Insights Into the Patient Experience of Hormone Therapy for Early Breast Cancer Treatment Using Patient Forum Discussions and Natural Language Processing.

PURPOSE: Understanding the real-world experience of patients with early breast cancer (eBC) is imperative for optimizing outcomes and evolving patient care. However, there is a lack of patient-level data, hindering clinical development. This social listening study was performed to understand patient insights into symptoms and impacts of hormone therapy (HT) for eBC using posts from patient forums on breastcancer.org to inform future clinical research. METHODS: Natural language processing (NLP) and machine learning techniques were used to identify themes related to eBC from a sample of 500,000 posts. After relevant data selection, 362,074 eBC posts were retained for further analysis of symptoms and impacts related to HT, as well as insights into symptom severity, pain locations, and symptom management using exercise and yoga. RESULTS: Overall, 32 symptoms and nine impacts had significant associations with ≥one HT. Hot flush (relative risk [RR], 6.70 [95% CI, 3.36 to 13.36]), arthralgia (RR, 6.67 [95% CI, 3.53 to 12.59]), weight increased (RR, 4.83 [95% CI, 3.20 to 7.28]), mood swings (RR, 7.36 [95% CI, 5.75 to 9.42]), insomnia (RR, 4.76 [95% CI, 3.14 to 7.22]), and depression (RR, 3.05 [95% CI, 1.71 to 5.44]) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥one HT despite their low overall prevalence in eBC posts. CONCLUSION: The social listening approach allowed the identification of real-world insights from posts specific to eBC HT from a large-scale online breast cancer forum that captured experiences from a uniquely diverse group of patients. Using NLP has a potential to scale analysis of patient feedback and reveal actionable insights into patient experiences of treatment that can inform the development of future therapies and improve the care of patients with eBC.

Patient Preferences Influencing Treatment Decision-Making in Early-Stage Breast Cancer in Germany, Italy, and Japan.

Purpose: Patients with early breast cancer (eBC) are increasingly provided with different options, which may involve a sequence of different treatments and treatment modalities, and eligibility for certain adjuvant treatments depending upon pre-surgical and surgical outcomes. This study examined patient preferences around aspects of treatment decision-making in eBC. Patients and Methods: A total of 452 patients with self-reported eBC in Germany (n=151), Italy (n=151), and Japan (n=150) completed an online survey about physician interactions and treatment side effects. The survey included best-worst scaling (BWS) to assess prioritization of 13 statements reflecting aspects of treatment decision-making. In a series of choice tasks, participants chose their most and least preferred options among subsets of 4 statements. Hierarchical Bayesian modeling was used to estimate BWS preference scores for each statement. BWS scores were based on the number of times a statement was chosen as most versus least preferred; scores total 100 for each patient. Results: The most preferred aspects of treatment decision-making were "treatment aggressiveness matches personal risk" (mean BWS score = 13.49), "being told about what is coming" (13.18), deciding based on "own surgical outcome" (11.90), "avoiding unnecessary treatment" (10.35), and "involving in treatment decisions" (9.44). The least preferred aspects were "not being asked about treatment decisions along the way" (3.27) and "receiving the same treatment as other patients" (3.41). Patients in Japan preferred "being told about what is coming", "deciding based on own surgical outcome", "avoiding unnecessary treatment", and being "involved in decisions" more than patients in Italy and Germany. Patients in Germany were more satisfied with their physician interactions and care, although their outcomes were not always better than those in Italy and Japan. Conclusion: Patients value individualized treatment tailored to their risk of recurrence and tolerance of side effects, highlighting the need for focused patient education about options, to encourage their engagement.

New treatment pathways based on promising biomarkers are being studied in early breast cancer. This study aimed to understand the importance that patients may place on different features describing how decisions are made along potential treatment pathways for early breast cancer. Participants in Italy, Germany, and Japan were asked to compare various aspects of treatment decision-making and choose those that were most and least important to them. Among the aspects tested, the top 4 were similar across countries: the desire to receive treatment with a level of aggressiveness that matches their individual prognosis, the need to receive adequate and timely information about their upcoming treatment, the need to tailor treatment decisions based on their individual surgery outcomes, and a desire to avoid overtreatment. Not being involved in treatment decisions was the least preferred of the aspects. Patients in Germany and Italy most valued the ability to tailor the aggressiveness of their treatment based on their individual risk of recurrence, whereas patients in Japan prioritized being knowledgeable and prepared for their treatment journey. The results from this study emphasize patients' desire to be adequately informed about available treatment choices for early breast cancer, to avoid unnecessary treatments, and to be involved in treatment decisions.

