The development and analysis of a Japanese modern comprehensive clinical data management training program.

Background: Clinical data management (CDM) collects, integrates, and makes data available. It plays a vital role in clinical research. However, there are few opportunities for Japanese clinical data managers to learn about its systematic framework, particularly in academic research organizations. While Japanese-language CDM training exists, its effectiveness in a Japanese context requires clarification. Objectives: We aimed to develop an advanced program of instruction for professionals to understand CDM and to determine the effectiveness of the training program. Methods and results: We developed an advanced program including risk-based monitoring and the Clinical Data Interchange Standards Consortium on a trial basis for clinical data managers to provide them with a comprehensive understanding of CDM. Fifty-two people attended the program and reported that they were highly satisfied with it. Conclusions: To provide comprehensive CDM training in Japan, it is imperative to continue improving the content and develop an advanced program. Due to the recent tightening of clinical research regulations and the development and dissemination of various systems for conducting clinical research, the competency-based educational program requires further development.

Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

Protocol for the ASTRO study (SSOP-01): a multicentre prospective cohort study investigating adverse events based on electronic patient-reported outcomes in patients with breast cancer after adjuvant chemotherapy.

INTRODUCTION: Symptom-related adverse events associated with perioperative chemotherapy in patients with breast cancer include short-term adverse events such as nausea and vomiting. However, changes in the severity and duration of prolonged symptom-related adverse events have not been fully investigated. We present a protocol of a study that aims to clarify the prevalence of symptom-related adverse events in patients with breast cancer 1 year after neoadjuvant or adjuvant chemotherapy using an electronic patient-reported outcomes (ePRO) system. METHODS AND ANALYSIS: This multicentre prospective observational cohort study will include patients with breast cancer who have received preoperative or postoperative adjuvant chemotherapy. The final injection date of the cytotoxic agent will be the study initiation date. Patients will report every 2 weeks from the initiation date to 12 weeks and every 4 weeks from 12 weeks to 1 year, and they can enter this information into the ePRO system from anywhere. The primary outcome will be the prevalence of symptom-related adverse events according to the ePRO system 1 year after the date of the last injection of the cytotoxic drug used in neoadjuvant or adjuvant chemotherapy for breast cancer. To increase multi-institutional enrolment, two cohorts will be included. Cohort 1 will comprise patients with acquisition of baseline patient information regarding preoperative chemotherapy and presurgery characteristics. Cohort 2 will comprise patients without acquisition of baseline patient information. The target sample size is ≥250 per year. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee at each participating institution. The results will be presented at major national and international conferences and submitted to peer-reviewed journals. TRIAL STATUS: Registration was started in October 2021. By August 2022, a total of 132 participants were enrolled. Follow-up will be continued through December 2024. TRIAL REGISTRATION NUMBER: UMIN000045422.

Preoperative steroid for enhancing patients' recovery after head and neck cancer surgery with free tissue transfer reconstruction: protocol for a phase III, placebo-controlled, randomised, double-blind study (J-SUPPORT 2022, PreSte-HN Study).

INTRODUCTION: There is no established methodology for the perioperative management of head and neck cancer surgery and free tissue transfer reconstruction (HNS-FTR). A single dose of corticosteroid administered immediately before surgery has been shown to reduce postoperative pain and nausea/vomiting after some types of surgery. However, the efficacy of this strategy has not been demonstrated in HNS-FTR, and the increased risk of infectious complications associated with its use cannot be ruled out. This phase III, placebo-controlled, randomised, double-blind, comparative, multicentre study seeks to determine if preoperative administration of corticosteroid hormone has an adjunctive effect in terms of reducing pain and nausea/vomiting after surgery and improving the quality of postoperative recovery. METHODS AND ANALYSIS: Using the minimisation method, patients undergoing HNS-FTR are currently being recruited and randomly assigned to a study arm at a 1:1 allocation rate. The study treatment arm consists of 8.0 mg of dexamethasone phosphate dissolved in 100 mL of saline administered as a single dose by intravenous infusion. These treatments will be administered in a double-blind fashion. All patients will receive perioperative care according to the common multicentre enhanced recovery after surgery programme. The primary endpoint is the quality of postoperative recovery, as determined by the area under the curve (AUC) for total score on the Japanese version of the Quality of Recovery Score (QOR-40J) on postoperative days 2 and 4. The point estimate and CI for the difference in the AUC between the groups on postoperative days 2 and 4 will be calculated. ETHICS AND DISSEMINATION: The study will be performed in accordance with the Declaration of Helsinki and Japan's Clinical Trials Act. The study protocol was approved by the Certified Review Board of National Cancer Center Hospital East (Reference K2021004). TRIAL REGISTRATION NUMBER: The study was registered in the Japan Registry of Clinical Trials (jRCTs031210593; V.3.0, November 2021, available at https://jrct.niph.go.jp/en-latest-detail/jRCTs031210593).

