Measuring dengue illness intensity: Development and content validity of the dengue virus daily diary (DENV-DD).

BACKGROUND: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations. METHODS: The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. RESULTS: Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. CONCLUSIONS: Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Dengue is the most common viral infection transmitted to humans by mosquitos, and affects an estimated 50­60 million individuals globally per year. However, there are few resources for understanding and capturing the patient experience of dengue throughout illness. Most research studies are based on healthcare provider assessment, which lack consistency in terms of assessment time points and the signs/symptoms assessed. The 'Dengue Illness Index Report Card (DII-RC)' was used as a foundation to create the new 'Dengue Virus Daily Diary (DENV-DD)' to better capture the patient experience of symptom intensity and dengue disease burden for the duration of illness. Forty-eight individuals and caregivers of younger children from Peru and Ecuador who recently had symptomatic dengue were interviewed to understand the patient experience over the time of illness and to test whether the DENV-DD is understood by patients and caregivers and includes all relevant and important signs/symptoms and health-related quality of life impacts. Nine individuals with active dengue infection also completed the DENV-DD daily for 28-days as part of a clinical study. We found that > 70% of patients experienced fever, headache, body ache/pain, loss of appetite and body weakness. The DENV-DD instructions, questions and response option(s) were well understood, feasible to complete and the concepts assessed by the DENV-DD were relevant to the dengue experience. Our study adds to the understanding of the dengue illness experience and supports the DENV-DD for use in future dengue studies as an assessment of signs/symptoms throughout the duration of illness.

Content validity of the EORTC quality of life questionnaire QLQ-C30 for use in cancer.

AIM: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) is among the most widely used patient-reported outcome measures in cancer research and practice. It was developed prior to guidance that content should be established directly from patients to confirm it measures concepts of interest and is appropriate and comprehensive for the intended population. This study evaluated the content validity of the QLQ-C30 for use with cancer patients. METHODS: Adults undergoing cancer treatment in Europe and the USA participated in open-ended concept elicitation interviews regarding their functional health, symptoms, side-effects and impacts on health-related quality of life. Thematic analysis was conducted, and similarities across cancer types, disease stages and countries or languages were explored. RESULTS: Interviews with 113 patients with cancer (85 European, 28 USA) including breast, lung, prostate, colorectal and other cancers were conducted between 2016 and 2020. Conceptual saturation was achieved. The most frequently reported concepts were included in the QLQ-C30 conceptual framework. QLQ-C30 items were widely understood across language versions and were relevant to patients across cancer types and disease stages. While several new concepts were elicited such as difficulty climbing steps or stairs, weight loss, skin problems and numbness, many were not widely experienced and/or could be considered sub-concepts of existing concepts. CONCLUSIONS: The QLQ-C30 demonstrates good evidence of content validity for the assessment of functional health, symptom burden and health-related quality of life in patients with localised-to-advanced cancer.

Patient experience of moderate asthma attacks: qualitative research in the USA and Germany.

BACKGROUND: There is limited information available on the impact of moderate asthma exacerbations, often called "asthma attacks" (i.e., those not requiring hospitalisation or treatment with systemic corticosteroids) on patients' lives. This multi-country qualitative study explored the patient experience of these events. METHODS: Semi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients' experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation. RESULTS: Twenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model. CONCLUSIONS: Findings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients' lives.

Linguistic Validation of the Canine Brief Pain Inventory (CBPI) for Global Use.

A valid and reliable quantitative measure of chronic pain is essential for developing and evaluating interventions that aim to treat pain. In dogs, the Canine Brief Pain Inventory (CBPI) was originally adapted from a human measure, the Brief Pain Inventory, to assess owner-perceived pain and the impact of such pain on a dog's daily functioning. To be reliable and valid, data collected using a translated instrument should have evidence it is an accurate representation of the original instrument and is culturally appropriate for use in the intended context. To achieve this, instruments should undergo a rigorous translation process and be debriefed in the intended population of use. The CBPI is widely accepted and has been fully validated for use in US-English, Swedish, Italian, and French (France); further translation and validation of the CBPI is required to increase access to and use in other languages and countries. The objective of this study was to linguistically validate the CBPI for global use (Australia, China, Germany, Hungary, Ireland, Japan, Netherlands and Portugal). In cognitive debriefing with a representative sample of dog owners in the target countries it was confirmed that the translations of the CBPI adequately convey the concepts in the original US-English version and that items are easily understood by dog owners. The results of the linguistic validation process thus produced measures that are conceptually equivalent to the original US-English-language CBPI and are culturally appropriate for use in the target countries.

A qualitative exploration of the patient experience of erosive and non-erosive hand osteoarthritis.