A Novel Approach to Computing Preference Estimates for Different Treatment Pathways: An Application in Oncology.

BACKGROUND: Patients with cancer may progress through multiple treatments with differing adverse effect profiles. Moreover, pathways may be fixed or flexible in allowing for escalation or de-escalation of treatment depending on interim outcomes. We sought to develop a methodology capable of estimating preferences for the entirety of a pathway involving a sequence of different treatments. METHODS: Patients with early breast cancer completed an online discrete choice experiment to assess preferences for eight key early breast cancer attributes. Hierarchical Bayesian modeling was used to calculate attribute-level preference weights. Preference weights for hypothetical pathways were estimated by summing the respective weights for efficacy, flexible or fixed pathway, duration, administration regimen, and adverse event risk, the last two of which were time-adjusted by multiplying each weight by the proportion of time spent on a selected treatment. RESULTS: Increases in the risk of a serious adverse event were most influential in treatment pathway preferences, followed by increases in efficacy and decreases in overall pathway duration. Patients preferred a flexible pathway versus a fixed pathway. Pathway preference estimates fluctuated in a logically consistent manner. Switching from a flexible to a fixed pathway yielded a significantly lower pathway preference. For this same pathway, when adjuvant treatment was replaced with a treatment with a more favorable toxicity profile and shorter duration, it offset the negative impact of the more toxic neoadjuvant chemotherapy. CONCLUSIONS: This novel methodology accounts for patient preference throughout a sequence of treatments, allowing for comparison of preferences across complex treatment pathways.

Using qualitative interviews to identify patient-reported clinical trial endpoints and analyses that are the most meaningful to patients with advanced breast cancer.

BACKGROUND: Designing clinical trials with the emphasis on the patient-centered approach and focusing on clinical outcomes that are meaningful to patients is viewed as a priority by drug developers, regulatory agencies, payers, clinicians, and patients. This study aimed to capture information on clinical trial endpoints that would be most important and relevant for patients with advanced breast cancer, based on patient-reported outcomes. METHODS: Patients with either advanced triple-negative breast cancer [TNBC] and a maximum of two lines of systemic therapy or hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR+/HER2-] breast cancer and a maximum of three lines of systemic therapy, participated in semi-structured concept elicitation interviews. Concept saturation was assessed. A sign, symptom, or impact was defined as "salient" if mentioned by ≥ 60% of participants, with an average bother rating of ≥ 5 (0-10 Scale). Participants were also asked about treatment priorities and to evaluate hypothetical scenarios showing different health-related functioning and quality-of-life treatment outcomes, using graphical representations. RESULTS: Thirty-two participants (97% women; aged 29+ years) with TNBC (n = 17) or HR+/HER2- breast cancer (n = 15) provided generally similar reports on symptom experience, with fatigue and pain being most salient, though importance of certain treatment-related symptoms varied between the two groups. Patients reported consistent perspectives on the importance of treatment outcomes: when considering a new treatment, they prioritized efficacy of the therapy, acceptable tolerability, stability, predictability of symptoms over time, and the duration of preserved health-related quality of life and physical functioning. The meaningful difference in preserved physical functioning was 2-3 months for 46% of participants with TNBC, whereas for most participants with HR+/HER2- breast cancer it started from 6-7 months. Both groups of participants found it easier to accept some toxicity at the beginning of therapy if it was followed by improvement, as opposed to improvement followed by deterioration. CONCLUSION: The results may help to inform the design of patient-centered clinical trials, to interpret health-related quality of life and/or patient-reported outcomes, and to optimize care for patients with advanced breast cancer.

Development of the PREMature Infant Index (PREMII™), a clinician-reported outcome measure assessing functional status of extremely preterm infants.

