Search

Bruce Crawford,1 Elizabeth Piault,2 Walter Gotlieb,3 Florence Joulain41Mapi Values, Tokyo, Japan; 2Mapi Values, Boston, MA, USA; 3McGill University, Montreal, Quebec, Canada; 4Sanofi, Paris, FranceBackground: The Ascites Impact Measure (AIM) was developed to record patients' daily experiences of symptoms that trigger a request for a paracentesis.Methods: Development of the AIM followed a rigorous step-wise approach, including a review of the literature, expert opinions, and qualitative research involving patients who experience symptomatic malignant ascites. The AIM's measurement properties were assessed using data from two international trials, including 59 ovarian cancer patients with symptomatic malignant ascites.Results: Following the literature review and expert discussions to develop the conceptual model, ten patients with symptomatic malignant ascites were interviewed in the item elicitation phase, resulting in a draft questionnaire with four questions. Validation analyses consisted of 59 patients pooled from two international trials. Inter-items correlations for the AIM were good (r > 0.60), except for the Pain item. Internal consistency reliability (α = 0.89) improved after removing the Pain item from the Total Symptom score (TSS). Test-retest reliability was sufficient. Scores significantly improved after paracentesis except for the Pain item. Preliminary estimates indicate that a two-point improvement on the three-item TSS (without the Abdominal Pain item) could be interpreted as clinically meaningful.Conclusion: The Abdominal Pain item appears to behave differently than the other three items, and could be more related to cancer. While the validity of the AIM TSS (four-item) is acceptable, removing the Pain item from the TSS scoring algorithm demonstrated better construct validity. In addition, test-retest reliability and responsiveness were found to be similar to the results for the four-item AIM TSS. The Pain item should be used as a supplemental item to the three-item AIM TSS, as it provides additional information about the underlying cancer state.Keywords: ascites impact measure, symptoms, ovarian cancer, paracentesis

Purpose: Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated., Methods: Adults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end., Results: In total, 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% were ever smokers, 30% had lung metastases, 9% had thoracic radiation, 6% had chronic obstructive pulmonary disease, and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI 6%, 12%), with a median follow-up of 23 months. Smoking (HR 2.2, 95% CI 1.1, 4.8) and Black/African-American race (HR 3.4, 95% CI 1.6, 7.5) were significantly associated with ILD; HRs for preexisting lung conditions (HR 1.8, 95% CI 0.9, 3.8) and thoracic radiation (HR 2.3, 95% CI 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic., Conclusions: This real-world population of patients with mBC had a high prevalence of ILD prior to HER2-directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2-directed therapy for mBC augments prior reports. Symptomatic presentation suggests an opportunity for early intervention., (© 2022. The Author(s).)

Purpose: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non-small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC., Methods: Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13., Results: Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly., Conclusion: ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.

As new cancer treatment regimens demonstrate increased potential to improve patients' survival, more focus is directed toward the quality of that extension of life and to obtaining additional information from patients regarding their experience with treatment. The utility of capturing patient-reported treatment-related symptoms to complement traditional clinician-rated symptomatic adverse event reporting is well-documented. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library aimed at capturing patient-reported symptoms to inform the patient perspective on a treatment's tolerability. The U.S. Food and Drug Administration has recommended using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in clinical trials. A practical guideline is needed to inform a priori selection of specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items for use in any given industry-sponsored oncology clinical trial. Standardizing this selection process will foster systematic and consistent data collection as part of drug development and enhance our knowledge on how to use patient-relevant information as part of a treatment's risk/benefit assessment. This article presents methods and consensus recommendations for selecting specific Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events items to include in early-phase and late-phase oncology clinical trials.

Established in 2008, the Patient-Reported Outcome (PRO) Consortium is a collaboration among the US Food and Drug Administration's Center for Drug Evaluation and Research, the Critical Path Institute, the pharmaceutical/biotechnology industry, and other stakeholders. The purpose of the consortium is to qualify PRO instruments through the Center for Drug Evaluation and Research's drug development tool qualification process for use as clinical trial endpoints to support drug approval and product labeling claims. The PRO Consortium has made notable progress toward collaborative development of PRO instruments in the following areas: asthma, mild cognitive impairment, depression, functional dyspepsia, irritable bowel syndrome, non-small cell lung cancer, and rheumatoid arthritis. This progress has come with considerable challenges, including navigating a new and evolving regulatory initiative, gaining consensus on key issues, and maintaining communication and engagement in a precompetitive environment. The purpose of this paper is to describe some of the challenges and lessons learned since the creation of the PRO Consortium in hopes that this information may provide direction and insight for similar collaborations.

