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BACKGROUND: Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. METHODS: In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients. RESULTS: Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 log10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibody-negative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group. CONCLUSIONS: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.).
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Factores Inmunológicos/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Carga Viral/efectos de los fármacos , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Neutralizantes/efectos adversos , COVID-19/diagnóstico , COVID-19/virología , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/genéticaRESUMEN
BACKGROUND: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. METHODS: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. RESULTS: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. CONCLUSIONS: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.).
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Neutralizantes/administración & dosificación , Antivirales/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Neutralizantes/farmacología , Antivirales/farmacocinética , Antivirales/farmacología , COVID-19/mortalidad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Carga Viral/efectos de los fármacos , Adulto JovenRESUMEN
PURPOSE: Symptoms of schizophrenia fall into three categories (positive, negative and cognitive symptoms), which probably impact differently on patient's health-related quality of life (HRQoL). The present study aimed to explore HRQoL in patients with prominent negative symptoms. METHODS: In the 323 patients with prominent negative symptoms included in a multicenter Phase II trial investigating the safety and efficacy of bitopertin, HRQoL was assessed using the Schizophrenia Quality of Life Scale (SQLS), symptoms severity using the Positive and Negative Syndrome Scale and functioning using the Personal and Social Performance Scale. SQLS measurement properties were assessed; HRQoL was compared between treatment arms, and relationships between HRQoL, symptoms and functioning at baseline were explored. RESULTS: Both SQLS scores (Vitality/Cognition and Psychosocial Feelings) demonstrated good test-retest (ICC = 0.77 and 0.74) and internal consistency reliability (Cronbach's α = 0.86 and 0.93). Clinical validity with regard to schizophrenia severity and ability to detect change in severity of symptoms of schizophrenia were satisfactory. The SQLS structure was not formally disconfirmed. No statistically significant difference was observed between treatment arms. Negative symptoms were more strongly associated with functioning than positive symptoms. Functioning and Anxiety/Depression were strongly related to both SQLS domains. CONCLUSION: Overall, SQLS measurement properties were supported in these patients with prominent negative symptoms of schizophrenia. The impact of negative symptoms on functioning and HRQoL suggests that improving these symptoms will be a meaningful benefit in this population of patients.
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Estado de Salud , Piperazinas/uso terapéutico , Calidad de Vida/psicología , Esquizofrenia/tratamiento farmacológico , Sulfonas/uso terapéutico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Esquizofrenia/diagnóstico , Encuestas y CuestionariosRESUMEN
BACKGROUND: The Schizophrenia Caregiver Questionnaire (SCQ) was developed to assess the impact on caregivers of caring for patients with schizophrenia. The objective of this study was to develop a scoring algorithm for the SCQ, and evaluate its measurement properties. METHODS: The SCQ was administered to 358 caregivers of patients with schizophrenia included in the observational PATTERN study of stabilized patients with persistent symptoms of schizophrenia receiving outpatient care. SCQ item selection and creation of scores were based on exploration of item response distribution, factor analyses, and Rasch model. Construct validity, reliability, and ability to detect change of the SCQ scores were investigated. RESULTS: The final questionnaire comprised a 'Humanistic impact' supra-domain composed of a global score and four subdomain scores ('Physical'; 'Emotional'; 'Social'; 'Daily life'), and eight other domain scores related to the caregiving role ('Exhaustion with caregiving'; 'Feeling alone'; 'Patient Dependence'; 'Worries for the patient'; 'Perception of caregiving'; 'Financial dependence of the patient'; 'Financial impact of caregiving'; 'Overall difficulty of caregiving'). Two items from the SCQ were deleted. SCQ scores showed very good construct validity: Item convergent/discriminant validity were satisfactory; SCQ scores of caregivers of patients with more severe symptoms were higher indicating more impact (p < 0.05 for all scores); SCQ scores were meaningfully associated with measures of schizophrenia severity (PANSS and PSP) and caregivers' Health-Related Quality of Life (Medical Outcome Survey Short Form 36 items). The SCQ Humanistic impact supra-domain scores demonstrated very good internal consistency reliability (Cronbach's alphas between 0.80 and 0.96) and test-retest reliability (Intraclass Coefficient correlations ranging from 0.75 and 0.87); Other SCQ domain scores showed lower but still acceptable reliability coefficients. SCQ scores clearly increased for caregivers of patients whose schizophrenia worsened. CONCLUSIONS: Overall, the 30-item SCQ demonstrated very good measurement properties supporting its relevance to comprehensively measure the experience of caregivers of patients with schizophrenia.