BACKGROUND: Comprehensive measures to evaluate the effectiveness of medical interventions in extremely preterm infants are lacking. Although length of stay is used as an indicator of overall health among preterm infants in clinical studies, it is confounded by nonmedical factors (e.g. parental readiness and availability of home nursing support). OBJECTIVES: To develop the PREMature Infant Index (PREMII™), an electronic content-valid clinician-reported outcome measure for assessing functional status of extremely preterm infants (<28 weeks gestational age) serially over time in the neonatal intensive care unit. We report the development stages of the PREMII, including suggestions for scoring. METHODS: We developed the PREMII according to US Food and Drug Administration regulatory standards. Development included five stages: (1) literature review, (2) clinical expert interviews, (3) Delphi panel survey, (4) development of items/levels, and (5) cognitive interviews/usability testing. Scoring approaches were explored via an online clinician survey. RESULTS: Key factors reflective of functional status were identified by physicians and nurses during development of the PREMII, as were levels within each factor to assess functional status. The resulting PREMII evaluates eight infant health factors: respiratory support, oxygen administration, apnea, bradycardia, desaturation, thermoregulation, feeding, and weight gain, each scored with three to six gradations. Factor levels are standardized on a 0-100 scale; resultant scores are 0-100. No usability issues were identified. The online clinician survey identified optimal scoring methods to capture functional status at a given time point. CONCLUSIONS: Our findings support the content validity and usability of the PREMII as a multifunction outcome measure to assess functional status over time in extremely preterm infants. Psychometric validation is ongoing.

Patient Global Impression of Benefit-Risk (PGI-BR): Incorporating Patients' Views of Clinical Benefit-Risk into Assessment of New Medicines.

INTRODUCTION: There is a need to understand how patients assess perceived benefits and risks of treatments. OBJECTIVES: The study aimed to (i) elucidate how patients evaluate treatment experiences and (ii) develop a brief patient-reported outcome (PRO) instrument for use across disease areas for perceived benefit-risk evaluation of a new medicine in a clinical trial setting. METHODS: Concepts relating to patient-perceived benefit-risk were identified from literature reviews and qualitative concept elicitation interviews with patients across a variety of primary medical conditions. Draft instrument items were developed from identified concepts and evaluated for clarity, relevance and appropriateness of response options in cognitive interviews. Items were iteratively revised to address patient feedback. RESULTS: Qualitative interviews were conducted with 47 patients (primary condition: 20 oncological, 12 respiratory, 10 metabolic, 5 cardiovascular), of whom 32 contributed to concept elicitation and 42 to cognitive debriefing. Elicited concepts could be grouped into four medication-related categories: effectiveness of treatment, burden of side effects, convenience of use and overall acceptance/satisfaction. Cost, trial experience and altruism were additional concept categories unrelated to medication. The final instrument contained one item each on the medication's effectiveness, side effects and convenience, and an overall item capturing patient benefit-risk assessment. An upfront question was included to separate out non-medication aspects of patients' experiences. CONCLUSION: We developed a brief PRO instrument, the Patient Global Impression of Benefit-Risk (PGI-BR), which can be applied across disease areas to assess patient views of benefit-risk of a new medicine in the clinical trial setting.

Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial.

BACKGROUND: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. METHODS: SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0-1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy-Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.gov, NCT01844986. FINDINGS: Between Sept 3, 2013, and March 6, 2015, 1084 patients were enrolled. 693 patients were ineligible, leaving 391 eligible patients who were randomly assigned to olaparib (n=260) or placebo (n=131; one placebo patient withdrew before receiving any study treatment), with a median duration of follow-up of 40·7 months (IQR 34·9-42·9) for olaparib and 41·2 months (32·2-41·6) for placebo. There was no clinically meaningful change in TOI score at 24 months within or between the olaparib and placebo groups (adjusted mean change in score from baseline over 24 months was 0·30 points [95% CI -0·72 to 1·32] in the olaparib group vs 3·30 points [1·84 to 4·76] in the placebo group; between-group difference of -3·00, 95% CI -4·78 to -1·22; p=0·0010). Mean quality-adjusted progression-free survival (olaparib 29·75 months [95% CI 28·20-31·63] vs placebo 17·58 [15·05-20·18]; difference 12·17 months [95% CI 9·07-15·11], p<0·0001) and the mean duration of TWiST (olaparib 33·15 months [95% CI 30·82-35·49] vs placebo 20·24 months [17·36-23·11]; difference 12·92 months [95% CI 9·30-16·54]; p<0·0001) were significantly longer with olaparib than with placebo. INTERPRETATION: The substantial progression-free survival benefit provided by maintenance olaparib in the newly diagnosed setting was achieved with no detrimental effect on patients' HRQOL and was supported by clinically meaningful quality-adjusted progression-free survival and TWiST benefits with maintenance olaparib versus placebo. FUNDING: AstraZeneca and Merck Sharp & Dohme.

