Exploration of baseline patient-reported side effect bother from cancer therapy.

BACKGROUND: Patient reports of expected treatment side effects are increasingly collected as part of the assessment of patient experience in clinical trials. A global side effect item that is patient-reported has the potential to inform overall tolerability. Therefore, the aim of this study was to examine the completion and distribution of such a global single-item measure of side effect burden in five cancer clinical trials. METHODS: Data from five trials from internal Food and Drug Administration databases that included the Functional Assessment of Cancer Therapy-General single-item measure of overall side effect burden (i.e. impact on degree of bother) were analyzed. Completion rates for the side effect bother item, items adjacent to this item, and two non-adjacent items on the Functional Assessment of Cancer Therapy-General that are related to health-related quality of life were calculated at the baseline assessment and at the 3-month assessment. To evaluate the distribution, the percentage of patients reporting high levels (quite a bit or very much bother) of side effect bother at baseline and 3 months was assessed. RESULTS: Completion rates for all items were at least 80% regardless of time point or trial population. However, in three of the five trials, completion rates for the side effect bother item were lower at baseline compared to adjacent and non-adjacent items. This difference was not observed at 3 months. Up to 9.4% of patients reported high levels of side effect bother at baseline. CONCLUSION: Patients may enter trials already reporting some bother from side effects. This can make interpretation of results with respect to the investigational agent under study challenging. Patients may skip an item evaluating side effect bother at baseline, suggesting some difficulty with interpretation of what is being asked. Further study of the wording and utility of a baseline side effect bother assessment is warranted.

Development and Validation of the Eyelash Satisfaction Questionnaire.

BACKGROUND: Patient-reported outcome (PRO) measures have been used to assess treatment benefit in a variety of therapeutic areas and are now becoming increasingly important in aesthetic research. OBJECTIVES: The objective of the current study was to develop and validate a new PRO measure (Eyelash Satisfaction Questionnaire [ESQ]) to assess satisfaction with eyelash prominence. METHODS: The content of the questionnaire (including conceptual framework and questionnaire items) was generated by review of literature, participant interviews, and expert opinion. Cognitive interviews were conducted to pilot test the questionnaire. Psychometric properties of the questionnaire were examined in a combined sample of participants (n = 970) completing Internet- (n = 909) and paper-based (n = 61) versions. Item- and domain-level properties were examined using modern and classical psychometrics. RESULTS: Content-based analysis of qualitative data demonstrated the presence of 3 distinct domains (Length, Fullness, Overall Satisfaction; Confidence, Attractiveness, and Professionalism; and Daily Routine). Initial confirmatory factor analysis (CFA) results of 23 items revealed insufficient model-data fit (comparative fit index [CFI] of 0.86 and a non-normed fit index [NNFI] of 0.82). A revised model using 9 items (3 per domain) achieved appropriate fit (CFI of 0.99 and NNFI of 0.97). Analyses revealed measurement equivalence across the Internet- and paper-based versions. The 3 ESQ domains had strong internal consistency reliability (Cronbach's α [range] = 0.919-0.976) and adequate convergent and discriminant validity. CONCLUSIONS: The ESQ was found to be a reliable and valid PRO measure for assessing satisfaction with eyelash prominence. LEVEL OF EVIDENCE 3: Therapeutic.

Subject satisfaction with onabotulinumtoxinA treatment of glabellar and lateral canthal lines using a new patient-reported outcome measure.

