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 nonadherence 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, our 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

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

Acceptability in the Older Population: The Importance of an Appropriate Tablet Size

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).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 y 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.Peer reviewedFinal Published versio

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

Evolutionary history of hepatitis C virus genotype 5a in France, a multicenter ANRS study

The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921–1956], and the tMRCA of isolates from central France was dated to 1954 [1942–1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion

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.peer-reviewe

Conception d'un outil d'évaluation de l'acceptabilité des médicaments

Medicine development must satisfy efficiency and safety objectives. Patient compliance with physician’s prescription is an essential condition to achieve these objectives. Patient acceptability of a medicine improves patient compliance and thus ensures drug success, in particular in paediatric and geriatric populations. Acceptability could be defined as the overall ability and willingness of the patient to use, and its care giver to administer, the medicine as intended. Acceptability is driven by the users’ and the products’ characteristics. Thus, designers have to consider the specific features of the targeted users to develop a medicine with the most adapted characteristics to reach the best acceptability. Evaluation of the acceptability should be an integral part of pharmaceutical and clinical development. Today, knowledge on this complex phenomenon is still fragmented and there are no internationally agreed methods available to assess this multidimensional concept. This document sets out the development of a validated tool, the acceptability reference framework, providing standardized medicines acceptability evaluation and relevant knowledge usable by designers from the early stage of medicine development. As this research was carried out in a medical field, we propose a formalized methodology transferable to other domains.Le développement d’un médicament est réalisé dans le but de répondre à des objectifs thérapeutiques tout en prévenant les risques pour les patients. L’observance, qui correspond au suivi rigoureux de la prescription du médecin, est une condition primordiale de la réussite du traitement. L'acceptabilité, qui peut être définie comme la capacité et la bonne volonté du patient à utiliser, et de son donneur de soins à administrer, le médicament tel que est prévu, joue un rôle crucial dans l’observance, notamment chez les individus les plus vulnérables. L’acceptabilité d'un médicament est déterminée par ses caractéristiques et celles des utilisateurs. De ce fait, le concepteur se doit de considérer les spécificités des utilisateurs cibles pour assurer l’adéquation d’un nouveau produit avec leurs besoins et leurs attentes. Intégrer l'évaluation de l’acceptabilité au développement pharmaceutique et clinique des médicaments apparaît alors d’une importance de premier ordre. A ce jour, il n’existe aucun outil validé et reconnu internationalement permettant d’évaluer ce concept multi-dimensionnel. Cette carence s’accompagne d’un manque de connaissances sur ce phénomène complexe. Ces travaux de thèse présente la conception d’un outil, le référentiel d’acceptabilité, qui permet, d’une part, d’évaluer de manière standardisée l’acceptabilité des médicaments, et d’autre part, d’extraire des connaissances utilisables dès les phases amonts du processus de conception de nouveaux produits. La démarche développée et appliquée dans le domaine des médicaments a été formalisée pour être utilisable dans d’autres univers d’étude

Medicines Acceptability in Hospitalized Children: An Ongoing Need for Age-Appropriate Formulations

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

Development of a validated tool to assess patient acceptability of medicines

Le développement d’un médicament est réalisé dans le but de répondre à des objectifs thérapeutiques tout en prévenant les risques pour les patients. L’observance, qui correspond au suivi rigoureux de la prescription du médecin, est une condition primordiale de la réussite du traitement. L'acceptabilité, qui peut être définie comme la capacité et la bonne volonté du patient à utiliser, et de son donneur de soins à administrer, le médicament tel que est prévu, joue un rôle crucial dans l’observance, notamment chez les individus les plus vulnérables. L’acceptabilité d'un médicament est déterminée par ses caractéristiques et celles des utilisateurs. De ce fait, le concepteur se doit de considérer les spécificités des utilisateurs cibles pour assurer l’adéquation d’un nouveau produit avec leurs besoins et leurs attentes. Intégrer l'évaluation de l’acceptabilité au développement pharmaceutique et clinique des médicaments apparaît alors d’une importance de premier ordre. A ce jour, il n’existe aucun outil validé et reconnu internationalement permettant d’évaluer ce concept multi-dimensionnel. Cette carence s’accompagne d’un manque de connaissances sur ce phénomène complexe. Ces travaux de thèse présente la conception d’un outil, le référentiel d’acceptabilité, qui permet, d’une part, d’évaluer de manière standardisée l’acceptabilité des médicaments, et d’autre part, d’extraire des connaissances utilisables dès les phases amonts du processus de conception de nouveaux produits. La démarche développée et appliquée dans le domaine des médicaments a été formalisée pour être utilisable dans d’autres univers d’étude.Medicine development must satisfy efficiency and safety objectives. Patient compliance with physician’s prescription is an essential condition to achieve these objectives. Patient acceptability of a medicine improves patient compliance and thus ensures drug success, in particular in paediatric and geriatric populations. Acceptability could be defined as the overall ability and willingness of the patient to use, and its care giver to administer, the medicine as intended. Acceptability is driven by the users’ and the products’ characteristics. Thus, designers have to consider the specific features of the targeted users to develop a medicine with the most adapted characteristics to reach the best acceptability. Evaluation of the acceptability should be an integral part of pharmaceutical and clinical development. Today, knowledge on this complex phenomenon is still fragmented and there are no internationally agreed methods available to assess this multidimensional concept. This document sets out the development of a validated tool, the acceptability reference framework, providing standardized medicines acceptability evaluation and relevant knowledge usable by designers from the early stage of medicine development. As this research was carried out in a medical field, we propose a formalized methodology transferable to other domains

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