Financial Toxicity Questionnaire (FIT): Development and Validation of the Italian Version (FITALY) in Head and Neck Cancer patients

doi:10.21203/rs.3.rs-4313686/v1

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Financial Toxicity Questionnaire (FIT): Development and Validation of the Italian Version (FITALY) in Head and Neck Cancer patients

https://doi.org/10.21203/rs.3.rs-4313686/v1

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Background. Financial toxicity from cancer treatments is rising as an important patient-reported outcome. Its relevance was first assessed in the context of privately financed healthcare system, where the financial hardship caused by out-of-pocket payments negatively affects survival, while fewer evidence exists on its role in countries where care is financed by the public health care system. Head and Neck Cancer (HNC) patients face an increased risk for financial toxicity due to multimodal treatment and relevant out of pocket costs. The aim of this study was to develop and validate an Italian version of the Canadian Financial Index of Toxicity (FIT) questionnaire, defined FITALY.

Methods. FIT questionnaire was translated through a forward-backward process by two investigators independently, and the process was reviewed by a certified medical scientific English native speaker. Once reached consensus upon Italian translation, two Health Economics experts were consulted to adapt the questionnaire to Italian socio-economic context. The FITALY questionnaire v1.0 hereby developed was anonymously administered to two consecutive groups of 30 patients who had received curative, multimodal treatment for HNC cancer at ASST Spedali Civili of Brescia, Italy. A cognitive debriefing form was simultaneously administered to ask patients to exclude recurring and redundant items and include new relevant items.

Results. The 14-item FITALY questionnaire provides a global evaluation of financial toxicity ranging from 0 to 100. The questionnaire is divided into 4 domains: financial burden (6 items), exploring the objective financial toxicity burden; financial distress (2 items), which refers to the psychological distress related to financial toxicity; out-of-pocket costs (4 items), which focus on medical expenses paid by the patient; and loss of productivity (2 items), that investigates the disease impact on both patient’s and caregiver’s job activity.

Conclusions. Starting from the Canadian 9-item FIT questionnaire, we developed and validated the Italian 14-item FITALY questionnaire. Prospective application to a cohort of Italian HNC patients is ongoing.

financial toxicity

head and neck cancer

questionnaire development and validation

supportive care

patient financial burden

Head and Neck Cancer (HNC) represents the fifth most common cancer worldwide (1). Due to a locally advanced presentation at diagnosis in most cases, the therapeutic approach encompasses a multimodal treatment including surgical procedures, radiation therapy, and systemic treatments (2). The intricate and diverse nature of these interventions places a considerable distress on patients, impacting their quality of life, emotional well-being, and financial stability (3). The financial challenges associated with cancer care, also known as “financial toxicity”, represent an emerging issue that can compromise treatment adherence, lead to delayed care-seeking in case of toxicities, and ultimately affect survival outcomes (4-6). Financial toxicity prominence was certified with a survey on patients undergoing active cancer treatments presented at ASCO 2018: on average, patients were more worried about the financial effect of their disease and of the treatments administered than about the risk of dying from cancer (7). Up to 40% of patients experience financial toxicity during their treatment (8). In countries with a private healthcare system, or were out-of-pocket (OOP) payments are the norm, financial toxicity has been identified as a relevant patient-reported outcome (PRO) (9), but its relevance was also proven in countries with social insurance (10-12) or universal healthcare (13-15). Most recent randomized controlled trials started taking into consideration financial toxicity as a relevant PRO, albeit such assessment lacks generalizability to real-world settings due to the use of QoL questionnaires which are not validated to evaluate financial difficulties and the fact that drugs are provided by study sponsor for free, while financial toxicity occurs in real-life settings when patients must pay for the drugs and other medical expenses (16). Moreover, financial toxicity largely depends upon the Healthcare system (universalistic versus private) and socio-economic peculiarities of the single country, so that universal tools for its assessment are unrealistic.

Among all cancer patients, HNC patients face heightened sensitivity to financial toxicity due to social issues, substantial disease burden, treatment-related toxicities requiring support and leading to inability to work and subsequent income loss, and the frequent need for multimodal treatments (17). Few validated questionnaires have been developed to investigate financial toxicity, with some limitations in terms of financial toxicity domains coverage and the health care finance system of the countries considered (18). Among those questionnaires, the Canadian FIT questionnaire emerges as being specific for HNC patients living in a universal healthcare system country (13). However, adaptation of the FIT questionnaire to every single country is paramount to have a tool able to depict precisely financial toxicity in that given nation.

