Longitudinal investigation of the factor structure of the Parkinson's disease activities of daily living, interference and dependence instrument.

The Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument© (PD-AID) is a patient-reported outcome (PRO) instrument, recently developed to assess the clinical benefit of Parkinson's Disease (PD) treatment. The PD-AID consists of morning and evening assessments, administered daily. To benefit from the full set of the repeated observations over time, analytic approaches that account for both within- and between-individual variability are required. The current study aimed to employ the advantages of exploratory Multilevel Factor Analysis (MFA) on data collected from 93 participants with moderate to advanced PD, currently using and responding to Levodopa (L-Dopa), who completed the PD-AID twice daily as part of a prospective, non-intervention, observational study for ~28 days. Average daily completion rates were comparable for the Morning and the Evening PD-AID (78% and 74%, respectively). The intraclass correlation coefficients for the Morning and Evening PD-AID items were in the range of 0.70-0.90, with an average of 0.81 for the Morning PD-AID items and 0.83 for the Evening PD-AID items, suggesting that most variability (81%-83%) in responses was due to between-individual variability. For the Morning PD-AID, one factor (including nine out of 10 Morning PD-AID items) emerged at the between-individual level and four factors (core physical actions, basic self-care activities, feeding, and interference & dependence) at the within-individual level. For the Evening PD-AID, there were four between-individual factors (basic activities of daily living ADLs, life interference, impact on planning, and emotional consequences) and five within-individual factors (basic ADLs, toileting, life interference, medication planning, and emotional impact). The factors had high reliability.

Meaningful Changes in What Matters to Individuals with Vitiligo: Content Validity and Meaningful Change Thresholds of the Vitiligo Area Scoring Index (VASI).

INTRODUCTION: This study explored patients' and dermatologists' priority outcomes for treatment to address, clinical outcome assessments (COA) for use in vitiligo clinical trials, and perceptions of within-patient meaningful change in facial and total body vitiligo. METHODS: Semistructured, individual, qualitative interviews were conducted with patients living with non-segmental vitiligo in the USA and with expert dermatologists in vitiligo. Concept elicitation discussions included open-ended questions to identify patient priority outcomes. Vitiligo COAs were reviewed by dermatologists. Tasks were completed by patients to explore their perceptions of meaningful changes in vitiligo outcomes; dermatologists' opinions were elicited. Data were analyzed using thematic methods; meaningful change tasks were descriptively summarized. RESULTS: Individuals with vitiligo (N = 60) included adults (n = 48, 63% female) and adolescents (n = 12, 67% female). All Fitzpatrick Skin Types were represented. Eight (13%) were first- or second-generation immigrants to the USA. Expert dermatologists (N = 14) participated from the USA (n = 8), EU (n = 4), India (n = 1), and Egypt (n = 1). All individuals with vitiligo reported experiencing skin depigmentation; an observable clinical sign of vitiligo. Most confirmed that lesion surface area (n = 59/60, 98%) and level of pigmentation (n = 53/60, 88%) were important to include in disease assessments. Following an explanation, participants (n = 49/60, 82%) felt that the Facial Vitiligo Area Scoring Index (F-VASI) measurement generally made sense and understood that doctors would use it to assess facial vitiligo. Most participants felt that a 75% (n = 47/59, 80%) or 9 0% improvement in their facial vitiligo would be indicative of treatment success (n = 55/59, 93%). In the context of evaluating a systemic oral treatment for vitiligo, dermatologists perceived a 75% improvement on the F-VASI as successful (n = 9/14, 64%). Regarding the Total VASI (T-VASI) score, n = 30 participants considered 33% improvement as treatment success; an additional n = 10 endorsed 50% improvement and a further n = 5 endorsed 75% improvement. Clinicians most frequently identified 50% (n = 6/14, 43%) or 75% (n = 4/14, 29%) improvement in T-VASI as successful. CONCLUSION: Repigmentation is a priority outcome for patients. The VASI was considered an appropriate tool to assess the extent of vitiligo. A minimum 75% improvement from baseline in the F-VASI and minimum 50% improvement from baseline in the T-VASI were identified as within-patient clinically meaningful thresholds.

The Measurement Performance of the Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument.

