Content validity of a novel patient-reported and observer-reported outcomes assessment to evaluate ocular symptoms associated with infectious conjunctivitis in both adult and pediatric populations.

BACKGROUND: Acute infectious conjunctivitis is a common condition most frequently caused by viruses or bacteria. Clinical outcome assessments have been used to assess signs and symptoms of bacterial and viral conjunctivitis, but have not been evaluated for content validity. We aimed to develop content-valid patient- (PRO) and observer-reported outcome (ObsRO) instruments to assess symptoms of ocular discomfort associated with viral or bacterial conjunctivitis in adult and pediatric patients. METHODS: Draft items were developed from a previous review of published studies from 2001 to 2015. Patients and caregivers of patients with a diagnosis of viral or bacterial conjunctivitis within the past 6 months were recruited. Concept elicitation with open-ended questions explored signs and symptoms, followed by cognitive interviewing to assess clarity and relevance of the draft items. Patients aged ≥8 years were interviewed for the PRO; parents/caregivers of children aged 1-10 years were interviewed for the ObsRO. Interviews were conducted in three rounds to allow changes. Concept saturation was documented using a saturation grid. Cognitive interview data were analyzed iteratively and focused on clarity, relevance and inconsistent interpretation of the instrument's content. RESULTS: Overall, 23 patients or parents/caregivers participated (round 1, n = 10; round 2, n = 6; round 3, n = 7). Data saturation was reached by the 16th interview. The most frequent spontaneously reported signs/symptoms were: discharge, red/pink eyes, itchiness, swelling/puffiness, watery eyes, pain, burning and foreign body sensation. Itching, pain/burning/stinging and foreign body sensation were most commonly reported as the top three most bothersome symptoms. Interview results indicated that items on pain, itching and foreign body sensation for the PRO and pain or discomfort for the ObsRO were relevant to the patients' experience of conjunctivitis and were clear and easy to understand. CONCLUSIONS: PRO and ObsRO items were found to be clear, relevant and appropriate in assessing key viral and bacterial conjunctivitis symptoms in adult and pediatric patients.

Patient preferences for diabetes treatment attributes and drug classes.

OBJECTIVE: To identify which treatment attributes are most influential in determining patient preferences for diabetes treatments and explore patient preferences for diabetes drug classes. RESEARCH DESIGN AND METHODS: US adults with type 1 or type 2 diabetes completed an online adaptive conjoint analysis survey. The survey examined 14 attributes, including efficacy, regimen, and risk of common side effects and rare but serious adverse events. Respondents selected between hypothetical treatments with different attributes. Sawtooth Software, ordinary least-squares regression, and hierarchical Bayes regression were used to calculate utilities (i.e. preference weights), importance ratings, and shares of preference across 13 diabetes drug classes or combination products. RESULTS: A total of 167 adults (mean age 58 years; 55% female) with type 1 or type 2 diabetes completed the survey. Based on importance ratings, the most influential attributes driving preferences were regimen, risk of diarrhea, weight change, risk of hypoglycemia, and efficacy. Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) were highly preferred in direct comparison to each of the other classes (range: 84.2-99.9%), with the exception of dipeptidyl peptidase-4 inhibitors (DPP-4is); DPP-4is (52.9%) were preferred over SGLT-2is (47.1%). CONCLUSIONS: Although preferences varied across participants, attributes with the greatest likelihood of affecting daily life and routine were generally more influential in determining patient preferences. DPP-4is and SGLT-2is were overwhelmingly preferred over other drug classes, primarily due to favorable regimen and side effect profiles. Understanding patient preferences can help optimize patient-centered treatment and may lead to improved patient satisfaction, adherence, and outcomes. LIMITATIONS: The primary limitations of this study are that a small sample size of type 1 diabetes patients were included, which may reduce the reliability of the preference estimates, and patients were recruited from a patient panel and may not be representative of patients with diabetes in the US.

Evaluating preference weights for the Asthma Symptom Utility Index (ASUI) across countries.

