Symptoms and Treatment Needs of People with Dementia-Related Psychosis: A Mixed-Methods Study of the Patient Experience.

OBJECTIVES: This study describes the person-centered experience and impact of symptoms and the treatment needs of dementia-related psychosis (DRP) from a patient and care partner perspective. METHODS: Qualitative interviews and a quantitative survey were used to collect patient experience data from persons with DRP or their care partners. RESULTS: Sixteen participants (1 person with DRP, 15 care partners) completed the qualitative interview; 212 participants (26 persons with DRP, 186 care partners) completed the quantitative survey. The most commonly reported symptoms were visual hallucinations, auditory hallucinations, persecutory delusions, and distortion of senses. The most common impacts were difficulty differentiating what is real from what is not real, increased anxiety, and effects on personal relationships. Current treatments were less than moderately helpful, and the ability to distinguish what is real from what is not real and overall symptom improvement were described as the most important benefits of an ideal treatment. CONCLUSIONS: Patient experience data provide insights into urgent therapeutic needs of patients by describing the nature, frequency, and severity of symptoms and the impacts they have on individuals' lives. CLINICAL IMPLICATIONS: Patient experience data demonstrate an unmet need for treatments to reduce the symptoms and impacts of DRP.

A Review of Patient-Reported Outcome Labeling in the United States (2011-2015).

BACKGROUND: A review of new drug approvals (NDAs) by the Food and Drug Administration (FDA) for 2006 to 2010 showed that 24.1% of new drugs had patient-reported outcome (PRO) labeling. OBJECTIVES: To review PRO labeling for NDAs for 2011 to 2015 and to compare key findings reported previously. METHODS: A review of the FDA drug approval reports for NDAs was conducted using the FDA Web site to determine the number of NDAs for the period 2011 to 2015. For all identified NDAs, drug approval package and product labeling were reviewed to identify PRO end-point status and PRO labeling. NDAs for the period 2006 to 2015 were grouped by disease category as per the International Classification of Diseases, Tenth Revision. Data were summarized for all NDAs and for approvals in diseases that traditionally rely on PROs for evaluating treatment benefit (PRO-dependent). Results were compared with NDAs for the period 2006 to 2010. RESULTS: In the period 2011 to 2015, 16.5% of the 182 NDAs had PRO labeling. For PRO-dependent NDAs, this figure was 46.9% and 46.0% for the period 2006 to 1010 and the period 2011 to 2015, respectively. Most of the PRO labeling for the period 2011 to 2015 was based on primary end points (76.7%). Almost all PRO labeling was for concepts proximal to the disease. CONCLUSIONS: There is potential for increased PRO labeling, especially for drug approvals in diseases that traditionally rely on PROs for evaluating treatment benefit to satisfy regulatory needs. Less PRO labeling based on secondary end points may be indicative of drug manufacturers' reluctance to aid and enhance the value propositions of their products to all stakeholders, including patients.

Development of the sporadic inclusion body myositis physical functioning assessment.

INTRODUCTION: Sporadic inclusion body myositis (sIBM) is a progressive idiopathic inflammatory myopathy characterized by atrophy and weakness of proximal and distal muscle groups that results in a loss of independence and the need for assistive devices and supportive care. To assess treatment benefit of new therapies, a patient-reported outcome measure of physical function was developed. METHODS: The tool was rigorously developed in accordance with the United States Food and Drug Administration (FDA) patient-reported outcomes (PRO) guidance. A single-visit, observational study was conducted. Standard qualitative analytical methods were employed to analyze interview data and generate questionnaire items. RESULTS: Twenty concept elicitation and 19 cognitive debriefing interviews were conducted, and 6 expert physicians were consulted. The tool consists of 11 items scored on a 0-10 numerical rating scale. Subjects completed the questionnaire utilizing either paper or electronic administration. CONCLUSION: We have developed a PRO tool in alignment with FDA PRO guidance for use in the functional assessment of treatment benefit in sIBM. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 653-657, 2016.