Parkinson's disease is a neurodegenerative disease that can be associated with motor fluctuations that result in substantial negative impact to an individual's activities of daily living. Understanding the patient's perspective about the impact of Parkinson's disease therapies is an important part of drug development and shared treatment decision-making. The objective of this research was to examine the structure, scoring, internal consistency, test-retest reliability, and concurrent and known groups validity of the Parkinson's Disease Activities of Daily Living, Interference and Dependence (PD-AID) instrument, a new, patient-reported outcomes instrument, developed to assess the clinical benefit of Parkinson's disease treatment from the patient's perspective. This was a non-interventional study among persons with mild-to-moderate Parkinson's disease currently using and responding to L-Dopa. The structure of the measure was confirmed applying item response theory to data from baseline, supporting 4 candidate scores. Baseline Patient Global Impression of Severity ratings facilitated known-groups analysis. Data from all participants were used to estimate test-retest reliability. Concurrent validity was assessed using correlations with related measures. Participants (n = 94) were mean age 69 years (mean time since diagnosis 6.9 years); 34 experienced L-Dopa-related dyskinesia. Psychometric models supported 4 candidate scoring regimes for the PD-AID. All exhibited adequate reliability and validity characteristics and strong internal consistency. Correlations with reference measures were in the expected direction and range of magnitude. Analyses supported the PD-AID as fit-for-purpose, producing psychometrically sound scores. Further research to confirm the measurement properties of the PD-AID in an expanded sample and to establish thresholds for meaningful score changes is recommended.

Memory-Assisted Global Impression of Change (MAGIC).

BACKGROUND: The United States Food and Drug Administration is developing a series of patient-focused drug development guidance documents regarding the collection of patient experience data, including methods for understanding treatment benefit from the patient perspective. The goal of this research was to investigate the concern that the global impression of change scale is subject to recall error and thus not optimal for use as an anchor for estimating meaningful within-person change thresholds. We explored whether memory assistance for recalling baseline status would make a difference in how study participants diagnosed with Parkinson's disease (PD) responded to a patient global impression of change (PGIC) and patient global impression static (PGIS) item. METHODS: The research was completed as a secondary objective of a non-interventional 28-day (± 4 days) study among persons with Parkinson's disease and associated motor fluctuations. At baseline, participants completed the PGIS and then recorded a voice message to their future self in which they spoke about how their PD had affected their "day-to-day" activities over the preceding few days. At the final visit, the PGIC and PGIS were completed, after which participants listened to their memory assistance voice recording, and then completed both items for a second time to calculate a memory-assisted global impression static and change scores (MAGIS and MAGIC, respectively). Spearman correlations (ρ) were examined for the pre- and post- memory assistance evaluations. The degree of agreement pre- and post-memory assistance was quantified using the Shrout & Fleiss intraclass correlation coefficient (ICC [2,1]). An ICC(2,1) ≥ 0.7 served as the pre-specified criterion of acceptability for both the ρ and ICC(2,1) values. RESULTS: Participants in the analytic sample were mean age 68.7 and mostly white (91.7%) and male (69.4%). The average length of time since PD diagnosis was 6.5 years. Correlations between the PGIS and MAGIS were ρ = 0.88; correlations between PGIC and MAGIC were ρ = 0.86. The estimated ICC(2,1) for both the PGIS/MAGIS and PGIC/MAGIC exceeded target success criterion of ICC(2,1) ≥ 0.70. CONCLUSION: Our results show that the MAGIS/MAGIC methodology is feasible and that memory assistance did not substantially alter the PGIS/PGIC scores at the final visit.

Payer perceptions on the use of patient-reported outcomes in oncology decision making.