BACKGROUND: The Asthma Symptom Utility Index (ASUI) is a preference-based outcome measure used in US clinical trials and cost-effectiveness studies for asthma. This study evaluated ASUI preference weights in Europe to determine whether the multi-attribute utility function, based on preferences from a US population, is generalizable across countries. METHODS: Data were collected from ninety asthma patients from Italy, France, and the United Kingdom using the Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire, and the ASUI. Subjects rated their preferences for 10 asthma health states using a visual analogue scale (VAS) and a standard gamble (SG) interview. RESULTS: All multi-symptom states showed statistically significant differences (p < 0.001) between countries in mean VAS scores. Mean SG utility scores between the US and France and the US and Italy demonstrated statistically significant differences (p < 0.001) for three states: severe wheeze; moderate cough and wheeze; and moderate cough and dyspnea. Because of these differences, the multi-attribute utility functions derived within countries were somewhat different. Despite these differences, country-specific algorithms captured a similar rank ordering of patients by disease severity, were strongly correlated (r = 0.971 to 0.995), and demonstrated similar relationships with symptom and AQLQ scores. CONCLUSION: Results of this study suggest that the ASUI may be a complementary patient-reported outcome for clinical studies and may be useful for applications in cost-effectiveness studies comparing different asthma treatments.

Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women.

BACKGROUND: The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. METHODS: The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS) can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL), and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC) via a follow-up questionnaire completed by participants 2 weeks post baseline. RESULTS: 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%), living with someone (74%), and not currently employed (58.7%). 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data). On a scale of 0-100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70) (range 0.72 to 0.89). Reproducibility ranged from 0.62 (Daily Activities) to 0.79 (Side Effects) for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p < 0.001). CONCLUSION: The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite score. They also support the use of the OPSAT-Q to examine the impact of bisphosphonate dosing frequency on patient satisfaction.

Cognitive Testing of an Electronic Version of the Faces Pain Scale-Revised with Pediatric and Adolescent Sickle Cell Patients.

BACKGROUND: Patient diaries and pain scales can capture the course and complications of pain managed at home in children. The Faces Pain Scale-Revised (FPS-R) is a validated scale showing reliability in children, but it has not been validated in children with sickle cell disease (SCD). OBJECTIVE: The purpose of this study was to evaluate comprehension and usability of an electronic modified version of the FPS-R among pediatric patients with SCD. METHODS: This was a cross-sectional, qualitative study involving in-person interviews with children/adolescents from the USA and their parents/legal guardians. Interviews involved cognitive debriefing and usability testing of the FPS-R. RESULTS: In total, 22 children with SCD aged 4-17 years participated. Children aged 4-6 were generally unable to demonstrate clear understanding of the FPS-R and its response scale. Overall, children aged ≥7 years understood the instrument and could complete it on the electronic device, although children aged 7-8 often needed assistance from the parent. Children aged 9-17 years were able to read and complete the instrument independently. Most participants considered the electronic device easy to use. CONCLUSIONS: The FPS-R was shown to be a comprehensible and usable pain measure for children aged 7-17 with SCD and to be beneficial for future clinical studies.

Demonstrating measurement equivalence of the electronic and paper formats of the Urticaria Patient Daily Diary in patients with chronic idiopathic urticaria.

BACKGROUND: The Urticaria Patient Daily Diary (UPDD), originally developed on paper, is a measure of key symptoms of chronic idiopathic urticaria (CIU). The development of the electronic version (eUPDD) involved moderate modifications to the appearance of the paper version. OBJECTIVE: This study assessed the measurement equivalence of the electronic and paper versions of the UPDD in a sample of patients with CIU. METHODS: This was a cross-over study of patients with moderate-severe CIU refractory to H1 antihistamines. Patients were randomized to either the eUPDD followed by the paper UPDD or vice versa. The UPDD includes morning and evening questions; both sets were administered together in this study. An hour-long filler task was given between paper and electronic administrations. Patients with stable symptoms between the two assessments were included in the analyses. Cohen's kappa coefficients and intraclass correlation coefficients (ICC) were computed as applicable to assess equivalence. RESULTS: A total of 91 patients participated (mean age 43 years, 79.1 % female). Symptoms were stable between assessments for 67-74 (74-81 %) patients (varied by symptom). Kappa coefficients ranged from 0.82 to 1.00 for the individual UPDD items. For the Urticaria Activity Score (the sum of the 'itch severity' and 'number of hives' item scores) the ICC was 0.90 for the morning (Wilcoxon p = 0.331) and 0.95 for the evening (Wilcoxon p = 0.836). CONCLUSIONS: All test-retest statistics in this study were well above the accepted threshold, indicating excellent agreement between the two administration methods. Findings support the measurement equivalence of the electronic and paper versions of the UPDD to measure CIU symptoms.