Psychometric validation of a patient-reported measure of physical functioning in sporadic inclusion body myositis.

INTRODUCTION: To assess self-reported physical functioning in patients with sporadic inclusion body myositis (sIBM), the sIBM Physical Functioning Assessment (sIFA) was developed. This research establishes the validity, reliability, and responsiveness of the sIFA in patients with sIBM. METHODS: Data from 3 small, noninterventional, observational studies were analyzed. Several measures of physical function were included to assess validity. Reliability (Cronbach alpha, test-retest intraclass correlations), construct validity (correlations, analyses of variance), and responsiveness (effect size estimates) were evaluated. RESULTS: Cronbach alphas (range = 0.86-0.91) and test-retest reliability (0.91) were highly satisfactory. Correlations with other measures provided evidence of convergent validity. sIBM patients able to walk without assistive devices scored significantly better on the sIFA (means = 36.0-47.05) than those who required power mobility or wheelchairs (means = 54.9-71.5), demonstrating the discriminating ability of the sIFA. Effect size estimates of responsiveness suggested mild functional progression. CONCLUSIONS: Psychometric analyses of the sIFA demonstrate satisfactory reliability, validity, and responsiveness. Muscle Nerve 54: 658-665, 2016.

Proxy-reported questionnaires for young children with asthma: a structured review.

Which proxy-reported outcome measures have been developed for use with children aged 6 years and younger to assess asthma symptoms, asthma control, and asthma-specific health-related quality of life, and do these questionnaires' measurement properties support their use as end-points in clinical trials? A two-phase literature search was conducted: 1) studies describing relevant questionnaires were identified, and the questionnaires were assessed against predefined criteria; 2) studies providing information on the measurement properties of questionnaires meeting the predefined inclusion criteria were identified. Literature sources included PubMed and EMBASE databases, scientific conference proceedings, a clinical trial registry, and a quality of life instrument database. The initial search of literature databases and conference abstracts identified 631 records. 20 paediatric asthma proxy-reported outcome instruments were identified; seven met the inclusion criteria: Childhood Asthma Control Test, Control de Asma en Niños Questionnaire, Pediatric Asthma Caregiver Diary, Pediatric Asthma Control Tool, PedsQL 3.0 Short-Form 22 Asthma Module, PedsQL Asthma Symptoms Scale, and Test for Respiratory and Asthma Control in Kids. Three proxy-reported outcome instruments were considered suitable for use as end-points in paediatric asthma clinical trials; the Pediatric Asthma Caregiver Diary possesses the strongest measurement properties of the three.

Assessment of PRO label claims granted by the FDA as compared to the EMA (2006-2010).

BACKGROUND: The US Food and Drug Administration (FDA) provides formal guidance for the use of patient-reported outcomes (PROs) in support of labeling claims, whereas the European Medicines Agency (EMA) offers insight in a reflection paper relating to health-related quality of life in lieu of formal guidance. OBJECTIVES: PRO label claims granted for new molecular entities and biologic license applications from 2006 through 2010 were reviewed to evaluate consistencies and discrepancies in PRO label claims granted by the FDA and the EMA and to highlight trends in the acceptance of PRO claims across agencies. METHODS: Products approved by both the FDA and the EMA were identified. By using US Drug Approval Packages and European Public Assessment Reports packages, any PRO label claims made for the same product by the same company were compared. RESULTS: Both agencies approved a total of 75 products. Of these, 35 (47%) had at least one EMA-granted PRO label claim compared with 14 (19%) by the FDA. Most FDA-grated claims focused on symptoms; however, EMA-granted claims were more likely to include higher order concepts. Few (~12%) were granted the same label claims. Despite this discordance between the two agencies, where PRO label claims were granted by both the FDA and the EMA, there was similarity in the type of label claim. CONCLUSIONS: The EMA is more likely than the FDA to grant PRO claims and for higher order constructs. On a macro level, there appears to be poor concordance between claims granted by both agencies. On close examination, however, there appears to be greater concordance than previously recognized, which may be instructive in formulating future PRO strategies. Further research to create strategic alignment across agencies may be beneficial.