BACKGROUND: In oncology, especially with accelerated regulatory approvals and niche populations, US payers appreciate all evidence that can help support formulary decision making, including evidence beyond traditional safety and efficacy data from clinical trials. Research suggests payers incorporate patient-reported outcome (PRO) evidence in their decision making and expect the importance of PRO evidence to grow. Greater understanding on payers' use of PRO information in oncology is needed. OBJECTIVE: To assess US payer perceptions regarding the use of PRO evidence in informing oncology formulary decision making. METHODS: A multidisciplinary steering committee involving a measurement specialist, health economics and outcomes research experts, and payers developed a survey containing single-answer, multiple-answer, and free-response questions. The pilot survey was tested at a mini-advisory board with 5 US payers and revised based on feedback. In February 2020, the survey was distributed to 221 US payers through the AMCP Market Insights program and 10 additional payer panelists who were invited to discuss and contextualize the survey results. Results were presented primarily as frequencies of responses and evaluated by plan size, type of health plan, and geography (regional vs national). Differences in categorical data responses were compared using Pearson chi-square or Fisher exact tests. Two-tailed values are reported and a P value less than or equal to 0.05 was used to indicate statistical significance. RESULTS: Overall, 106 of 231 payers (45.9%) completed the survey; 45.5% represented small plans (< 1 million lives), and 54.5% represented large plans (≥ 1 million lives). Respondents were largely pharmacists (89.9%), with 55.6% of all respondents indicating their job was pharmacy administrator. The majority of payers (60.0% of small health plans and 57.8% of large plans) felt PRO evidence from clinical trials is useful. Similarly, the majority of payers (57.8% of small plans and 51.9% of large plans) felt PRO evidence from real-world studies is useful. Almost half (47.1%) suggested formulary review would be influenced by a lack of PRO evidence from oncology clinical trials either somewhat, much, or a great deal. Most payers (78.2%) thought PRO evidence is useful for providing additional context for safety of oncology therapies. More than one-third of payers (34.3%) valued PRO evidence when comparing 2 similar therapies, and 51.5% felt PRO evidence may help in measuring value for value-based agreements. Panelists indicated PRO evidence can be useful for developing treatment pathways for addressing health-related quality of life, informing provider-patient dialogues, and defining progression-free survival length and quality. CONCLUSIONS: US payers view PRO evidence from both clinical trials and real-world studies as useful for supplementing traditional clinical trial data when making oncology formulary decisions and for refining treatment pathways and care delivery models. Manufacturers of oncology therapies should collect and consider leveraging PRO evidence from both settings when engaging with US payers. DISCLOSURES: Pfizer provided funding for this research, and employees of Pfizer contributed to the development of the survey instrument, were involved in the interpretation of the data, and contributed to the discussion and output as authors. Biskupiak, Oderda, and Brixner are managers of Millcreek Outcomes Group and were paid as consultants on this project. Burgoyne was a consultant for Pfizer on this project. Arondekar, Deal, and Niyazov are employees of Pfizer and own Pfizer stock. Qwek was an employee of Pfizer at the time of this project and owns Pfizer stock.

Development of a New Patient-Reported Medication Adherence Instrument: Concerns Influencing Medication Adherence.

PURPOSE: The purpose of this research was to conceptualize and develop a tool for identifying persons who are, or are likely to be, non-adherent to medications prescribed by their healthcare provider(s) by identifying concerns that patients have regarding their treatments. PATIENTS AND METHODS: The target populations were persons diagnosed with atrial fibrillation or osteoarthritis, who were prescribed anticoagulants or over-the-counter or prescription pain medications, respectively. In this two-stage, multi-year, qualitative research study, relevant concepts were explored, confirmed and refined. The focus was on non-adherence due to active (thus potentially modifiable) patient decisions to forego taking medications as prescribed. RESULTS: The most common concerns among participants with atrial fibrillation were medication-related side effects and fear of bleeding. Participants with osteoarthritis were most concerned about short-term stomach problems and long-term kidney and liver side effects. The Concerns Influencing Medication Adherence (CIMA) instrument was developed based on these concerns and those identified in the literature. It is comprised of 16 items: a core set of 11 items potentially applicable to multiple disease states, 3 items specific to atrial fibrillation, and 2 items unique to osteoarthritis. The instrument is intended to be completed electronically, and publicly available for use in direct patient care in the United States or in population health management. CONCLUSION: To our knowledge, this is the first instrument focused on medication adherence that includes documented details of patient input as recommended by the United States Food and Drug Administration guidance. Patient input is considered a key component of content validity. In this research, for example, the concerns that patients have regarding their treatments can be expected to have affected past medication adherence and can potentially impact future adherence. Although applicability outside atrial fibrillation or osteoarthritis was not assessed, the general items may be useful in assessing adherence in other chronic diseases.

