Health technology assessment of paediatric medicines: European landscape, challenges and opportunities inside the conect4children project.

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost-effectiveness of a new children's treatment has several non-trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms.

Acceptability of oral liquid pharmaceutical products in older adults: palatability and swallowability issues.

BACKGROUND: In institutional care, oral liquid pharmaceutical products are widely prescribed for older patients, especially for those with swallowing disorders. As medicines acceptability is a key factor for compliance in the older population, this study investigated the acceptability of oral liquid pharmaceutical products in this targeted population. METHODS: An observational, multicenter, prospective study was conducted in eight geriatric hospitals and eight nursing homes in France. Observers reported several behaviours/events describing the many aspects of acceptability for various pharmaceutical products' uses in patients aged 65 and older. Acceptability scores of oral liquid pharmaceutical products were obtained using an acceptability reference framework (CAST - ClinSearch Acceptability Score Test®): a 3D-map summarizing the different users' behaviors, with two clusters defining the positively and negatively accepted profiles materialized by the green and red zones, respectively. RESULTS: Among 1288 patients included in the core study and supporting the acceptability reference framework, 340 assessments were related to the administration of an oral liquid pharmaceutical product. The mean age of these patients was 87 (Range [66-104y]; SD = 6.7), 68% were women and 16% had swallowing disorders. Globally, the oral liquid pharmaceutical products were classified as "positively accepted," the barycenter of the 340 assessments, along with the entire confidence ellipses surrounding it, were positioned on the green zone of the map. Sub-populations presenting a different acceptability profile have also been identified. For patients with swallowing disorders, the oral liquid pharmaceutical products were classified as "negatively accepted," the barycenter of the 53 assessments along with 87% of its confidence ellipses were associated with this profile. A gender difference was observed for unflavored oral liquids. In women, they were classified "negatively accepted," the barycenter of the 68 assessments with 75% of its confidence ellipses were located in the red zone, while they were classified "positively accepted" in men. CONCLUSION: This study showed that oral liquid pharmaceutical products are a suboptimal alternative to solid oral dosage forms in patients with swallowing disorders. To ensure an optimal acceptability, prescribers should also consider the presence of a taste-masker in these oral liquids. As highlighted herein, palatability remains crucial in older populations, especially for women.

Anticholinergic drug use and cognitive performances in middle age: findings from the CONSTANCES cohort.

BACKGROUND: Previous studies have shown associations between the use of anticholinergics (AC) and cognitive performance in the elderly, considering AC as a homogeneous set of drugs. The present study aims to assess the relationship between exposure to AC drugs and cognitive performance in middle-aged adults according to AC potency and drug class. METHODS: Our cross-sectional study used baseline data of 34 267 participants aged 45-70 from the Consultants des centres d'examen de santé de la sécurité sociale (CONSTANCES) cohort. The cumulative exposure to AC was measured using national reimbursement databases over the 3-year period preceding assessment of cognitive performance. Eight classes of AC drugs were differentiated. Episodic verbal memory, language abilities and executive functions were evaluated by validated neuropsychological tests. Analyses were controlled on lifestyle and health status variables. RESULTS: This study showed a negative association between overall cumulative AC exposure and cognitive performances after adjustment. The use of drugs with possible AC effect according to the Anticholinergic Cognitive Burden scale (ACB-1 score) was only associated with executive functions. Analyses of AC exposure across drug classes showed a negative association between the use of AC antipsychotics and all cognitive functions assessed. Heterogeneous associations were found for the use of AC anxiolytics, AC opioids and AC drugs targeting the gastrointestinal tract or metabolism. We did not find significant associations between the use of antihistamines, antidepressants, cardiovascular system or other AC medications and cognitive function. CONCLUSION: Association between AC drugs and cognitive performance was highly heterogeneous across drug classes; this heterogeneity will have to be considered by future studies.

A Decision Support Tool Facilitating Medicine Design for Optimal Acceptability in The Older Population.

PURPOSE: Medicine acceptability, which is of the utmost importance for vulnerable patients' adherence, is driven by both user and product characteristics. Herein, a novel multivariate approach integrating the many aspects of acceptability is used to discriminate positively and negatively accepted medicines in the older population. METHODS: An observational study was carried out in eight hospitals and eight nursing homes to collect a large set of real-life data on medicines uses in older patients (≥65 years). Mapping and clustering explored these multiple observational measures and summarised the main information into an intelligible reference framework. Resampling statistics were used to validate the model's reliability. RESULTS: A three-dimensional map and two clusters defining acceptability profiles, as positive or negative, emerged from the 1079 evaluations. Factors of interest (medicines, user features…) were positioned on the map at the barycentre of their evaluations and assigned to an acceptability profile. Focusing on patients' ability to swallow, we have highlighted the tool's efficacy in demonstrating the impact of user features on medicine acceptability. CONCLUSIONS: This multivariate approach provides a relevant judgement criterion for this multi-dimensional concept. Facilitating the choice of the most appropriate dosage form to achieve optimal acceptability in a targeted population, this tool is of real potential to improve clinical decisions.