Potential of patient-reported outcomes as nonprimary endpoints in clinical trials.

BACKGROUND: The purpose of this research was to fully explore the impact of endpoint type (primary vs. nonprimary) on decisions related to patient-reported outcome (PRO) labeling claims supported by PRO measures and to determine if nonprimary PRO endpoints are being fully optimized.This review examines the use of PROs as both primary and nonprimary endpoints in support of demonstration of treatment benefit of new molecular entities (NMEs) and biologic license applications (BLAs) in the United States in the years 2000 to 2012. METHODS: All NMEs and BLAs approved by the Food and Drug Administration (FDA) between January 2000 and June 2012 were identified using the FDA Drug Approval Reports Web page. Generic products granted tentative approvals were excluded. For all identified products, medical review sections from publicly available drug approval packages were reviewed to identify PRO endpoint status. Product labels (indication, clinical trials sections) were reviewed to determine the number and type of PRO claim. RESULTS: A total of 308 NMEs/BLAs were identified. Of these, 70 NMEs/BLAs (23%) were granted PRO claims. The majority of product claims were for disease- or condition-specific signs and symptoms. Of the 70 products with PRO claims, a PRO was a primary endpoint for the vast majority (57 [81%]). A total of 19 of the 70 products were granted a PRO claim based on a nonprimary endpoint. While nonprimary endpoints were used most often to support claims of improved signs or symptoms, nonprimary endpoints were much more likely to support claims of higher order impacts. CONCLUSIONS: Successful PRO labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels granted by the FDA show that they can indeed be candidates for PRO labeling claims as long as they are supported by evidence.

Understanding the patient experience and treatment benefits in patients with non-small-cell lung cancer with brain metastasis.

BACKGROUND: Despite the high prevalence of brain metastases (BM) secondary to non-small-cell lung cancer (NSCLC) (NSCLC/BM), patients' experiences (symptoms and impacts) are not fully understood. This study sought to understand the patient experience with NSCLC/BM and identify a patient-reported outcome (PRO) measure fit to capture the most important NSCLC/BM symptoms and impacts. METHODS: A targeted literature review was completed; the National Comprehensive Cancer Network (NCCN)/Functional Assessment of Cancer Therapy-Brain Symptom Index, 24-item version (NFBrSI-24) was identified as a relevant measure that assessed the core symptoms and impacts associated with NSCLC/BM. Qualitative interviews composed of concept elicitation and cognitive debriefing with oncologists (n = 3) and adult patients (n = 16) with NSCLC/BM were conducted to confirm the content validity and evaluate the relevance and appropriateness of the NFBrSI-24 for this condition. RESULTS: The NSCLC/BM symptoms and impacts identified in the literature and reported by oncologists and patients were consistent and captured in the NFBrSI-24. Study participants reported significant burden associated with the symptoms (commonly fatigue, headache) and impacts of NSCLC/BM. Participants indicated that the NFBrSI-24 captured their most salient experiences with NSCLC/BM and that symptom improvement or a delay in progression, as measured by the NFBrSI-24, would be meaningful. During the cognitive debriefing, participants generally indicated that the NFBrSI-24 was comprehensive and easy to understand/answer and that it assessed symptoms they considered most important to treat. CONCLUSIONS: These results suggest that the NFBrSI-24 adequately captures an appropriate measure of NSCLC/BM symptoms and impact.

A review of patient-reported outcome labels in the United States: 2006 to 2010.

