Patient experience of medication administration and development of a Patient Experience and Preference Questionnaire (PEPQ) for patients with advanced or metastatic cancer.

Introduction: A better understanding of patient experience of intravenous (IV) or subcutaneous (SC) routes of administration is fundamental to providing optimal administration of medical therapies to oncology patients. The objective of this study was to examine patient experiences of IV and SC treatment with nivolumab and confirm the relevance of item concepts in the Patient Experience and Preference Questionnaire (PEPQ). The PEPQ is a clinical outcomes' assessment instrument developed to obtain patient-centric data and understand the experience with IV and SC treatment administration. Methods: Embedded qualitative interviews were conducted with a subset of participants from three treatment cohorts with metastatic non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), unresectable or advanced metastatic melanoma, hepatocellular carcinoma (HCC), or colorectal cancer (CRC) from the CA209-8KX clinical trial. Concept elicitation interviews were conducted within 14 days of the initial treatment cycle and patient experiences with IV and SC treatment administration were assessed. Concepts from interviews were mapped to the PEPQ version 1.0 questions to assess relevance and convergence of concepts. Results: Interviews were conducted with 43 trial participants from clinical sites opting to participate from six countries (Argentina, France, the Netherlands, Poland, Spain, and New Zealand). The mean age of sub-study participants was 66 ± 11.3 years (range 24-80 years), and 67.4% (N = 29) were male. Sub-study participants with experience of SC most frequently reported symptoms or signs of injection-related redness (27.9%), itching (14.0%), and pain (of needle), and described the pain as pricking, stinging, or tingling (11.0% each). The amount of pain and time burden were widely endorsed as important factors for satisfaction and related to the route of medication administration. For 11 sub-study participants with experience with both IV and SC treatments, 10 (90.9%) preferred SC over IV treatment administration. Conclusion: This study summarizes the experience and satisfaction of receiving IV or SC treatment and confirms the relevance of the PEPQ in a subgroup of CA209-8KX clinical trial participants with metastatic NSCLC, RCC, melanoma, HCC, and CRC. Participant treatment experience and satisfaction with the route of medication mapped to the PEPQ question content support the relevance of PEPQ v2.0 in clinical trials as a self-report measure.

How patients being treated for non-small cell lung cancer value treatment benefit despite side effects.

PURPOSE: To describe symptoms and side effects experienced by patients with advanced non-small cell lung cancer (NSCLC), assess how patients allocate sensations (i.e. symptoms or side effects) to either the disease or its treatment, and evaluate how patients balance side effects with treatment benefits. METHODS: Qualitative sub-studies were conducted as part of two clinical trials in patients treated for advanced NSCLC (AURA [NCT01802632]; ARCTIC [NCT02352948]). RESULTS: Interviews were conducted with 23 patients and 19 patients in the AURA and ARCTIC sub-studies, respectively. The most commonly experienced symptoms/side effects were respiratory (81% of patients), digestive (76%), pain and discomfort (76%), energy-related (71%), and sensory (62%). Patients identified a sensation as a treatment side effect if they had not experienced it before, if there was a temporal link between the sensation and receipt of treatment, and/or if their doctors consistently told or asked them about it in relation to side effects. Themes that emerged when patients talked about their cancer treatment and its side effects related to the serious nature of their advanced disease and their treatment expectations. Patients focused on treatment benefits, wanting a better quality of life, being hopeful, not really having a choice, and not thinking about side effects. CONCLUSIONS: In these two qualitative sub-studies, patients with advanced NSCLC valued the benefits of their treatment regardless of side effects that they experienced. Patients weighed their options against the seriousness of their disease and expressed their willingness to tolerate their side effects in return for receiving continued treatment benefits.

Willingness to report treatment-related symptoms of immunotherapy among patients with non-small cell lung cancer.