High quality standards for a large-scale prospective population-based observational cohort: Constances.

BACKGROUND: Long-term multicentre studies are subject to numerous factors that may affect the integrity of their conclusions. Quality control and standardization of data collection are crucial to minimise the biases induced by these factors. Nevertheless, tools implemented to manage biases are rarely described in publications about population-based cohorts. This report aims to describe the processes implemented to control biases in the Constances cohort taking lung function results as an example. METHODS: Constances is a general-purpose population-based cohort of 200,000 participants. Volunteers attend physical examinations at baseline and then every 5 years at selected study sites. Medical device specifications and measurement methods have to comply with Standard Operating Procedures developed by experts. Protocol deviations are assessed by on-site inspections and database controls. In February 2016, more than 94,000 participants yielding around 30 million readings from physical exams, had been covered by our quality program. RESULTS: Participating centres accepted to revise their practices in accordance with the study research specifications. Distributors of medical devices were asked to comply with international guidelines and Constances requirements. Close monitoring enhanced the quality of measurements and recordings of the physical exams. Regarding lung function testing, spirometry acceptability rates per operator doubled in some sites within a few months and global repeatability reached 96.7 % for 29,772 acceptable maneuvers. CONCLUSIONS: Despite Constances volunteers being followed in multiple sites with heterogeneous materials, the investment of significant resources to set up and maintain a continuous quality management process has proved effective in preventing drifts and improving accuracy of collected data.

Ceftolozane/Tazobactam for the Treatment of Complicated Infections in Hospital Settings-A French Real-world Study.

Background: This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. Methods: This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. Results: A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. Conclusions: This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.

Dosage Forms Suitability in Pediatrics: Acceptability of Antibiotics in a German Hospital.

Although drug acceptability can have a significant impact on patient adherence in pediatric therapy, data are limited, even for common therapeutic areas. We present the second part of an acceptability study conducted at the University Children's Hospital Düsseldorf, Germany. The study investigated the acceptability of most commonly used antibiotics in a pediatric hospital setting. The researchers used the acceptability reference framework to score the acceptability of five antibiotics based on 150 real-life observer reports of medicine intake. Four antibiotics assessed in this study were formulated as preparations for injection (ampicillin, ampicillin/sulbactam, ceftriaxone, and gentamicin) and one as a powder for oral liquid suspension (co-amoxiclav). All the antibiotics formulated as preparations for injection were rated negatively due to high rates of negative reactions (80%), the use of restraint (51%), the use of extra devices (99%), and long preparation and administration times (100%). The antibiotic formulated as a powder was significantly more well accepted. The study concluded that there is a lack of appropriate formulations for antibiotics for use in children. These findings are important in improving knowledge on acceptability drivers and might help in formulating and prescribing better medicines for children. The study highlights the need for healthcare professionals to have knowledge about the acceptability of different products to select the best-adapted product for each patient.

A review of paediatric injectable drug delivery to inform the study of product acceptability - An introduction.

AIM: The EMA defines acceptability as "the overall ability and willingness of the patient to use, and their caregiver to administer, the medicine as intended" [1]. This paper seeks to outline issues of acceptability in relation to injectable therapy, namely intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration routes, and to lay a foundation to identify a minimum set of data that would satisfy Regulatory Authorities when discussing the acceptability of an injectable product. In addition, it will alert drug product developers to other factors that might contribute to good practice, alternative administration strategies and overall adherence to achieve successful treatment. Whilst the term 'parenteral' means "outside the intestine" [2,3] and so potentially covers a range of administration routes including intranasal and percutaneous administration, this review focuses on IV, IM and SC administration by injection. The use of indwelling canulae or catheters to reduce venepuncture and facilitate prolonged treatment is common and may impact acceptability [4]. This may be influenced by information provided by the manufacturer but is not always in their direct control. Other injectable products suitable for routes such as intradermal, intra-articular, intraosseous and intrathecal, share the requirement to be acceptable but are not specifically covered in this paper [2,5].

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations.

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients.

Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart-Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.

Indications and outcomes of antifungal therapy in French patients with haematological conditions or recipients of haematopoietic stem cell transplantation.