OBJECTIVE: In 2004, Willke and colleagues reviewed the efficacy endpoints reported in the labels of new drugs approved in the United States from 1997 through 2002 to evaluate the use of patient-reported outcome (PRO) endpoints. Of the labels reviewed, 30% included PROs. Our study aimed to build on this work by describing the current state of PRO label claims granted for new molecular entities (and biologic license applications since February 2006 after the release of the US Food and Drug Administration (FDA) draft PRO guidance. METHODS: All new molecular entities and biologic license applications approved by the FDA from January 2006 through December 2010 were identified by using the Web page of the FDA Drug Approval Reports. For all identified products, drug approval packages and approved product labels were reviewed to identify PRO endpoint status and to determine the number and type of PRO claims. RESULTS: Of the 116 products identified, 28 (24%) were granted PRO claims; 24 (86%) were for symptoms, and, of these, 9 (38%) claims were pain related. Of the 28 products with PRO claims, a PRO was a primary endpoint for 20 (71%), all symptom related. CONCLUSIONS: The FDA continues to approve PRO claims, with 24% of new molecular entities and biologic license applications being granted. Successful PRO label claims over the past 5 years have generally supported treatment benefit for symptoms specified as primary endpoints.

Reasons for rejection of patient-reported outcome label claims: a compilation based on a review of patient-reported outcome use among new molecular entities and biologic license applications, 2006-2010.

OBJECTIVES: Previous analyses of patient-reported outcome (PRO) label claims concentrated only on successful label claims. The goal of this research was to explore the reasons why PRO label claims were denied and to compile regulatory feedback regarding the use of PROs in clinical trials. METHODS: By using the Food and Drug Administration's Drug Approval Report Web page, all new molecular entities and biologic license applications approved between January 2006 and December 2010 were identified. For identified drug products, medical review sections from publicly available drug approval packages were reviewed to identify PRO end-point status and any Study Endpoints and Label Development team comments. RESULTS: Of the 116 new molecular entities and biologic license applications with accompanying drug approval packages identified and reviewed, 44.8% of the products included PROs as part of the pivotal studies; however, only 24.1% received PRO label claims. Primary reasons for denial included issues of fit for purpose, issues of study design, data quality or interpretation, statistical issues, administrative issues, and lack of demonstrated treatment benefit. CONCLUSIONS: Based on drug approval packages, nearly half (45%) of new molecular entitity/biologic license application products in the years 2006 to 2010 included PROs in the clinical trials supporting their approval, yet this rate is not reflected by claims granted. Understanding the nature of PRO claims granted under the current regulatory guidance is important. In addition, a clear understanding of denied claims yields valuable insight into where sponsors may improve implementation of PROs in clinical trials and submission of PRO evidence to increase the likelihood of obtaining PRO label claims.

Longitudinal Trajectories of Participant- and Study Partner-Rated Cognitive Decline, in Relation to Alzheimer's Disease Biomarkers and Mood Symptoms.

Whereas discrepancies between participant- and study partner-reported cognitive concerns on the Alzheimer's disease (AD) continuum have been observed, more needs to be known regarding the longitudinal trajectories of participant- vs. study partner-reported concerns, particularly their relationship to AD biomarkers and mood symptomology. Additionally, it is unclear whether years of in-clinic data collection are needed to observe relationships with AD biomarkers, or whether more frequent, remote assessments over shorter periods of time would suffice. This study primarily sought to examine the relationships between longitudinal trajectories of participant- and study partner-rated cognitive decline and baseline biomarker levels [i.e., amyloid and tau positron emission tomography (PET)], in addition to how mood symptomatology may alter these trajectories of concerns over a 2-year period. Baseline mood was associated with longitudinal participant-rated concerns, such that participants with elevated depression and anxiety scores at baseline had decreasing concerns about cognitive decline over time (fixed estimate = -0.17, 95% CI [-0.29 to -0.05], t = -2.75, df = 457, adj. p = 0.012). A significant interaction between baseline amyloid (fixed estimate = 4.07, 95% CI [1.13-7.01], t = 2.72, df = 353, adj. p = 0.026) and tau (fixed estimate = 3.50, 95% CI [0.95-6.06], t = 2.70, df = 331, adj. p = 0.030) levels was associated with increasing study partner concerns, but not participant concerns, over time. The interaction between amyloid and study partner concerns remained significant when utilizing only the first year of concern-related data collection. Overall, these results suggest that frequent, remote assessment of study partner-reported concerns may offer additional insight into the AD clinical spectrum, as study partners appear to more accurately update their concerns over time with regard to pathology, with these concerns less influenced by participants' mood symptomatology.

