Patient Perceptions Regarding Multiple Myeloma and Its Treatment:Qualitative Evidence from Interviews with Patients in the United Kingdom, France, and Germany

BACKGROUND: The current standard of care for multiple myeloma requires several regimens of treatment, with patients experiencing high symptom burden and side effects, which negatively impact health-related quality of life (HRQoL). Thus, it is crucial to understand patient perceptions of multiple myeloma and how patients value different treatment options. OBJECTIVE: The purpose of this study was to conduct an exploratory investigation into concepts that could form attributes that influence treatment choices for patients with multiple myeloma and to identify trade-offs that patients are willing to make between treatment attributes. METHODS: In total, 30 patients with newly diagnosed or relapsed/refractory multiple myeloma from the UK, France, and Germany participated in semistructured interviews talking about their disease experience and symptoms, treatment benefits, treatment burden, perceived side effects, and benefit/risk trade-offs in treatment. The interview audio recordings were transcribed and analyzed using content analysis to identify treatment and disease aspects relevant to patients. RESULTS: Symptoms of fatigue and bone pain and treatment side effects of peripheral neuropathy, diarrhea, and constipation were cited by patients as the most disruptive to their HRQoL. Treatment duration was reported most frequently as a major treatment burden, and patients emphasized the importance of increased life expectancy as a treatment benefit. All patients showed good understanding of benefit/risk trade-offs in treatment, and some patients expressed a preference for more convenient modes of treatment administration. CONCLUSIONS: Qualitative interviews identified key aspects of multiple myeloma treatment that are most important to patients. These findings will inform a wider patient-preferences study, which could improve treatment choice and HRQoL for patients with multiple myeloma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00501-7

Health-related quality of life in patients with relapsed/refractory multiple myeloma treated with pomalidomide and dexamethasone ± subcutaneous daratumumab: Patient-reported outcomes from the APOLLO trial

In the phase 3 APOLLO trial, daratumumab in combination with pomalidomide and dexamethasone (D-Pd) significantly reduced the rate of disease progression or death by 37% relative to Pd alone in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. Here, we present patient-reported outcomes (PROs) from APOLLO. Median treatment duration was 11.5 months with D-Pd and 6.6 months with Pd. PRO compliance rates were high and similar in both groups. No changes from baseline were observed for EORTC QLQ-C30 global health status scores in either group, while physical and emotional functioning, disease symptoms, and adverse effects of treatment remained at baseline levels with D-Pd but worsened with Pd. Reductions (p < 0.05) in pain and fatigue were seen at several time points with D-Pd versus Pd. Overall, these results suggest patients' health-related quality of life remained stable when daratumumab was added to Pd, with several results favoring D-Pd versus Pd. These findings complement the significant clinical improvements observed with D-Pd and support its use in patients with RRMM.The APOLLO study was sponsored by the European Myeloma Network (EMN) in collaboration with Janssen Research & Development, LLC. Medical writing and editorial support were provided by Justine Lempart, PhD, and Linda V. Wychowski, PhD, of Eloquent Scientific Solutions and were funded by Janssen Global Services, LL

Treatment success for overactive bladder with urinary urge incontinence refractory to oral antimuscarinics: a review of published evidence

<p>Abstract</p> <p>Background</p> <p>Treatment options for overactive bladder (OAB) with urinary urge incontinence (UUI) refractory to oral antimuscarinics include: botulinum toxin type A (BoNTA), sacral neuromodulation (SNM), and augmentation cystoplasty (AC). A standard treatment success metric that can be used in both clinical and economic evaluations of the above interventions has not emerged. Our objective was to conduct a literature review and synthesis of published measures of treatment success for OAB with UUI interventions and to identify a treatment success outcome.</p> <p>Methods</p> <p>We performed a literature review of primary studies that used a definition of treatment success in the OAB with UUI population receiving BoNTA, SNM, or AC. The recommended success outcome was compared to generic and disease-specific health-related quality-of-life (HRQoL) measures using data from a BoNTA treatment study of neurogenic incontinent patients.</p> <p>Results</p> <p>Across all interventions, success outcomes included: complete continence (n = 23, 44%), ≥ 50% improvement in incontinence episodes (n = 16, 31%), and subjective improvement (n = 13, 25%). We recommend the OAB with UUI treatment success outcome of ≥ 50% improvement in incontinence episodes from baseline. Using data from a neurogenic BoNTA treatment study, the average change in the Incontinence Quality of Life questionnaire was 8.8 (95% CI: -4.7, 22.3) higher for those that succeeded (N = 25) versus those that failed (N = 26). The average change in the SF-6D preference score was 0.07 (95% CI: 0.02, 0.12) higher for those that succeeded versus those that failed.</p> <p>Conclusion</p> <p>A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of ≥ 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.</p