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Cuidadores/psicología , Esquizofrenia/enfermería , Encuestas y Cuestionarios , Adulto , Análisis Factorial , Femenino , Humanos , Masculino , Modelos Estadísticos , Psicometría , Calidad de Vida , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: The Schizophrenia Caregiver Questionnaire (SCQ) was developed to provide a comprehensive view of caregivers' subjective experiences of the impacts of caring for someone with schizophrenia. The Caregiver Global Impression (CaGI) scales were designed to assess their perception of the severity of the schizophrenia symptoms, of change in schizophrenia symptoms and in the experience of caring since the beginning of the study. The objectives of the study were to translate the SCQ and CaGI scales in 11 languages [French (Canada, France), English (Canada, UK, Australia), German (Germany), Italian (Italy), Spanish (Spain), Dutch (the Netherlands), Finnish (Finland), and Swedish (Sweden)], to present evidence that the translations capture the concepts of the original questionnaires and are well understood by caregivers of patients with schizophrenia in each target country. METHODS: The different language versions were developed using a standard or adjusted linguistic validation process fully complying with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommended procedures. RESULTS: Interviews were conducted with 55 caregivers of patients with schizophrenia from 10 countries representing the 11 different languages. Participants ranged in age from 28 to 84 years and had 5 to 16 years of education. Women represented 69.1 % (38/55) of the sample. Fourteen out of the 32 items of the SCQ generated difficulties which were mostly of semantic origin (13 items). The translation of the CaGI scales did not raise any major difficulty. Only five out of the 55 caregivers had difficulty understanding the meaning of the translations of "degree" in the expressions "degree of change in experience of caring" and "degree of change in symptoms". CONCLUSIONS: Translations of the SCQ and CaGI scales into 11 languages adequately captured the concepts in the original English versions of the questionnaires, thereby demonstrating the conceptual, semantic, and cultural equivalence of each translation.
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Cuidadores/psicología , Comparación Transcultural , Lenguaje , Esquizofrenia/terapia , Encuestas y Cuestionarios/normas , Adulto , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Psicología del Esquizofrénico , Traducciones , Adulto JovenRESUMEN
OBJECTIVES: There is limited qualitative research on patients' experiences with long COVID-19, and how specific symptoms impact their daily lives. The study aimed to understand patients' lived experiences of long COVID-19 and to develop a conceptual model representing the symptoms and their impact on overall quality of life. SETTING: Qualitative study consisting of a comprehensive literature review, and in-depth clinician and patient semistructured interviews. PARTICIPANTS: Forty-one adult patients with long COVID-19, of whom 18 (44%) were recruited through Regeneron Pharmaceuticals's clinical trials and 23 (56%) through recruitment agencies; 85.4% were female and 73.2% were White. Five independent clinicians treating patients with long COVID-19 were interviewed. Concept saturation was also assessed. PRIMARY AND SECONDARY OUTCOMES: Interview transcripts were analysed thematically to identify concepts of interest spontaneously mentioned by patients, including symptoms and their impacts on daily life, to guide the development of the conceptual model. RESULTS: Findings from the literature review and clinician and patient interviews resulted in the development of a conceptual model comprising two overarching domains: symptoms (upper respiratory tract, lower respiratory tract, smell and taste, systemic, gastrointestinal, neurocognitive and other) and impacts (activities of daily living, instrumental activities of daily living, physical impacts, emotional, social/leisure activities and professional impacts). Saturation was achieved for the reported impacts. The symptoms reported were heterogenic; neurocognitive symptoms, such as numbness, ringing in ears, haziness, confusion, forgetfulness/memory problems, brain fog, concentration, difficulties finding the right word and challenges with fine motor skills, were particularly pertinent for several months. CONCLUSION: The conceptual model, developed based on patient experience data of long COVID-19, highlighted numerous symptoms that impact patients' physical and mental well-being, and suggests humanistic unmet needs. Prospective real-world studies are warranted to understand the pattern of long COVID-19 experienced in larger samples over longer periods of time.
