia without need of oral risperidone supplementation or loading doses. Both doses were safe and well tolerated.

Self-reported use and understanding of food label information among tertiary education students in Ghana

Food packaging labels attract consumers' attention in stores and market areas, and communicates relevant food safety and nutrition information that allows them to distinguish between food product alternatives. Therefore, the objective of this study was to assess consumers' self-reported use, knowledge and understanding of food labels among tertiary students in Ghana. A validated questionnaire was used to recruit 1478 students from fourteen (14) public tertiary institutions across the 10 regions to collect information on demographic characteristics of respondents, usage and understanding of information provided on food labels, using proportional quota and convenience sampling techniques. The majority of respondents 956 (64.7%) were between the ages of 21 and 30. A total of 463 (31.3%) students read food label ‘very often’ while 892 (60.4%) read food labels ‘sometimes’. While 963 (65.2%) of respondents indicated that information on food labels are very important, 934 (63.2%) still believe that food label information are often not credible. Respondents considered expiring date 1269 (85.9%), date of manufacture 1106 (74.8%) and health warning 1097 (74.2%) as the top three very important information on food labels whereas product value/weight, 654 (44.2%) was considered as least important in choosing particular food products. Respondents generally depend on television programs/advertisement, 1349 (91.3%); internets, 1290 (87.3%) and friends and neighbors, 1213 (82.1%) as sources of knowledge regarding food label information. When participants were provided with a sample food label to assess their understanding of food label information, 916 (62.0%) of respondents did not answer the question at all. Out of 562 (38%) who answered the question, only 243 (16.5%) correctly interpreted the information. No significant difference (P > 0.05) exist between ages, sexes, institutions, and university and training college students regarding their understanding of food label information. Eventhough tertiary education students in Ghana read and attach importance to food label information, they have limited understanding of the information provided on food labels.

How effective are community pedestrian safety training workshops? Short-term findings from a program in California

IntroductionPedestrians and bicyclists make up a disproportionate share of road deaths and injuries, and low-income, majority person-of-color communities tend to face the greatest danger. Comprehensive pedestrian safety programs targeted toward such communities have the potential to build communities’ capacity to address safety issues, but there is a lack of systematic research and evaluation on how effective these programs are. MethodsWe use a mixed-methods approach of surveys, participant observation, and follow-up interviews to evaluate a community-based pedestrian and bicycle safety program in 13 California communities for its short-term effectiveness in meeting five goals: providing relevant safety information to participants, building community partnerships, increasing walking and cycling in host communities, improving perceptions of pedestrian and bicyclist safety, and planning for additional safety countermeasures. ResultsWorkshops have beneficial effects on identifying community needs, developing partnerships between stakeholders, and changing perceptions of safety in historically disadvantaged communities. The program improves participants’ perceptions of the role that community organizations and community events play in pedestrian safety efforts. The program also provides a critical space for community stakeholders to meet, learn a common language about safety, and develop partnerships around pedestrian and bicycle safety. Host communities have used the workshops as support for grant applications, and several have obtained funding for pedestrian and bicycle improvements. ConclusionThe workshops intervene in the short-term on multiple levels to improve pedestrian safety as described in program goals. This study provides a model for evaluating a program for its short-term effects, providing a baseline set of conditions for longer-term evaluation.

Belgian community pharmacists' pharmacovigilance perspective and practice.

Pharmacovigilance legislation was introduced back in 2012 with new concepts such as the inverted black triangles and risk minimisation activities. Healthcare professionals need to familiarize themselves with these new notions in order to comply with their obligations such as risk mitigation and reporting of adverse drug reactions. To measure the magnitude and relevance of these new concepts and the impact on everyday dispensing in Belgian community pharmacies. An inventory database was constructed containing all relevant pharmacovigilance information at product level, and this data was made available within the pharmacy dispensing software. Furthermore, for a typical community pharmacy, the number of concerned products and the number of dispensed products with supplementary pharmacovigilance responsibilities was determined. The number of available and dispensed medicines with black triangle or additional risk minimisation activities has increased significantly since July 2014. During July 2017, each pharmacy dispensed around 120 packs with risk minimisation obligations and around 70 with a black triangle, clearly illustrating the relevance of having all information at hand. With relevant safety information available at the point of dispensing, pharmacists can now focus on complying with their pharmacovigilance responsibilities.

Guideline on safety evaluation of cell-based medicinal products for animal use.

With the increased use of cell therapy in the veterinary sector, there is a growing demand for the development of cell-based medicinal products and the determination of their safety. Currently, the Korean Animal and Plant Quarantine Agency has established a guideline for evaluating the safety of cell-based medicinal products for animal use. The guideline includes items related to definition, classification, management, manufacturing procedure and quality control (standard and test method), stability testing, toxicity testing, pharmacological testing, and performance of clinical trials. In addition, testing protocols related to safety assessment of animal cell-based products such as chromosome karyotyping, tumorigenicity testing, confirmatory testing of biodistribution and kinetics, and target animal safety testing are described in detail. Moreover, because cell-based medicinal products are novel therapies, deviations from traditional designs may be justified in order to obtain relevant safety information on the treatment. Additionally, this guideline can be amended on the basis of new scientific findings.

