Cross-sectional study to develop and describe psychometric characteristics of a patient-reported instrument (PROFFIT) for measuring financial toxicity of cancer within a public healthcare system.

OBJECTIVES: To measure and explain financial toxicity (FT) of cancer in Italy, where a public healthcare system exists and patients with cancer are not expected (or only marginally) to pay out-of-pocket for healthcare. SETTING: Ten clinical oncological centres, distributed across Italian macroregions (North, Centre, South and Islands), including hospitals, university hospitals and national research institutes. PARTICIPANTS: From 8 October 2019 to 11 December 2019, 184 patients, aged 18 or more, who were receiving or had received within the previous 3 months active anticancer treatment were enrolled, 108 (59%) females and 76 (41%) males. INTERVENTION: A 30-item prefinal questionnaire, previously developed within the qualitative tasks of the project, was administered, either electronically (n=115) or by paper sheet (n=69). PRIMARY AND SECONDARY OUTCOME MEASURES: According to the protocol and the International Society for Pharmacoeconomics and Outcomes Research methodology, the final questionnaire was developed by mean of explanatory factor analysis and tested for reliability, internal consistency (Cronbach's α test and item-total correlation) and stability of measurements over time (test-retest reliability by intraclass correlation coefficient and weighted Cohen's kappa coefficient). RESULTS: After exploratory factor analysis, a score measuring FT (FT score) was identified, made by seven items dealing with outcomes of FT. The Cronbach's alpha coefficient for the FT score was 0.87 and the item-total correlation coefficients ranged from 0.53 to 0.74. Further, nine single items representing possible determinants of FT were also retained in the final instrument. Test-retest analysis revealed a good internal validity of the FT score and of the 16 items retained in the final questionnaire. CONCLUSIONS: The Patient-Reported Outcome for Fighting FInancial Toxicity (PROFFIT) instrument consists of 16 items and is the first reported instrument to assess FT of cancer developed in a country with a fully public healthcare system. TRIAL REGISTRATION NUMBER: NCT03473379.

A qualitative analysis and development of a conceptual model assessing financial toxicity in cancer patients accessing the universal healthcare system.

PURPOSE: This paper illustrates a conceptual model for a new patient-reported outcome measure (PROM) aimed at measuring financial toxicity (FT) in oncological setting in Italy, where citizens are provided universal healthcare coverage. METHODS: Focus groups with overall 34 patients/caregivers in three different Italian centers (from Northern, Centre, and Southern Italy) and an open-ended survey with 97 medical oncologists were undertaken. Transcripts from focus groups and the open-ended survey were analyzed to identify themes and links between themes. Themes from the qualitative research were supplemented with those reported in the literature; concepts identified formed the basis for item development that were then tested through the importance analysis (with 45 patients) and the cognitive debriefing (with other 45 patients) to test relevance and comprehension of the first draft PRO instrument. RESULTS: Ten domains were extracted by analyzing 156 concepts generated from focus groups and the open-ended survey. After controlling for redundancy, 55 items were generated and tested through the importance analysis. After controlling comprehension and feasibility through cognitive debriefing interviews, a first version of the questionnaire consisting of 30 items was devised. CONCLUSIONS: This qualitative study represents the first part of a study conducted to develop a new PROM to assess FT in Italy, by using a bottom-up approach that makes the most of patients' experiences and the health system analysis. TRIAL REGISTRATION: clinicaltrials.gov NCT03473379 first posted on March 22, 2018.

Development and validation of a patient-reported outcome tool to assess cancer-related financial toxicity in Italy: a protocol.

INTRODUCTION: Financial toxicity (FT) is a well-recognised problem in oncology. US-based studies have shown that: (a) cancer patients have a 2.7 times risk of bankruptcy; (b) patients who declare bankruptcy have a 79% greater hazard of death; (c) financial burden significantly impairs quality of life (QoL) and (d) reduces compliance and adherence to treatment prescriptions. The aim of the project is to develop and validate a patient-reported-outcome (PRO) measure to assess FT of cancer patients in Italy, where, despite the universal health coverage provided by the National Health Service, FT is an emerging issue. METHODS AND ANALYSIS: Our hypothesis is that a specific FT measure, which considers the relevant sociocultural context and healthcare system, would allow us to understand the main determinants of cancer-related FT in Italy, in order to address and reduce these factors. According to the International Society for Pharmaco-economics and Outcomes Research guidelines on PROs, the project will include the following steps: (1) concept elicitation (from focus groups with patients and caregivers; literature; oncologists; nurses) and analysis, creating a coding library; (2) item generation (using a format that includes a question and a response on a 4-point Likert scale) and analysis through patients' cognitive interviews of item importance within different coding categories to produce the draft instrument; (3) factor analysis and internal validation (with Cronbach's alpha and test-retest for reliability) to produce the final instrument; (4) external validation with QoL anchors and depression scales. The use of the FT measure in prospective trials is also planned. ETHICS AND DISSEMINATION: The protocol is approved by the ethical committees of all the participating centres. The project will tentatively produce a validated tool by the spring 2021. The project might also represent a model and the basis for future cooperation with other European countries, with different healthcare systems and socioeconomic conditions. TRIAL REGISTRATION NUMBER: NCT03473379.