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study.

Esketamine nasal spray (ESK) is indicated, in conjunction with an oral antidepressant (OAD), for the management of treatment-resistant depression (TRD) in adults. Select US-based patients from an open-label, long-term extension safety study of ESK (NCT02782104) participated in this study through semi-structured interviews. The study evaluated patient-reported early health changes related to emotional health, daily functioning, and social functioning in adults with TRD treated with ESK plus OAD. Eligible patients were responders to ESK who had begun initial ESK treatment ≤30 months before enrollment and were currently receiving ESK plus OAD. Results from 23 patients (9 men, 14 women; mean age, 46 years) were analyzed. Patients described the degree to which ESK treatment changed the effects of depression on aspects of health as either being much improved or improved (91.8%, 156/170). Key characteristics noted regarding treatment with ESK plus OAD included degree of effectiveness (n = 11), rapid onset of action (n = 7), and side-effect profile (n = 5). All patients reported being either satisfied (52%) or very satisfied (48%) with ESK plus OAD treatment. Adverse events were consistent with the known safety profile of ESK. Study insights may help prepare patients with TRD and their clinicians to anticipate potential health changes experienced with ESK.

A New Single-Item Sleep Quality Scale: Results of Psychometric Evaluation in Patients With Chronic Primary Insomnia and Depression.

STUDY OBJECTIVES: A single-item sleep quality scale (SQS) was developed as a simple and practical sleep quality assessment and psychometrically evaluated. METHODS: SQS measurement characteristics were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and morning questionnaire-insomnia (MQI) according to prespecified analysis plans in separate clinical studies of patients with insomnia and depression. Patients with insomnia (n = 70) received 4 weeks' usual care with an FDA-approved hypnotic agent; patients with depression (n = 651) received 8 weeks' active or experimental therapy. RESULTS: Concurrent criterion validity (correlation with measures of a similar construct) was demonstrated by strong (inverse) correlations between the SQS and MQI (week 1 Pearson correlation -.76) and PSQI (week 8 Goodman-Kruskal correlation -.92) sleep quality items in populations with insomnia and depression, respectively. In patients with depression, stronger correlations between the SQS and PSQI core sleep quality components versus other items supported convergent/divergent construct validity (similarity/dissimilarity to related/unrelated measures). Known-groups validity was evidenced by decreasing mean SQS scores across those who sleep normally, those borderline to having sleep problems, and those with problems sleeping. Test-retest reliability (intraclass correlation coefficient) was .62 during a 4-week period of sleep stability in patients with insomnia and .74 in stable patients with depression (1 week). Effect sizes (standardized response means) for change from baseline were 1.32 (week 1) and .67 (week 8) in populations with insomnia and depression, respectively. Mean SQS changes from baseline to week 8 convergently decreased across groups of patients with depression categorized by level of PSQI sleep quality improvement. CONCLUSIONS: The SQS possesses favorable measurement characteristics relative to lengthier or more frequently administered sleep questionnaires in patients with insomnia and depression. CLINICAL TRIAL REGISTRATION: Registry: ClincalTrials.gov, Title: Treatment of Patients With Major Depressive Disorder With MK0869, Identifier: NCT00034983, URL: https://clinicaltrials.gov/ct2/show/NCT00034983.