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COVID-19 , Calidad de Vida , Adulto , Humanos , Femenino , Masculino , Calidad de Vida/psicología , Síndrome Post Agudo de COVID-19 , Actividades Cotidianas , Estudios Prospectivos , Investigación CualitativaRESUMEN
INTRODUCTION: This study aimed to assess the effects of a monoclonal antibody (mAb) combination on symptoms, daily function, and overall health-related quality of life. METHODS: We analyzed patient-reported outcomes data from symptomatic outpatients in a phase 1/2/3 trial. Patients with confirmed SARS-CoV-2 infection and ≥ 1 risk factor for severe COVID-19 received mAb treatment (casirivimab plus imdevimab 1200 mg) or placebo. Prespecified exploratory assessments included time to sustained symptoms resolution, usual health, and return to usual activities (assessed daily for 29 days). The trial was conducted from September 2020 to February 2021, prior to widespread COVID-19 vaccination programs and Omicron-lineage variants against which casirivimab + imdevimab is not active. RESULTS: In this analysis 736 outpatients received mAb and 1341 received placebo. Median time to sustained symptoms resolution was consistently shorter with mAb versus placebo (≥ 2 consecutive days: 14 vs 17 days, [nominal p = 0.0017]; ≥ 3 consecutive days: 17 vs 21 days, [nominal p = 0.0046]). Median time to sustained return to usual health and usual activities were both consistently shorter with mAb versus placebo (≥ 2 consecutive days: 12 vs 15 days [nominal p = 0.0001] and 9 vs 11 days [nominal p = 0.0001], respectively; ≥ 3 consecutive days: 14 vs 18 days [nominal p = 0.0003] and 10 vs 13 days [nominal p = 0.0041], respectively). CONCLUSIONS: mAb treatment against susceptible SARS-CoV-2 strains improved how patients feel and function, as evidenced by shortened time to sustained symptoms resolution and return to usual health and activities. Future studies are warranted to assess the patient experience with next generation mAbs. CLINICALTRIALS: GOV: Registration number, NCT04425629; Submission date June 11, 2020.
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BACKGROUND: The field of long COVID research is rapidly evolving, however, tools to assess and monitor symptoms and recovery of the disease are limited. The objective of the present study was to develop a new patient-reported outcomes instrument, the Symptoms Evolution of Long COVID19 (SE-LC19), and establish its content validity. METHODS: The 40-item SE-LC19 instrument was developed based on patient-relevant empirical evidence from scientific literature and clinical guidelines that reported symptoms specific to long COVID. A 2-part mixed-method approach was employed. Part 1: Qualitative interviews with a purposive sample of 41 patients with confirmed long COVID were conducted for the content validation of SE-LC19. During cognitive debriefing interviews, patients were asked to describe their understanding of the instrument's instructions, specific symptoms, response options, and recall period to ensure its relevance and comprehensiveness. Five clinicians of different medical specialties who regularly treated patients with long COVID were also interviewed to obtain their clinical expert opinions on SE-LC19. Part 2: Exploratory Rasch Measurement Theory (RMT) analysis was conducted to evaluate the psychometric properties of the SE-LC19 data collected during the interviews. RESULTS: Overall, patients reported that the instructions, questions, recall period, and response options for SE-LC19 were comprehensive and relevant. Minor conceptual gaps reported by patients captured nuances in the experience of some symptoms that could be considered in future studies. Some patients suggested a revision of the recall period from 24 h to 7 days to be able to capture more symptoms given the waxing and waning nature of some symptoms. Clinicians found the instrument comprehensive with minimal suggestions regarding its content. Exploratory RMT analyses provided evidence that the SE-LC19 questionnaire performed as intended. CONCLUSION: The present mixed-methods study in patients with confirmed long COVID supports the content validity and applicability of the SE-LC19 instrument to evaluate the symptoms of patients with long COVID. Further research is warranted to explore the psychometric properties of the instrument and refine a meaningful and robust patient-relevant endpoint for use in different settings such as clinical trials and clinical practice to track the onset, severity, and recovery of long COVID.
