Effects of smartphone-based music intervention on improving emotional and psychosomatic symptoms of patients with hematological malignancy: A study protocol for a non-inferiority randomized controlled trial

Abstract

Objectives

Smartphone-based music intervention (S-MI) may increase the accessibility and feasibility for benefiting patients. This study aims to assess the effectiveness of S-MI in alleviating emotional and psychosomatic symptoms in patients with hematological malignancies, compared to the smartphone delivered Mindfulness-Based Stress Reduction Training (S-MBSR).

Methods

This study will be a non-inferiority randomized controlled trial design. A total of 120 eligible participants with hematological malignancies will be randomly assigned to either the experimental group (S-MI) (n = 60) or the comparison group (S-MBSR) (n = 60). Participants will use the Mind Habit app to participate in daily sessions of S-MI or S-MBSR, lasting 5–10 min each, for 2 weeks. The primary outcome, anxiety, and the secondary outcomes, depression, sleep quality, psychological perceived harmony, emotional regulation self-efficacy, as well as the exploratory outcome performance status, will be assessed four times (i.e., pre-test, mid-test, post-test, and follow-up) using validated instruments: the General Anxiety Disorder-7, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index Inventory, Balanced Index of Psychological Mindedness, Regulatory Emotional Self-Efficacy Scale and Zubrod/ECOG/WHO. In addition, participants will provide daily self-reports on their mood and psychosomatic symptoms both before and after each day's intervention. Physiological parameters will be collected at pre- and post-test. Compliance will be measured at pre-test and follow-up. Intent-to-Treat and Per Protocol Set analysis will be used for data analysis.

Results

The primary outcome will focus on evaluating the change of anxiety. Secondary outcomes will examine the changes in depression, sleep quality, psychological perceived harmony, and emotional regulation self-efficacy. The exploratory outcomes will encompass assessments of performance status, self-reported evaluations, physiological parameters, and compliance.

Conclusion

This study aims to provide empirical evidence supporting the efficacy of S-MI in mitigating emotional and psychosomatic symptoms in patients with hematological malignancies.

Trial Registration

The trial was registered and identified as ChiCTR2200065896.

Introduction

Cancer stands as one of the world's primary causes of mortality, imposing a substantial economic burden on public healthcare systems.^1,2 In 2020, there were 19.3 million newly reported cancer cases worldwide, leading to 10.0 million cancer-related deaths. ² By 2020, China recorded nearly 4.57 million newly diagnosed cancer and approximately 3 million cancer fatalities. ³ Hematological malignancy is defined as a highly diverse group of diseases affecting blood, bone marrow, and organs, characterized by variable prognoses and commonly relapse following treatment.^4–7 These malignancies account for 1.2 million new cases each year globally, constituting approximately 7% of all newly diagnosed cancers. ⁴ Data from the National Central Cancer Registry of China (2015) ranked hematological malignancies among the top ten cancer types in terms of both incidence and mortality. ⁸

Patients with advanced cancer endure a range of emotional and psychosomatic symptoms, such as anxiety, depression, pain, fatigue, weakness, weight loss, insomnia, and irritability.^9,10 Research shows that 31% of terminally ill cancer patients self-reported anxiety symptoms. ¹¹ Our previous cross-sectional survey of 308 Chinese patients diagnosed with hematological malignancies revealed a higher prevalence (44.58%) of anxiety symptoms. The prevalence of depressive disorder in hematology-oncology patients is reported at 20.7%, ¹² while pain affects 66.4% of those with advanced, metastatic, or terminal cancer, with over one-third rating it as moderate to severe. ¹³ Research highlights the interplay between anxiety, depression, pain, and fatigue, ¹⁴ alongside frequent co-occurrence of affective disorders with endocrine dysfunction and immune dysregulation. ¹⁵

Furthermore, patients with hematological malignancy in active treatment have to face an array of severe symptoms, treatment-related side effects, heavy financial burdens, uncertainty, reduced capacity to fulfill familial and social roles, and separation from family, resulting in substantial emotional stress.^10,16 Few studies have explored emotional-related physiological indices in cancer patients, and the results remain inconclusive.^17,18 Several studies demonstrated that certain physiological mechanisms, including the β-adrenergic receptors (β-AR)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, might be associated with the growth of certain cancers on account of noradrenaline upregulating the expression of VEGF, IL-8, and IL-6 in C8161 cells.^19–22