Development of the Observable Behaviors of Autism Spectrum Disorder Scale.

BACKGROUND: The objective of this research was to develop a caregiver-reported clinical outcome assessment (COA) measure designed to assess observable behaviors of children, ages 4 to 12 years, with autism spectrum disorder (ASD) for supporting labeling claims of treatment benefit. METHODS: Development of the measure included a review of the literature and existing instruments, conceptual disease model development, concept elicitation focus groups, item generation, and cognitive debriefing interviews. RESULTS: Predominant characteristics and behaviors of ASD identified by the literature and instrument reviews included sociability, communication deficits, stereotypy, inattention and hyperactivity, irritability, anxiety, and familial impact. In each of the 10 instruments reviewed, evidence of content validity was limited or nonexistent. Predominant themes arose across 8 major categories during concept elicitation. A total of 27 concepts were identified through focus group feedback and formed the basis for item development and cognitive pre-testing. Revisions to the items yielded a final version of a daily diary containing 21 items assessing observable behaviors and characteristics of ASD in children 4 to 12 years old. CONCLUSIONS: The Observable Behaviors of ASD Scale (OBAS) was developed as a self-administered, caregiver-reported measure containing 8 predominant themes. Items are scored on one of two 5-point ordinal categorical response scales, and the recall period for each item is "the past 24 hours." This research provides evidence that the OBAS is content valid for assessing treatment benefit, which was found to be lacking in other instruments.

Payer Perspectives on Patient-Reported Outcomes in Health Care Decision Making: Oncology Examples.