PURPOSE: Immunotherapy is an evolving therapeutic approach for non-small cell lung cancer (NSCLC). This study explored factors involved in patients' perceptions about reporting or not reporting treatment-related symptoms experienced while undergoing immunotherapy. METHODS: Patients receiving immunotherapy for NSCLC were recruited in the USA and Europe. Qualitative interviews were conducted to elicit treatment-related symptoms and explore patients' reasons and motivations for either reporting or not reporting these to their medical teams. Interviews were audio-recorded, transcribed, and coded for qualitative analysis. RESULTS: Sixty-six patients were interviewed (mean age: 62 years; 55% male; 91% with stage IV NSCLC). The most frequent symptoms that patients experienced but did not report were gastrointestinal (23% of patients), respiratory (17%), and energy related (12%). The most common reasons for not reporting symptoms included a perception that they were not severe enough, being unsure whether the experiences were side effects, and deciding that the experiences were expected and could be managed without assistance. Fear of having treatment discontinued was also mentioned but was not a prominent reason. The most common reasons for reporting symptoms were to ascertain if these were normal and expected, and to let the medical team know. Patients emphasized the importance of survival over treatment burden when balancing symptoms with treatment benefits. CONCLUSION: Patients have a range of reasons for not reporting their treatment-related symptoms when undergoing immunotherapy for NSCLC. Reasons are more strongly related to determination of the severity versus manageability of patients' experiences of symptoms than they are to the fear of having treatment discontinued.

The Cystic Fibrosis Impact Questionnaire: qualitative development and cognitive evaluation of a new patient-reported outcome instrument to assess the life impacts of cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) experience significant disease burden, including progressive pulmonary decline and reduced survival. This multicenter qualitative study was conducted to develop a new patient-reported outcome (PRO) measure to assess the impact of CF on patients' quality of life: the Cystic Fibrosis Impact Questionnaire (CF-IQ). Semi-structured qualitative concept elicitation (CE) interviews with patients and caregivers documented CF-related symptoms, impacts, and treatment experiences. Coded interview data were considered alongside existing PROs, published literature, and expert opinion to develop an initial scale. Three rounds of cognitive interviews evaluated respondent comprehension and facilitated refinement of the CF-IQ. RESULTS: Adult (N = 20) and pediatric (N = 22) patients with CF and their parents/caregivers (N = 22) completed CE interviews at 7 US clinics. The sample included patients aged 6-58 years, 57% females, and represented a broad range of disease severity (forced expiratory volume in 1 s range: 22%-127% predicted). Interviews identified 59 unique CF-related impact concepts in domains, including activity limitations (physical, social, leisure), functional limitations (school, work), vulnerability/lack of control, emotional impact, treatment burden, and future outlook. Concept saturation was achieved, and a draft questionnaire was developed. Findings from the cognitive interviews (n = 18) confirmed that instructions, items, and response scales were relevant and clear, and interpreted as intended by patients. CONCLUSION: The CF-IQ is a 40-item novel PRO scale assessing a comprehensive set of patient-relevant concepts to characterize the multifaceted nature of CF. Qualitative interview data support the content validity of the CF-IQ, which is currently undergoing additional psychometric evaluation in patients with CF.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis.

BACKGROUND: Patient-reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies. AIMS: To develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research). METHODS: Concept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi-structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status. RESULTS: In all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31-item Symptoms and Impacts Questionnaire for CD (SIQ-CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29-item Symptoms and Impacts Questionnaire for UC (SIQ-UC) was developed. Both instruments include four symptom and six impact domains. CONCLUSIONS: We developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.

"Lower abdominal pains, as if I was being squeezed in a clamp": A Qualitative Analysis of Symptoms, Patient-Perceived Side Effects and Impacts of Ovarian Cancer.

BACKGROUND: Understanding the patient's perception of their disease is vital for guiding care decisions. The current study aimed to identify the most predominant experiences in women diagnosed with, and treated for, ovarian cancer in terms of disease-related symptoms, treatment-attributed side effects and their impacts. METHODS: Semi-structured qualitative interviews about disease-related symptoms, treatment-attributed side effects and their impacts were conducted with women who were being treated for ovarian cancer in Europe (n = 55) or in the USA (n = 9). The women were also asked to rate the bothersomeness of the symptoms, side effects and impacts that they mentioned during the interview. Symptoms, side effects and impacts were identified from coded interview transcripts using an iterative coding framework. RESULTS: Bloating, abdominal pain, tiredness and frequent urination were the most frequently expressed symptoms, and were reported by 72%, 67%, 64% and 55% of women, respectively, which together constituted approximately 30% of all symptom expressions. The most bothersome symptoms were reported as bloating, abdominal pain, pain in the side, tiredness and fatigue. The most frequently expressed side effects were hair loss, neuropathy, tiredness and nausea, which were reported by 84%, 63%, 61% and 61% of women, respectively. The most bothersome reported side effects were constipation, nausea, diarrhoea, pain in general, fatigue, weakness, reduced sleep quality and hair loss. Feelings of anxiety, concerns about the future, physical functioning, work limitations and the adoption of coping strategies were the most frequently expressed impacts and were reported by 72-80% of women. Impacts reported as the most difficult to deal with were concerns about the future, emotional difficulties in general, physical functioning, sexual functioning, negative self-image, fatigue, sleep difficulties, financial burden and work limitations. CONCLUSIONS: In our qualitative study, the most common and most bothersome experiences reported by women treated for ovarian cancer were symptoms of bloating, abdominal pain and tiredness; side effects of hair loss, nausea and tiredness/fatigue; and impacts relating to concerns about the future, physical functioning and work limitations. We suggest that clinicians measure these experiences consistently and take them into consideration when making treatment decisions.