OBJECTIVES: Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD. METHODS: In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria. RESULTS: The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank P = 0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation. CONCLUSIONS: In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.

Dosage Forms Suitability in Pediatrics: Acceptability of Analgesics and Antipyretics in a German Hospital.

Although medicine acceptability is likely to have a significant impact on the patient's adherence in pediatrics and therefore on therapy success, there is still little data even for common therapeutic areas. For analgesics/antipyretics, healthcare professionals face a wide variety of products and need knowledge to select the best adapted product for each patient. We investigated acceptability of those products most used at the University Children's Hospital Düsseldorf, Germany. Based on 180 real-life observer reports of medicine intake, we used the acceptability reference framework to score acceptability of six distinct medicines. Both ibuprofen and paracetamol tablets, mainly used in adolescents, were positively accepted. This was not the case for the solution for injection of metamizole sodium. Regarding syrups, mainly used in children under 6 years of age, ibuprofen flavored with strawberry and provided with an oral syringe was positively accepted, while paracetamol flavored with orange and provided with a measuring cup was not. Suppository appeared to be an alternative to oral liquids in infants and toddlers with palatability and administration issues. Differences appeared to be driven by dosage forms and formulations. These findings improve knowledge on acceptability drivers and might help formulating and prescribing better medicines for children.

Acceptability of different oral dosage forms in paediatric patients in hospital setting.

OBJECTIVE: The understanding of acceptability of existing dosage forms is limited in most of the world and hinders the development of acceptable, age-appropriate medicines. The attributes of paediatric medicine acceptability may differ from country to country based on culture, healthcare infrastructure and health policies. This study was designed to map the acceptability of oral medicines in paediatric patients treated in hospital in India. METHODS: An observational, cross-sectional study was conducted in patients aged below 18 years and taking any form of oral medication. Acceptability scores were obtained using CAST-ClinSearch Acceptability Score Test tool. FINDINGS: 490 patients were recruited and 193 evaluations of different pharmaceutical products available in 20 dosage forms and 7 routes of administration were studied. Oral liquids (50%) and tablets (35%) were the most commonly prescribed and administered forms. Regardless of the therapeutic class and age, the oral liquids were 'positively accepted' in infants and toddlers. Acceptability of tablets improved with age and appeared to be generally good from the age of 6. CONCLUSION: This study indicates the limited progress towards adoption of age-appropriate dosage forms in India and thus impact on the acceptability of existing oral dosage forms. The key challenges posed by the adoption of age-appropriate formulations in India are (1) awareness of importance of appropriate administration and acceptability of medicines to children in India, (2) availability of age-appropriate dosage forms and (3) lack of child-appropriate medicine policies.

Medicine acceptability for older people in hospital and care home: the influence of setting.

OBJECTIVE: Medicines acceptability is likely to have a significant impact on older people's adherence and, consequently, treatment effectiveness. The objective was to explore the influence of setting on medicines acceptability in older people. METHODS: A multi-centre, prospective, cross-sectional, observational study was conducted in one care home and one elderly care hospital ward in London, UK, involving individuals on ≥1 medicine(s) and aged ≥65 years. Data-driven approach was applied using multiple observer-reported outcomes analysis tool to distinguish between positively and negatively accepted medicines. KEY FINDINGS: 263 observer reports from the care home (n = 97) and hospital ward (n = 166) involving 155 distinct medicinal products were assessed. Collectively, medicines appeared better accepted by patients at the hospital. Differences appeared to be driven by variations in solid oral dosage form (SODF) acceptability. Patients with dysphagia poorly accepted medicines in both settings, as expected. SODFs were unexpectedly better accepted in the hospital than in the care home in patients without dysphagia. CONCLUSIONS: Medicines acceptability was affected by patient's characteristics, dosage form type and setting. Changes in care practices between care home and hospital may affect medicine administration and lead to variations in the ability and willingness of patients and carers to use the product as intended.

Rational and practical considerations to guide a target product profile for patient-centric drug product development with measurable patient outcomes - A proposed roadmap.

The increasing awareness of acceptability and usability of pharmaceutical drug products by the patient as a key quality requirement continues to drive need for integrating patient centric drug product design into the pharmaceutical development process. The complex matrix of multiple drug product related decisions during the early drug development process often limits patient-centric drug product (PCDP) design options in the final commercial drug product development phase. To integrate the specific needs and perspectives of patients into drug development and product design process, a rational approach integrated into the complex development matrix is required from the start and weighs product development decision options accordingly. The aim of this work was to develop a roadmap for PCDP design in a multidisciplinary approach that leads to better usability, adherence and acceptance of the drug by patients via early integration into the development matrix. The proposed rational approach is based upon regulatory requirements and lessons learned from pediatric and geriatric drug development.