BACKGROUND: Many patients with hand osteoarthritis (HOA) experience reduced health-related quality of life. This study sought to better understand the disease and treatment experience of individuals with HOA, explore any differences in experiences between erosive and non-erosive HOA sub-types, and evaluate content validity of the Michigan Hand Outcomes Questionnaire (MHQ) in HOA. METHODS: Thirty subjects from the United States (n = 15 erosive HOA; n = 15 non-erosive HOA) participated in semi-structured interviews: concept elicitation explored symptoms/impacts important to patients; cognitive interviews assessed understanding and relevance of the MHQ. A sub-sample participated in real-time data capture (RTDC) activities via a smartphone/tablet app over 7 days. Verbatim transcripts were coded using Atlas.ti software and thematically analyzed. Concept saturation and MHQ content validity were evaluated. RESULTS: Most participants reported experiencing pain, swelling and stiffness, symptoms that most commonly had a direct impact on physical functioning. Substantial impacts on activities of daily living, emotional functioning, sleep and work were also reported. RTDC findings corroborated concept elicitation findings. There were no notable differences between erosive and non-erosive HOA, except nodules were reported more frequently in erosive disease. Most participants used analgesic treatments, but effects were short-lived. Pain was the symptom most frequently reported as most bothersome and important to treat. Concept saturation was achieved. MHQ items and instructions were well understood and relevant to most participants; stiffness and swelling were reported as important symptoms not included in the MHQ. CONCLUSIONS: This study characterizes key symptoms of HOA which are burdensome for patients and not well controlled by current therapies, highlighting an unmet treatment need. Although the study is limited by a small sample size that may not be representative of the broader erosive and non-erosive HOA population, concept saturation was achieved, and our findings suggest that disease experience is similar for patients with erosive and non-erosive HOA. Evaluation of stiffness and swelling items in conjunction with the MHQ may enhance relevance and improve measurement precision to assess important domains of HQRoL in an HOA population.

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

INTRODUCTION: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties. METHODS: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib. RESULTS: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively. CONCLUSIONS: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.

Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII).

INTRODUCTION: Prophylactic treatment of severe hemophilia A is burdensome, requiring frequent intravenous injections. Extended half-life (EHL) factor VIII replacement therapies offer longer intervals between infusions while still meeting efficacy and safety outcomes; however, patient perspectives following long-term use of such products in the real-world remain unknown. OBJECTIVE: We aimed to explore the importance of infusion frequency and the potential benefits of reduced infusion frequency among patients receiving prophylactic treatment with an EHL product (BAY 94-9027). METHODS: Patients with severe hemophilia A participating in the PROTECT VIII extension study were invited to participate in a semi-structured, concept elicitation 'exit' interview to discuss their experiences. Participants were recruited from Israel, The Netherlands, and the US. Interview transcripts were translated into English and analyzed using thematic analysis methods. RESULTS: Sixteen participants (29-68 years of age) infusing with BAY 94-9027 once every 7 days, once every 5 days, or twice weekly were interviewed. Participants reported infusion frequency (alongside efficacy) as the most important treatment attribute influencing their satisfaction with therapy. Patient-reported benefits of reduced infusion frequency and longer duration of factor coverage included greater ability to participate in physical activities; better vein health; less time to schedule and administer factor VIII; reduced impact on work; and improved emotional well-being. CONCLUSIONS: This study provides rich insights into the experiences of patients with EHL products and the value of reduced infusion frequency. Such data could be of value to a range of stakeholders (e.g. regulators, payers) and facilitate patient-clinician discussions to promote tailored treatment decisions.

The Humanistic Burden of Small Cell Lung Cancer (SCLC): A Systematic Review of Health-Related Quality of Life (HRQoL) Literature.

Background: Little is known about the humanistic burden of small cell lung cancer (SCLC), specifically the impact on health-related quality of life (HRQoL). The aim of this systematic literature review was to explore the impact of SCLC on HRQoL and the patient reported outcomes (PROs) used to capture this impact. Methods: We conducted a systematic search of Medline®, Embase, and PsycINFO, oncology organization websites and conference proceedings within the past 10 years. Articles reporting HRQoL outcomes of SCLC patients were selected. Results: Twenty-seven eligible publications were identified. Global or overall impact on HRQoL (n = 21) was reported most often, with considerably fewer reporting individual domains that comprise HRQoL. Results indicated that HRQoL was negatively impacted in SCLC patients in comparison to the normal population in most domains. Overall, the domains measuring physical functioning and activities of daily living were most impacted. However, results on cognitive and emotional functioning were inconclusive. The impact on HRQoL may be least in both limited disease and extensive disease (ED) SCLC patients who have responded to treatment, and greatest in ED patients who were treatment naïve. The most frequently used PROs were the EORTC QLQ-C30 core cancer instruments, the lung cancer specific module the EORTC QLQ-LC13, LCSS, and EQ-5D. Conclusion: There exists a paucity of reporting on SCLC HRQoL outcomes. This extends to the reporting of domain level scores and by patient sub-group. Greater reporting at a granular level is recommended to allow for more robust conclusions to be made.