Development of the Alopecia Areata Patient Priority Outcomes Instrument: A Qualitative Study.

INTRODUCTION: Although alopecia areata (AA) profoundly impacts patients' physical appearance, emotional state, and daily activities, no treatment approved for AA currently exists. Patient-reported outcome (PRO) instruments currently used to capture patients' AA experiences do not meet the requirements to support claims of treatment benefit as described in the US Food and Drug Administration's 2009 PRO guidance. Our objective was to explore the consequences and priority treatment outcomes among individuals with AA and develop a PRO measure consistent with regulatory requirements that assesses these priorities and represents clinical benefit from the AA patient perspective. METHODS: Targeted literature and instrument reviews informed an initial concept set. Concept elicitation interviews with 20 adults with AA confirmed the relevance and importance of the initial concepts, identified additional relevant concepts, and informed an AA consequence model. Thematic analysis yielded a draft item pool, which was evaluated through two iterative rounds of cognitive debriefing interviews with 16 patients with AA (9 adults; 7 adolescents). RESULTS: Hair loss was the primary consequence of importance to patients with AA. Patients emphasized the need to differentiate hair loss by location: scalp, eyebrows, eyelashes, and body. Consequences of AA include difficulty conducting daily activities, particularly outdoor activities and exercise, and emotional impacts such as sadness, frustration, and negative self-image. Following cognitive debriefing interviews, 11 items were included to form the Alopecia Areata Patient Priority Outcome (AAPPO), assessing AA-related symptoms and impacts over the past week. CONCLUSIONS: The AAPPO is a novel, content-valid PRO that captures the consequences of AA of the highest priority to patients.

The atopic dermatitis itch scale: development of a new measure to assess pruritus in patients with atopic dermatitis.

Introduction: Pruritus is the primary symptom of atopic dermatitis (AD). The objective of this study was to develop a patient-reported outcome (PRO) instrument for daily administration in clinical trials to measure AD-related itch in adolescents and adults that would meet the standards described in the US Food and Drug Administration's (FDA's) PRO Guidance.Materials and methods: Six focus groups were conducted with 49 patients with AD (32 adults; 17 adolescents). Three iterative rounds of cognitive debriefing interviews were conducted in 26 patients with AD (17 adults; 9 adolescents) to pretest and refine the instrument.Results: AD-related itching was considered the most bothersome AD symptom by nearly two-thirds of the focus group participants. The items in the initial version of the instrument, named the Atopic Dermatitis Itch Scale (ADIS), were developed to reflect concepts most relevant to the assessment of itching as described during the focus groups. Based on results of the cognitive debriefing interviews, an 8-item final version of the ADIS was created.Conclusion: The ADIS is a content valid PRO instrument addressing the concepts critical to the measurement of AD-related itching. To our knowledge, it is the first instrument developed to assess AD-related itch in patients as young as 12 years following the recommendations of the PRO Guidance.

The Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument.

BACKGROUND: Individuals with Parkinson's disease often experience periods of off time when their motor symptoms are poorly controlled, significantly impacting their lives. OBJECTIVES: To identify the consequences of motor fluctuations on day-to-day activities and areas of unmet treatment priority among individuals with moderate to advanced Parkinson's disease, to assess whether existing patient-reported outcome instruments adequately capture these consequences and priorities, and based on these evaluations, to adapt an existing or develop a new instrument. METHODS: The research was conducted in 2 stages: concept exploration and content confirmation. Concept exploration included direct input from individuals with Parkinson's disease representing the intended context of use via concept elicitation interviews. Content confirmation and item refinement was achieved through 5 rounds of cognitive debriefing. Final rounds of cognitive debriefing also included usability testing of the draft instrument for electronic data capture. RESULTS: Concept elicitation interviews were conducted among 29 individuals with Parkinson's disease (55% male; mean age 60.8 years). Concept saturation was achieved quickly with more than 90% of concepts identified by the end of the 16th interview. None of the existing outcome instruments were found to be fit for purpose in the intended context of use; therefore, a new instrument was developed. After 5 rounds, cognitive debriefing participants indicated clear and consistent interpretation of the items. CONCLUSIONS: Evidence from this study supports the content validity of the Parkinson's Disease Activities of Daily Living, Interference and Dependence Instrument as the basis of a clinical trial endpoint for capturing priority treatment benefit outcomes to individuals with moderate to advanced Parkinson's disease experiencing motor fluctuations.