The majority of psychological interventions for cancer patients include cognitive behavioral therapy (CBT), psychoeducation, and mindfulness-based interventions (MBIs).^23–25 CBT relies on Top-Down cognitive restructuring, challenging negative thought patterns, and developing coping skills, therefore helps patients break the cycle of negative thinking that exacerbates emotional problems. ²⁶ Psychoeducation addresses misconceptions about cancer and concurring emotional symptoms, and provides knowledge to increase patients’ control over information and sense of empowerment, leading to a better emotional well-being. ²⁵ Mindfulness as a more experiential method, teaches patients to observe their emotions without judgement, fostering greater cognitive function on emotional awareness, acceptance, and regulation. ²⁷ These interventions have proven effective in alleviating anxiety, depression, and enhancing the quality of life or patients with diagnosis of cancer.^23–25 Moreover, the psychological interventions also enhanced the cancer patients’ immune function, leading to improvement of the levels of lymphocyte subsets, including CD3+, CD4+, CD8+, and immunoglobulins such as IgG. ²⁸

Music intervention as a bottom-up approach is complementary to the above-mentioned psychological interventions for patients with cancer. While psychological interventions require a certain level of physical and cognitive resources of patients, ²⁹ music interventions require fewer cognitive demands, transcend language barriers, and impact emotions directly. ³⁰ The influence of music on emotion is a multifaceted process. In terms of neurological mechanisms, music listening can activate the reward system of the brain including ventral tegmental area and nucleus accumbens, stimulate the release of dopamine, and bring pleasurable emotions. Music listening also can activate and regulate the activities of brain regions associated with emotion responses and processing, such as auditory cortex, limbic systems, and prefrontal cortex, as well as their functional connections, influencing the overall emotional experiences.^31–33 In addition, musical characteristics and personal associations also play an important role in shaping individual's emotional experiences with music. ³⁴

Music therapy is defined as “a systematic process of intervention wherein the therapist helps the client to promote health, using music experiences and the relationships that develop through them as dynamic forces of change.” ³⁵ Music therapy utilizes either active or receptive experiences of music. In active activities, clients actively participate in creating or playing music using musical instrument, voice, or movement. In receptive activities, clients engage in passive listening to live or rerecorded music. ³⁶ Research has shown cancer patients’ preference towards receptive methods overactive ones.^36,37 There is a distinction between music therapy implemented by trained music therapists and music medicine provided by medical personnel, sometimes also called music intervention.^38,39 Music listening is the most common method of music intervention. Several systematic reviews and meta-analyses have highlighted music therapy and music intervention as a low-risk and effective complementary approach that positively affects both the psychological and physiological aspects of cancer patients. These effects include anxiety alleviation,^12,40 depression mitigation,^41,42 improved sleep, ⁴³ mood disorders management,^12,42 fatigue reduction, enhanced quality of life,^44–46 pain reduction,^12,47–49 and the fulfillment of psychosocial needs. ⁵⁰ The combination of music therapy with chemotherapy not only led to an improvement in immune function, evident through increased total lymphocyte count and the absolute number of CD3, CD4, and CD8 cell subsets but also contributed to maintaining optimal levels of 5-HT and BDNF. ⁵¹

However, the treatment demands of the vast number of cancer patients are far beyond the limited availability of music intervention. Digital technology-assisted interventions that are delivered through computer- or mobile-based online platform have been developing in recent decades. ⁵² These interventions have been effectively applied to individuals with cancer, such as online interventions for gynecological cancer patients, ⁵³ online support groups for prostate cancer patients, ⁵⁴ internet-based cognitive-behavioral therapy for sexual dysfunctions in women treated for breast cancer, ⁵⁵ and online exercise programs for bone health in pediatric cancer survivors. ⁵⁶ There are a few studies of online music therapy and music intervention for cancer patients. Folsom and colleagues conducted remote music therapy online courses utilizing iPads in a major cancer hospital. Music therapists employed pre-recorded instructional videos to assist patients in reducing anxiety, enhancing coping skills, and increasing social support. ⁵⁷ Another randomized controlled study compared the effects of online music listening group or an online meditation group for cancer patients. Patients in each group received a 30-min music or meditation intervention, followed by a 30-min group discussion. The results revealed that patients in the music intervention group experienced a significant reduction in perceived pain. ⁵⁸ However, no study has examined the effects of music interventions on patients with hematological malignancy.