Challenges and Benefits of Repurposing Products for Use during a Radiation Public Health Emergency: Lessons Learned from Biological Threats and other Disease Treatments.

The risk of a radiological or nuclear public health emergency is a major growing concern of the U.S. government. To address a potential incident and ensure that the government is prepared to respond to any subsequent civilian or military casualties, the U.S. Department of Health and Human Services and the Department of Defense have been charged with the development of medical countermeasures (MCMs) to treat the acute and delayed injuries that can result from radiation exposure. Because of the limited budgets in research and development and the high costs associated with bring promising approaches from the bench through advanced product development activities, and ultimately, to regulatory approval, the U.S. government places a priority on repurposing products for which there already exists relevant safety and other important information concerning their use in humans. Generating human data can be a costly and time-consuming process; therefore, the U.S. government has interest in drugs for which such relevant information has been established (e.g., products for another indication), and in determining if they could be repurposed for use as MCMs to treat radiation injuries as well as chemical and biological insults. To explore these possibilities, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop including U.S. government, industry and academic subject matter experts, to discuss the challenges and benefits of repurposing products for a radiation indication. Topics covered included a discussion of U.S. government efforts (e.g. funding, stockpiling and making products available for study), as well unique regulatory and other challenges faced when repurposing patent protected or generic drugs. Other discussions involved lessons learned from industry on repurposing pre-license, pipeline products within drug development portfolios. This report reviews the information presented, as well as an overview of discussions from the meeting.

Adherence of safety information on over‐the‐counter product labels and leaflets to the regulatory guidelines in Malaysia

AbstractAimTo evaluate the adherence of medication safety information provided on over‐the‐counter (OTC) product labels and patient information leaflets (PILs) to the Malaysian and international regulatory guidelines.MethodsA total of 133 randomly sampled OTC medications (gastrointestinal = 31, pain = 36, skin = 35, coughs and colds = 31) from 17 community pharmacies located around Klang Valley, Malaysia were evaluated. The adherence of relevant safety information provided on the OTC product labels and PILs from the manufacturing companies to the Malaysian and international regulatory guidelines was evaluated.ResultsThe majority of the products (n = 81) were locally manufactured, followed by 34 products from the European region. About 31% (n = 41) of the sampled OTC products were sold without PILs. Overall, 98% of the labels adhered to all the criteria, but none of the PILs adhered to all the parameters. Information on action to be taken in the case of a missed dose (96%), advice on consulting a doctor/pharmacist for further information (92%) and disposal instructions (98%) were generally missing. Surprisingly, none of the PILs included the compulsory statement which is essential for adverse drug reaction reporting. In addition, only 30% of the studied PILs provided information on the date of revision. Overall, imported products had slightly better adherence compared to locally manufactured products.ConclusionThe safety information stated on the OTC products marketed in Malaysia has room for improvement to ensure safe and effective use of these products. A uniform format and collective effort is needed to ensure consumers receive adequate information about OTC products.

Does talking the talk matter? Effects of supervisor safety communication and safety climate on long-haul truckers’ safety performance

This study examines the distinct contribution of supervisory safety communication and its interaction with safety climate in the prediction of safety performance and objective safety outcomes. Supervisory safety communication is defined as subordinates’ perceptions of the extent to which their supervisor provides them with relevant safety information about their job (i.e., top-down communication) and the extent to which they feel comfortable discussing safety issues with their supervisor (i.e., bottom-up communication). Survey data were collected from 5162 truck drivers from a U.S. trucking company with a 62.1% response rate. Individual employees’ survey responses were matched to their safety outcomes (i.e., lost-time injuries) six months after the survey data collection.Results showed that the quality of supervisor communication about safety uniquely contributes to safety outcomes, above and beyond measures of both group-level and organization-level safety climate. The construct validity of a newly-adapted safety communication scale was demonstrated, particularly focusing on its distinctiveness from safety climate and testing a model showing that communication had both main and moderating effects on safety behavior that ultimately predicted truck drivers’ injury rates. Our findings support the need for continued attention to supervisory safety communication as an important factor by itself, as well as a contingency factor influencing how safety climate relates to safety outcomes.

“When This Breaks Down, It’s Black Gold”: Race and Gender in Agricultural Health and Safety

ABSTRACTFarmers are growing older, and fewer new agriculturists are rising to take their place. Concurrently, women and minorities are entering agriculture at an increasing rate. These rates are particularly curious viewed in light of the racialized and gendered nature of agriculture. Slavery and agriculture share strong historical roots, with many male slaves performing agricultural labor. So then, why would African American women choose to engage in agriculture in any form? Participant observation and in-depth interviews with a group of African American women urban farmers in the southeastern United States were asked this question. Interviews with seven such women revealed their perception of self-sustainable small-scale agriculture as a departure from, not return to, slavery. The women drew metaphors between the Earth and femininity, believing their work to be uniquely feminine. Production of food for consumption and trade provides a source for community and healthy food amid urban poverty and the plight of food deserts. These data encourage agricultural health and safety professionals and researchers to tackle the health-promoting nature of such work, with the entrée of anthropology and other social sciences into the field. In many ways, these women portrayed small-scale food cultivation as an important component of, rather than a threat to, health and safety. Indeed, they viewed such labor as wholly health promoting. Their strong social connections provide a potential means for community-led dissemination of any relevant health and safety information.