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COVID-19 , Medición de Resultados Informados por el Paciente , Síndrome Post Agudo de COVID-19 , Psicometría , SARS-CoV-2 , Humanos , COVID-19/psicología , Femenino , Masculino , Psicometría/métodos , Psicometría/instrumentación , Persona de Mediana Edad , Anciano , Adulto , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Following a review of patient-reported outcome (PRO) instruments in the literature, existing PRO instruments may not adequately capture the experience of receiving treatment for proliferative diabetic retinopathy (PDR). Therefore, this study aimed to develop a de novo instrument to comprehensively assess the patient experience of PDR. METHODS: This qualitative, mixed-methods study comprised item generation for the Diabetic Retinopathy-Patient Experience Questionnaire (DR-PEQ), content validation in patients with PDR, and preliminary Rasch measurement theory (RMT) analyses. Adult patients with diabetes mellitus and PDR who received aflibercept and/or panretinal photocoagulation within 6 months of study initiation were eligible for participation. The preliminary DR-PEQ comprised four scales: Daily Activities, Emotional Impact, Social Impact, and Vision Problems. DR-PEQ items were generated using existing knowledge of patient experiences in PDR and conceptual gaps identified from existing PRO instruments. Patients indicated the level of difficulty conducting daily activities and frequency experiencing emotional impacts, social impacts, and vision problems attributed to diabetic retinopathy and its treatment in the past 7 days. Content validity was evaluated in two rounds of in-depth, semi-structured patient interviews. Measurement properties were investigated via RMT analyses. RESULTS: The preliminary DR-PEQ comprised 72 items. Overall, mean (SD) patient age was 53.7 (14.7) years. Forty patients completed the first interview; of these, 30 completed the second interview. Patients reported that the DR-PEQ was easily understood and relevant to their experience. Minor revisions, including removal of the Social Impact scale and addition of a Treatment Experience scale, were implemented to generate 85 items spanning four scales: Daily Activities, Emotional Impact, Vision Problems, and Treatment Experience. RMT analyses provided preliminary evidence that the DR-PEQ performed as intended. CONCLUSION: The DR-PEQ evaluated a broad spectrum of symptoms, functional impacts, and treatment experiences relevant to patients with PDR. Additional analyses are warranted to evaluate psychometric properties in a larger patient population.
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Diabetes Mellitus , Retinopatía Diabética , Adulto , Humanos , Persona de Mediana Edad , Retinopatía Diabética/cirugía , Retina , Medición de Resultados Informados por el Paciente , Encuestas y Cuestionarios , Coagulación con LáserRESUMEN
INTRODUCTION: Few qualitative studies have explored the patient experience of daily life with proliferative diabetic retinopathy (PDR) and associated treatments. Herein, a conceptual model was developed to comprehensively examine symptoms, functional impacts, and treatment experiences in PDR. METHODS: A qualitative, mixed-methods study comprising a literature search and semi-structured interviews with clinicians and patients was conducted. Published literature and online patient resources were searched to identify concepts relevant to patients, including symptoms, functional impacts, and treatment experiences of PDR. Semi-structured interviews with experienced clinicians were conducted to identify symptoms and impacts reported by patients with PDR and to receive feedback regarding concepts identified from the literature search. A preliminary conceptual model was then developed based on findings from the literature search and clinician interviews. Patients with PDR participated in two rounds of semi-structured interviews to identify additional concepts relevant to the patient experience in PDR and associated treatments, which informed revisions to the conceptual model. Saturation of patient interviews was assessed. RESULTS: Findings from the literature search and clinician interviews yielded 109 concepts that were included in a preliminary conceptual model with three overarching domains: symptoms, impacts, and managing the disease. Clinicians confirmed concepts identified from the literature search. During interviews, patients reported a broad spectrum of symptoms (e.g., red vision); functional impacts relating to activities of daily living (e.g., reading), emotional functioning (e.g., loss of independence), and social functioning (e.g., problems recognizing faces); and treatment experiences (e.g., improves eye problems, no change) associated with PDR. Additional concepts elicited in patient interviews informed revisions to the conceptual model. Saturation was achieved in the patient sample. CONCLUSIONS: A wide variety of symptoms, functional impacts, and treatment experiences that significantly affect health-related quality of life were identified in patients with PDR. These insights are critical for understanding PDR symptomology and assessing treatment response.