Smartphone Psychotherapy Reduces Fear of Cancer Recurrence Among Breast Cancer Survivors: A Fully Decentralized Randomized Controlled Clinical Trial (J-SUPPORT 1703 Study).

PURPOSE: Fear of cancer recurrence (FCR) is a common distressing condition. We investigated the efficacy of smartphone problem-solving therapy and behavioral activation applications in breast cancer survivors. METHODS: This was a decentralized randomized trial. Participants were disease-free breast cancer survivors age 20-49 years who were randomly assigned to the smartphone-based intervention or waitlist control. Both groups received treatment as usual. The control group could access the smartphone apps during weeks 8-24. The intervention comprised smartphone problem-solving therapy and behavioral activation apps. The primary end point was the Concerns About Recurrence Scale at week 8. Secondary outcomes included the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), the Hospital Anxiety and Depression Scale (HADS), the Short-form Supportive Care Needs Survey (SCNS-SF34), and the Posttraumatic Growth Inventory at weeks 8 and 24 (trial registration: UMIN-CTR: UMIN000031140). RESULTS: The intervention group included 223 participants, and the control group included 224 participants. Primary outcome data were obtained for 444 participants, and 213 participants in the intervention arm completed the week 24 assessment. The intervention group had statistically greater improvements than controls at week 8 on the Concerns About Recurrence Scale (difference -1.39; 95% CI, -1.93 to -0.85; P < .001), FCRI-SF (difference -1.65; 95% CI, -2.41 to -0.89; P < .001), HADS depression (difference -0.49; 95% CI, -0.98 to 0; P < .05), and SCNS-SF34 psychological domain (difference -1.49; 95% CI, -2.67 to -0.32; P < .05). These scores at week 24 were not statistically significant compared with week 8 although the HADS depression score at week 24 was significantly reduced (P = .03). CONCLUSION: Novel smartphone psychotherapy offers a promising way to reduce FCR given the large number of survivors and a limited number of therapists to competently conduct psychotherapy.

Phase 3 Randomized Trial of Topical Steroid Versus Placebo for Prevention of Radiation Dermatitis in Patients With Head and Neck Cancer Receiving Chemoradiation.

PURPOSE: Radiation dermatitis is one of the most common acute toxicities induced by chemoradiation therapy (CRT) for head and neck cancer (HNC). The benefit of topical steroids in the management of radiation dermatitis is still unclear. This phase 3, multi-institutional, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of topical steroids for radiation dermatitis in patients with locally advanced HNC receiving CRT. METHODS AND MATERIALS: Eligible patients were scheduled to receive bilateral neck irradiation (≥66 Gy) with concurrent cisplatin (≥200 mg/m2) as definitive or postoperative CRT. Patients were randomly assigned to receive either topical steroid or placebo when grade 1radiation dermatitis was observed or the total radiation dose reached 30 Gy. Basic skin care including gentle washing and moistening in the head and neck region was performed in both groups. The primary endpoint was the frequency of grade ≥2 radiation dermatitis, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grading of radiation dermatitis was performed by independent central review using photographs taken weekly. RESULTS: A total of 211 patients were enrolled (intention to treat: steroid 101 and placebo 102). The frequency of grade ≥2 radiation dermatitis was not significantly reduced with the steroid (73.3%; 95% confidence interval, 64.6%-81.9%) compared with the placebo (80.4%; 95% confidence interval, 72.7%-88.1%; P = .23), whereas the steroid significantly reduced the frequency of grade ≥3 radiation dermatitis (13.9% vs 25.5%; P = .034). No significant differences in adverse events, including local infection or compliance with CRT, were observed between the groups. CONCLUSIONS: Topical steroid may reduce the severity of radiation dermatitis in patients with HNC and thus may become an important therapeutic tool in the management of radiation dermatitis.

