Families driven drug development and clinical trials: a pilot study in Dravet Syndrome to delineate what really matters

Abstract Background Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Patients rapidly develop drug resistant seizures but patients with DS develop non-seizures disorders that are often age related. We aimed to identify the caregivers’ opinion on the outcome measures that matters in clinical trials in individuals with DS and their correlation with the age of the individual with DS. Methods We conducted a prospective international study with convenience sample based on a 11-closed questions survey developed with three European patients’ advocacy groups (PAG) for DS (France, Italy and Germany). The items were about seizures and daily life outcomes that a clinical trial should target according to family opinion. Items were scored from 1 (not important at all) to 5 (highly important). Statistical analyses were performed to evaluate country (ANOVA and khi2 tests) and age effect (Spearman's ρ). Results Hundred and fifty-three caregivers answered the survey (68%: France, 28%: Germany and 24%: Italy; affected individuals’ characteristics: 86 males, age: 11.4 [25th -75th percentile:7-20.4] years). Demographic characteristics were not significantly different between countries. Families ranked as important almost all the items proposed. However, most of the items related to daily life had the highest rank in all 3 countries compared to items about seizures (p = 0.02). Positive correlation between age and age at diagnosis (ρ = 0.26, p = 0.02) and negative correlations between age and targeting seizure duration and between age (ρ =-0.25, p = 0.005) and targeting the need of referral to hospital (ρ =-0.26, p = 0.005) were identified. Conclusions This study emphasized the DS families’ expectations from therapies beyond seizure efficacy. These data can help to adapt patients-centered outcome measures in future clinical and real-life trials in DS.

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Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements

Translational Vision Science & Technology ◽

10.1167/tvst.4.3.6 ◽

2015 ◽

Vol 4 (3) ◽

pp. 6 ◽

Cited By ~ 20

Author(s):

Irmela Mantel

Keyword(s):

Clinical Trials ◽

Macular Degeneration ◽

Treatment Strategy ◽

Real Life ◽

Age Related Macular Degeneration ◽

Anti Vegf ◽

Age Related

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Epileptic Encephalopathies: An Overview

Epilepsy Research and Treatment ◽

10.1155/2012/403592 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Sonia Khan ◽

Raidah Al Baradie

Keyword(s):

Slow Wave Sleep ◽

Epileptic Encephalopathy ◽

Dravet Syndrome ◽

Management Options ◽

Epileptic Encephalopathies ◽

Age Related ◽

Ohtahara Syndrome ◽

Cerebral Dysfunction ◽

Epileptic Syndromes

Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. In the classification of the International League Against Epilepsy eight age-related epileptic encephalopathy syndromes are recognized. These syndromes include early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, West syndrome and Dravet syndrome in infancy, myoclonic status in nonprogressive encephalopathies, and Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike waves during slow wave sleep in childhood and adolescences. Other epileptic syndromes such as migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added. In this paper, we provide an overview of epileptic encephalopathies including clinical neurophysiological features, cognitive deterioration, and management options especially that these conditions are generally refractory to standard antiepileptic drugs.

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Cross Gender Oral Communication from Biological Difference and Socialized Identity to Mutual Understanding

Journal of World Englishes and Educational Practices ◽

10.32996/jweep.2021.3.5.2 ◽

2021 ◽

Vol 3 (5) ◽

pp. 13-27

Author(s):

Ismail Benfilali ◽

Bendaoud Nadif ◽

Brahim Khartite ◽

Driss Benattabou ◽

Abdelouahed Bouih

Keyword(s):

Real Life ◽

Oral Communication ◽

Effective Communication ◽

Communication Styles ◽

Human Beings ◽

Biological Difference ◽

Convenience Sample ◽

Gender Communication ◽

Communication Breakdown ◽

The Individual

Language is an indispensable instrument whereby we organize and build our social ties in our communities, and society at large. Human language is critically interwoven into the processes whereby human beings communicate, build knowledge, transmit information, and determine the identity of both the addresser and the addressee in any communicational exchange. We could hypothetically assert that if there is unmistakably one thing without which man as a species can hardly live in the social realm, it is language par excellence. In an admittedly multi-layered and inherently complex sociolinguistic configuration, the individual speaker’s linguistic choice, the different roles he or she plays, be they in a position of addresser or addressee, and the various situations where the speech takes place do serve as markers reflecting one’s identity and communication styles. In this respect, factors such as sex, age, level of education, occupation, race, and geographical origin can virtually be reflected via one’s speech. This article sets out to analyze (1) the influential role of speech, (2) gender and identity, (3) dominance/difference, and (4) cross-gender oral communication in the Moroccan context using a homogenous convenience sample of Moroccan participants. This study falls within the scope of gender studies. Its major aim is to demonstrate the roles that mixed-gendered interlocutors can play in order to maintain effective communication. Therefore, their perceptions regarding interruptions, conversation dominance, turn-taking and choice of topics in conversations are analyzed. Different research instruments have been implemented to collect data including recordings of real-life conversational speech, classroom observation, and interviews. The findings indicate that gender-based differences permeate the conversational styles of both men and women across cultures and with divergent degrees of strength and expression. It has also been shown that although communication breakdown is a source of frustration, it remains a common phenomenon in social interactions. Therefore, overcoming difficulties in maintaining effective communication between members of different genders is dependent on the interlocutors’ belief that accepting difference in language and communication styles can make cross-gender communication a satisfactory social experience. This study is expected to raise awareness regarding the socialization processes the two sex groups have gone through which shape in substantial ways the way they speak, behave and interact among each other.