A survey of children's preferences for influenza vaccine attributes.

BACKGROUND: While annual influenza vaccination is recommended by the CDC for children 6 months and older, vaccination rates remain suboptimal. For healthy, US children 2 years of age and older, influenza vaccine is available as an intramuscular injection (TIV) or an intranasal spray (LAIV), respectively. Little is known about children's experiences and preferences for influenza vaccine attributes. OBJECTIVE: To examine preferences for influenza vaccine attributes and their relative importance among children. METHODS: A quantitative web-survey was administered to children aged 8-12 years sampled from a standing online panel representative of the US population. Children were stratified by age, gender and parent's influenza vaccination behavior. The survey included questions to ascertain children's preferences for influenza vaccine attributes, including efficacy, chance of common side effects, and mode of administration. It included conjoint (trade-off) questions in which children traded-off different attributes in their choice between two influenza vaccines with differing features. We also surveyed children's comprehension of and ability to complete the conjoint questions. RESULTS: 544 children completed the survey (response rate 37%). Children most frequently selected efficacy as the most important vaccine attribute followed by mode of administration (45% and 31%, respectively). When asked for their preference to receive influenza vaccine as a "shot" or a "nose spray", the majority (69%) preferred the nose spray. An evaluation of children's ability to complete the conjoint survey demonstrated that 85% of the sample was able to complete the conjoint tasks. Analysis of the conjoint responses demonstrated that mode of administration and efficacy had the greatest impact on preferences, with a relative importance of 40.5% and 30.6%, respectively. In a direct comparison of vaccine profiles representing the efficacy, side effects, and other characteristics of LAIV and TIV, 79% of children preferred the LAIV-like profile. CONCLUSION: Children in the sample had consistent opinions regarding influenza vaccine attributes and consider vaccine efficacy and mode of administration to be important. Children can be informed participants in influenza prevention and can be included in discussions regarding influenza vaccination.

Children's perceptions of influenza illness and preferences for influenza vaccine.

INTRODUCTION: In this qualitative study we explored children's perceptions of influenza, preferences for influenza vaccines, and ability to understand "risk" of vaccine adverse effects and different attributes between injectable and intranasal vaccines. METHOD: In-person, semi-structured interviews were conducted among 28 U.S. children aged 6 through 12 years. RESULTS: Many children understood the concept of influenza illness and believed vaccination was important. Efficacy, adverse effects, and mode of administration affected their preferences for influenza vaccines. Children 8 years of age and older were able to consider multiple attributes when selecting between hypothetical vaccines, and their responses were consistent with their previously stated preferences for individual attributes. Most children would prefer a nasal spray over a shot vaccine when all other vaccine attributes were equal. DISCUSSION: Efficacy, adverse effects, and mode of administration were important factors in children's preferences for influenza vaccine. Children as young as 8 years of age appeared to understand vaccine "risk" and were able to consider multiple attributes simultaneously when choosing between vaccine alternatives.

Parent preferences for pediatric influenza vaccine attributes.

Influenza vaccine is available as an intramuscular injection or an intranasal spray for eligible children. This study was conducted to examine parents' preferences for influenza vaccine attributes and the attributes' relative importance regarding the vaccination of their children. A quantitative Web survey was administered to 500 parents of children aged 2 to 12 years. The survey included general preference questions and conjoint (trade-off) questions. Parents most frequently selected efficacy, risk of temporary side effects, and physician recommendation as important vaccine attributes from a provided list (92%, 75%, and 59%, respectively). For attributes selected as important, parents rated the importance of the attribute; the highest mean importance ratings were given to efficacy, presence of mercury-containing preservative, and physician recommendation.The highest relative importance ratings in the conjoint section were given to efficacy and presence of mercury-containing preservative. Parental education on influenza vaccine efficacy and safety may help to improve pediatric vaccination rates.

Parents' decision-making regarding vaccinating their children against influenza: A web-based survey.