Literature review to characterize the empirical basis for response scale selection in pediatric populations

Abstract Background Despite the importance of response option selection for patient-reported outcome measures, there seems to be little empirical evidence for the selected scale type. This article provides an overview of the published research on response scale types and empirical support within pediatric populations. Methods A comprehensive review of the scientific literature was conducted to identify response scale option types appropriate for use in pediatric populations and to review and summarize the available empirical evidence for each scale type. Results Eleven review/consensus guideline/expert opinion articles and 20 empirical articles that provided guidance or evidence regarding pediatric response scale selection were identified. There was general consensus that 5-point verbal rating scales, including Likert scales, were appropriate for children aged 7 or 8 and older, while graphical or faces scales are often used in pediatric studies with children of younger ages. Conclusion In general, the verbal rating scale, numeric rating scale, visual analogue scale, and graphical scales have each demonstrated to be reliable and valid response option formats in specific contexts among pediatric populations; however, their appropriateness is dependent upon sample age. When selecting response scales, it is important to consider target population and context of use during the development of patient-reported outcome measures, especially with respect to tense, recall period, attribution, number of options, etc. In addition to age, cognitive development is an important aspect to consider for optimizing pediatric self-reported measures. More research is needed to determine clinically relevant changes and differences within pediatric research, which includes different response scale options

Response scale selection in adult pain measures: results from a literature review

Abstract Background The purpose of this literature review was to examine the existing patient-reported outcome measurement literature to understand the empirical evidence supporting response scale selection in pain measurement for the adult population. Methods The search strategy involved a comprehensive, structured, literature review with multiple search objectives and search terms. Results The searched yielded 6918 abstracts which were reviewed against study criteria for eligibility across the adult pain objective. The review included 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles providing insights into optimal response scale selection for pain assessment in the adult population. Based on the extensive and varied literature on pain assessments, the adult pain studies typically use simple response scales with single-item measures of pain—a numeric rating scale, visual analog scale, or verbal rating scale. Across 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles, the NRS response scale was most often recommended in these guidance documents. When reviewing the empirical basis for these recommendations, we found that the NRS had slightly superior measurement properties (e.g., reliability, validity, responsiveness) across a wide variety of contexts of use as compared to other response scales. Conclusions Both empirical studies and review articles provide evidence that the 11-point NRS is likely the optimal response scale to evaluate pain among adult patients without cognitive impairment

An Adaptation of the Profile of Mood States for Use in Adults With Phenylketonuria

Adults with phenylketonuria (PKU) experience disturbances in mood. This study used qualitative and quantitative techniques to adapt the 65-item Profile of Mood States (POMS) for the assessment of key mood domains in adults with PKU. First, cognitive interviews on 58 POMS items (excluding 7 Friendliness domain items) among 15 adults and adolescents (age ≥16 years) with PKU were conducted to eliminate items poorly understood or considered irrelevant to PKU; 17 items were removed. Next, the remaining POMS items were quantitatively examined (Mokken scaling and Rasch analysis) in 115 adult patients with PKU. An additional 21 items were removed iteratively, resulting in the 20-item draft PKU-POMS. Finally, the psychometric properties of the draft PKU-POMS were examined. The instrument displayed strong psychometric properties (reliability, validity, and responsiveness) over 6 domains (Anxiety, Depression, Anger, Activity, Tiredness, and Confusion) and all items were well understood in the final cognitive interviews with 10 adults with PKU

Assessing the Content Validity of the Investigator-Rated ADHD Rating Scale Version IV Instrument Inattention Subscale for Use in Adults With Phenylketonuria

