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Introduction: Medicine acceptability is a multi-faceted concept driven by both product and user characteristics. Although a key factor for treatment effectiveness, especially in vulnerable populations, knowledge of those medicine features that best promote individual user acceptability remains fragmented. Focusing on paracetamol, this study has explored the appropriateness of pharmaceutical products in different dosage forms to achieve adequate patient acceptability from infants to centenarians. Methods: This observational, multicentre, prospective study was carried out in 10 hospitals, 8 nursing homes and over 150 community dispensaries. Observers reported several behaviours/events evaluating acceptability for 1016 different pharmaceutical product uses in paediatrics (<18y.) and 1288 in the elderly (≥65y.). Using mapping and clustering, a multivariate approach offered an intelligible reference framework for each population, providing comprehensive scores: positively or negatively accepted. Results: Among all the evaluations supporting the acceptability reference frameworks, there were 502 reports on paracetamol products intake. Herein we focused on the 5 products with ≥30 evaluations. Although oral suspension and powder for oral solution were positively-accepted in the paediatric group, the powder had a higher rate of negative patient reaction (p<0.001). Of those that received this formulation, 72% were ≤8y., and therefore suitable to receive the better accepted oral suspension. In the elderly, patients with swallowing disorders were preferentially treated with such powders (p<0.001), which were less often fully taken than orally disintegrating tablets (p<0.001). Even in those patients ≥90y., capsule formulations appeared to be the best accepted product in patients without swallowing alterations, and thus could be a suitable alternative to the powder in this population. Conclusions: By better integrating patient characteristics when choosing dosage forms, clinicians and caregivers may improve treatment acceptability and adherence. Moreover, hospitals and healthcare institutions could optimise purchasing to best suit their local population, disseminating information to help staff align specific dosage forms to targeted patients. [ABSTRACT FROM AUTHOR]

Objectives Our novel tool to standardise the evaluation of medicine acceptability was developed using observational data on medicines use measured in a paediatric population included for this purpose (0-14 years). Using this tool, any medicine may be positioned on a map and assigned to an acceptability profile. The present exploration aimed to verify its statistical reliability. Methods Permutation test has been used to verify the significance of the relationships among measures highlighted by the acceptability map. Bootstrapping has been used to demonstrate the accuracy of the model (map, profiles and scores of acceptability) regardless of variations in the data. Lastly, simulations of enlarged data sets (×2; ×5; ×10) have been built to study the model's consistency. Key findings Permutation test established the significance of the meaningful pattern identified in the data and summarised in the map. Bootstrapping attested the accuracy of the model: high RV coefficients (mean value: 0.930) verified the mapping stability, significant Adjusted Rand Indexes and Jaccard coefficients supported clustering validity (with either two or four profiles), and agreement between acceptability scores demonstrated scoring relevancy. Regarding enlarged data sets, these indicators reflected a very high consistency of the model. Conclusions These results highlighted the reliability of the model that will permit its use to standardise medicine acceptability assessments. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this article was to present an original standardized tool assessing the medicine's acceptability whichever their characteristics and the patient features. Methods An acceptability map was built with objective measures from medicine use assessments collected in real-life conditions. Multiple correspondence analysis ( MCA) was used for the mapping process. Hierarchical classification on the principal components ( HCPC) of the MCA was performed for the clustering process corresponding to distinct acceptability profiles. Key findings The results presented here focus on 234 evaluations issued from the paediatric population and gathered in four clusters: 'well-accepted' (50%), 'accepted' (19%), 'poorly accepted' (25%) and 'not accepted' medicines (6%). The first one was characterized by a dose fully taken, in a short time, with a patient's positive reaction; the second by a longer administration time, a neutral reaction and the use of methods to achieve administration (reward, divided dose). Differentiation between the two last clusters was, respectively, originated by a required dose partially taken or not taken. Conclusions The acceptability profile of each medicine can be evaluated with the map position of the related patient's assessments barycentre. This tool should satisfy expectations in terms of methods for appropriate acceptability evaluation and standardized comparison among medicines. [ABSTRACT FROM AUTHOR]