Aims: To discuss the importance of patients' treatment goals and perceived goal attainment to better address expectations in the treatment of lower urinary tract symptoms (LUTS), including overactive bladder (OAB)., Methods: The development of the Self-Assessment Goal Achievement (SAGA) questionnaire was driven by measurement principles from the field of qualitative and psychometric research adapted to elicit patients' treatment goals. At baseline, SAGA solicits individualized responses of patient's treatment expectations and goals, and at follow-up SAGA uses a goal-attainment scale (GAS) to document goal achievement., Results: The SAGA questionnaire provides a basis for the patient and physician to discuss realistic treatment expectations and to measure the alignment between patients' expectations and treatment outcomes in terms of improvement in symptoms and impact on function. Therefore, incorporating the SAGA questionnaire into clinical trials may provide an additional dimension of treatment efficacy by incorporating data on treatment satisfaction from the patient's perspective., Conclusions: The SAGA questionnaire is a useful tool for patient-centered discussions about the treatment and management of LUTS, including OAB, and assisting physicians in tracking progress and managing patient expectations during therapy., (© 2013 Wiley Periodicals, Inc.)

Background: A linguistic validation of the Self-Assessment Goal Achievement (SAGA) questionnaire was conducted for 12 European languages, documenting that each translation adequately captures the concepts of the original English-language version of the questionnaire and is readily understood by subjects in the target population., Methods: Native-speaking residents of the target countries who reported urinary problems/lower urinary tract problems were asked to review a translation of the SAGA questionnaire, which was harmonized among 12 languages: Danish, Dutch, English (UK), Finnish, French, German, Greek, Icelandic, Italian, Norwegian, Spanish, and Swedish. During a cognitive debriefing interview, participants were asked to identify any words that were difficult to understand and explain in their own words the meaning of each sentence in the questionnaire. The qualitative analysis was conducted by local linguistic validation teams (original translators, back translator, project manager, interviewer, and survey research expert)., Results: Translations of the SAGA questionnaire from English to 12 European languages were well understood by the participants with an overall comprehension rate across language of 98.9%. In addition, the translations retained the original meaning of the SAGA items and instructions. Comprehension difficulties were identified, and after review by the translation team, minor changes were made to 7 of the 12 translations to improve clarity and comprehension., Conclusions: Conceptual, semantic, and cultural equivalence of each translation of the SAGA questionnaire was achieved thus confirming linguistic validation.

Objectives: To document 1) the content validity and 2) measure improvements in fatigue, using the Fatigue Visual Analogue Scale (VAS) assessment tool in patients with fibromyalgia., Methods: The relevance and comprehensiveness of the Fatigue VAS were tested through a qualitative analysis of 20 subjects' verbatim transcripts from semi-structured qualitative interviews. Data from two randomised, controller trials in fibromyalgia (n=1121) were used to conduct correlation analyses with the Fatigue and Tiredness items from the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form-36 Vitality scale. Known-groups and cross classification analyses were conducted to demonstrate the ability to measure improvement in fatigue using the Fatigue VAS., Results: All subjects spontaneously reported that fatigue was an important symptom to capture in fibromyalgia. The Fatigue VAS was well understood by most subjects (n=18/20). High correlations (Pearson r>0.75) and good agreement (k>0.66) were found between the Fatigue VAS and the FIQ tiredness items no. 16 and 17 and SF-36™ Vitality scale. In both clinical trials there was a substantial separation of approximately 20 points on the mean change in the Fatigue VAS score between responders (>30% improvement in pain VAS) and non-responders., Conclusions: Previous studies have confirmed that fatigue is a major component of the fibromyalgia experience. This current study reports that fibromyalgia patients spontaneously rated fatigue as a highly significant feature of their illness, and supports the use of the Fatigue VAS as a valid questionnaire in fibromyalgia clinical trials.