BACKGROUND: Despite the recommendation from the Centers for Disease Control and Prevention that children between the ages of 6 months and 18 years be vaccinated against influenza annually, vaccination rates remain suboptimal. OBJECTIVES: This study was conducted to explore factors that influence parents' decisions regarding influenza vaccination for children aged 2 to 12 years, to quantify the relative importance of these factors, to identify an appropriate theoretical model for illustrating the relationships among these factors, and to characterize parents by their likelihood of vaccinating their children against influenza. METHODS: A quantitative Web-based survey was administered to a sample of parents from an online panel representative of the US population. Parents were stratified based on self-reported rates of their personal influenza vaccination (every year, sometimes, or never) and the age of their child (2-4 years or 5-12 years). The results were examined by parents' likelihood of vaccinating their child in the next year (high, medium, or low). Participants were asked to rank their agreement with statements representing various beliefs and perceptions about influenza and influenza vaccine on a scale from 1 = strongly agree to 5 = strongly disagree. Parents who indicated that they vaccinate their child every year were asked to select the drivers of their decision to vaccinate; parents who indicated that they never vaccinate their child were asked to select the barriers affecting their decision not to vaccinate; and parents who responded that they sometimes vaccinate their child were asked to select both the drivers and barriers affecting their decision. Participants were then asked to rank the importance of each driver or barrier on a scale from 1 = a little important to 5 = extremely important. Mean agreement ratings were calculated for parents' beliefs and perceptions about influenza and influenza vaccine and were compared across likelihood subgroups. Mean importance ratings of the drivers and barriers to vaccination were also calculated and compared across likelihood subgroups. RESULTS: The survey sample consisted of 500 parents; their mean (SD) age was 37.4 (6.82) years, 57.2% were female, and 78.2% were non-Hispanic white. Among those who reported that they vaccinated their child against influenza every year or sometimes, the major drivers of vaccination were prevention of influenza (95.1%), a doctor's recommendation (89.5%), and the desire to reduce influenza symptoms (83.3%). Among those who reported sometimes or never vaccinating their child against influenza, barriers to vaccination were more variable. The most common barriers were low perceived risk of influenza (46.0%), the perception that the vaccine caused influenza (44.0%), and side effects caused by the vaccine (36.6%). Distinct differences were found in beliefs and perceptions of influenza and influenza vaccine according to respondents' likelihood of vaccination. A high likelihood of vaccination was associated with a greater perceived threat of influenza and less concern about the efficacy and safety of the vaccine. Convenience was an important factor among parents with a medium likelihood of vaccination. The Health Belief Model was identified as an appropriate theoretical framework for illustrating the factors influencing parents' decision-making about influenza vaccination. CONCLUSIONS: Prevention of influenza, reduction of influenza symptoms, and doctor recommendation were the main drivers of parents' decision to vaccinate their child against influenza. Barriers to vaccination were more variable and primarily included the risk of adverse effects and the perceived low risk of influenza. Increasing parents' awareness of the threat of influenza and the efficacy and safety of the vaccine, as well as improving the convenience of getting vaccinated, may help improve rates of pediatric influenza vaccination.

Patient and caregiver perspective on pediatric eosinophilic esophagitis and newly developed symptom questionnaires*.