The patient journey to diagnosis and treatment of congenital sucrase-isomaltase deficiency.

PURPOSE: Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic disorder characterized by a deficiency of the sucrase-isomaltase (SI) enzyme complex within the brush border membrane of the small intestine. Mutations in the SI gene result in abnormal synthesis and/or incorrect transport of the SI enzyme. Patients with CSID generally have reduced sucrase activity, but levels of isomaltase activity range from absent to almost normal. This study sought to better understand the experience of patients with CSID prior to, during, and after their diagnosis and its subsequent treatment with sacrosidase. METHODS: This was a cross-sectional interview study conducted in conjunction with a longitudinal, observational study of US patients prescribed and taking sacrosidase for at least three consecutive months as treatment for CSID. The observational study included both children and adults. RESULTS: This qualitative interview study explored the experiences of 43 adult and pediatric patients (n = 8 adults and n = 35 children/adolescents) with CSID pre-, during, and post-diagnosis. Findings suggest that a CSID diagnosis is particularly problematic given the disparate range of more commonly understood gastrointestinal (GI) disorders. After diagnosis and treatment with sacrosidase, participants reported considerable improvement in symptoms and health-related quality of life (HRQL), yet symptoms persist that continue to affect daily life, indicating areas of potential unmet need. CONCLUSION: Educating clinicians about CSID may help improve the overall diagnosis experience. As this research is the first of its kind in CSID, additional research, qualitative and quantitative, will be important to furthering the understanding of HRQL impact and unmet need experienced by this population and identifying ways to best meet those needs.

Agreement Among Paper and Electronic Modes of the EQ-5D-5L.

INTRODUCTION: While the EQ-5D-5L has been migrated to several electronic modes, evidence supporting the measurement equivalence of the original paper-based instrument to the electronic modes is limited. OBJECTIVES: This study was designed to comprehensively examine the equivalence of the paper and electronic modes (i.e., handheld, tablet, interactive voice response [IVR], and web). METHODS: As part of the foundational work for this study, the test-retest reliability of the paper-based, UK English format of the EQ-5D-5L was assessed using a single-group, single-visit, two-period, repeated-measures design. To compare paper and electronic modes, three independent samples were recruited into a three-period crossover study. Each participant was assigned to one of six groups to account for order effects. Descriptive statistics, mean differences (i.e., split-plot analysis of variance [ANOVA]), and intraclass correlation coefficients (ICCs) were calculated. RESULTS: The test-retest results showed mean differences near zero and ICC values > 0.90 for both the index and the EQ VAS scores. For the electronic comparisons, mean difference confidence intervals (CIs) for the EQ-5D index scores and EQ VAS scores reflected equivalence of the means across all modes, as the CIs were wholly contained inside the equivalence interval. Further, the ICC 95% lower CIs for the index and EQ VAS scores showed values above the thresholds for denoting equivalence across all comparisons in each sample. No significant mode-by-order interactions were present in any ANOVA model. CONCLUSIONS: Overall, our comparisons of the paper, screen-based, and phone-based formats of the EQ-5D-5L provided substantial evidence to support the measurement equivalence of these modes of data collection.

Patient perspectives on the pathway to psoriatic arthritis diagnosis: results from a web-based survey of patients in the United States.