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Use of composite endpoints in early and intermediate age-related macular degeneration clinical trials – state-of-the-art and future directions

Ophthalmologica ◽

10.1159/000513591 ◽

2020 ◽

Author(s):

Jan Henrik Terheyden ◽

Steffen Schmitz-Valckenberg ◽

David P. Crabb ◽

Hannah Dunbar ◽

Ulrich F. O. Luhmann ◽

...

Keyword(s):

Clinical Trials ◽

Outcome Measures ◽

Clinical Studies ◽

Composite Endpoint ◽

Age Related Macular Degeneration ◽

Sensitivity Analyses ◽

Surrogate Endpoints ◽

Qualitative Synthesis ◽

Age Related ◽

Composite Endpoints

The slow progression of early AMD stages to advanced AMD requires the use of surrogate endpoints in clinical trials. The use of combined endpoints may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite endpoints as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite endpoints used in early/intermediate AMD studies published during the last 10 years. A total of 673 articles of interest were identified. After reviewing abstracts and applicable full-text articles, 33 articles were eligible and thus included in the qualitative synthesis. The main composite endpoint categories were: Combined structural and functional endpoints, combined structural endpoints, combined functional endpoints and combined multi-categorical endpoints. The majority of the studies included binary composite endpoints. There was a lack of sensitivity analyses of different endpoints against accepted outcomes (i.e. progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined endpoints in clinical studies of early stages of AMD exists and no surrogate endpoints have been accepted for AMD progression.

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Patient-reported outcome measures in presbyopia: a literature review

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2020-000453 ◽

2020 ◽

Vol 5 (1) ◽

pp. e000453

Author(s):

Garima Sharma ◽

Sima Chiva-Razavi ◽

Daniel Viriato ◽

Christel Naujoks ◽

Francesco Patalano ◽

...

Keyword(s):

Clinical Trials ◽

Outcome Measures ◽

Psychometric Evaluation ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Near Vision ◽

Fda Guidance ◽

Age Related ◽

Regulatory Standards ◽

Patient Reported

Presbyopia is the age-related loss of near-distance focusing ability. The aim of this study was to identify patient-reported outcome measures (PROMs) used in clinical trials and quality-of-life studies conducted in individuals with presbyopia and to assess their suitability for use in individuals with phakic presbyopia. Literature searches were performed in Medline and Embase up until October 2017. Specific search terms were used to identify presbyopia studies that included a PROM. All clinical trials with PROM-supported endpoints in presbyopia were identified on ClinicalTrials.gov. Further searches were conducted to retrieve articles documenting the development and psychometric evaluation of the PROMs identified. A total of 703 records were identified; 120 were selected for full-text review. Twenty-one clinical trials employed PROMs to support a primary or secondary endpoint. In total, 13 PROMs were identified; a further 23 publications pertaining to the development and validation of these measures were retrieved. Most PROMs were developed prior to release of the Food and Drug Administration (FDA) 2009 patient-reported outcome guidance and did not satisfy regulatory standards. The Near Activity Visual Questionnaire (NAVQ) was identified as the most appropriate for assessing near-vision functioning in presbyopia. While the NAVQ was developed in line with the FDA guidance, the items do not reflect changes in technology that have occurred since the questionnaire was developed in 2008 (eg, the increase in smartphone use), and the measure was not validated in a purely phakic presbyopia sample. Further research is ongoing to refine the NAVQ to support trial endpoints related to changes in near-vision functioning associated with phakic presbyopia.

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BioDay Registry: Prospective, observational data collection regarding the use of new systemic treatment options in patients with atopic diseases in daily practice (Preprint)

10.2196/preprints.20403 ◽

2020 ◽

Author(s):

Jorien BioDay Registry ◽

Lieneke Ariens ◽

Lotte Spekhorst ◽

Ischa Kummeling ◽

Judith Thijs ◽

...