Use and Value of the 7-Item Binge Eating Disorder Screener in Clinical Practice.

OBJECTIVE: To evaluate physician knowledge of and attitudes about binge-eating disorder (BED) and the value and ease-of-use of the 7-item Binge Eating Disorder Screener (BEDS-7) in clinical practice. METHODS: Two internet surveys (wave 1: April 15-May 6, 2015; wave 2: August 19-25, 2015) were administered to primary care physicians serving adults (PCPs-adults) and psychiatrists. Wave 1 invitees were US-based physicians spending ≥ 50% of their time in direct patient care and reporting "no" to "some to average" experience with eating-disorder patients. Respondents completing wave 1 qualified for wave 2. RESULTS: Among the 1,047 physicians who responded, 313 did not meet at least 1 of the screening criteria, including 3.15% of respondents who spent < 50% of their time in direct patient care. Overall, 122 PCPs-adults and 123 psychiatrists completed both waves. Physician groups spent similar mean ± SD amounts of time providing direct patient care (PCPs-adults: 94.66% ± 8.4%, psychiatrists: 91.15% ± 12.2%). Based on composite scores, BED knowledge increased from wave 1 to wave 2 in PCPs-adults (P < .001) and psychiatrists (P < .05). Composite scores pertaining to knowledge of and comfort with diagnosing and treating BED were lower for PCPs-adults than psychiatrists in both waves (all P < .001). Based on wave 2 responses, the BEDS-7 was used by 32.0% of PCPs-adults and 26.8% of psychiatrists. All BEDS-7 users (100%) indicated the screener was "very" or "somewhat" valuable, and nearly all users (psychiatrists: 100%, PCPs-adults: 97.4%) reported it was "very" or "reasonably" easy to use. BEDS-7 users reported that important uses of the screener included assisting clinicians in identifying BED patients and encouraging/initiating doctor-patient discussions about BED. CONCLUSIONS: These results support the utility of the BEDS-7 in clinical practice, with BEDS-7 users reporting that it is a highly valued and easy-to-use screener. Furthermore, both PCPs-adults and psychiatrists acknowledged the importance of being knowledgeable about BED.

Challenges of Developing an Observable Parent-Reported Measure: A Qualitative Study of Functional Impact of ADHD in Children.

BACKGROUND: Informant-reported outcome measures, usually completed by parents, are often administered in pediatric clinical trials with the intention of collecting data to support claims in a medical product label. Recently, there has been an emphasis on limiting these measures to observable content, as recommended in the US Food and Drug Administration guidance on patient-reported outcomes. This qualitative study explores the concept of observability using the example of childhood attention deficit/hyperactivity disorder (ADHD). METHODS: Concept elicitation interviews were conducted with children (aged 6-12 years) diagnosed with ADHD and parents of children with ADHD to identify concepts for a potential parent-reported measure of functional impact of childhood ADHD. The observability of each concept was considered. RESULTS: Of the 30 parents (90% females; mean age = 42.0 years), 24 had a child who was also interviewed (87.5% males; mean age = 9.6 years). Areas of functional impact reported by parents and/or children included the following: 1) functioning within the home/family, 2) academic performance, 3) school behavior, 4) social functioning, 5) emotional functioning, and 6) decreased self-efficacy. Parents cited many examples of direct observation at home, but opportunities for observation of some important areas of impact (e.g., school behavior and peer relationships) were limited. CONCLUSIONS: Findings illustrate the substantial functional impairment associated with childhood ADHD while highlighting the challenges of developing informant-reported outcome measures limited to observable content. Because ADHD has an impact on children's functioning in a wide range of contexts, a parent-report measure that includes only observable content may fail to capture important aspects of functional impairment. Approaches for addressing this observability challenge are discussed.