BACKGROUND: There are limited real-world data on the diagnostic experiences of patients with psoriatic arthritis (PsA), including medical care sought and potential barriers to diagnosis. We aim to describe patient experiences related to receiving a PsA diagnosis. METHODS: Ours was a mixed-method, 2-phase study. Phase 1 comprised concept elicitation and cognitive interviews with clinical experts and adults diagnosed with PsA to develop a cross sectional, web-based survey. US adults with a self-reported PsA diagnosis were recruited through a patient support community (CreakyJoints), an online patient research registry (ArthritisPower), and social media outreach. In Phase 2, the online survey collected data on sociodemographics, clinical symptoms, disease burden, and diagnosis history of survey respondents with PsA. RESULTS: Of the 203 respondents included, 172 (84.7%) were female, and the mean (SD) age was 51.6 (10.8) years. The time between seeking medical attention and receiving a diagnosis was < 6 months for 69 respondents, 6 months to 4 years for 68 respondents, and ≥ 5 years for 66 respondents. Most respondents sought care from general practitioners (79.8%) and rheumatologists (66.5%). Common initial symptoms that led respondents to seek medical attention were joint pain (70.0%) and stiffness (53.7%). Among the initial symptoms that led respondents to seek care, joint pain, swollen joints, and sausage-like fingers or toes (indicating dactylitis) were more common among respondents with shorter time to diagnosis, whereas stiffness, fatigue, enthesitis (indicated by foot problems, tendon and ligament pain), and back pain were more common among respondents with longer time to diagnosis. Common misdiagnoses were psychosomatic issues (26.6%) and osteoarthritis (21.7%). Respondents with shorter times to diagnosis had lower frequencies of misdiagnosis. CONCLUSIONS: Respondents with PsA reported delays in diagnosis and misdiagnoses on their journey to a PsA diagnosis. Symptom differences, such as enthesitis and stiffness, were noted among respondents with shorter vs longer time to diagnosis. Increased understanding of diagnostic barriers may lead to earlier diagnosis and appropriate management to improve outcomes.

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.

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 attributes of tyrosine kinase inhibitor treatments for EGFR mutation-positive non-small-cell lung cancer.

Aim: EGFR-tyrosine kinase inhibitors (TKIs) vary in efficacy, side effects (SEs) and dosing regimen. We explored EGFR-TKI treatment attribute preferences in EGFR mutation-positive metastatic non-small-cell lung cancer. Materials & methods: Patients completed a survey utilizing preference elicitation methods: direct elicitation of four EGFR-TKI profiles describing progression-free survival (PFS), severe SE risk, administration; discrete choice experiment involving 12 choice tasks. Results: 90 participated. The preferred profile (selected 89% of times) had the longest PFS (18 months) and the lowest severe SE risk (5%). Patients would need compensation with ≥three-times longer PFS for severe SEs. Patients would accept ≤7 months PFS reduction for oral treatments versus intravenous. Conclusion: Patients preferred longer PFS but were willing to accept reduced PFS for more favorable SEs and dosing convenience.

Healthcare provider perspectives on diagnosing and treating adults with attention-deficit/hyperactivity disorder.

Objective: This study examined adult attention-deficit/hyperactivity disorder (ADHD) screening and management patterns among healthcare provider (HCP) subgroups. Methods: An online survey of US-based HCPs (neurologists, n = 200; nurse practitioners [NPs], n = 100; psychiatrists, n = 201; primary care physicians [PCPs], n = 201) was conducted from May to June 2017. The survey assessed issues relating to adult ADHD screening and management and HCP perceptions of factors influencing patient choice of pharmacotherapy. Participants were required to be experienced in diagnosing and/or treating ADHD in adults (≥5 patients/month for neurologists and NPs; ≥10 patients/month for psychiatrists and PCPs). Results: Significantly greater percentages of psychiatrists than non-psychiatrists were confident in diagnosing ADHD (P < 0.001) and screened/evaluated for ADHD in patients with depression/anxiety disorders (P < 0.001). Significantly greater percentages of psychiatrists versus non-psychiatrists prescribed once-daily long-acting (LA) stimulants (71.6% vs 62.2%; P = 0.023) or short-acting (SA) stimulants more than once daily (40.3% vs 29.7%; P = 0.009) as first-line therapy. In contrast, a significantly greater percentage of non-psychiatrists than psychiatrists prescribed once-daily SA stimulants (32.9% vs 17.4%; P < 0.001). Psychiatrist and non-psychiatrist HCPs viewed insurance coverage/treatment costs (79.9%), perceived duration of effect (72.2%), and side effects (66.5%) as important factors to patients when choosing treatment. HCPs reported that the greatest mean ± SD percentages of patients changed their treatment regimen in the past 6 months because of perceptions of insufficient duration of effect (35.4% ± 22.1%) and lack of efficacy (30.3% ± 21.0%). Conclusion: Compared with psychiatrists, non-psychiatrists exhibited less confidence in diagnosing adult ADHD and experienced greater difficulty determining optimal treatment regimens.