Quality of life patient-reported outcomes for locally advanced cutaneous melanoma.

Locally advanced cutaneous melanoma has marked quality-of-life implications; however, the patient experience of symptom management and subsequent impact on quality of life has not been well described. This study aims to address the impact on patients of advanced cutaneous melanoma through qualitative interviews. Adults with stage IIIB, IIIC, or IV (M1a) cutaneous melanoma were recruited from two cancer centers in the USA and one in Australia. Telephone interviews were conducted to assess how locoregionally advanced cutaneous melanoma impacted everyday life. Interviews were recorded, transcribed, and coded for qualitative analysis. Twenty-two melanoma patients were interviewed, mean age 69.7 years (range: 52-83), 64% male. The study included stage IIIB (36%), stage IIIC (59%), and stage IV M1a (5%) patients. Emotional health/self-perception issues were the most commonly identified (41% of patient impact expressions), including worry, concern, embarrassment, self-consciousness, fear, and thoughts of death. Limitations of lifestyle and activities were also identified (28% of expressions) including leisure and social activities, physical functioning, general functioning, and personal care. Coping strategies such as modified clothing choices, increased use of pain and/or anti-inflammatory medications, and avoidance/protection from the sun represented 20% of all impact expressions. Ratings of the degree of difficulty patients experienced (using an 11-point numerical rating scale) ranged from 0.0 to 10.0 (mean 5.7, SD 2.9). Condition-related and treatment-related factors were well characterized in patients with locally advanced cutaneous melanoma. This provides a strong foundation for assessment of how cutaneous melanoma impacts quality of life.

Understanding polycystic ovary syndrome from the patient perspective: a concept elicitation patient interview study.

BACKGROUND: The aim of this study was to explore the need for a new disease-specific patient reported outcome (PRO) measure for use in clinical trials of drugs designed to target the underlying causes of polycystic ovary syndrome (PCOS), and in the process contribute to our understanding of the symptoms and impacts that define the patient experience with PCOS. METHODS: Semi-structured interviews were conducted in 20 women diagnosed with PCOS according to the Rotterdam criteria who had not menstruated in the previous month. The relative importance of PCOS symptoms and impact concepts to patients was determined by analyzing the frequency of their expression in the interview transcripts. These insights were compared to clinicians' perceptions of PCOS. RESULTS: Pain- and discomfort-related symptoms accounted for the highest proportion (27.6%) of the 735 patient expressions, although clinicians did not consider pain to be important to patients with PCOS. The most frequently expressed individual symptoms were cramping (70% of patients; 14.7% of concepts), irregular menstruation (95% of patients; 12.2% of concepts), facial hair growth (75% of patients; 10.6% of concepts), heavy bleeding (70% of patients; 8.8% of concepts), infertility (70% of patients; 5.4% of concepts), and bloating (60% of patients; 5.2% of concepts). Cramping, heavy bleeding, and bloating were not identified by clinicians as being important to patients with PCOS. The impacts most frequently reported by patients with PCOS related to emotional well-being (e.g. anxiety/stress) and coping behaviors (e.g. acne medication, hair removal). CONCLUSIONS: The only validated PCOS-specific PRO, the PCOSQ, does not capture some key PCOS symptoms and impacts expressed by patients with PCOS, most notably those related to pain and discomfort, bleeding intensity and coping behaviours. Furthermore, some key PCOS symptoms may be under-recognized in the clinic.

Patient Experience of Symptoms and Side Effects when Treated with Osimertinib for Advanced Non-Small-Cell Lung Cancer: A Qualitative Interview Substudy.

