Patient-guided dose reduction of tyrosine kinase inhibitors in chronic myeloid leukaemia (RODEO study): study protocol for a prospective, multicentre, single-arm trial.

BACKGROUND: Dose reduction of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukaemia (CML) with an optimal response to TKIs may support cost-effective medication use by maintaining therapeutic effectiveness while reducing adverse events and medication costs. As the choice for dose reduction depends on patients' individual needs and preferences, a patient-centred approach is warranted. Therefore, a study to evaluate the effectiveness of patient-guided dose reduction in patients with CML who are in a major or deep molecular response is designed. METHODS: This study is a prospective, multicentre, single-arm study. 147 patients with CML (aged ≥ 18 years) in chronic phase, who are treated with imatinib, bosutinib, dasatinib, nilotinib or ponatinib, and have reached at least major molecular response (defined as having BCR-ABL levels < 0.1% for an uninterrupted period of 6 months) are eligible. Patients will use an online patient decision aid and a shared decision making consultation will be held, after which patients who choose to will receive a personalised, lower TKI dose. Primary outcome is the proportion of patients with intervention failure at 12 months after dose reduction, defined as patients who have restarted their initial dose due to (expected) loss of major molecular response. For this, BCR-ABL1 levels will be analysed from blood samples drawn at baseline, 6 weeks after dose reduction and 3-monthly thereafter. Secondary outcomes include the proportion of patients with intervention failure at 6 and 18 months after dose reduction. Other outcomes include differences before and after dose reduction regarding the number and severity of patient-reported side effects; quality of life; beliefs about medicines; and medication adherence. Patients' level of decisional conflict and regret after choosing dose reduction will be assessed, as will the decisional process experienced by patients and healthcare providers. DISCUSSION: Outcomes of this trial using a personalised approach will provide clinical and patient-reported data to guide future dose reduction of TKIs in CML. If the strategy appears to be effective, it may be implemented as another valid option to offer next to standard of care to prevent potential unnecessary exposure to higher TKI doses in this selected group of patients. TRIAL REGISTRATION: EudraCT number 2021-006581-20.

A comprehensive eHealth implementation guide constructed on a qualitative case study on barriers and facilitators of the digital care platform CMyLife.

BACKGROUND: Substantial proliferation of eHealth has enabled a move in patient-centred cancer care from the traditional in-person care model to real-time, dynamic, and technology supported on-demand care. However, in general, the uptake of these innovations is low. Studies show that eHealth is helpful in providing patient empowerment through e.g. providing high quality and timely information, enabling self-monitoring and shared decision making, but dropout rates are high and guidance for optimal implementation is lacking. AIM: To explore barriers to and facilitators for nationwide implementation and consolidation of CMyLife, a multi-component, patient-centred, digital care platform, and to construct a comprehensive implementation guide for launching digital care platforms in daily clinical practice. METHODS: The first qualitative case study of a digital care platform like CMyLife was performed including five focus group- and eighteen in-depth interviews with stakeholders. Data were collected using a semi-structured interview guide, based on the frameworks of Grol and Flottorp. Transcripts of the interviews were analysed and barriers and facilitators were identified and categorized according to the frameworks. An iterative process including participation of main stakeholders and using the CFIR-ERIC framework led to creating a comprehensive implementation guide for digital care platforms. RESULTS: In total, 45 barriers and 41 facilitators were identified. Main barriers were lack of connectivity between information technology systems, changing role for both health care providers and patients, insufficient time and resources, doubts about privacy and security of data, and insufficient digital skills of users. Main facilitators mentioned were motivating patients and health care providers by clarifying the added value of use of a digital care platform, clear business case with vision, demonstrating (cost) effectiveness, using an implementation guide, and educating patients and health care providers about how to use CMyLife. Based on these barriers and facilitators a clear and comprehensive implementation guide was developed for digital care platforms. CONCLUSION: Several barriers to and facilitators for implementation were identified, a clear overview was presented, and a unique comprehensive implementation guide was developed for launching future digital care platforms in daily clinical practice. The next step is to validate the implementation guide in other (oncological) diseases.

The Development of a Web-Based, Patient-Centered Intervention for Patients With Chronic Myeloid Leukemia (CMyLife): Design Thinking Development Approach.