To shed light on the financial toxicity endured by Italian HNC patients, we developed and validated an Italian version of the FIT questionnaire, which we have named “FITALY”.

Questionnaire development procedure included translation and adaption to Italian context. The translation process consisted of a forward-backward Italian translation, performed by two Italian-native speaking research team members (CC and DS). First, they independently translated the FIT questionnaire into Italian and then reached consensus upon a unique translation (Supplementary S1). Subsequently, the Italian questionnaire was translated back into American English, and once again a unique translation was agreed by the two different team members (LL and DM). The entire forward-backward translation process was then reviewed by a certified medical scientific English native speaker, who also evaluated the similarity of the original and back-translated English versions of the questionnaire.

Italian context adaption was performed by two experts in the field of Health Economics (RL and RM), with the aim to make the questionnaire items suitable to Italian health and social care system.

Questionnaire validation process was carried out by administering the provisional questionnaire (v 1.0, Supplementary S2) and a Cognitive Debriefing (CD) form (Supplementary, S5) to 60 patients who already received a multimodal curative treatment for HNC (defined as at least two treatments received between surgery, radiotherapy, and systemic treatment), regardless of their disease status at the time of questionnaire administration. Patients were consecutively enrolled at the Medical Oncology Unit and the ENT Department of the ASST Spedali Civili of Brescia. Salivary glands, nasopharyngeal, and sinonasal primaries were allowed, while skin and thyroid cancers were excluded. The choice of including only patients who had already been treated was aimed at depicting real-life patients own insights and experience with financial toxicity during curative treatment rather than their worries and expectations before treatment start. The 60 patients were divided into two subsequent rounds of 30 patients to obtain a 2-step validation process.

CD questioned the patients about the ease of understanding the questionnaire, the presence of items that were superfluous or deemed as repetitive, and the possibility of including additional items suggested by the patients themselves according to their personal experience, with the aim of investigating fields not explored by the original questionnaire. The cut-off for applying the changing suggested by patients through the CD form was set at ≥ 10% disagreement rate for each item.

The final version of the FITALY questionnaire underwent a backward American English translation, with the process then being reviewed by a certified medical scientific English native speaker.

The study was approved by the Ethical Committee of ASST Spedali Civili of Brescia (NP 5560).

Metterei anche qui le iniziali tra parentesi

Il provisional questionnaire lo metterei come supplementary, mentre il CD lo metterei come figura nel testo, serve per capire come è stato fatto il processo di validazione

The translation process led to an Italian version of the FIT questionnaire, consisting of 9 items. Health Economics experts adapted the questionnaire to the Italian peculiarities checking the appropriateness of items wording and including 1 item about the possibility for patients to use personal savings to address financial toxicity (item 6 in the final version of the FITALY questionnaire). The 10-item questionnaire hereby developed was defined FITALY v1.0 (Supplementary S2) and underwent the validation process. In detail, between December 2022 and January 2023 the FITALY v1.0 questionnaire and the CD form were administered to two groups of 30 consecutive outpatients each. The first round of the validation process led to: modify 3 items (in the final version, items 4, 13, and 14); eliminate item 2; and include 4 new items concerning about out-of-pocket costs upon patients’ suggestion (in the final version, items 8, 9, 10-11, and 12). The so-developed 13-item FITALY questionnaire v2.0 (Supplementary S3) then underwent the second round of the validation process, being administered along with the CD to 30 HNC patients different from the ones of the first round. A significant disagreement was observed only for the newly introduced items: one item was modified according to patients’ comments (in the final version, item 9) and one was split into 2 items (in the final version, items 10 and 11) (Supplementary S4). The entire process of questionnaire development and validation is graphically described in Fig. 1.

The 14 items of the final version of the FITALY questionnaire (Fig. 2) were divided into four subdomains, to integrate the inner subdivision of the FIT questionnaire: financial burden (“financial stress” in the FIT questionnaire), which analyzes the objective burden of financial toxicity faced by the patient (items 3, 4, 5, 6, 7, and 12); financial distress (“financial strain” in the FIT questionnaire), which focuses on the psychological distress felt by the patient and correlated to financial toxicity (items 1 and 2); out-of-pocket cost (not existing in the FIT questionnaire), which focuses on the costs not covered by the universal health care system and therefore paid by the patients (items 8, 9, 10, and 11); and loss of productivity (equal to the subdomain present in the FIT questionnaire), which investigates the impact on patient’s and caregiver’s working capability. This internal division allows to calculate 5 scores: one for each of the three subdomains and a global score (Fig. 3). Each score can be calculated by multiplying by 100 the average value of responses to items defining a given domain/subdomain.