BACKGROUND: Patient satisfaction with treatment is an important outcome in facial aesthetic medicine. OBJECTIVE: To evaluate subject satisfaction with onabotulinumtoxinA treatment of glabellar lines (GL) and crow's feet lines (CFL) using the validated Facial Line Satisfaction Questionnaire (FLSQ). METHODS: In this randomized double-blind study, subjects with moderate/severe GL and CFL received onabotulinumtoxinA (20 U, GL; 24 U, CFL) or placebo. Over 120 days, the following were assessed: satisfaction, achievement of treatment expectations, satisfaction with duration of treatment (FLSQ), severity of GL and CFL (Facial Wrinkle Scale [FWS]), and aesthetic improvement (Global Aesthetic Improvement Scale). RESULTS: Satisfaction in the per-protocol population was significantly greater at Day 60 in the onabotulinumtoxinA group (n = 60) compared with placebo (n = 57) for GL (81.7% vs 0%; p < .001). Most subjects treated with onabotulinumtoxinA remained satisfied up to 120 days. Achievement of treatment expectations (86.7%; Day 60), satisfaction (81.7%; Day 60), and satisfaction with the duration of treatment (61.6%; Day 90) were significantly better with onabotulinumtoxinA than placebo (p < .001) for GL and CFL combined. Efficacy (FWS) and aesthetic improvement were observed in most subjects at Days 30 and 60, respectively. CONCLUSION: High satisfaction rates are achieved and sustained in subjects treated with onabotulinumtoxinA for GL and CFL combined.

Validation of a New Patient-Reported Outcome Measure for Facial Acne: The Acne Symptom and Impact Scale (ASIS).

OBJECTIVE: The objective of this study was to evaluate the psychometric performance of the Acne Symptom and Impact Scale (ASIS) for use in adolescents and adults with acne vulgaris. METHODS: Psychometric evaluation was performed using both traditional psychometrics in line with proposed US Food and Drug Administration (FDA) criteria and new psychometric methods, Rasch Measurement Theory (RMT). Assessment of equivalence was also evaluated between Caucasians and Non-Caucasians on individual items. RESULTS: One-hundred fifty subjects completed baseline and follow-up assessments (89 [59.33%] in the Caucasian group and 61 [40.67%] in the Non-Caucasian group). Psychometric analyses demonstrated that the ASIS Sign and Impact domains both performed well. Each domain fulfilled traditional psychometric criteria (Cronbach's alpha=0.79-0.92; test-retest reliability=0.75-0.78) and mostly satisfied Rasch psychometric criteria (person-reliability=0.72-0.93; person-separation=1.61-3.69). Select individual ASIS Items also performed well across all measures and were shown to be reliable and valid as stand-alone items. A similar pattern of results were found for both Caucasian and Non-Caucasian racial subgroups. CONCLUSIONS: These findings provide empirical evidence that the ASIS is a reliable and valid PRO measure that can accurately assess the severity of symptoms and impacts associated with acne vulgaris.

Impact of female acne on patterns of health care resource utilization.

BACKGROUND: Limited data are available on acne treatment patterns in females through their adult years. OBJECTIVE: The purpose of this analysis was to evaluate health care resource utilization (HRU) and treatment patterns in cohorts with and without the use of acne medication and predictors of use. METHODS: A cross-sectional, web-based survey was administered to US females (25-45 years) with facial acne (≥ 25 visible lesions). Data collected included: sociodemographics and self-reported clinical characteristics, acne treatments, and health care professional (HCP) visits. Subject characteristics associated with medication use were examined by logistic regression. RESULTS: Approximately half of the total sample (N=208, mean age: 35 ± 6) ever visited an HCP for acne and reported more over-the counter (OTC) medication use (51.0%) than prescription (Rx) medication use (15.4%). Subjects did not use medications daily, averaging from 12-18 days over the previous 4 weeks. Logistic regression showed that race and prior HCP visits for acne were significant predictors of medication use (P<.05). CONCLUSIONS: Adult females generally self-treated their acne using primarily OTC medications; however, poor compliance was observed for Rx and OTC. Race and prior HCP visits for acne were significant predictors of current medication use.

Development of a new patient-reported outcome measure for facial acne: the Acne Symptom and Impact Scale (ASIS).