Proposed Tool to Compare and Assess the Applicability of Taste Assessment Techniques for Pharmaceuticals.

Palatability is amongst the most important determinants of whether or not a child will take a medicine. In order to increase concordance with treatment regimens it is often necessary to utilise a range of formulation techniques to improve the palatability of medicines. These can include selecting a different molecule or version of a molecule (such as a different polymorph or salt form), various taste masking techniques and/or the inclusion of flavours and sweeteners. In order to be able to understand the taste of the Active Pharmaceutical Ingredient (API) and to validate the formulation approach used, it is necessary to be able to use the most reliable taste evaluation method possible. Multiple in vivo and in vitro methods exist nowadays or are proposed in the literature but are often little understood by the pharmaceutical product development community. In particular, different methods may be more relevant at different stages of product development. The aim of this article is to propose a tool to guide the selection of the most appropriate method for the desired evaluation. A spreadsheet-based tool is proposed that is designed to allow the systematic assessment of the applicability of any taste assessment technique existing or new to the users proposed application. A series of criteria are defined that will allow the user to assess the analytical, usability and availability factors for the technique that is being considered. Such a systematic review will help the user to understand the benefits and risks of using each methodology for that application. The use of the tool is illustrated based on currently available data and literature. As new/existing methods are developed/improved, the outcomes of the tool may change.

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study.

The APTIMA HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US+ in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.

Acceptability of Mebendazole Chewable Tablet in Children Aged 2 to 4 Years in Peru.

Soil-transmitted helminthiasis (STH) is among the most common of parasitic infections, affecting vulnerable populations in tropical/subtropical areas globally. In endemic countries, children, a high-risk population, require treatment and preventive interventions. Mebendazole, a WHO-recommended medicine, originally formulated as a tablet that was often crushed for administration to young children unable to swallow it, was reformulated as a chewable tablet. Acceptability is a key aspect for treatment effectiveness in pediatrics. Herein, we used a validated data-driven approach to investigate the acceptability of the 500-mg mebendazole chewable tablet in children aged 2 to 4 years in Peru. Observer-reported outcomes were collected for 182 medicine intakes. Acceptability was scored using the acceptability reference framework: a three-dimensional map juxtaposing "positively accepted" and "negatively accepted" profiles. Results found that the 500-mg mebendazole chewable tablet was classified as "positively accepted" in children aged 2 to 4 years. Acceptability increased with age and some acceptability issue remain for the younger children. Nevertheless, this formulation was considerably better accepted than the conventional tablets regardless of treatment in young children. This chewable formulation appears to be an appropriate alternative to the hard tablet of mebendazole for treatment of STH and preventive interventions in children aged 2 to 4 years.

Acceptability of generic versus innovator oral medicines: not only a matter of taste.

Optimum use of generic products would require equivalence, not only in terms of quality, safety, and efficacy in clinical studies, but also patient acceptability to not jeopardize treatment success because of non-adherence which would de facto limit the potential cost saving anticipated by their use. Although acceptability is a requirement for the authorization of pediatric innovator products, a survey of European Union (EU) regulatory authorities showed that few have a formal process for assessing patient acceptability of generic products during the registration processes. The current International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) focus on unifying guidance for the development and scrutiny of generics but should include acceptability alongside the other factors being considered for harmonization.

Adherence and Acceptability of an Oral Antibiotic Used for the Prevention of Pediatric Urinary Tract Infection in Japan.

Urinary tract infection (UTI) is a common health care-associated adverse event and the leading nosocomial complication following pediatric urological surgery. While continuous antimicrobial prophylaxis effectively reduces the risk of UTI following such a surgery, non-adherence is common and represents a distinct clinical entity that is associated with renal scarring. Acceptability is likely to have a significant impact on patient adherence. Herein we used a validated data-driven approach-the ClinSearch acceptability score test (CAST)-to investigate the acceptability of cefaclor, an oral antibiotic widely used for the prevention of pediatric UTI in Japan. Standardized observer reports were collected for 58 intakes of cefaclor 10% fine granules in patients aged from 0 to 17 years. The medicine was classified as positively accepted on the acceptability reference framework. According to the percentage of the prescribed dose taken reported at the end of the treatment, patients exhibited good adherence to this well-accepted medicine. Nonetheless, requirements for greater dosing frequency or poor acceptability in certain patients could affect adherence. Acceptability should be established to ensure patient adherence to medicines used for long-term prophylaxis and consequently guarantee the safety and efficacy of the treatment.