To our knowledge, there is no research on online music interventions in China, and the effects of online music intervention for Chinese cancer patients remain unclear. Online mindfulness intervention has emerged as a widely recognized and established standard intervention. ²⁴ During the mindfulness session, patients listen to the pre-recorded audios and follow the trainer's guidance to practice. Compared to CBT or psychoeducation, the receptive and experiential nature of mindfulness training is more similar to music intervention. A randomized controlled trial with a non-inferiority design is recommended to assess whether a novel intervention, such as an online music intervention, is at least no worse than the established standard of online mindfulness intervention. This design is particularly advantageous for evaluating interventions beyond mere efficacy.

Aims and hypotheses

This study aims to investigate the effectiveness of Smartphone-based Music Intervention (S-MI) in comparison to Mindfulness-Based Stress Reduction (S-MBSR) training delivered via a smartphone app in improving emotional and psychosomatic symptoms in patients diagnosed with hematological malignancies. We hypothesize that S-MI will be no worse than S-MBSR in achieving the following outcomes: (i) primary outcome: anxiety; (ii) secondary outcomes: depression, sleep quality, psychological perceived harmony, emotional regulation self-efficacy; and (iii) exploratory outcomes: physiological parameters; general health status and treatment tolerance; physiological parameters; daily self-assessment; and compliance.

Methods

Study design and randomization procedure

After trial registration, we determined that a non-inferiority design better validates our hypothesis. Thus, this study will use a 1:1 parallel group non-inferiority randomized controlled trial design. The trial will adhere to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting non-pharmacological interventions. ⁵⁹ Eligible participants will sign an informed consent and complete the baseline assessments. Then they will be randomly assigned to either the S-MI or S-MBSR group. A researcher will instruct each participant to download an application (app) called Mind Habit, and then log into this app with a designated account and password. Patients in each group will be instructed to practice S-MI or S-MBSR daily using the app for two weeks. Participants will continue their medical treatment during the intervention period, and they can choose to complete the intervention at any time of each day. Anxiety, depression, sleep quality, psychological perceived harmony, emotional regulation self-efficacy, and performance status will be assessed using validated instruments including General Anxiety Disorder-7, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index Inventory, Balanced Index of Psychological Mindedness, Regulatory Emotional Self-Efficacy Scale and Zubrod/ECOG/WHO. Outcome assessments will be conducted at pre-test, mid-test (1 week), post-test (2 weeks), and follow-up (4 weeks after intervention) using the app (Table 1). In addition, participants will also fill in the daily assessment in terms of mood and psychosomatic symptoms before and after each day's intervention in the app. Furthermore, Physiological parameters will be collected at pre- and post-test. Compliance will be measured at the post-test and follow-up.

Table 1.

Schedule of enrollment, interventions, and assessments.

The app will send messages automatically to remind and encourage participants’ daily practice. If participants do not log in the app for 2 consecutive days, they will receive an additional reminding text message of participating in daily intervention. A flowchart illustrating the study design and process is presented in Figure 1.

Figure 1.

Flowchart of the study.

Participants

A total of 120 participants will be enrolled in this study. The inclusion criteria for eligible participants are as follows: patients diagnosed with hematological malignancy who are receiving active treatment, aged between 18 and 55 years, no history of psychiatric illness with symptoms of hallucinations and delusions, meeting the criteria for mild to severe anxiety defined as a score of ≥5 on the GAD-7 (The GAD-7 score of 5 has been chosen because it represents the recommended cutoff score for “mild anxiety” symptoms according to the scale's authors. ⁶⁰ The threshold for GAD-7 symptoms is set relatively low to ensure that individuals who complain distress and QOL impairment, are not excluded from the study), proficient in reading and understanding Chinese, normal hearing, verbal expression ability, and have a smartphone with the ability to use it independently. The exclusion criteria include participants who cannot read and understand Chinese, with visual acuity or corrected visual acuity of <1.0, experiencing active psychotic episodes or severe physical conditions that may hinder participation in the experiment, do not have a smartphone or not able to use it independently, are engaged in other concurrent psychological intervention programs, and with an expected life expectancy of less than 3 months.