INTRODUCTION: Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. METHODS: Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations. RESULTS: During the first interview (23 patients), the most commonly reported symptoms/side effects were coughing, itching, tiredness (each reported by 56.5% of patients), and rash (43.5%). During the second interview (21 patients), compared with the first interview, shortness of breath and diarrhea were reported by more patients (57.1 and 38.1%, respectively; both increased from 34.8%); tiredness remained predominant (42.9%); and itching (38.1%), coughing (38.1%), and rash (14.3%) were reported by fewer patients. At both interviews, the most frequently reported symptoms/side effects were also those most often rated by patients for bothersomeness and severity, and generally received mean scores in the low-to-moderate range. However, several rarely expressed symptoms/side effects (e.g., abdominal pain, frequent day time urination) received high bothersomeness ratings. At the second interview, patients were highly satisfied with osimertinib and had a low level of difficulty in coping with side effects during treatment. CONCLUSIONS: These data enhance our understanding of patients' experiences of symptoms/side effects, which could increase the accuracy of the osimertinib benefit-risk assessment, guide management of adverse events, and improve the information given to patients receiving the drug.

Impact of erythropoiesis-stimulating agents on energy and physical function in nondialysis CKD patients with anemia: a systematic review.

BACKGROUND: Previous analyses report the impact of erythropoiesis-stimulating agents (ESAs) on health-related quality of life across various populations. In this analysis, we review published studies and quantify the effect of ESA therapy on energy/fatigue and physical function in nondialysis patients with chronic kidney disease (CKD) related anemia. STUDY DESIGN: Systematic literature search to identify articles (1980-2008) that evaluated effects of ESAs on patient-reported energy and physical function. SETTING & POPULATION: Nondialysis CKD patients with anemia enrolled in prospective trials. SELECTION CRITERIA FOR STUDIES: Prospective studies measuring energy or physical function with both baseline and follow-up measurement. INTERVENTION: ESA treatment. OUTCOMES: Improvements in energy and physical function assessed using effect size, a measure of treatment responsiveness. RESULTS: 14 studies were identified: 11 measured energy and 14 measured physical function. The 36-Item Short-Form Health Survey (SF-36) was the most common instrument used to report energy and physical function. Of 11 studies measuring energy, 2 were double-blind randomized placebo-controlled trials (RCTs), 5 were open-label RCTs, and 4 were single-arm open-label studies. Eight of 11 studies reported statistically significant improvements in energy. Effect size for energy ranged from small (0.24) to large (1.90) in ESA-treated groups and was moderate in each arm of the low- versus high-hemoglobin target RCTs. Of 14 studies measuring physical function, 2 were double-blind RCTs, 6 were open-label RCTs, and 6 were single-arm open-label studies. Ten of 14 studies reported statistically significant improvements in physical function. Effect size for physical function ranged from small (0.37) to large (2.38) in ESA-treated groups and was negligible to moderate in each arm of low- versus high-hemoglobin target studies. LIMITATIONS: Findings and conclusions were limited by the available evidence. CONCLUSION: RCTs and single-arm studies indicate that treatment of anemia with ESAs improves energy and physical function in nondialysis CKD patients.

Development and validation of a quality-of-life measure for men with nocturia.

OBJECTIVES: To develop and assess the psychometric properties of a short self-report nocturia-specific Quality-of-Life (QOL) questionnaire. METHODS: The Nocturia Quality-of-Life questionnaire (N-QOL) was developed using focus group interviews with men experiencing nocturia. To refine it further and psychometrically validate the questionnaire, 107 men with nocturia (from four urology clinics in the United Kingdom) completed the pilot N-QOL, along with measures of health status and sleep quality. To assess reproducibility, men from one clinic completed the pilot N-QOL again at 1 week. RESULTS: After standard item reduction analyses, 18 items were dropped from the pilot questionnaire. The psychometric properties of the remaining 13-item instrument were tested in accordance with standard criteria. Factor analysis identified two subscales, sleep/energy and bother/concern, loading at 0.5 and greater. The N-QOL overall score and subscales proved to be internally consistent (alpha = 0.84 to 0.90) and reproducible (intraclass correlation coefficient = 0.74 to 0.82). N-QOL scores correlated with sleep quality (P <0.01) as measured by the Pittsburgh Sleep Quality Index and energy/vitality and social functioning (P <0.01) as measured by the SF-36 Health Survey, demonstrating good convergent validity. The N-QOL also demonstrated statistically significant differences between the scores of those experiencing one, two, and three or more episodes of nocturia on an average night, indicating excellent discriminant validity. CONCLUSIONS: These analyses provide support for the psychometric validity of the N-QOL for use in a male population with nocturia.