OBJECTIVE: Facial acne has been associated with impaired health-related quality of life, which is an essential patient outcome for evaluating the success of acne treatment. In consideration of the US Food and Drug Administration's (FDA) new recommendations on patient reported outcome (PRO) measures, the objectives of this study were to (1) establish the need for a new PRO measure that assesses facial acne outcomes and satisfies the criteria set forth by the FDA and (2) develop the content of a new facial acne PRO measure appropriate for use in both adolescents and adults as well as adherent to the FDA PRO Guidance. METHODS: A literature and PRO review, patient interviews (concept elicitation), and input from clinical experts were used to develop a conceptual framework for the outcomes deemed important to facial acne patients, and to construct items for a preliminary PRO measure: the Acne Symptom and Impact Scale (ASIS). Cognitive interviews were conducted to pilot test the ASIS. RESULTS: A review of the literature and PROs revealed that, of the 34 measures identified, no suitable PRO measure for the population of interest was available. The conceptual framework comprised two main themes: symptoms and psychosocial impacts. Concept elicitation interviews included a diverse set of patients (n=48) with facial acne, of various ages: 12-17 years (n=15), 18-25 years (n=20), and 26-50 years (n=13). The most frequently reported symptoms were: pimples, oily skin, scabs/scars/marks, blackheads, acne, and whiteheads. The most frequently reported impacts were impacts on appearance, self-consciousness, annoyance, bothersomeness, mood, social criticism, embarrassment, confidence, and social withdrawal. These reported symptoms and impacts constituted the 15-item draft ASIS. The draft ASIS was modified following the analysis of 20 cognitive interviews, resulting in the current 17-item ASIS. CONCLUSIONS: Results from both the concept elicitation and cognitive interviews demonstrated that the ASIS is content valid in both adolescents and adults with facial acne. The ASIS will undergo psychometric evaluation to further support its validity in both adolescents and adults with facial acne.

Measuring What Matters to Patients in Dermatology Drug Development: A Regulatory Perspective.

Incorporating the patient voice into drug development and regulatory review process allows for the science of drug development to be more patient-centered. Dermatology is one therapeutic area where patients have the potential to provide valuable perspectives on symptoms, functional impacts, and aesthetic outcomes. Patient-reported and observer-reported outcomes play an important role in capturing concerns related to the disease or condition and its treatment. Patient experience data from well-designed trials are critical for regulatory decision-making and ultimately enable prescribers and patients to make better informed treatment decisions at the point of care.

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma.

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma-related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51-79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit-risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early-Stage HER2-Positive Breast Cancer.

On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified HR of 0.66 [95% confidence interval (CI), 0.49-0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%-95.4%) in patients treated with neratinib versus 91.9% (95% CI, 90.2%-93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Clin Cancer Res; 24(15); 3486-91. ©2018 AACRSee related commentary by Unni et al., p. 3483.

U.S. Food and Drug Administration Approval: Cabozantinib for the Treatment of Advanced Renal Cell Carcinoma.

On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which patients with RCC who had received prior antiangiogenic therapy were treated with either cabozantinib 60 mg orally once daily (n = 330) or everolimus 10 mg orally once daily (n = 328). The major efficacy outcome measure was progression-free survival (PFS) as assessed by a blinded independent radiology review committee in the first 375 randomized patients. A statistically significant improvement in PFS was seen, with a median PFS of 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45-0.74; P < 0.0001]. At a second interim analysis, a statistically significant improvement in overall survival (OS) in the intent-to-treat population was also demonstrated, with a median OS of 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively (HR, 0.66; 95% CI, 0.53-0.83; P = 0.0003). The most common (greater than or equal to 25%) adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. Clin Cancer Res; 23(2); 330-5. ©2016 AACR.

Acne treatment patterns, expectations, and satisfaction among adult females of different races/ethnicities.