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INTRODUCTION: Generalized myasthenia gravis (gMG) is a rare autoimmune disease. Symptoms of gMG are diverse, and understanding of their impact on patients is limited. This qualitative study aimed to provide an in-depth exploration of patients' daily experiences of gMG. METHODS: Published qualitative studies were reviewed to identify the most important signs, symptoms, and functional impacts related to the patient experience in gMG. Semi-structured hybrid concept elicitation interviews (allowing spontaneous generation of disease concepts) and cognitive debriefing interviews (assessing the validity of existing disease assessments) were conducted with clinicians and adult patients with gMG. Signs, symptoms, and impacts were reviewed to understand which were most salient (i.e., reported by at least 50% of patients, with disturbance rating 5 or higher [10-point numeric scale]); concept saturation was also assessed. The disease conceptual model was updated. Existing clinical outcomes assessments (COAs) that capture how patients feel, function, and survive were assessed. RESULTS: Interviews with patients (n = 24) identified seven new signs and symptoms and 37 new impacts compared with the literature. Concept saturation was reached. Signs and symptoms identified by patients as most important (salient) were shortness of breath, general fatigue, muscle weakness of arms, legs, and neck, dysphonia, dysarthria, trouble swallowing liquids, choking, and heat sensitivity. Patient-identified salient impacts were work life, depression, difficulty walking, grooming hair, showering, and brushing teeth, eating, personal relationships, family life, and participating in social activities. Clinicians considered ocular, respiratory, swallowing, speech/talking, and extremity function as key clinical manifestations of gMG. Patients and clinicians found clinical outcome assessments (COAs) to be conceptually relevant and comprehensive. CONCLUSION: This research provides a holistic understanding of gMG signs, symptoms, and impacts experienced by patients, as observed by patients and clinicians. The conceptual model of gMG highlights the range of signs, symptoms, and impacts that adult patients with gMG experience in their everyday lives, emphasizing the humanistic impact and unmet needs.
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INTRODUCTION: Evidence of patients' experiences of living with advanced basal cell carcinoma (aBCC) are limited, particularly after hedgehog pathway inhibitor (HHI) treatment. We explored the burden of aBCC on symptoms and patients' everyday lives post HHI treatment. METHODS: In-depth, semi-structured, approximately 1-h qualitative interviews of US patients with aBCC and prior HHI treatment were conducted. Data were assessed using thematic analysis with NVivo 1.0 software. Saturation analysis was performed to ensure all concepts were captured. RESULTS: Fifteen patients (median age, 63 years; locally advanced BCC, n = 9; metastatic BCC, n = 6) were interviewed. A patient-led conceptual model was developed from the responses using 10 symptoms and 15 impact categories (comprising emotional/psychological, physical, and social domains) identified as most commonly discussed and important to patients. Overall, reported impacts were discussed more commonly than reported symptoms. Impacts most commonly discussed were related to emotions (e.g., anxiety, worry, fear [n = 14; 93%]; low mood, depression [n = 12; 80%]) and physical function (e.g., hobbies or leisure activities [n = 13; 87%]). Symptoms most commonly discussed were fatigue and tiredness (n = 14; 93%) and itch (n = 13; 87%). Out of all reported impacts and symptoms, fatigue and tiredness (n = 7, 47%) and anxiety, worry, and fear (n = 6; 40%) were most bothersome to patients. As a descriptive exercise, participant responses were mapped to commonly used patient-reported outcome scales in aBCC clinical trials. Most expressed concepts were captured across two common measures in oncology/skin conditions (European Organization for Research and Treatment of Cancer Quality of Life-Core 30 [EORTC QLQ-C30] and Skindex-16 questionnaires), but sun avoidance and others' perception of skin cancer were not explicitly mentioned by these instruments. CONCLUSION: Patients with aBCC experienced a significant disease burden post first-line HHI therapy, including major emotional and lifestyle impacts. Accordingly, through this study, patients with aBCC highlighted a significant unmet need for second-line treatment options post HHI therapy.