Nurse-led, screening-triggered, early specialised palliative care intervention programme for patients with advanced lung cancer: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: It has been suggested that palliative care integrated into standard cancer treatment from the early phase of the disease can improve the quality of life of patients with cancer. In this paper, we present the protocol for a multicentre randomised controlled trial to examine the effectiveness of a nurse-led, screening-triggered, early specialised palliative care intervention programme for patients with advanced lung cancer. METHODS AND ANALYSIS: A total of 206 patients will be randomised (1:1) to the intervention group or the control group (usual care). The intervention, triggered with a brief self-administered screening tool, comprises comprehensive need assessments, counselling and service coordination by advanced-level nurses. The primary outcome is the Trial Outcome Index of the Functional Assessment of Cancer Therapy (FACT) at 12 weeks. The secondary outcomes include participants' quality of life (FACT-Lung), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), illness perception (Prognosis and Treatment Perceptions Questionnaire), medical service use and survival. A mixed-method approach is expected to provide an insight about how this intervention works. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of the National Cancer Center Japan (approval number: 2016-235). The findings will be disseminated through peer-reviewed publications and conference presentations and will be reflected on to the national healthcare policy. TRIAL REGISTRATION NUMBER: UMIN000025491.

Hydrocolloid dressing as a prophylactic use for hand-foot skin reaction induced by multitargeted kinase inhibitors: protocol of a phase 3 randomised self-controlled study.

INTRODUCTION: Although topical use of moisturisers is slightly effective for the prevention and avoiding the aggravation of hand-foot syndrome induced by multikinase inhibitors, there is still room for improvement. Hydrocolloid dressing is a type of wound dressing often used for wounds such as decubitus ulcers. The purpose of this study is to verify the usefulness of application of hydrocolloid dressings as prophylaxis against development of hand-foot syndrome induced by multikinase inhibitors by comparing the effects of this dressing and standard supportive care (moisturising care alone) within the same individuals. METHODS: This study is a phase 3 randomised, self-controlled study to compare prophylactic moisturising care with or without hydrocolloid dressing for hand-foot syndrome induced by multikinase inhibitors. Patients with radically unresectable advanced or recurrent colorectal carcinoma, gastrointestinal stromal tumour and hepatocellular carcinoma who scheduled to receive regorafenib or sorafenib therapy are eligible for enrolment.Supportive care for hand-foot syndrome will consist of basic moisturising care with or without hydrocolloid dressing. If hand-foot syndrome occurs, a steroid ointment will be applied two times per day at the affected sites. The primary endpoint is an incidence rate of grade 2 or more severe hand-foot syndrome (soles of the feet only) assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events V.4.0. Grading of hand-foot syndrome will be performed by central review using photographs taken weekly by blinded trained physicians. The ethical approval was obtained from National Cancer Center Hospital. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conference. DISCUSSION: If the positive results are found in this study, it is shown that hydrocolloid dressing is effective not only as a symptom management but also as a prevention in hand-foot syndrome induced by multikinase. TRIAL STATUS: The enrolment was started in January 2019, and planned to closed in January 2021. As of February 2020, 26 patients enrolled in this study. TRIAL REGISTRATION NUMBER: UMIN Clinical Trial Registry (UMIN000034853). PROTOCOL VERSION: V.1.4, 9 January 2020.