Content validity of the 18-item Investigator-Rated Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale IV (I-ADHD RS-IV) with adult prompts was investigated using qualitative interviews of US clinicians who had prior experience rating adults with phenylketonuria (PKU) using the I-ADHD RS-IV. Fourteen qualitative interviews were conducted to obtain key symptom experiences of adults with PKU and assessed the relevance, clarity, and administration of the I-ADHD RS-IV. Participants (n = 13, 92.9%) endorsed the inattention symptoms as key experiences by adults with PKU and endorsed the instrument as fit for purpose for adults with PKU. Participants generally reported low frequencies of occurrence for the 9 I-ADHD RS-IV hyperactivity/impulsivity items. Despite some clinicians’ concerns for the lack of patient self-awareness, the participants reported no difficulty selecting a rating on these items. This in-depth study of the content validity of the I-ADHD RS-IV provides evidence that this clinician-reported instrument captures the severity of important inattention symptoms in adults with PKU

Bortezomib, thalidomide, and dexamethasone with or without daratumumab for transplantation-eligible patients with newly diagnosed multiple myeloma (CASSIOPEIA): health-related quality of life outcomes of a randomised, open-label, phase 3 trial

Background: In part 1 of the two-part CASSIOPEIA study, treatment before and after autologous haematopoietic stem-cell transplantation (HSCT) with daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) significantly improved rates of stringent complete response and progression-free survival versus bortezomib, thalidomide, and dexamethasone (VTd) in patients with newly diagnosed multiple myeloma. Methods: CASSIOPEIA is an ongoing randomised, open-label, active-controlled, parallel-group, phase 3 trial done at 111 academic and community practice centres in Europe. Transplantation-eligible adults with newly diagnosed multiple myeloma were randomly assigned (1:1) to D-VTd or VTd. Treatment consisted of four 28-day cycles of induction therapy before autologous HSCT and two 28-day cycles of consolidation therapy after. In this prespecified secondary analysis, patient-reported outcomes were assessed using the European Organization for Research and Treatment of Cancer quality of life questionnaire-core 30-item (EORTC QLQ-C30) and EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaire at baseline, after induction (cycle 4, day 28), and after consolidation (day 100 after autologous HSCT). The analysis was done in all patients in the intention-to-treat population with a baseline and at least one post-baseline patient-reported outcome assessment. The trial is registered at ClinicalTrials.gov (NCT02541383). Findings: Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled and randomly assigned D-VTd (n=543) or VTd (n=542). Questionnaire completion rates were high at baseline (511 [94%] of 543 in the D-VTd group vs 510 [94%] of 542 in the VTd group). Compliance rates (calculated from the number of completed surveys as a proportion of the predicted number of participants still on study treatment) were high at post-induction (431 [84%] of 513 vs 405 [80%] of 509) and post-consolidation (414 [90%] of 460 vs 386 [88%] of 438) assessments and were similar between treatment groups. Mean changes in global health status scores from baseline to post-induction were not different between the D-VTd group (3·8 [95% CI 1·6 to 6·0]) and VTd group (2·9 [0·7 to 5·1]; p=0·43), or from baseline to post-consolidation between the two groups (D-VTd group, 9·7 (95% CI 7·4 to 11·9) vs VTd group, 8·7 (6·5 to 11·0; p=0·45). Improvements from baseline in EORTC QLQ-C30 global health status and EQ-5D-5L visual analogue scale scores were observed in post-consolidation scores in both groups. Post-consolidation scores showed significantly greater mean decreases in pain (−23·3 [95% CI −26·6 to −20·0] in the D-VTd group vs −19·7 [−23·0 to −16·3] in the VTd group; p=0·042), significantly smaller reductions in cognitive functioning (−5·0 [−7·6 to −2·4] vs −7·9 [−10·6 to −5·3]; p=0·036), and significantly greater improvements in emotional functioning (13·0 [10·4 to 15·5] vs 9·5 [6·9 to 12·1]; p=0·013) and in constipation (–3·2 [–7·3 to 0·9] vs 1·8 [–2·4 to 6·0]; p=0·025) with D-VTd versus VTd. Between-group differences in change from baseline for all other scales were not significant. Interpretation: D-VTd and VTd were associated with on-treatment health-related quality of life improvements from baseline in transplantation-eligible patients with newly diagnosed multiple myeloma. The significantly greater reductions in pain, less deterioration of cognitive functioning, and greater emotional functioning improvements complement the clinical benefits observed with D-VTd versus VTd, and support the addition of daratumumab to standard regimens in patients with newly diagnosed multiple myeloma. Funding: Intergroupe Francophone du Myélome, The Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research and Development