Keyword(s):

Clinical Trials ◽

Medical Ethics ◽

Outcome Measures ◽

Systemic Treatment ◽

Treatment Options ◽

Real Life ◽

Daily Practice ◽

Ethics Committee ◽

Atopic Diseases ◽

New Treatment

BACKGROUND Dupilumab is the first antibody based treatment for atopic dermatitis (AD). It is expected that many new treatment options become available for the treatment of atopic diseases in the near future. Despite the high quality of clinical trials, results are not always generalizable to daily practice. OBJECTIVE Registry based collection of real life data can add information that is not gained in clinical trials. METHODS The BioDay Registry prospectively collects real life treatment results regarding effectiveness and safety of patients treated with new systemic treatment options for AD in a multicenter setting. Effectiveness is assessed based on both physician measured clinical eczema scores as well as patient-reported outcome measures. Long-term safety risks are monitored. The possibility for dose reduction in patients with disease control can be investigated. The treatment effect on other atopic co-morbidities will be monitored. The BioDay Registry can be easily adjusted, and new modules on new treatment options can be added. As outcome measures are in line with the core outcomes for eczema recommended by the global Harmonising Outcome Measures for Eczema (HOME) initiative, it is possible to merge data with other registries in future. RESULTS The BioDay Registry was considered as non-interventional by the local Medical Ethics Committee and the collection of data is performed according to the Helsinki Declaration. Protocol amendments will always be submitted for review to the Medical Ethics Committee. CONCLUSIONS The BioDay Registry will provide unique prospectively collected data on the use of targeted therapies in daily practice for AD patients. The results of this registry will contribute to the development of more personalized treatment strategies for patients with moderate to severe AD. CLINICALTRIAL ClinicalTrials.gov identifier: NCT03549416, retrospectively registered June 8, 2018.

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Outcome Measures in Clinical Trials of Patients With Myasthenia Gravis

Frontiers in Neurology ◽

10.3389/fneur.2020.596382 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jan Lykke Scheel Thomsen ◽

Henning Andersen

Keyword(s):

Clinical Trials ◽

Myasthenia Gravis ◽

Outcome Measures ◽

Patient Reported Outcomes ◽

Clinical Scales ◽

The Past ◽

Patient Reported ◽

Specific Outcome ◽

The Individual ◽

Clinical Deficits

Myasthenia gravis (MG) is a heterogeneous disorder whose clinical presentation ranges from mild ocular deficits to severe widespread weakness. This variance poses a challenge when quantifying clinical deficits. Deficits and symptoms are quantified using standardized clinical scales and questionnaires which are often used as outcome measures. The past decades have seen the development of several validated outcome measures in MG, which are used in clinical trials to obtain regulatory approval. In recent years, emphasis has moved from objective assessments to patient-reported outcomes. Despite a growing body of literature on the validity of the MG-specific outcome measures, several unresolved factors remain. As several novel therapeutics are currently in clinical development, knowledge about capabilities and limitations of outcome measures is needed. In the present paper, we describe the most widely used clinical classifications and scales in MG. We highlight the choice of outcome measures in published and ongoing trials, and we denote whether trial efficacy was reached on these outcomes. We discuss advantages and limitations of the individual scales, and discuss some of the unresolved factors relating to outcome assessments in MG.

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AI-based structure-function correlation in age-related macular degeneration

Eye ◽

10.1038/s41433-021-01503-3 ◽

2021 ◽

Author(s):

Leon von der Emde ◽

Maximilian Pfau ◽

Frank G. Holz ◽

Monika Fleckenstein ◽

Karsten Kortuem ◽

...

Keyword(s):

Artificial Intelligence ◽

Clinical Trials ◽

Visual Acuity ◽

Structure Function ◽

Macular Degeneration ◽

Outcome Measures ◽

Multimodal Imaging ◽

Age Related Macular Degeneration ◽

Age Related ◽

Function Correlation

AbstractSensitive and robust outcome measures of retinal function are pivotal for clinical trials in age-related macular degeneration (AMD). A recent development is the implementation of artificial intelligence (AI) to infer results of psychophysical examinations based on findings derived from multimodal imaging. We conducted a review of the current literature referenced in PubMed and Web of Science among others with the keywords ‘artificial intelligence’ and ‘machine learning’ in combination with ‘perimetry’, ‘best-corrected visual acuity (BCVA)’, ‘retinal function’ and ‘age-related macular degeneration’. So far AI-based structure-function correlations have been applied to infer conventional visual field, fundus-controlled perimetry, and electroretinography data, as well as BCVA, and patient-reported outcome measures (PROM). In neovascular AMD, inference of BCVA (hereafter termed inferred BCVA) can estimate BCVA results with a root mean squared error of ~7–11 letters, which is comparable to the accuracy of actual visual acuity assessment. Further, AI-based structure-function correlation can successfully infer fundus-controlled perimetry (FCP) results both for mesopic as well as dark-adapted (DA) cyan and red testing (hereafter termed inferred sensitivity). Accuracy of inferred sensitivity can be augmented by adding short FCP examinations and reach mean absolute errors (MAE) of ~3–5 dB for mesopic, DA cyan and DA red testing. Inferred BCVA, and inferred retinal sensitivity, based on multimodal imaging, may be considered as a quasi-functional surrogate endpoint for future interventional clinical trials in the future.