Introduction and Hypothesis: The Self-Assessment Goal Achievement (SAGA) questionnaire was developed to identify treatment goals and assess goal-achievement in patients with lower urinary tract symptoms (LUTS)., Methods: This study consisted of (1) gathering information on goal setting/attainment concepts, (2) goal elicitation (n = 41 patients with LUTS), (3) cognitive debriefing of draft questionnaire (n = 11), and (4) pilot testing (n = 104)., Results: SAGA consists of baseline (goal-assessment; ranking) and follow-up (goal-achievement) modules. In addition to goals most frequently mentioned, patients can list up to five open goals. Goals most commonly reported as "very important" in pilot testing included reducing urgency (72%), incontinence (65%), and nocturia (64%). Treatment goals spontaneously reported as "very important" were reducing incontinence (45%), nocturia (40%), and frequency (26%)., Conclusions: SAGA may be used to identify treatment goals and assess goal-achievement in patients with LUTS in the clinic and for research (with additional validation). This information may promote patient-physician interaction and help patients establish realistic treatment goals, which may in turn improve treatment adherence and outcomes.

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours., Methods: A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated., Results: Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels., Conclusions: Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.

Objectives: To investigate the validity of a rescored version of the Jenkins Sleep Scale (JSS) to assess the extent of possible bias of a 4-week recall period in assessing sleep in patients with fibromyalgia., Methods: A rescoring algorithm of the JSS was developed. The psychometric properties of the rescored JSS were examined using blinded, observed data from a Phase 2 trial (n=195) in subjects with fibromyalgia. In addition, data from two Phase 3, randomised, controlled trials (n=1,121) in subjects with fibromyalgia were used to further validate the rescored JSS by conducting correlation analyses with other assessments expected to correlate with sleep. These included fatigue and tiredness items from the Fibromyalgia Impact Questionnaire (FIQ), the Functional Outcomes of Sleep Questionnaire (FOSQ), and the Short Form-36 (SF-36™) Vitality scale., Results: Construct validity of the rescored JSS was found to be acceptable, with an internal consistency reliability of α=0.70. Test-retest reliability on stable subjects, defined using the FIQ total score, was also acceptable (ICC=0.70). Moderate to high correlations (Pearson r>0.66) were found with two FIQ items, addressing fatigue and non-restorative sleep, and the SF-36™ Vitality scale; correlations with the original JSS were similar. Both JSS versions were found to be responsive (p<0.0001), and the rescored version accounted for 90% of the variance captured in the original version., Conclusions: These results showed the rescored JSS performed similarly to the original scale, suggesting the original scale's 4-week recall period did not introduce substantial bias in capturing the experience of fibromyalgia-related sleep disturbances.

Aims: To develop and validate a measure of patient satisfaction with treatment in overactive bladder: the Overactive Bladder Satisfaction Questionnaire (OAB-S)., Methods: Development of the questionnaire included a comprehensive literature review, development of a conceptual model, item elicitation and cognitive debriefing interviews with US-English and US-Spanish patients, and assessment of the questionnaire's translatability in other languages. Psychometric validation of the questionnaire was run on a longitudinal, non-randomized study involving 201 OAB patients. Analyses included construct validity, concurrent validity, tests of reliability, known-group validity, and responsiveness (exploratory)., Results: The OAB-S is a patient-completed questionnaire including five scales: OAB Control Expectations (ten items); Impact on Daily Living with OAB (ten items); OAB Control (ten items); OAB Medication Tolerability (six items); and Satisfaction with Control (ten items) and five single-item overall assessments of patient's fulfillment of OAB medication expectations, interruption of day-to-day life due to OAB, overall satisfaction with OAB medication; willingness to continue OAB medication and improvement in day-to-day life due to OAB medication. The hypothesized structure of the questionnaire was supported by statistical analyses. Internal consistency reliability coefficients (ranging from 0.76 to 0.94) and test-retest reliability coefficients (ranging from 0.72 to 0.87) were good for all dimensions. All dimensions except tolerability discriminated well according to self-reported OAB severity level and incontinence status., Conclusion: The OAB-S is a valid, comprehensive instrument to assess satisfaction with treatment of OAB based on independent scales that have demonstrated satisfactory psychometric performance., ((c) 2007 Wiley-Liss, Inc.)