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Severe, protracted symptoms are associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a placebo-controlled study of casirivimab and imdevimab (CAS + IMD) in persons at high risk of severe coronavirus disease 2019 (COVID-19; n = 3816), evolution of individual symptoms was assessed for resolution patterns across risk factors, and baseline SARS-CoV-2-specific antibody responses against S1 and N domains. CAS + IMD versus placebo provided statistically significant resolution for 17/23 symptoms, with greater response linked to absence of endogenous anti-SARS-CoV-2 immunoglobulin (Ig)G, IgA, or specific neutralizing antibodies at baseline, or high baseline viral load. Resolution of five key symptoms (onset days 3-5)-dyspnea, cough, feeling feverish, fatigue, and loss of appetite-independently correlated with reduced hospitalization and death (hazard ratio range: 0.31-0.56; P < 0.001-0.043), and was more rapid in CAS + IMD-treated patients lacking robust early antibody responses. Those who seroconverted late still benefited from treatment. Thus, highly neutralizing COVID-19-specific antibodies provided by CAS + IMD treatment accelerated key symptom resolution associated with hospitalization and death in those at high risk for severe disease as well as in those lacking early, endogenous neutralizing antibody responses.
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COVID-19 , Humanos , SARS-CoV-2 , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
Digital health technologies such as wearable sensors are increasingly being used in clinical trials. However, the endpoints created from these useful tools are wide and varied. Often, digital health technologies such as wearable sensors are used either to collect a raw metric like "step count" or with artificial intelligence algorithms to define a biomarker for improvement. In the case of the former, improvements in such a raw metric is difficult to attribute to the patient health in a meaningful way. In the case of the latter, despite the potential predictive accuracies of machine learning and artificial intelligence approaches, the resulting biomarkers are a black box, which has limited direct interpretability to the patient's specific health concerns. The paper represents a call to arms to really place the patient at the heart of the endpoint. By designing trial endpoints which are measured by digital health technologies using a patient centered approach from the outset, the patient benefits from understanding the implications of approved medication for their life.
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Algoritmos , Inteligencia Artificial , Biomarcadores , HumanosRESUMEN
INTRODUCTION: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, autosomal dominant, congenital disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Past FOP studies have focused on the clinical aspects of the disease; therefore, there is a paucity of qualitative research on the patient experience. Our objective was to better understand the experience of children and adolescents living with FOP from their and their parents' perspectives. METHODS: We conducted a qualitative research study comprising in-depth, open-ended interviews with children and adolescents with FOP and their parents. Semi-structured interviews were conducted via phone call or Microsoft Teams with parent-child dyads (n = 11), adolescents (n = 6), and two clinicians. Children/adolescents and their parents were asked open-ended questions to elicit their daily experience of FOP. RESULTS: Concepts were organized into two major themes: symptoms of FOP and the impact of FOP on daily life. Symptoms of FOP reported by children/adolescents, parents, and clinicians were pain, swelling, redness, and stiffness. Functional impacts of flares and FOP in general included accommodations, mobility, activities of daily living, daily activities, and social activities. Impacts were attributed to the difficulties children and adolescents faced living with a disease that prohibited common activities. CONCLUSIONS: This research documented the experience of children and adolescents with FOP and its effects on their daily lives. It provides a conceptual model for further exploration of the symptoms and impacts important to children and adolescents with FOP and their parents. Children and adolescents and their parents offered novel insights into life with the disease that have not previously been discussed in published literature. Future studies should build upon our conceptual model to create a holistic view of the patient experience of FOP, to inform clinical practice, and the assessment of the patient experience in clinical trials for the disease.