BACKGROUND: With the global rise in chronic health conditions, health care is transforming, and patient empowerment is being emphasized to improve treatment outcomes and reduce health care costs. Patient-centered innovations are needed. We focused on patients with chronic myeloid leukemia (CML), a chronic disease with a generally good long-term prognosis because of the advent of tyrosine kinase inhibitors. However, both medication adherence by patients and guideline adherence by physicians are suboptimal, unnecessarily jeopardizing treatment outcomes. OBJECTIVE: The aim of this study was to develop a patient-centered innovation for patients with CML using a design thinking methodology. METHODS: The 5 phases of design thinking (ie, empathize, define, ideate, prototype, and test) were completed, and each phase started with the patient. Stakeholders and end users were identified and interviewed, and observations in the care system were made. Using tools in human-centered design, problems were defined and various prototypes of solutions were generated. These were evaluated by patients and stakeholders and then further refined. RESULTS: The patients desired (1) insights into their own disease; (2) insights into the symptoms experienced, both in terms of knowledge and comprehension; and (3) improvements in the organization of care delivery. A web-based platform, CMyLife, was developed and pilot-tested. It has multiple features, all targeting parts of the bigger solution, including a website with reliable information and a forum, a guideline app, personal medical records with logs of symptoms and laboratory results (including a molecular marker and linked to the guideline app), tailored feedback based on the patients' symptoms and/or results, screen-to-screen consulting, delivery of medication, and the collection of blood samples at home. CONCLUSIONS: The multifeatured innovation, CMyLife, was developed in a multidisciplinary way and with active patient participation. The aim of developing CMyLife was to give patients the tools to monitor their results, interpret these results, and act on them. With this tool, they are provided with the know-how to consider their results in relation to their personal care process. Whether CMyLife achieves its goal and the evaluation of the added value will be the focus of future studies. CML could become the first malignancy for which patients are able to monitor and manage their disease by themselves.

Filling the gaps of patient information needs and information perception in chronic myeloid leukemia with the patient-physician co-produced web-based platform CMyLife.

BACKGROUND: For patients with chronic myeloid leukemia, a web-based platform CMyLife was developed. Its aim is to enhance patient empowerment, by adequate information provision, among others. Before evaluating its effect, information provision and needs in current care were assessed. OBJECTIVE: To assess patients' evaluation of received information and information needs before CMyLife utilization and whether this information source is used correspondingly. Additionally, we explored predicting patient factors in information perception. PATIENT INVOLVEMENT: CMyLife platform was developed with active patient participation. METHODS: We conducted a cross-sectional survey among 203 CML patients before launch of the CMyLife platform, using validated questionnaires on information provision and predictive factors. We focused on website utilization during the first 3 years, using Google Analytics. Regression analyses were performed to determine influence of patient factors on information perception. RESULTS: Global perceived information provision was scored 42.8 (0-100). Information on other services such as rehabilitation and psychological support, and effects of treatment on sexuality showed room for improvement. One out of 3 knew where to find useful health information online. But more information was desired by 36% of them. Age ≥65 years, time since diagnosis and low education were positively associated with this need. Pages on medication and side effects were visited the most. DISCUSSION: To fill the gap in perceived provision and needs, information should be adjusted more to the individual in content, manner and timing. Age, time since diagnosis, and educational level are of influence in perceived information, and specific needs within these groups should be further explored. PRACTICAL VALUE: CMyLife provides reliable and up-to-date information for low eHealth literacy skilled patients concerning multiple topics indicated by patients.

Cancer Survivorship Care: Person Centered Care in a Multidisciplinary Shared Care Model.

Survivors of childhood and adult-onset cancer are at lifelong risk for the development of late effects of treatment that can lead to serious morbidity and premature mortality. Regular long-term follow-up aiming for prevention, early detection and intervention of late effects can preserve or improve health. The heterogeneous and often serious character of late effects emphasizes the need for specialized cancer survivorship care clinics. Multidisciplinary cancer survivorship care requires a coordinated and well integrated health care environment for risk based screening and intervention. In addition survivors engagement and adherence to the recommendations are also important elements. We developed an innovative model for integrated care for cancer survivors, the "Personalized Cancer Survivorship Care Model", that is being used in our clinic. This model comprises 1. Personalized follow-up care according to the principles of Person Centered Care, aiming to empower survivors and to support self management, and 2. Organization according to a multidisciplinary and risk based approach. The concept of person centered care is based on three components: initiating, integrating and safeguarding the partnership with the patient. This model has been developed as a universal model of care that will work for all cancer survivors in different health care systems. It could be used for studies to improve self efficacy and the cost-effectiveness of cancer survivorship care.

Impact of Oral Side Effects from Conditioning Therapy Before Hematopoietic Stem Cell Transplantation: Protocol for a Multicenter Study.