Development of the Impact of Juvenile Metachromatic Leukodystrophy on Physical Activities scale.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a rare disease with three forms based on the age at onset of signs and symptoms. The objective of this study was to develop a caregiver-reported clinical outcome assessment that measures impairments in physical functioning related to activities of daily living in patients with juvenile MLD. METHODS: A targeted literature review and exploration of proprietary research, including a conceptual model, were conducted. Concept elicitation interviews were conducted to elicit additional concepts related to impairments in patients' physical functioning with caregivers of five individuals with juvenile MLD. Based on the research review and concept elicitation interviews, the conceptual model was updated and the Impact of Juvenile Metachromatic Leukodystrophy on Physical Activities (IMPA) scale draft items were created. Cognitive debriefing interviews were conducted with six additional caregivers to finalize the conceptual model and to refine the IMPA scale. RESULTS: Initially, 17 potentially important concepts were identified and addressed in the draft IMPA scale. Following the cognitive debriefing interviews, 15 activities/items remained: brush teeth, comb/brush hair, bathe/shower, dress self, eat, drink, use pencil/crayon, sit upright, use toilet, get on/off toilet, walk, use stairs, get in/out of bed, get in/out of chair/wheelchair, and get in/out of vehicle. Items that did not uniquely contribute to the purpose of the instrument were removed. CONCLUSION: The IMPA scale, developed according to regulatory standards, provides a means of detecting changes in activities of daily living in individuals with juvenile MLD and can hence be used in future studies to measure benefits of therapeutic interventions.

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.

Patient Voice in Rare Disease Drug Development and Endpoints.

While planning for a successful clinical trial in a prevalent condition is no trivial orchestration, even more complicated is the coordination of novel, delicate and critical operational components necessary for the successful conduct of clinical trials of rare disease (RD). We highlight some of the inherent and practical challenges to conducting clinical trials and selecting or developing endpoints for RD and the importance of including the patient voice or perspective. These challenges include the lack of regulatory precedent for proposed endpoints, a void of available measures, little or no published literature or natural history information, the practicalities of obtaining access to patients, and the appropriateness of placebo-controlled trials. As part of our review, we include practical considerations for addressing these issues along with a regulatory perspective regarding potential logistic and methodologic challenges. We conclude that the patient perspective is a critical component in defining treatment benefit and in interpreting the meaningfulness of a change (or lack thereof). Engaging with patients is needed at multiple steps along the long road of drug discovery.

Development of the 7-Item Binge-Eating Disorder Screener (BEDS-7).

OBJECTIVE: Develop a brief, patient-reported screening tool designed to identify individuals with probable binge-eating disorder (BED) for further evaluation or referral to specialists. METHODS: Items were developed on the basis of the DSM-5 diagnostic criteria, existing tools, and input from 3 clinical experts (January 2014). Items were then refined in cognitive debriefing interviews with participants self-reporting BED characteristics (March 2014) and piloted in a multisite, cross-sectional, prospective, noninterventional study consisting of a semistructured diagnostic interview (to diagnose BED) and administration of the pilot Binge-Eating Disorder Screener (BEDS), Binge Eating Scale (BES), and RAND 36-Item Short-Form Health Survey (RAND-36) (June 2014-July 2014). The sensitivity and specificity of classification algorithms (formed from the pilot BEDS item-level responses) in predicting BED diagnosis were evaluated. The final algorithm was selected to minimize false negatives and false positives, while utilizing the fewest number of BEDS items. RESULTS: Starting with the initial BEDS item pool (20 items), the 13-item pilot BEDS resulted from the cognitive debriefing interviews (n = 13). Of the 97 participants in the noninterventional study, 16 were diagnosed with BED (10/62 female, 16%; 6/35 male, 17%). Seven BEDS items (BEDS-7) yielded 100% sensitivity and 38.7% specificity. Participants correctly identified (true positives) had poorer BES scores and RAND-36 scores than participants identified as true negatives. CONCLUSIONS: Implementation of the brief, patient-reported BEDS-7 in real-world clinical practice is expected to promote better understanding of BED characteristics and help physicians identify patients who may have BED.

A review of empirical research related to the use of small quantitative samples in clinical outcome scale development.