BACKGROUND: Limited data are available on acne treatment patterns, expectations, and satisfaction in the adult female subpopulation, particularly among different racial and ethnic groups. OBJECTIVE: Describe acne treatment patterns and expectations in adult females of different racial/ethnic groups and analyze and explore their potential effects on medication compliance and treatment satisfaction. METHODS: A cross-sectional, Web-based survey was administered to US females (25-45 years) with facial acne (≥25 visible lesions). Data collected included sociodemographics, self-reported clinical characteristics, acne treatment use, and treatment expectations and satisfaction. RESULTS: Three hundred twelve subjects completed the survey (mean age, 35.3±5.9 years), comprising black (30.8%), Hispanic (17.6%), Asian/other (17.3%), and white (34.3%). More than half of the subjects in each racial group recently used an acne treatment or procedure (black, 63.5%; Hispanic, 54.5%; Asian/other, 66.7%; white, 66.4%). Treatment use was predominantly over-the-counter (OTC) (47.4%) versus prescription medications (16.6%). OTC use was highest in white subjects (black, 42.7%; Hispanic, 34.5%; Asian/other, 44.4%; white, 59.8%; P<0.05). The most frequently used OTC treatments in all racial/ethnic groups were salicylic acid (SA) (34.3%) and benzoyl peroxide (BP) (32.1%). Overall, compliance with acne medications was highest in white versus black (57.0±32.4 vs 42.7±33.5 days, P>0.05), Hispanic (57.0±32.4 vs 43.2±32.9 days, P>0.05), and Asian/other (57.0±32.4 vs 46.9±37.2 days, P>0.05) subjects. Most subjects expected OTC (73.7%) and prescription (74.7%) treatments to work quickly. Fewer than half of the subjects were satisfied with OTC treatment (BP, 47.0%; SA, 43.0%), often due to skin dryness (BP, 26.3%; SA, 44.3%) and flakiness (BP, 12.3%; SA, 31.1%). No statistically significant differences were observed among racial/ethnic groups in their level of satisfaction with OTC or prescription acne treatments. CONCLUSION: Racial/ethnic differences were observed in acne treatment patterns in adult females, while treatment expectations were similar. Results indicate that treatment patterns and expectations may impact treatment satisfaction and medication compliance.

Acne-Related Quality of Life Among Female Adults of Different Races/Ethnicities.

BACKGROUND: Acne impairs quality of life, but its effect on different races/ethnicities is unclear. This study evaluated racial/ethnic differences in acne-related quality of life and psychological symptoms among female adults. METHODS: A Web-based survey was conducted with U.S. female adults (25-45 years old) with facial acne (≥25 visible lesions). Outcomes included sociodemographics, clinical characteristics, acne-related quality of life (Acne-Specific Quality of Life Questionnaire), psychological symptoms (Patient Health Questionnaire), and work/school productivity. Racial/ethnic differences were evaluated using descriptive statistics and analysis of variance/chi-square analyses. RESULTS: Three-hundred twelve subjects (Black = 30.8%, Hispanic = 17.6%, Asian/other = 17.3%, White = 34.3%) completed the survey (mean age = 35.3 ± 5.9 years). Acne negatively impacted quality of life for all subjects. Black subjects reported significantly less negative impact on self-perception versus Asian/other (Black = 12.6 ± 9.9, Asian/other = 8.4 ± 8.6; p = .05). Social functioning was less negatively impacted in White and Black subjects versus Asian/other (White = 12.7 ± 7.5, Asian/other = 8.4 ± 7.8, p < .05; Black = 12.1 ± 9.2, Asian/other = 8.4 ± 7.8, p = .06). Over one third (total sample = 40.7%, Black = 31.3%, Hispanic = 36.4%, Asian/other = 50.0%, White = 46.7%) reported moderate/severe anxiety/depression symptoms. Acne also impacted ability to concentrate on work/school. CONCLUSION: Racial/ethnic differences were observed in acne-related quality of life and psychological symptoms in female adults; acne negatively impacted self-perceptions and social/emotional functioning.