BACKGROUND: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens. OBJECTIVE: The objectives of this prospective international observational multicenter study in hematopoietic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal relationship of oral complications related to conditioning regimens (chemotherapy with or without total body irradiation), stem cell transplantation and the immunologic reactions (mainly graft-vs-host-disease) that may follow, and to determine what subjective and objective oral complications related to treatment can predict negative clinical and economic outcomes and reduced quality of life. METHODS: Adult patients at six study sites receiving full intensity conditioning, reduced intensity conditioning or nonmyeloablative conditioning, followed by autologous or allogeneic hematopoietic stem cell infusion, are included. A pre-treatment assessment includes medical conditions, planned chemo- and radiation therapy regimen, medications, allergies, social history, patient report of oral problems, dental history, subjective oral complaints, objective measures of oral conditions, current laboratory values, dental treatment recommended and untreated dental disease. Starting 1-3 days after hematopoietic stem cell infusion, a bedside assessment is completed 3 days per week until resolution of neutropenia. A patient questionnaire is also completed during hospitalization. Beyond this time, patients with continued oral mucositis or other oral problems are followed 1 day per week in an inpatient or outpatient setting. Additional visits for urgent care for acute oral problems after hospitalization are documented. Autologous transplant patients are being followed up at 100 days (SD 30 days) and at 1 year (SD 30 days) post-transplantation to identify any long-term side effects. Patients treated with allogeneic transplantation are being followed at 100 days (SD 30 days), 6 months (SD 30 days), and 12 months (SD 30 days). The follow-up assessments include cancer response to therapy, current medical conditions, medications, subjective and objective oral findings, quality of life measures and laboratory values. The targeted enrollment is 254 patients who have received HSCT. RESULTS: A total of 260 participants have been enrolled, with 233 (91%) who have received HSCT. We anticipate enrollment of 20-30 additional participants to obtain the sample size of 254 enrolled participants who have received HSCT. CONCLUSIONS: The results of the ongoing prospective study will provide a unique dataset to understand the impact of oral complications on patients undergoing HSCT and provide needed evidence for guidelines regarding the management of this patient cohort.

Development and Evaluation of an Educational E-Tool to Help Patients With Non-Hodgkin's Lymphoma Manage Their Personal Care Pathway.

BACKGROUND: An overload of health-related information is available for patients on numerous websites, guidelines, and information leaflets. However, the increasing need for personalized health-related information is currently unmet. OBJECTIVE: This study evaluates an educational e-tool for patients with non-Hodgkin's lymphoma (NHL) designed to meet patient needs with respect to personalized and complete health-related information provision. The e-tool aims to help NHL patients manage and understand their personal care pathway, by providing them with insight into their own care pathway, the possibility to keep a diary, and structured health-related information. METHODS: Together with a multidisciplinary NHL expert panel, we developed an e-tool consisting of two sections: (1) a personal section for patients' own care pathway and their experiences, and (2) an informative section including information on NHL. We developed an ideal NHL care pathway based on the available (inter)national guidelines. The ideal care pathway, including date of first consultation, diagnosis, and therapy start, was used to set up the personal care pathway. The informative section was developed in collaboration with the patient association, Hematon. Regarding participants, 14 patients and 6 laymen were asked to evaluate the e-tool. The 24-item questionnaire used discussed issues concerning layout (6 questions), user convenience (3 questions), menu clarity (3 questions), information clarity (5 questions), and general impression (7 questions). In addition, the panel members were asked to give their feedback by email. RESULTS: A comprehensive overview of diagnostics, treatments, and aftercare can be established by patients completing the questions from the personal section. The informative section consisted of NHL information regarding NHL in general, diagnostics, therapy, aftercare, and waiting times. Regarding participants, 6 patients and 6 laymen completed the questionnaire. Overall, the feedback was positive, with at least 75% satisfaction on each feedback item. Important strengths mentioned were the use of a low health-literacy level, the opportunity to document the personal care pathway and experiences, and the clear overview of the information provided. The added value of the e-tool in general was pointed out as very useful for preparing the consultation with one's doctor and for providing all information on one website, including the opportunity for a personalized care pathway and diary. The majority of the revisions concerned wording and clarity. In addition, more explicit information on immunotherapy, experimental therapy, and psychosocial support was added. CONCLUSIONS: We have developed a personal care management e-tool for NHL patients. This tool contains a unique way to help patients manage their personal care pathway and give them insight into their NHL by providing health-related information and a personal diary. This evaluation showed that our e-tool meets patients' needs concerning personalized health-related information, which might serve as a good example for other oncologic diseases. Future research should focus on the possible impact of the e-tool on doctor-patient communication during consultations.