Topical steroid versus placebo for the prevention of radiation dermatitis in head and neck cancer patients receiving chemoradiotherapy: the study protocol of J-SUPPORT 1602 (TOPICS study), a randomized double-blinded phase 3 trial.

BACKGROUND: To date, the clinical benefit of topical steroid use has only been demonstrated for radiation dermatitis induced by 50-60 Gy irradiation in breast cancer. However, these agents are also often used clinically for the control of radiation dermatitis induced by high-dose (>60Gy) irradiation with chemotherapy in head and neck cancer. Despite this, the prophylactic efficacy of topical steroids for radiation dermatitis induced by high-dose irradiation is still unclear. The aim of this study is to clarify the benefit of topical steroids in basic nursing care for radiation dermatitis induced by chemoradiotherapy in patients with head and neck cancer. METHODS: The study is being conducted as a multicenter 2-arm randomized double-blinded placebo-controlled Phase 3 trial in Japan. The study was started in May 2017, with participant enrollment between May 2017 and April 2019. Patients scheduled to receive definitive or postoperative chemoradiotherapy for head and neck cancer are eligible for enrollment. All patients will receive chemoradiotherapy, consisting of single agent CDDP and 70-Gy irradiation. Bilateral neck irradiation is mandatory. Supportive care for radiation dermatitis will consist of basic nursing care with topical steroid or placebo. When radiation dermatitis grade 1 is seen or total radiation dose reaches 30 Gy, minimally required intervention will be started as a first step. If radiation dermatitis worsens to grade 2, the irradiated area will be covered with a moderately absorbent surgical pad and steroid or placebo topical cream. The primary endpoint is a comparison of the proportion of patients with ≥ grade 2 radiation dermatitis by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Ethical approval has been obtained from all participating sites. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. DISCUSSION: Evidence supporting the benefit of adding topical steroids in general nursing care for radiation dermatitis induced by high-dose irradiation with chemotherapy is insufficient. This trial aims to clarify the clinical benefit of topical steroid for radiation dermatitis induced by high-dose irradiation with chemotherapy. The trial is ongoing and is currently recruiting. TRIAL REGISTRATION NUMBER: UMIN000027161 . Protocol version 3.0, 18 April 2017.

Leisure-time physical activity in youth as a predictor of adult leisure physical activity among Japanese workers: a cross-sectional study.

BACKGROUND: Workers in Japan are not sufficiently active; however, it remains unclear how their leisure-time physical activity habits may be developed. This cross-sectional study investigated the relationship of age- and intensity-specific leisure-time physical activity in youth to adulthood leisure-time physical activity habits among Japanese workers. METHODS: In 2012, 968 workers (333 males and 635 females) from three companies and six hospitals in the Tokai region of Japan agreed to complete and submit a self-administered questionnaire. Intensity-specific leisure-time physical activity at ages 12 and 20 years was assessed retrospectively, and workers' current participation in regular leisure-time physical activity was assessed as an outcome measure. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. RESULTS: Mean ages for males and females were 40 and 37 years, respectively. Strenuous leisure-time physical activity at age 12 years was significantly positively associated with adulthood participation in leisure-time physical activity among male workers [adjusted OR (95% CI) = 2.29 (1.02, 5.14)]. Additionally, both strenuous and moderate physical activity at age 20 years was significantly positively associated with participation in regular leisure-time physical activity in adulthood among males and females. CONCLUSIONS: Our results suggest that some leisure-time physical activity in youth may predict adult workers' participation in regular leisure-time physical activity in Japan. Encouragement of leisure-time physical activity in youth could therefore be an effective measure to develop adult leisure-time physical activity habits among workers.

An exploratory study on the efficacy and safety of a BCAA preparation used in combination with cardiac rehabilitation for patients with chronic heart failure.

BACKGROUND: Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. METHODS: This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. DISCUSSION: In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. TRIAL REGISTRATION: This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).