The final version of the FITALY questionnaire was finally backward translated to American English, in order to make this tool accessible to further language validation works in other countries with a universal health care system (Supplementary S6).

The process of backward-forward translation of the FIT questionnaire, Italian adaptation by two Health Economics experts, and validation, based on patients’ opinion collected throughout a two-round cognitive debriefing procedure, has led to develop a 14-item questionnaire specific for Italian HNC patients undergoing curative treatment, with a specific focus on out-of-pocket costs in a universal health care system and patient’s psychological distress related to financial toxicity.

Understanding the financial toxicity of cancer patients is becoming paramount for healthcare practitioners and the healthcare system. Several studies have outlined the association between cancer and financial hardship regardless of healthcare finance models, leading to consider financial toxicity as a relevant PRO that should be kept into consideration in each patient undergoing cancer treatments. Moreover, this aspect could not only impact on patients’ quality of life after treatment, but also on the quality of treatments themselves, meaning that patients could choice to not pursue the best treatment options due to economical constraints, with a detrimental effect on oncological outcomes. In order to tackle this issue, defining its real scope and identifying the tools most useful for patients to overcome it, several questionnaires have been developed – even if most of them focus on privately financed health care countries and do not properly assess the financial distress of the patients (18). The administration of such questionnaires has led to identify HNC patients as a target population at risk for financial hardship. In a retrospective analysis of cancer surveyors from the Medical Expenditure Panel Survey dataset, HNC patients (489 patients) compared to patients with other cancers (16,282 patients) reported higher median annual medical expenses ($8,384 vs $5,978; difference $2,406, 95% CI: $795-$4,017) and higher relative OOP expenses (3.93% vs 3.07%; difference 0.86%, 95% CI: 0.06%-1.66%) (4). In a prospective survey based on the administration of COST questionnaire to HNC patients in follow-up at an academic US cancer center, patients with lower COST scores reported greater privations, such as decreasing spending on food and clothing (54%), using savings (43%), and borrowing money (13%) in order to pay for treatment, and were significatively more likely to make medical sacrifices such as not taking all prescribed/recommended nutritional supplements, supportive medications, and pain medications, skipping clinic visits, and refusing recommended tests when compared to non-HNC cancer patients (19). Another prospective survey was conducted in Leipzig University Hospital, administering a slightly modified version of the questionnaire by Mehlis et al. (20) to 209 HNC survivors in the aftercare setting (12). About 60% of patients reported a significant financial burden as a consequence of OOP costs, esteemed to be on average 1’716€ per year, and/or income loss, with mean monthly income loss of 620€ (12). Advanced TNM stage, T3 or T4 category, and larynx/hypopharynx site were statistically significant predictors of higher financial burden [OR 2.908 (1.539–5.493); p-value 0.0008] (12). A recent systematic review of published studies measuring financial toxicity in HNC patients confirms the relevance of financial toxicity in HNC patients but highlights high discrepancies for what concerns the magnitude of patients’ hardship considering heterogeneity in definitions and tools of measurement along with different countries healthcare systems – thus limiting the chance to produce solid evidence (21). Even fewer evidence is reported about the strategies to tackle financial toxicity (21). A possible solution model comes from the results of a single institution, retrospective analysis of a cohort of American HNC patients treated with radiotherapy, where from a specific date a financial counsellor was offered to patients: those who did not receive financial counseling showed a significantly worsening of financial difficulty after treatment (based on EORTC QLQ-C30), while no relevant difference was seen in patients who received financial counseling (22). A recent published ESMO Expert Consensus on the screening and management of financial toxicity in cancer patients state that financial counselling by a dedicated professional (i.e., a social worker) should be offered to all patients starting a treatment with curative or palliative intent, as well as to cancer survivors, tailoring the frequency according to factors such as cancer stage, risk of cancer recurrence and potential for late complications, including secondary cancers (23).

Moving our focus to the Italian picture, a survey led by the Italian Federation of Volunteer Associations in Oncology (FAVO) in 2018 showed that Italian health care system covers 74% of healthcare expenses, with an average annual OOP expense for each cancer patient estimated to be €1,841 (24). A pooled analysis of the results of the administration of EORTC QOL C30 questionnaire item 28 in 3,670 Italian patients from 16 prospective, multicenter trials in lung, breast and ovarian cancer showed that financial burden at baseline was not associated with the risks of death (HR 0.94, 95% CI: 0.85-1.04, p 0.23) and severe toxicity (OR 0.90, 95% CI: 0.76-1.06, p 0.19), but was predictive of worse global QOL response (OR 1.35, 95% CI: 1.08-1.70, p 0.009) (25). Financial toxicity developed during treatment was significantly associated with an increased risk of death (HR 1.20, 95% CI: 1.05-1.37, p 0.007) (25).