Real-World Patient Experience on the Path to Diagnosis of Ankylosing Spondylitis.

INTRODUCTION: We describe the journey to diagnosis of ankylosing spondylitis (AS) from the patient perspective and examine differences in this journey by sex. METHODS: US adults aged ≥ 18 years with a self-reported AS diagnosis were recruited online through CreakyJoints, a patient support community, and ArthritisPower, a patient research registry. Respondents completed a web-based survey on sociodemographics, disease burden, and diagnosis history. Results were stratified by sex and time to diagnosis using two-sample t tests and χ2 tests, respectively, to observe differences across the groups; P < 0.05 was considered statistically significant. RESULTS: Among 235 respondents, 174 (74.0%) were female. Mean (SD) ages of female and male respondents were 48.6 (10.6) and 53.1 (10.3) years, respectively. From the time respondents began seeking medical attention, 87 were diagnosed within ≤ 1 year, 71 in 2-9 years, and 77 after ≥ 10 years. Symptoms that led respondents to seek treatment were back pain (73.2%) and joint pain (63.8%); fatigue and difficulty sleeping were more common among respondents with longer times to diagnosis. During the diagnosis process, men with AS tended to receive quicker AS diagnosis compared with women. Overall, commonly reported initial diagnoses among respondents with longer time to AS diagnosis included back problems and psychosomatic disorders. Significantly more women reported misdiagnoses of fibromyalgia (20.7 vs. 6.6%) and psychosomatic disorders (40.8 vs. 23.0%) compared with men. CONCLUSIONS: Diagnosis delays and misdiagnoses were common among respondents with AS. Increasing awareness about AS among referring providers may minimize diagnosis delay. FUNDING: Novartis Pharmaceuticals Corporation. Plain language summary available for this article.

The evolving role of patient preference studies in health-care decision-making, from clinical drug development to clinical care management.

Introduction: There is a growing trend of using patient preference studies to help incorporate the patient perspective into clinical drug development, care management, and health-care decision-making. Collecting and interpreting patient preference data is integral to multi-stakeholder engagement, patient-centric drug development, and clinical care management. Operationally, challenges exist in understanding 'when' and 'how' to embark on patient preference studies. This review will provide a brief overview of stated-preference methods, discuss applications throughout the clinical drug development and care management, and highlight how preference studies serve as a powerful tool for quantifying patient experiences for better outcomes. Areas covered: We present case studies to complement the different applications of stated-preference methods in clinical drug development and care management. We discuss the applications of preference data to help inform evidence-based patient advocacy, clinical development strategy, operational feasibility, regulator benefit-risk assessments, health technology assessments, and clinical decision-making. Expert commentary: Patient preference studies can serve as a powerful tool to engage patients and their communities as well as quantify the patient voice across different stages of clinical drug development and care management to support patient-centric health-care decision-making. It is expected that the application of these strategies will quickly advance in the coming years.

AcroVoice: eliciting the patients' perspective on acromegaly disease activity.

PURPOSE: To determine how patients define acromegaly disease activity and treatment success and to quantify from the patients' perspective the relative importance of each disease parameter included in the ACRODAT®. METHODS: One hundred acromegaly patients on medical therapy (mean age = 47.1 years; SD = 11.96) completed an online preference study evaluating hypothetical patient profiles described in terms of insulin-like growth factor-I (IGF-I) levels, tumor size, comorbid conditions, signs/symptoms, and quality of life (QoL). Participants first completed a single-profile task experiment by rating 20 single patient profiles as exhibiting stable, mild, or significant disease activity based on treatment success. Next, participants completed a double-profile discrete choice experiment (DCE) by selecting the patient that was doing "better" from 15 profile pairs. Results were analyzed using logistic and conditional logistic models. RESULTS: When choosing between stable vs. mild or significant disease activity, signs/symptoms, tumor size, and IGF-I levels were weighted equally; IGF-I and signs and symptoms were valued equally when selecting mild vs. significant disease activity. The DCE showed that, statistically, all disease parameters, except comorbid conditions, predicted health status equally. Tumor size and IGF-I levels each accounted for 23% of the decision-making process; QoL, signs/symptoms, and comorbid conditions accounted for 21%, 19%, and 14%, respectively. CONCLUSION: All five ACRODAT® parameters had some influence on disease activity from the patients' perspective. To account for patients' preferences and optimize treatment and outcomes, a holistic disease management approach should be employed.