BACKGROUND: Health authorities and payers increasingly recognize the importance of patient perspectives and patient-reported outcomes (PROs) in health care decision making. However, given the broad variety of PRO endpoints included in clinical programs and variations in the timing of PRO data collection and country-specific needs, the role of PRO data in reimbursement decisions requires characterization. OBJECTIVES: To (a) determine the effect of PRO data on market access and reimbursement decisions for oncology products in multiple markets and (b) assess the effect of PRO data collected after clinical progression on payer decision making. METHODS: A 3-part assessment (targeted literature review, qualitative one-on-one interviews, and online survey) was undertaken. Published literature was identified through searches in PubMed/MEDLINE and Embase. In addition, a targeted search was conducted of health technology assessment (HTA) agency websites in the United States, the United Kingdom, France, and Germany. Qualitative one-on-one interviews were conducted with 16 payers from the RTI Health Solutions global advisory panel in 14 markets (Australia, Brazil, France, Germany, Italy, South Korea, Netherlands, Poland, Spain, Sweden, Taiwan, Turkey, the United Kingdom, and the United States [n = 3]). Of the 200 payers and payer advisors from the global advisory panel invited to participate in the online survey, 20 respondents (China, France, Germany, Spain [n = 2], Taiwan, the United Kingdom, and the United States [n = 13]) completed the survey, and 6 respondents (Australia, South Korea, and the United States [n = 4]) partially completed the survey. RESULTS: Reviews of the literature and publicly available HTAs and reimbursement decisions suggested that HTA bodies and payers have varying experience with and confidence in PRO data. Payers participating in the survey indicated that PRO data may be especially influential in oncology compared with other therapeutic areas. Payers surveyed offered little differentiation by cancer type in the importance of PRO data but felt that it was most important to collect PRO data in phase 3 and postmarketing studies. Payers surveyed also anticipated an increasing significance for PRO data over the next 5-10 years. Characteristics of PRO data that maximize influence on payer decision making were reported to be (a) quality, well-controlled, and transparent PRO evidence; (b) psychometric validation of the PRO measure in targeted populations; and (c) publication in peer-reviewed journals. In markets with decentralized health care decision making, PRO data currently have more influence at the local level. Inclusion of PRO data in cancer treatment guidelines is key for centralized markets. Payers surveyed generally considered collecting PRO data postprogression to be useful. Of the 16 interviewees, 11 indicated that it is worthwhile to collect PRO data postprogression and that positive PRO data may support continued therapy at the physician's discretion upon regulatory approval, even in progressive disease. CONCLUSIONS: PRO data may help to differentiate treatments, particularly after clinical progression in oncology. Payers worldwide recognize high-quality PRO data as a key component of their decision-making process and anticipate the growing importance of PRO data in the future. DISCLOSURES: This study and preparation of this article were funded by Novartis Pharmaceuticals. This research was performed under a research contract between RTI Health Solutions and Novartis Pharmaceuticals. Brogan, Hogue, Demuro, and Barrett are employees of RTI Health Solutions. D'Alessio and Bal are employees of Novartis Pharmaceuticals. Study concept and design were contributed by DeMuro, Barrett, Bal, and Hogue. Brogan and Hogue took the lead in data collection, assisted by DeMuro and Bal. Data interpretation was performed by Brogan and Hogue, assisted by the other authors. The manuscript was written by D'Alessio and Brogan, along with the other authors, and revised primarily by Brogan, along with Hogue and assisted by the other authors. The abstract for this article was presented as a research poster at the following meetings: Hogue SL, Brogan A P, De Muro C, D'Alessio D, Bal V. Patient-reported outcomes (PRO) in post-progression oncology: implications in health technology assessments and payer decision making. Poster presented at the ISPOR 18th Annual European Meeting; November 7-11, 2015. Milan, Italy. Hogue SL, Brogan AP, De Muro C, D'Alessio D, Bal V. Influence of patient-reported outcomes (PRO) on market access decisions in markets with centralized healthcare systems. Poster presented at the ISPOR 18th Annual European Meeting; November 7-11, 2015. Milan, Italy. Hogue SL, Brogan AP, De Muro C, Barrett A, D'Alessio D, Bal V. Influence of patient-reported outcomes on market access decisions in decentralized markets (Brazil, Italy, Spain and the United States). Poster presented at the ISPOR 20th Annual Meeting; May 16-20, 2015. Philadelphia PA. Hogue SL, Brogan A P, De Muro C, Barrett A, McLeod L, D'Alessio D, et al. Payer Perspectives of Patient-Reported Outcomes Data: An Online Assessment. Poster presented at the ISOQOL 22nd Annual Meeting; October 21-24, 2015. Vancouver, British Columbia, Canada.

Development of a novel observer-reported outcome measure for the assessment of Respiratory Syncytial Virus (RSV) infection symptoms in pediatric clinical trials.

BACKGROUND: Respiratory syncytial virus (RSV) is a seasonal infection affecting most children by 2 years of age and the leading cause of lower respiratory tract infection requiring hospitalization in infants. Novel antiviral medications are in development to improve the clinical outcomes of RSV; however, no clinical outcome assessments (COAs) for RSV have been developed in alignment with the United States Food and Drug Administration patient-reported outcome guidance to assist in the evaluation of new therapies. To address this need, an observer-reported outcome (ObsRO) measure designed to assess observable RSV symptoms was created. METHODS: The literature was reviewed to evaluate existing COAs and identify constructs of interest. Individual caregiver interviews elicited concepts that informed item development, and candidate items were subsequently evaluated in two rounds of cognitive testing. Separate cohorts of caregivers of RSV-infected nonhospitalized and hospitalized infants participated. Therapeutic-area experts provided input throughout the instrument development process. RESULTS: Caregivers of 39 children < 24 months old with RSV (31 nonhospitalized, 8 hospitalized) participated in in-depth, individual interviews during concept elicitation and cognitive debriefing, resulting in 21 concepts identified as potentially observable and relevant to young children with RSV. The item pool was reduced to 12 cardinal symptoms and behavior impacts reported to be directly observable by caregivers, with 10 daytime and 9 nighttime symptoms to capture diurnal variation in severity. CONCLUSIONS: The RSV Caregiver Diary assesses RSV symptom severity and change from the parent or caregiver perspective in a standardized manner to measure treatment benefit. Following psychometric evaluation and refinement, this tool is expected to be suitable for assisting in the clinical development of RSV therapeutics.