In view of the great variability of Health systems and country-specific socio-economic and cultural peculiarities, it is paramount to have a dedicated tool for each single context. In Italy, the first questionnaire developed to assess financial toxicity was the 16-item PROFFIT questionnaire (Patient-Reported Outcome for Fighting FInancial Toxicity), which was validated on Italian patients affected by solid or hematological malignancies who were receiving or had received within the previous 3 months whatever type of medical anticancer treatment (including radiotherapy, chemotherapy, and other systemic treatments) (26). However, we found crucial to develop a new specific tool for HNC patients for several reasons: a) the special characteristics of HNC patients, whose socio-economic status is often lower compared to those with other types of cancer, and therefore with higher risk for financial toxicity; b) the peculiarity of the acute side effects of their multimodal treatments, with an impact on functions as eating, drinking, swallowing, breathing; c) the impact of long-term treatment-related sequelae (i.e., xerostomia, dysphagia, tracheotomy, etc.), which are associated to increased OOP medicaments and need for at home support, and may affect the ability to work; d) the need of pointing at the psychological distress felt by the patients, that is instead overlooked by the PROFFIT questionnaire. In light of the above, FITALY questionnaire may represent a precious tool for prospective trials investigating financial toxicity in HNC patients in Italy.

Starting from the Canadian FIT questionnaire, we developed and validated the FITALY questionnaire, which provides a new tool to investigate financial toxicity in Italian HNC patients. A prospective, observational, multicenter study based on this questionnaire is currently ongoing to investigate the impact of financial toxicity on oncological outcomes and quality of life in Italian HNC patients.

Ethics approval and consent to participate: The study was approved by the Ethical Committee of ASST Spedali Civili of Brescia (NP 5560)
Consent for publication: This manuscript does not contain any individual person’s data
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Competing interests: The authors declare that they have no competing interests.
Funding: This project received no funding
Authors contributions: Davide Smussi and Carlo Conti (conception, design of the work, data acquisition and analysis, manuscript writing, manuscript revision, graphic content), Luigi Lorini (conception, design of the work, manuscript revision), Davide Mattavelli (conception, design of the work, manuscript revision), Rossella Levaggi (conception, design of the work, manuscript revision), Raffaele Miniaci (design of the work), Stefano Calza (design of the work, data analysis), Alberto Deganello (conception), Consiglia Paduano (data management and acquisition), Andrea Alberti (manuscript revision), Salvatore Grisanti (manuscript revision), Carla Ida Ripamonti (design of the work, manuscript revision), Alfredo Berruti (manuscript revision, mentorship), Cesare Piazza (manuscript revision, mentorship), Paolo Bossi (conception, design of the work, mentorship, manuscript revision). All the authors have approved the submitted version
Acknowledgements: we would like to thank all the patients that voluntarily took part in the process of questionnaire validation

Head and Neck Cancer (HNC)
Financial Index of Toxicity (FIT)
Out-of-pocket (OOP)
Patient-reported outcome (PRO)
Quality of life (QoL)
Cognitive Debriefing (CD)
Italian Federation of Volunteer Associations in Oncology (FAVO)
Patient-reported outcome for fighting financial toxicity (PROFFIT)