Perceived Burden of Completion of Patient-Reported Outcome Measures in Clinical Trials:: Results of a Preliminary Study.

BACKGROUND: Understanding the perceived burden of clinical trial participation is an important element of patient-centric trial design and conduct. METHODS: We report the results of a study to gain preliminary insights into the perceived burden associated with patient-reported outcome (PRO) data collection among a sample (n = 61) of volunteers from the general population including people with various health conditions resulting in chronic pain. RESULTS: Participants identified morning completion as more burdensome than completion of PRO measures in the evening. Weekly completion was perceived as less burdensome than daily, and twice-a-day more burdensome than once-a-day. CONCLUSION: Our results, while not generalizable in isolation, provide a valuable starting point to understand the complex construct of subject burden. This preliminary work is intended to be a catalyst for more in-depth research to better understand and predict burden and acceptable burden thresholds in clinical trials. Understanding subject burden is a vital component of human subject research that will be valuable in helping to inform future clinical trial designs.

A Conceptual Model of Angelman Syndrome and Review of Relevant Clinical Outcomes Assessments (COAs).

BACKGROUND: Angelman syndrome (AS) is a rare, neurological genetic disorder for which no clinical outcomes assessments (COAs) or conceptual models (CM) have been developed. OBJECTIVE: This study aimed to identify symptoms and impacts relevant and important in this patient population and develop a conceptual model of AS, and to evaluate the content validity of selected COA instruments with potential for inclusion in clinical studies of AS to capture treatment benefit. METHODS: For both concept elicitation (CE) and cognitive interviews (CI), caregivers of children, adolescents, and adults with AS and clinicians with AS experience were targeted. For CI, clinicians discussed the Modified Performance-Oriented Mobility Assessment (MPOMA-G) and ProtoKinetics Zeno Walkway™ and caregivers reviewed the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT), the Anxiety, Depression and Mood Scale (ADAMS), the Aberrant Behavior Checklist-Community (ABC-C), and the Morning Diary. RESULTS: Four clinicians and 34 caregivers participated in CE interviews; three clinicians and 36 caregivers participated in CI. A conceptual model, initially informed by literature, was refined based on interview data. Five domains of symptoms, signs, and characteristics of AS were identified: cognitive and executive functioning, social-emotional, emotional-expressive behavior, sensory-compulsive behavior, and physical. Patient impacts were identified in three domains: activities of daily living, school, and social/community. Caregiver impacts were identified in five domains: mental health, physical health, work, home, and social. While all instruments demonstrated the ability to provide relevant data for the AS population, each instrument either contained some items irrelevant to individuals with AS or was missing important concepts based on the interviews. No single instrument covered all relevant domains specific to AS. CONCLUSION: Future work should consider the adaptation of existing COAs and the development of a novel AS-specific instrument for use in clinical research to ensure outcomes important to this patient population are captured.

The Potential Role of Individual-Level Benefit-Risk Assessment in Treatment Decision Making: A DIA Study Endpoints Community Workstream.

Benefit-risk assessment is the cornerstone of decision making in medical care, playing a critical role in bringing treatments to market by informing decisions regarding drug development, licensing and reimbursement, and informing treatment decisions made by health care professionals and patients in clinical practice. In regulatory approval decision making, benefit and risk attributes are identified and defined based on available, aggregated clinical data from registration trials. In the context of major developments in recent years for involvement of patients as partners in all phases of drug development and in health care improvement, decision makers increasingly recognize the importance of informing treatment decisions by patient needs, values, experiences, and preferences. Using this as a basis, a DIA workstream was convened to explore the potential of individual-level benefit-risk assessment as a supplement to traditional group-level benefit-risk assessment for evaluating treatment. Various approaches as to how this information could be collected, including via patient-reported outcome measures, open-ended questioning, and stated-preference methods are presented. The utility of this information for various stakeholders is discussed.