INTRODUCTION: There has been a notable increase in the advocacy of using small-sample designs as an initial quantitative assessment of item and scale performance during the scale development process. This is particularly true in the development of clinical outcome assessments (COAs), where Rasch analysis has been advanced as an appropriate statistical tool for evaluating the developing COAs using a small sample. METHODS: We review the benefits such methods are purported to offer from both a practical and statistical standpoint and detail several problematic areas, including both practical and statistical theory concerns, with respect to the use of quantitative methods, including Rasch-consistent methods, with small samples. CONCLUSIONS: The feasibility of obtaining accurate information and the potential negative impacts of misusing large-sample statistical methods with small samples during COA development are discussed.

Development of a Symptom-Based Patient-Reported Outcome Instrument for Functional Dyspepsia: A Preliminary Conceptual Model and an Evaluation of the Adequacy of Existing Instruments.

OBJECTIVES: The aim was to document, from the perspective of the empirical literature, the primary symptoms of functional dyspepsia (FD), evaluate the extent to which existing questionnaires target those symptoms, and, finally, identify any missing evidence that would impact the questionnaires' use in regulated clinical trials to assess treatment efficacy claims intended for product labeling. METHODS: A literature review was conducted to identify the primary symptoms of FD and existing symptom-based FD patient-reported outcome (PRO) instruments. Following a database search, abstracts were screened and articles were retrieved for review. The primary symptoms of FD were organized into a conceptual model and the PRO instruments were evaluated for conceptual coverage as well as compared against evidentiary requirements presented in the FDA's PRO Guidance for Industry. RESULTS: Fifty-six articles and 16 instruments assessing FD symptoms were reviewed. Concepts listed in the Rome III criteria for FD (n = 7), those assessed by existing FD instruments (n = 34), and symptoms reported by patients in published qualitative research (n = 6) were summarized in the FD conceptual model. Except for vomiting, all of the identified symptoms from the published qualitative research reports were also specified in the Rome III criteria. Only three of the 16 instruments, the Dyspepsia Symptom Severity Index (DSSI), Nepean Dyspepsia Index (NDI), and Short-Form Nepean Dyspepsia Index (SF-NDI), measure all seven FD symptoms defined by the Rome III criteria. Among these three, each utilizes a 2-week recall period and 5-point Likert-type scale, and had evidence of patient involvement in development. Despite their coverage, when these instruments were evaluated in light of regulatory expectations, several issues jeopardized their potential qualification for substantiation of a labeling claim. CONCLUSIONS: No existing PRO instruments that measured all seven symptoms adhered to the regulatory principles necessary to support product labeling. As such, the development of a new FD symptom PRO instrument is supported.

Patient-Centered Research to Support the Development of the Symptoms of Major Depressive Disorder Scale (SMDDS): Initial Qualitative Research.

BACKGROUND: Content valid, patient-reported outcome (PRO) measures of major depressive disorder (MDD) symptoms are needed to assess MDD treatment benefit. While a range of questionnaires are currently available to evaluate aspects of depression from the patient's perspective, their comprehensiveness and qualitative development histories are unclear. OBJECTIVE: The objective of this study was to describe the process and results of the preliminary qualitative development of a new symptom-based PRO measure intended to assess treatment benefit in MDD clinical trials. METHODS: Qualitative interviews were conducted with adult MDD patients in the USA who recently experienced a major depressive episode. Experienced interviewers conducted concept elicitation (CE) and cognitive interviews using semi-structured interview guides. The CE interview guide was used to elicit spontaneous reports of symptom experiences along with probing to further explore and confirm concepts. The cognitive interview guide was developed to evaluate concept relevance, understandability, and structure of the draft items, and to facilitate further instrument refinement. RESULTS: Forty patients participated in the CE interviews. A total of 3022 symptom codes, representing 84 different concepts were derived from the transcripts. Data from the CE interviews were considered alongside existing literature and clinical expert opinion during an item-generation process, leading to development of a preliminary version of the Symptoms of Major Depressive Disorder Scale (SMDDS). Fifteen patients participated in three waves of cognitive interviews, during which the SMDDS was further refined. CONCLUSIONS: The SMDDS is a 35-item PRO measure intended for use as an endpoint in MDD clinical trials to support medical product labeling. The SMDDS uses a 7-day recall period and verbal rating scales. It was developed in accordance with the US Food and Drug Administration (FDA)'s PRO Guidance and best practices. Qualitative interviews have provided evidence for content validity. Future quantitative studies will confirm the SMDDS's measurement properties and support FDA qualification.