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Artrogriposis , Miositis Osificante , Osificación Heterotópica , Actividades Cotidianas , Adolescente , Cabello , Humanos , Miositis Osificante/diagnóstico , Osificación Heterotópica/diagnósticoRESUMEN
Importance: Patient-reported outcome instruments are key in assessing COVID-19-related symptoms and associated burden. However, a valid and reliable instrument to assess symptom severity and progression among outpatients with COVID-19 is not yet available. Objectives: To assess the extent to which the Symptoms Evolution of COVID-19 (SE-C19) instrument is valid, reliable, and able to detect symptom changes in outpatients with COVID-19, as well as to establish a definition of symptom resolution. Design, Setting, and Participants: In this diagnostic/prognostic study, psychometric properties of SE-C19 were assessed in participants recruited into an ongoing, adaptive, phase 1/2/3, randomized, double-blind, placebo-controlled clinical trial, during 2020 to 2022. Adult outpatients with symptomatic COVID-19 were randomized 1:1:1 to receive 2.4 g or 8.0 g intravenous casirivimab and imdevimab or placebo, in outpatient centers at 114 sites, from 2 countries (US and Mexico). Main Outcomes and Measures: Reliability, validity, and sensitivity to change of the SE-C19 were assessed. SE-C19 and Patient Global Impression of Severity (PGIS) were administered daily from predose at day 1 to day 29. Results: Analysis was conducted on 657 adult outpatients (342 female patients [52.1%], 562 White patients [85.5%]), and 337 non-Hispanic patients [51.3%]. At baseline, patients reported a mean (SD) of 6.6 (3.9) symptoms (ie, rated as at least mild) with a mean (SD) of 3.8 (3.3) of these symptoms being rated as moderate or severe. Stable patients according to PGIS showed scores with intraclass correlation values indicating moderate-to-good test-retest reliability (ie, 0.50-0.90). At baseline, 20 item scores (87%) varied significantly across PGIS-defined groups, supporting the validity of the SE-C19. A symptom-resolution end point was defined after excluding the item sneezing due to its low ability to discriminate severity levels, and excluding confusion, rash, and vomiting, due to their low prevalence in this population. Symptom resolution required complete absence of all remaining items, except cough, fatigue, and headache, which could be mild or moderate in severity. A total of 19 of 23 items from the SE-C19 instrument were identified as valid and reliable to measure disease-related symptoms in outpatients with COVID-19. Conclusions and Relevance: This study identified 19 items that are valid and reliable to measure disease-related symptoms in outpatients with COVID-19, and proposed a definition of symptom resolution for potential use in future clinical trials.
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COVID-19 , Adulto , Humanos , Femenino , COVID-19/diagnóstico , Pacientes Ambulatorios , Reproducibilidad de los Resultados , Medición de Resultados Informados por el PacienteRESUMEN
OBJECTIVES: There is little in-depth qualitative evidence of how symptoms manifest themselves in outpatients with COVID-19 and how these in turn impact outpatients' daily lives. The objective of the study was therefore to explore the experience of outpatients with COVID-19 qualitatively, concerning the symptomatic experience and its subsequent impact on daily life. SETTING: Qualitative research study comprising virtual in-depth, open-ended interviews with outpatients and clinicians. PARTICIPANTS: Thirty US adult patients with COVID-19 were interviewed within 21 days of diagnosis. Patients were 60% female and 87% white, who had to self-report one of the following: fever, cough, shortness of breath/difficulty breathing, change/loss of taste/smell, vomiting/diarrhoea or body/muscle aches. Five independent clinicians were also interviewed about their experience treating outpatients. PRIMARY AND SECONDARY OUTCOME MEASURES: Transcripts were analysed thematically to organise symptoms and impacts of daily life into higher-order overarching categories, and subsequently propose a conceptual model. The adequacy of the sample size was assessed by conceptual saturation analysis. RESULTS: Patient-reported concepts were organised into six symptom themes (upper respiratory, lower respiratory, systemic, gastrointestinal, smell and taste, and other) and seven impact themes (activities of daily living, broad daily activities, leisure/social activities, and physical, emotional, professional and quarantine-specific impacts). Symptom type, severity, duration and time of onset varied by patient. Clinicians endorsed all patient-reported symptoms. CONCLUSIONS: The manifestation of symptoms in outpatients is heterogeneous and affects all aspects of daily life. Outpatients offered new detailed insights into their symptomatic experiences, including heterogeneous experiences of smell and taste, and the impacts that symptoms had on their daily lives. Findings of this research may be used to supplement existing knowledge of the outpatient experience of mild-to-moderate COVID-19, to further inform treatment guidelines and to provide an evidence base for evaluating potential treatment benefits.