OBJECTIVE: Eosinophilic esophagitis (EE), a rare chronic inflammatory condition of the esophagus, is predominantly observed in children and is primarily manifested with feeding difficulties. To our knowledge, no self- or caregiver-reported questionnaires are available to assess pediatric EE symptoms and their impact as reported directly by children or their parents/caregivers. The objectives of this study were to characterize the symptoms and impact of EE among children as reported by patients and parents/caregivers and to assess the content validity of two newly developed pediatric eosinophilic esophagitis symptom questionnaires, one parent/caregiver-reported questionnaire for ages 2-7 years and one child-reported questionnaire for ages 8-17 years. The questionnaires were developed based on a review of the literature and clinical expert consultation. RESEARCH DESIGN AND METHODS: This cross-sectional study involving one-on-one interviews with patients and caregivers was conducted at an American Partnership for Eosinophilic Disorders conference. Parents of patients aged 2-7 years (n = 12) and patients aged 8-17 years (n = 16) were first asked about symptoms and their impact on everyday life, using open-ended questions. Participants then completed the appropriate symptom questionnaire and were asked to provide feedback on the relevance, comprehensiveness, and clarity of each item and other questionnaire issues (time to complete, length, format, etc.). All reported symptoms were enumerated, and the feedback on the symptom questionnaires was analyzed qualitatively. RESULTS: The majority of study participants were white (82%) and male (86%). The most frequently reported symptoms of 2-7-year olds were vomiting (92%), "reflux" (50%), dysphagia (25%), abdominal pain (25%), and trouble sleeping (25%). The 8-17-year group reported abdominal pain (56%), vomiting (31%), throat pain (25%), diarrhea (25%), and food getting stuck (25%). Symptoms and treatment were reported to have a major impact on daily life, particularly on school, after-school activities and social events, feeling frustrated regarding symptoms and treatment, and feeling "different". Overall, participants thought that the questionnaires were clear, relevant, and appropriate for symptom assessment. LIMITATION: This study was based on a small and convenient sample of participants attending an EE conference and hence may not be representative of the general EE patient population. CONCLUSIONS: EE is associated with a range of symptoms that vary in terms of the type, frequency and severity across and within patients. The results provide adequate support for the content validity of the self- and caregiver-reported versions of the symptom-specific questionnaires. Minor modifications were made based on the feedback obtained. A psychometric evaluation of the revised questionnaires is needed next to assess the construct validity, reliability, and responsiveness of the measures.

Assessment of health-related quality of life in children: a review of conceptual, methodological, and regulatory issues.

Recently, the FDA has encouraged testing of medications among pediatric patients during drug development. Pharmaceutical companies have responded by conducting more clinical trials among children, and researchers are becoming aware of the unique challenges of assessing pediatric health outcomes, including health-related quality of life (HRQL). Like adults, children experience effects of illness and treatment beyond physiologic outcomes. Further pediatric HRQL research is necessary to examine these broader psychosocial outcomes and provide a thorough understanding of the effects of treatment on children's health status. The purpose of the current review is to discuss key regulatory and methodologic developments and provide guidance for future research on pediatric HRQL. This review of pediatric HRQL assessment includes five sections: 1). recent pediatric regulatory developments in the United States; 2). issues in defining and conceptualizing pediatric HRQL, including the importance of contextual variables such as family and peer systems; 3). methodologic issues (e.g., the proxy question, developmental differences, response sets) with recommendations for addressing these issues in clinical trials; 4). validated generic and condition-specific pediatric HRQL measures; and 5). a recommendation for additional research on the HRQL impact of childhood psychiatric disorders. It is advocated that assessment of HRQL among children should be conducted regularly as an integral part of drug development.

Utility assessments of opioid treatment for chronic pain.

OBJECTIVE: The primary study objective was to assess preferences for pain treatment outcomes among patients with cancer and noncancer chronic pain. A secondary objective was to assess their quality of life. METHODS: Patients with cancer or noncancer chronic pain completed an interview using a computer to estimate utilities, or preference ratings, for health states related to pain treatment. The interview was devised using conjoint analysis methodology. Health states were characterized by four attributes (effectiveness of pain control, side effects, side effect severity, and opioid route of administration) and their levels, and each was assumed to last for a 14-day period. Participants also completed health-related quality of life and demographic questionnaires. RESULTS: Mean preference ratings for participants with noncancer chronic pain (N = 96) ranged from a high of 0.87 (well-controlled pain with no side effects) to a low of 0.18 (poorly controlled pain with severe mood changes/alterations, severe respiratory depression, or severe vomiting). Mean preference ratings for participants with cancer pain (N = 25) were similar and ranged from a high of 0.89 (well-controlled pain with no side effects) to a low of 0.19 (poorly controlled pain with severe respiratory depression or severe vomiting). Results confirmed previous findings that chronic pain has a severe, multidimensional impact on patients, and that the quality of life of persons with chronic pain is among the lowest observed for any medical condition. CONCLUSIONS: This study provides a valuable assessment, from the patient's perspective, of the balance between treatment tolerability and manifestation of disease symptoms. Heightened awareness of patients' preferences for treatment outcomes may lead to improved selection of treatments, better adherence, and ultimate treatment success.