Utilizing Six Sigma to develop standard attributes for a Safety for Facilities Management (SFFM) framework

IntroductionRepair and maintenance personnel in the field of facilities management (FM), have a much higher rate of injury and illness than the national average. Research has shown that a major contributing factor to these high incidence rates is the disorganization and fragmentation of relevant safety information, coupled with the often time sensitive nature of FM tasks. Practical applicationIn order to improve worker’s safety during the FM phase, a BIM-based Safety for Facilities Management (SFFM) framework is being developed to categorize, consolidate, process, and efficiently present job specific, relevant safety information to FM personnel. MethodIn order to properly develop the SFFM, the safety information that is applicable to FM staff must first be identified, organized, and categorized. This is executed through a number of research methods, structured within the theoretical framework of Six Sigma’s Define-Measure-Analyze-Design-Verify (DMADV). ResultsBy systematically collecting, analyzing, and categorizing data within the Define Phase of DMADV, an iterative process with validation steps provides a rigorous and a comprehensive evaluation of the data. ConclusionThis paper describes the data collection and analysis methods, known as the Define Phase, of Six Sigma’s Define-Measure-Analyze-Design-Verify (DMADV) methodology, in order to develop safety properties that are utilized within the BIM-based SFFM framework.

State-of-the-art biosimilar erythropoietins in the management of renal anemia: lessons learned from Europe and implications for US nephrologists.

The European Medicines Agency (EMA), under a strictly regulated pathway, has approved several biosimilar products since 2005, including biosimilar versions of the erythropoiesis-stimulating agent (ESA) epoetin alfa since 2007. Subsequent to these approvals, the use of biosimilar epoetin alfa in the management of renal anemia has grown steadily throughout Europe. With the enactment of the US Biologics Price Competition and Innovation Act of 2009, a US Food and Drug Administration regulatory approval process for biosimilars was legalized. Thus, biosimilar erythropoietin products are expected to be available for prescription in the USA by mid-decade, presumably at a price that is competitive with the originator brand-name reference products. In this paper, we describe the status of originator and biosimilar ESAs, review the clinical development and regulatory approval of biosimilar erythropoietins in Europe, and summarize relevant efficacy and safety information of biosimilar erythropoietins in relation to their reference products to provide a background for US nephrologists as they appraise biosimilar erythropoietins as treatment options for renal anemia. Key lessons learned from Europe are that (a) EMA-approved biosimilar erythropoietins have comparable efficacy and safety profiles to their reference product erythropoietin; (b) pharmacovigilance preapproval and postapproval are critical, especially with regard to immunogenicity and vascular thromboembolic events; (c) strict preapproval and postapproval requirements must guide the regulatory pathway for biosimilars; and (d) high-quality manufacturing and production processes must be established to ensure quality biosimilar products. The availability of biosimilar erythropoietins in the USA will provide nephrologists with alternative effective, and potentially more affordable, treatment options for patients with renal anemia.

Tsunami Waves of Destruction: The Creation of the “New Australian Catastrophe”

Tsunami Waves of Destruction: The Creation of the “New Australian Catastrophe”

PHP121 Drug Reimbursement Maintenance: A French Challenge in 2011

In France, reimbursement of drugs is based on the therapeutic value of drugs (SMR level for each indication) as assessed by HAS, going from “insufficient” (no reimbursement at all) to “weak” (15% reimbursement), “moderate” (30%) and “important” (65%). HAS and manufacturer have the right to ask for re-assessment anytime after the initial reimbursement listing; in all cases, a relisting process is compulsory every 5 years. We analyzed HAS's reassessment and relisting activity over the year 2011, based on the hypothesis that the Mediator safety “affair” would have impacted the process. We considered all complete procedures for relisting, re-assessments and class reviews and focused on drugs for which a HAS advice was published between Jan and Dec 2011. We compared previous and new SMR levels for each indication. Twenty-six drugs have gone the relisting process, corresponding to 33 different indications, out of which 31 cases were analyzable: HAS modified 14 SMRs while 17 SMRs remained unchanged. Almost 50% (6/13) of SMR initially rated as “important” were changed to “insufficient” (4) or “moderate” (2). All initially insufficient SMR (8) were confirmed. 19 drugs have gone through re-assessment process, corresponding to 24 SMRs/indication, out of each only 21 were analyzable: 10 SMRs have been modified (only 2 increased and the rest lowered) and 11 unchanged. In 8 of these cases, the manufacturer had asked for the re-assessment. 6 full therapeutic classes have been reviewed in 2011, including Alzheimer's and antipschychotics, resulting in a harmonization and a decrease of the SMR levels. Manufacturers should now ensure that reassessment and relisting dossiers in France incorporate as much of relevant clinical, safety and real-life information as possible in order to maintain the reimbursement level.