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On the Individual

European Psychologist ◽

10.1027//1016-9040.4.4.205 ◽

1999 ◽

Vol 4 (4) ◽

pp. 205-218 ◽

Cited By ~ 34

Author(s):

David Magnusson

Keyword(s):

School Psychologist ◽

Real Life ◽

Psychological Research ◽

Developmental Research ◽

Future Directions ◽

The 1950S ◽

The Individual ◽

Over Time

A description of two cases from my time as a school psychologist in the middle of the 1950s forms the background to the following question: Has anything important happened since then in psychological research to help us to a better understanding of how and why individuals think, feel, act, and react as they do in real life and how they develop over time? The studies serve as a background for some general propositions about the nature of the phenomena that concerns us in developmental research, for a summary description of the developments in psychological research over the last 40 years as I see them, and for some suggestions about future directions.

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CONHECIMENTO DOS PROFESSORES DE EDUCAÇÃO FÍSICA SOBRE PRIMEIROS SOCORROS NAS ESCOLAS DE SANTA CECILIA-SC

Professare ◽

10.33362/professare.v7i1.982 ◽

2018 ◽

Vol 7 (1) ◽

pp. 82

Author(s):

Angélica Wrublak ◽

Elaine Caroline Boscatto

Keyword(s):

Physical Education ◽

Daily Life ◽

Cardiopulmonary Arrest ◽

School Context ◽

Real Life ◽

First Aid ◽

Basic Knowledge ◽

Physical Education Teachers ◽

Emergency Situations ◽

Santa Cecilia

Acidentes e fatalidades podem acontecer desde simples contusões até as mais urgentes hemorragias e parada cardiorrespiratória. Os primeiros socorros realizados de forma adequada podem minimizar os agravos e até mesmo salvar vidas. No âmbito escolar, situações de emergência fazem parte do cotidiano e é essencial que Professores de Educação Física tenham um conhecimento básico para atender as necessidades escolares. O presente estudo teve como objetivo verificar o conhecimento dos Professores de Educação Física (EF) da rede pública de Ensino da Cidade de Santa Cecilia-SC com relação aos Primeiros Socorros (PS). Caracterizou-se em natureza descritiva, transversal, com análise quanti-qualitativa dos dados. Participaram do estudo 11 Professores de EF. Para a coleta de dados, foi desenvolvido um questionário abordando aspectos conceituais, procedimentos e atitudes referentes ao cotidiano profissional. Do total, apenas um professor não teve a disciplina de PS na graduação. Os professores na sua minoria se sentem aptos a prestar os PS e inclusive assumir as situações, demonstrando conhecimento satisfatório na teoria, mas na prática sentem-se inseguros para agir diante de situações mais graves. Destaca-se que mais de 80% sabem como agir em atendimentos menos agravantes. Já nas situações de parada cardiorrespiratória (RCP) e hemorragias, os mesmos relataram que necessitam de um treinamento mais atualizado. Em crianças principalmente eles não sentem muito seguros em prover o auxílio. Foi possível concluir que os professores de EF apresentaram um nível de conhecimento satisfatório na teoria, mas sugerem atualizações periódicas em forma de cursos.Palavras-chave: Primeiros Socorros. Docentes. Educação Física e Treinamento.<h3>ABSTRACT</h3>Accidents and fatalities can occur from simple bruises to the most urgent hemorrhages and cardiopulmonary arrest. First aid performed properly can minimize the aggravations and even save lives. In the school context, emergency situations are part of the daily life and it is essential that Physical Education Teachers have a basic knowledge to carry out the school needs. This study verified the Physical Education (PE) Teachers knowledge from Santa Cecilia-SC public teaching related to first aid. It featured in descriptive nature, transversal, with quantitative and qualitative analysis of the data. Eleven PE teachers participated of the study. For the data collection, it was developed a questionnaire addressing conceptual aspects, procedures and attitudes concerning professional daily life. From the total, only one teacher did not have the first aid subject at the college. Teachers in their minority feel able to provide the first aid and even take on the situations, showing satisfactory theory knowledge, however in real life they feel insecure to act on before serious situations. It points out that more than 80% know how to act before less aggravating calls. Nonetheless, during cardiopulmonary arrest (CPR) and hemorrhages, they reported the need of an updated training. Mainly in children, they do not feel safe to provide the aid. It was possible to conclude that Physical Education Teachers showed a satisfactory level of knowledge in theory, however it suggest courses periodic updates.Keywords: First Aid. Faculty. Physical Education and Training.

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