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
Chow LQM. Head and Neck Cancer. N Engl J Med. 2020;382(1):60-72.
Carrera PM, Kantarjian HM, Blinder VS. The financial burden and distress of patients with cancer: Understanding and stepping-up action on the financial toxicity of cancer treatment. CA Cancer J Clin. 2018;68(2):153-65.
Massa ST, Osazuwa-Peters N, Adjei Boakye E, Walker RJ, Ward GM. Comparison of the Financial Burden of Survivors of Head and Neck Cancer With Other Cancer Survivors. JAMA Otolaryngol Head Neck Surg. 2019;145(3):239-49.
Ma SJ, Iovoli AJ, Attwood K, Wooten KE, Arshad H, Gupta V, et al. Association of significant financial burden with survival for head and neck cancer patients treated with radiation therapy. Oral Oncol. 2021;115:105196.
Shariff-Marco S, DeRouen MC, Yang J, Jain J, Nelson DO, Weden MM, et al. Neighborhood archetypes and breast cancer survival in California. Ann Epidemiol. 2021;57:22-9.
The Harris Poll: ASCO 2018 Cancer Opinions Surveys. 2018.
Yabroff KR, Dowling EC, Guy GP, Banegas MP, Davidoff A, Han X, et al. Financial Hardship Associated With Cancer in the United States: Findings From a Population-Based Sample of Adult Cancer Survivors. J Clin Oncol. 2016;34(3):259-67.
de Souza JA, Yap BJ, Wroblewski K, Blinder V, Araújo FS, Hlubocky FJ, et al. Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST). Cancer. 2017;123(3):476-84.
Büttner M, König HH, Löbner M, Briest S, Konnopka A, Dietz A, et al. Out-of-pocket-payments and the financial burden of 502 cancer patients of working age in Germany: results from a longitudinal study. Support Care Cancer. 2019;27(6):2221-8.
Honda K, Gyawali B, Ando M, Kumanishi R, Kato K, Sugiyama K, et al. Prospective Survey of Financial Toxicity Measured by the Comprehensive Score for Financial Toxicity in Japanese Patients With Cancer. J Glob Oncol. 2019;5:1-8.
Rast J, Zebralla V, Dietz A, Wichmann G, Wiegand S. Cancer-associated financial burden in German head and neck cancer patients. Front Oncol. 2024;14:1329242.
Hueniken K, Douglas CM, Jethwa AR, Mirshams M, Eng L, Hope A, et al. Measuring financial toxicity incurred after treatment of head and neck cancer: Development and validation of the Financial Index of Toxicity questionnaire. Cancer. 2020;126(17):4042-50.
Martino R, Ringash J, Durkin L, Greco E, Huang SH, Xu W, et al. Feasibility of assessing patient health benefits and incurred costs resulting from early dysphagia intervention during and immediately after chemoradiotherapy for head-and-neck cancer. Curr Oncol. 2017;24(6):e466-e76.
Pauge S, Surmann B, Mehlis K, Zueger A, Richter L, Menold N, et al. Patient-Reported Financial Distress in Cancer: A Systematic Review of Risk Factors in Universal Healthcare Systems. Cancers (Basel). 2021;13(19).
Olivier T, Haslam A, Prasad V. Is financial toxicity captured in quality of life assessments in oncology randomized clinical trials? J Cancer Policy. 2023;36:100423.
de Souza JA, Kung S, O'Connor J, Yap BJ. Determinants of Patient-Centered Financial Stress in Patients With Locally Advanced Head and Neck Cancer. J Oncol Pract. 2017;13(4):e310-e8.
Witte J, Mehlis K, Surmann B, Lingnau R, Damm O, Greiner W, et al. Methods for measuring financial toxicity after cancer diagnosis and treatment: a systematic review and its implications. Ann Oncol. 2019;30(7):1061-70.
Beeler WH, Bellile EL, Casper KA, Jaworski E, Burger NJ, Malloy KM, et al. Patient-reported financial toxicity and adverse medical consequences in head and neck cancer. Oral Oncol. 2020;101:104521.
Mehlis K, Witte J, Surmann B, Kudlich M, Apostolidis L, Walther J, et al. The patient-level effect of the cost of Cancer care - financial burden in German Cancer patients. BMC Cancer. 2020;20(1):529.
Raggini E, Mattavelli D, Zigliani G, Bossi P, Piazza C. Measuring financial toxicity in head and neck cancer: a systematic review. Acta Otorhinolaryngol Ital. 2024;44(1):1-12.
Farrugia M, Yu H, Ma SJ, Iovoli AJ, Erickson K, Wendel E, et al. Financial Counseling Is Associated with Reduced Financial Difficulty Scores in Head and Neck Cancer Patients Treated with Radiation Therapy. Cancers (Basel). 2021;13(11).
Carrera PM, Curigliano G, Santini D, Sharp L, Chan RJ, Pisu M, et al. ESMO expert consensus statements on the screening and management of financial toxicity in patients with cancer. ESMO Open. 2024;9(5):102992.
De Lorenzo F, FDel C, Iannelli L. Indagine sui costi sociali ed economici del cancro nel 2018 in 11 Rapporto sulla condizione assistenziale dei malati oncologici. Oncologia FFIdAdVi. 2018.
Perrone F, Jommi C, Di Maio M, Gimigliano A, Gridelli C, Pignata S, et al. The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy. Ann Oncol. 2016;27(12):2224-9.
Riva S, Arenare L, Di Maio M, Efficace F, Montesarchio V, Frontini L, et al. 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. BMJ Open. 2021;11(10):e049128.

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Financial Toxicity Questionnaire (FIT): Development and Validation of the Italian Version (FITALY) in Head and Neck Cancer patients

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