Clinical assessment of patients with advanced non-small-cell lung cancer eligible for second-line chemotherapy: a prognostic score from individual data of nine randomised trials.

PURPOSE: Knowledge of prognostic factors for advanced non-small-cell lung cancer (NSCLC) patients eligible for second-line treatment is scarce. The aim of this study was to assess the prognostic role of a number of routinely collected clinical variables and to provide a summary index to discriminate patients according to probability of survival. METHODS: Individual data from nine randomised trials of second-line treatment in advanced NSCLC were analysed. Primary end-point was overall survival (OS). Cox model, stratified by trial, was used for multivariate analyses, and a prognostic index was provided and validated according to an internal/external procedure. RESULTS: Out of 1239 patients, 1197 patients (97%) had complete information. Median OS was 7.4months. At multivariate analysis, prognosis was significantly influenced by gender (worse in males), performance status (PS), tumour histology (worse in squamous and other histology versus adenocarcinoma), stage (worse in IV versus IIIB), type of previous treatment (worse for patients pretreated with platinum) and response to first-line (worse for patients not obtaining objective response). Prognostic score values range from 0 to 14. When three categories were derived, median overall survival values were equal to 11.6, 7.5 and 3.0months for best (<5), intermediate (5-9) and worst (>9) categories, respectively. CONCLUSION: Prognosis of patients eligible for second-line treatment of advanced NSCLC is significantly conditioned by gender, PS, histology, stage, previous use of platinum and response to first-line. A prognostic score was derived that discriminates well subjects with a relatively more favourable prognosis and those with very short life expectancy.

Cost of insurance policies for investigator-initiated cancer clinical trials in Italy.

BACKGROUND: Clinical trials with non-profit promoters are frequently performed in oncology and represent a highly valuable source of information. METHODS: To describe the costs of insurance policies and their determinants, data were collected from 12 Italian non-profit promoters of cancer trials. The cost of policies was expressed as per-patient premium. RESULTS: Sixty-two quotations issued by only two companies were collected, relative to 44 trials proposed for quotation between December 1998 and February 2003. Only the date of quotation was significantly associated with the cost (P = 0.0003) of quotations by Company A for policies with a deductible, with cost increasing over time. Date of quotation (P = 0.0002), sample size (P = 0.008) and number of study arms (P = 0.02) were independently associated with the cost of no-deductible policies quoted by Company A. Only the number of study arms was significantly associated with cost (P = 0.0001) in no-deductible policies quoted by Company B. CONCLUSION: There is insufficient competition among companies for insurance of cancer trials with non-profit promoters. Many variables that affect the trial risk profile from a clinical perspective are not associated with insurance cost. Date of quotation is among the strongest determinants of the cost, which has sharply increased over time. This trend may become a serious problem for non-profit promoters of cancer clinical trials.

Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.

PURPOSE: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. PATIENTS AND METHODS: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. RESULTS: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. CONCLUSIONS: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Survey of modalities of toxicity assessment and reporting in noncomparative prospective studies of chemotherapy in breast cancer.

PURPOSE: To review how toxicity, a main end point of phase II studies, is assessed and reported in published phase II chemotherapy trials in breast cancer. METHODS: A survey was performed by hand-searching studies published in seven distinguished journals between 1995 and 1999. All selected articles were independently evaluated by two investigators using an ad hoc study report form. Descriptive statistics, contingency tables, and the chi(2) test were applied. RESULTS: Overall, 122 articles were found; 65.6% lacked a statistical study design. Planned modalities for assessment of toxicity were inadequately reported in 20.5% of the studies. The scheduling of assessment of hematologic toxicity varied greatly. Toxicity was predominantly summarized per patient (69.7%). Although overall the World Health Organization scale was adopted more frequently (45.9%), the Common Toxicity Criteria (in different versions) were used more frequently in studies published in journals with a high impact factor (P =.001), in more recently initiated studies (P =.03), in sponsored studies (P =.0006), and in studies with an identifiable statistical design (P =.006). CONCLUSION: The wide diversity in modalities of toxicity assessment and reporting observed in this study suggests that the reliability of the body of published data on the toxicity of chemotherapy in breast cancer may be questionable. Current standards should be revised and harmonized to improve the reliability of such data. A checklist is proposed to help editorial evaluation of assessment and reporting of toxicity in phase II studies.