Psychometric evaluation of a caregiver diary for the assessment of symptoms of respiratory syncytial virus.

BACKGROUND: There are no clinical outcome assessment (COA) tools developed in accordance with Food and Drug Administration (FDA) guidance suitable for the evaluation of symptoms associated with respiratory syncytial virus (RSV) infection among infants. The Gilead RSV Caregiver Diary (GRCD) is being developed to fulfill this need; the present research evaluates the GRCD and documents its reliability, validity, and responsiveness among children < 24 months of age with acute RSV infection. METHODS: A prospective, observational study was conducted in the United States during the 2014-2015 northern hemisphere winter season. Subjects were < 24-month, full-term, previously healthy infants with confirmed RSV infection and ≤5 days of symptoms. The GRCD was completed twice daily for 14 days by caregivers. Additional data were collected during the initial visit, subsequent visits, and end-of-study interview. Test-retest reliability (kappa and intraclass correlation coefficients [ICCs]), construct validity (correlations and factor analyses), discriminating ability (analyses of variance and chi-square), and responsiveness (effect sizes and standardized response means) were evaluated. RESULTS: A total of 103 subjects were enrolled (mean age 7.4 ± 5.3 months). GRCD items were grouped into different subscales according to question content, which, with the exception of the behavior impact domain (ICC = 0.43), demonstrated internal consistency (alphas = 0.78-0.94) and test-retest reliability (ICCs = 0.77-0.94). Hypothesized correlations with parent global ratings of RSV severity ranged from 0.45 to 0.70 and provided support for construct validity. Support for discriminating ability was limited. Effect sizes ranged from - 1.48 to - 4.40, indicating the GRCD was responsive to change. CONCLUSIONS: These psychometric analyses support the validity, reliability, and responsiveness of the GRCD for assessing RSV symptoms in children < 24 months of age.

Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

PURPOSE: To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. METHODS: FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. RESULTS: Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. CONCLUSION: Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.

Mortality and Causes of Death in Patients with Sporadic Inclusion Body Myositis: Survey Study Based on the Clinical Experience of Specialists in Australia, Europe and the USA.

BACKGROUND: There is a paucity of data on mortality and causes of death (CoDs) in patients with sporadic inclusion body myositis (sIBM), a rare, progressive, degenerative, inflammatory myopathy that typically affects those aged over 50 years. OBJECTIVE: Based on patient records and expertise of clinical specialists, this study used questionnaires to evaluate physicians' views on clinical characteristics of sIBM that may impact on premature mortality and CoDs in these patients. METHODS: Thirteen physicians from seven countries completed two questionnaires online between December 20, 2012 and January 15, 2013. Responses to the first questionnaire were collated and presented in the second questionnaire to seek elaboration and identify consensus. RESULTS: All 13 physicians completed both questionnaires, providing responses based on 585 living and 149 deceased patients under their care. Patients were reported to have experienced dysphagia (60.2%) and injurious falls (44.3%) during their disease. Over half of physicians reported that a subset of their patients with sIBM had a shortened lifespan (8/13), and agreed that bulbar dysfunction/dysphagia/oropharyngeal involvement (12/13), early-onset disease (8/13), severe symptoms (8/13), and falls (7/13) impacted lifespan. Factors related to sIBM were reported as CoDs in 40% of deceased patients. Oropharyngeal muscle dysfunction was ranked as the leading feature of sIBM that could contribute to death. The risk of premature mortality was higher than the age-matched comparison population. CONCLUSIONS: In the absence of data from traditional sources, this study suggests that features of sIBM may contribute to premature mortality and may be used to inform future studies.