Racial differences in clinical characteristics, perceptions and behaviors, and psychosocial impact of adult female acne.

OBJECTIVE: Limited data are available on racial differences in clinical characteristics and burden in adult female acne. The objective was to describe racial differences in clinical characteristics, psychosocial impact, perceptions, behaviors, and treatment satisfaction in facial adult female acne. DESIGN: Cross-sectional, web-based survey. SETTING: Diverse sample of United States women. PARTICIPANTS: Women between the ages of 25 and 45 years with facial acne (≥25 visible lesions). MEASUREMENTS: Outcomes included sociodemographic characteristics, psychosocial impacts, perceptions, behaviors, and treatment satisfaction. Racial differences were evaluated using descriptive statistics and t-test/chi-square analyses. RESULTS: 208 females participated (mean age 35±6 years); 51.4 percent were White/Caucasian and 48.6 percent were non-White/Caucasian women [Black/African American (n=51); Hispanic/Latina (n=23); Asian (n=16); Other (n=ll)]. Age of acne onset (mean 14.8±5 vs. 17.0±8 years, p<0.05) and acne concern occurred earlier (16.6±7 vs. 19.3±9 years, p<0.05) in White/Caucasian than non-White/Caucasian subjects. Facial acne primarily presented on chin (28.0%) and cheeks (30.8%) for White/Caucasian women versus cheeks (58.4%) for non-White/Caucasian women. Non-White/Caucasian women experienced more postinflammatory hyperpigmentation than White/Caucasian women (p<0.0001). Facial acne negatively affected quality of life (QoL) in both groups, and most participants (>70%) reported some depression/anxiety symptoms. More White/Caucasian than non-White/Caucasian women were troubled by facial acne (88.8% vs. 76.2%, p<0.05). Lesion clearance was most important to White/Caucasian women (57.9 vs. non-White/Caucasian 31.7%, p<0.001); non-White/Caucasian females focused on postinflammatory hyperpigmentation clearance (41.6% vs. Caucasian 8.4%, p<0.0001). CONCLUSION: RESULTS highlight racial differences in participant-reported clinical characteristics, attitudes, behaviors, and treatment satisfaction. These findings may inform clinicians about racial differences in facial adult female acne and guide treatment recommendations toward improving care.

Understanding the burden of adult female acne.

OBJECTIVE: Typically regarded as an adolescent condition, acne among adult females is also prevalent. Limited data are available on the clinical characteristics and burden of adult female acne. The study objective was to describe clinical characteristics and psychosocial impact of acne in adult women. DESIGN: Cross-sectional, web-based survey. SETTING: Data were collected from a diverse sample of United States females. PARTICIPANTS: Women ages 25 to 45 years with facial acne (≥25 visible lesions). MEASUREMENTS: Outcomes included sociodemographic and clinical characteristics, perceptions, coping behaviors, psychosocial impact of acne (health-related quality of life using acne-specific Quality of Life questionnaire and psychological status using Patient Health Questionnaire), and work/productivity. RESULTS: A total of 208 women completed the survey (mean age 35±6 years), comprising White/Caucasian (51.4%), Black/African American (24.5%), Hispanic/Latino (11.1%), Asian (7.7%), and Other (5.3%). Facial acne presented most prominently on cheeks, chin, and forehead and was characterized by erythema, postinflammatory hyperpigmentation, and scarring. Average age of adult onset was 25±6 years, and one-third (33.7%) were diagnosed with acne as an adult. The majority (80.3%) had 25 to 49 visible facial lesions. Acne was perceived as troublesome and impacted self-confidence. Makeup was frequently used to conceal acne. Facial acne negatively affected health-related quality of life, was associated with mild/moderate symptoms of depression and/or anxiety, and impacted ability to concentrate on work or school. CONCLUSION: RESULTS highlight the multifaceted impact of acne and provide evidence that adult female acne is under-recognized and burdensome.