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COVID-19 , Pacientes Ambulatorios , Actividades Cotidianas , Adulto , Disnea/etiología , Femenino , Humanos , Masculino , Evaluación del Resultado de la Atención al Paciente , Investigación CualitativaRESUMEN
BACKGROUND: At the onset of the COVID-19 pandemic, there was limited understanding of symptom experience and disease progression. We developed and validated a fit-for-purpose disease-specific instrument to assess symptoms in patients with COVID-19 to inform endpoints in an interventional trial for non-hospitalized patients. METHODS: The initial drafting of the 23-item Symptoms Evolution of COVID-19 (SE-C19) Instrument was developed based on the Centers for Disease Control and Prevention symptom list and available published literature specific to patients with COVID-19 as of Spring 2020. The measurement principles outlined in the Food and Drug Administration (FDA) Patient-Reported Outcomes (PRO) guidance and the FDA's series of four methodological Patient-Focused Drug Development guidance documents were also considered. Following initial development, semi-structured qualitative interviews were conducted with a purposive sample of 30 non-hospitalized COVID-19 patients. Interviews involved two stages: (1) concept elicitation, to obtain information about the symptoms experienced as a result of COVID-19 in the patients' own words, and (2) cognitive debriefing, for patients to describe their understanding of the SE-C19 instructions, specific symptoms, response options, and recall period to ensure the content of the SE-C19 is relevant and comprehensive. Five clinicians treating COVID-19 outpatients were also interviewed to obtain their insights on symptoms experienced by patients and provide input on the SE-C19. RESULTS: Patients reported no issues regarding the relevance or appropriateness of the SE-C19 instructions, including the 24-h recall period. The comprehensiveness of the SE-C19 was confirmed against the conceptualization of the patient experience of symptoms developed in the qualitative research. Minor conceptual gaps were revealed to capture nuances in the experience of nasal and gustatory symptoms and systemic manifestations of sickness. Almost all items were endorsed by patients as being appropriate, well understood, and easy to respond to. The clinicians largely approved all items, response options, and recall period. CONCLUSIONS: The qualitative research provided supportive evidence of the content validity of the SE-C19 to assess the symptoms of outpatients with COVID-19, and its use in clinical trials to evaluate the benefit of treatment. Minor changes may be considered to improve conceptual clarity and ease of responding.
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BACKGROUND: Hereditary hemochromatosis (HH) is a genetic disorder resulting in increased accumulation of dietary iron. It is associated with various clinical complications such as liver cirrhosis and diabetes. The aim of this study was to explore patients' experiences of living with HH, the diagnosis process, and phlebotomy treatment. STUDY DESIGN AND METHODS: An online survey was developed and completed by a total of 210 HH patients across the United States (n = 70), France (n = 50), Ireland (n = 40), and the United Kingdom (n = 50). RESULTS: Of the 210 patients, 30% were induction patients, 49% were maintenance patients, and 22% had never received phlebotomy. The most common route to diagnosis was by chance (42%), although most patients (87%) reported experiencing symptoms they now associated with HH at the time of diagnosis. Fatigue (60%) and joint pain (50%) were the most frequently reported current symptoms. While 87% of patients felt that treatment with phlebotomy was "quite worthwhile" or "very worthwhile," 52% of induction patients and 37% of maintenance patients experienced side effects "always" or "most of the time" after phlebotomy and 16% of patients would "definitely" or "probably" decide not to receive phlebotomy if alternative options were available. CONCLUSION: Diagnosis of HH is likely made late in many patients and subsequent phlebotomy treatment, while considered worthwhile by most, leads to concerns over side effects and inconvenience, often impacting patients' lives. Greater efforts to promote awareness of the disease and reduce the treatment burden associated with phlebotomy are required to improve detection and management of this disease.
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Hemocromatosis/patología , Hemocromatosis/terapia , Flebotomía/efectos adversos , Adulto , Anciano , Femenino , Hemocromatosis/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Patient-reported outcomes of once-daily oral deferasirox (Exjade) in iron-overloaded patients with beta-thalassemia not achieving successful chelation with prior deferoxamine and/or deferiprone were investigated in a prospective, open-label, 1-year, multicenter study in the Middle East (ESCALATOR). The initial dose of deferasirox was 20 mg/kg/day, with subsequent dose adjustments. At baseline and the end of study (EOS), patients (n = 237) completed a 5-point rating scale for treatment satisfaction and convenience, and recorded time lost to treatment. At EOS, 90.7% of patients were 'satisfied'/'very satisfied' with their iron chelation therapy (ICT) versus 23.2% at baseline. 92.8% (EOS) versus 21.5% (baseline) of patients considered their therapy to be 'convenient'/'very convenient'. Time lost to therapy for daily activities was substantially reduced (3.2 +/- 8.6 [mean +/- SD; EOS] vs. 30.1 +/- 44.2 [baseline] h/month). Patients reported greater satisfaction and convenience, and lower impact on daily activities, with deferasirox than with previous ICT. This may help improve adherence to lifelong ICT in iron-overloaded beta-thalassemia patients.