Chemical submission is increasing by an occurring phenomenon that consists in administering psychoactive substances for criminal intent to an unaware victim. This diversion is usually achieved by adding a drug to the drink of the potential victim. This study aims essentially at providing a sensory method that would allow the detection of the sensory changes due to the drug. The complexity of this study stemmed from the large number of beverages and potential drugs that can be used for this ill-intentioned act. The alcoholic beverages and soft drinks studied here were selected as a result of an on-line survey, followed by a sorting task study, to which various drugs were added. A visual sensory profile was performed for all the different drug-beverage mixtures. The experienced sensory panel agreed on a lexicon of nine attributes that would allow the drug-beverage mixture to be characterized. A multivariate analysis was performed to study the effect of both the sample (drug-beverage pairs) and the panelists on the sensory profile. The pharmaceutical forms of the drug clearly impacted the following attributes: spotted surface, particles on the surface, suspended particles, cloudiness and sediment. The beverages also had an influence on the visual characteristics of the mixtures concerning opacity, color and effervescence. Practical Application Results of this study showed that visual sensory modification of drinks depends on both the drug and the beverage which suggests that the formulation of a drug must be designed to impact different sensory attributes. From a practical standpoint, both the sensory method and the lexicon presented in this article may be useful for researchers when developing drugs as these can be named according to the specific sensory changes created when mixed in beverages. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population. [ABSTRACT FROM AUTHOR]

In pediatrics, acceptability has emerged as a key factor for compliance, and consequently for treatment safety and efficacy. Polyvalent mechanical bacterial lysate (PMBL) in 50-mg sublingual tablets is indicated in children and adults for the prophylaxis of recurrent respiratory tract infections. This medication may be prescribed in children over 3 years of age; the appropriateness of this sublingual formulation should thus be demonstrated amongst young children. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for medication intake over the course of treatment (days 1, 2, and 10) in 37 patients aged 3 to 5 years, and then analyzed in an intelligible model: the acceptability reference framework. According to this multidimensional model, 50-mg PMBL sublingual tablets were classified as "positively accepted" in children aged 3 to 5 years on all three days of evaluation. As the acceptability evaluation should be relative, we demonstrated that there was no significant difference between the acceptability of these sublingual tablets and a score reflecting the average acceptability of oral/buccal medicines in preschoolers. These results highlight that sublingual formulations could be appropriate for use in preschoolers. [ABSTRACT FROM AUTHOR]

Although knowledge on medicine acceptability remains fragmented, this multi-faceted concept has emerged as a key factor for compliance in pediatrics. In order to investigate the acceptability of medicines used in the University Medical Centre Ibn Sina (CHIS) of Rabat, Morocco, an observational study was conducted. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for 570 medicine intakes in patients up to the age of 16, then analyzed on a reference framework. Tablets appeared to be well accepted in children greater than 6 years old, but were crushed/dissolved for 90% of the 40 children aged from 3 to 5, and 100% of the 38 patients younger than 3. Moreover, the prescribed dose was fully taken for only 52% and 16% of these younger children, respectively. Despite this, tablets represented 24% of evaluations in children from 3 to 5 and 20% in infants and toddlers. Oral liquid preparations appeared to be better accepted than tablets in preschoolers, but not for those under 3. Overall, these findings highlight the lack of suitable alternatives for the younger children, especially for formulations of antiepileptics, antithrombotic, and psycholeptic agents in the local context. [ABSTRACT FROM AUTHOR]

Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))—a 3D-map juxtaposing two acceptability profiles—to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients ≥65 years in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia (n = 790), while not in those with swallowing disorders (n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets <6.5 mm appeared to be accepted by patients with swallowing disorders. Among the 309 distinct tablets assessed in this study, ranging in size from 4.7 to 21.5 mm, 83% are ≥6.5 mm and consequently may be poorly accepted by institutionalized older people and older inpatients suffering from dysphagia. This underlines the need to develop and prescribe medicines with the best adapted characteristics to reach an optimal acceptability in targeted users. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Lack of formal scrutiny of the acceptability of generics may reduce patient adherence. 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. Reduced patient acceptability of generic products, especially oral ones, can undermine adherence and clinical effectiveness and, hence, compromise their potential benefits. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Palatability is a recognized driver of medicine acceptability in pediatrics but deemed less relevant in older populations due to sensory decline. Preliminary findings from an observational study implicated palatability problems with one Alzheimer's medicine. Among 1517 observer reports combining multiple measures on medicines uses in patients aged over 64, we focused on two original formulations of memantine (Ebixa®, tablets (n = 25) and oral solution (n = 60)). Evaluations were scored with an acceptability reference framework (CAST), the rodent Brief Access Taste Aversion (BATA) model tested aversiveness. Focusing on women treated with Ebixa® (n = 54), the oral formulation sub-group was classified as "negatively accepted", while the coated tablet was associated with the "positively accepted" cluster. In men, both formulations belonged to the "positively accepted" profile. Using BATA, the original oral solution was categorized as highly aversive/untolerated while solutions of excipients only were well tolerated. Furthermore, the number of licks was significantly lower in female than in male rats. These results revealed that medicine palatability remains important for acceptability in older populations. Moreover, converging results from humans and animal models highlighted that palatability profiles can significantly vary between the sexes. These drivers should be closely considered during drug development to enhance acceptability in this population. [ABSTRACT FROM AUTHOR]