Recruitment

The enrollment period for the study program has been extended from 1 March 2023 to 31 August 2024 for an expanded sample size. Participants will be recruited through recruitment advertisements in hospital wards and recommendations from clinicians and nurses. A researcher will provide study information to potential participants, and then the applicants will fill in the informed consent form and assessments for eligibility. Eligible participants will be instructed to complete baseline assessments, log in to the Mind Habit app, and perform a trial test to become familiar with its operation.

Setting

This study will take place in Lishui Central Hospital, Zhejiang, China. Established for nearly 40 years, Lishui Central Hospital is a national tertiary general hospital and a regional benchmark institution with 2000 beds and 64 clinical specialties. The hematology ward at this hospital comprises 85 beds, a clean laminar flow ward of grade 100 for bone marrow (stem cell) transplantation, and 21 laminar flow beds. The hospital treats approximately 3000 patients annually.

Interventions

Both online interventions will be in the form of audio, accompanied by written practice guidelines. All the recordings and guidelines will be uploaded to Mind Habit app. Before the intervention, participants will need to find a quiet, comfortable, and undisturbed environment, and then use headphones provided by the experimenter and adjust the volume to a comfortable level. They can choose a preferred time for each day's intervention. During the two-week intervention period, each day participants will unlock the intervention for that day with no limit to the number of uses. They also have access to practice all exercises prior to that day. During the period from the end of second week up to 1-month follow-up, the interventions will remain accessible to all participants.

The two-week intervention length decision was made based on a previous pilot study, the interviews with participants, the therapists’ clinical experiences, as well as the evidence of the previous study. The results of the pilot study showed a significant improvement in anxiety and depression in participants after two weeks of online music intervention. Moreover, out of 113 interviewed participants, 78% preferred an intervention length of two weeks rather than one week or four weeks. The therapist's clinical observation also found that most of the individuals who used the app were able to establish a habit of psychological exercise, and have developed a self-discipline to complete subsequent exercises independently. Previous study has also shown that 2 weeks of online mindfulness-based intervention can significantly decrease anxiety and depression. ⁶¹

Smartphone-based music intervention (S-MI). S-MI consists of 14 self-help exercises, including musical relaxation, music listening, and music imagery, adapted from receptive music therapy techniques. These exercises, recorded as digital audio by two credentialed music therapists, range from 5 to 10 min each. S-MI spans two weeks and incorporates three modules: relaxation (Module 1), emotion exploration (Module 2), and positive emotion induction (Module 3). Each module adheres to evidence-based principles grounded in receptive music therapy. ⁶² Modules focus on psychological relaxation, emotion expression, and positive emotion acquirement through music. The themes of the intervention audios include music and breathing relaxation, music and progressive muscle relaxation, music and relaxing imagery relaxation, nostalgic music listening, energetic music listening, calming music listening, music and positive resource imagery, music and inner peace imagery, music and healing imagery.

The musical relaxation recordings feature music with a tempo of 60–80 BPM and include verbal relaxation guidance. The music imagery recordings incorporate music in a major key, moderate tempo, A-B or A-B-A form, simple melody, and repetitive phrases. Each piece of music is coupled with verbal guidance from therapists to stimulate listeners’ imagery of relaxing and serene natural environments, as well as positive, soothing, or empowering experiences. Music will be composed by the music therapists using Cubase 12. ⁶³ The verbal guidance will be recorded and edited with music using Audition 2021. ⁶⁴

Mindfulness-based stress reduction (MBSR). Mindfulness-based stress reduction, founded by Kabat-Zin in 1979, comprises a series of meditation and mindfulness exercises aimed at teaching patients to harness their inner mental and physical strength for psychosomatic health. ⁶⁵ It emphasizes developing a mindful attitude and lifestyle, and has proven effective in reducing pain, stress, improving sleep, and enhancing immunity among patients with various physical and psychological conditions. ²⁴

MBSR encourages practitioners to focus on the experience of here and now. Central to this approach is cultivating an attitude that involves (1) refraining from judgment of personal experiences; (2) maintaining patience with all experiences; (3) staying motivated and curious; (4) trusting one's inner wisdom and capabilities; (5) avoiding the imposition of expectations, and instead fostering experiential learning; (6) accepting the present moment and observing all physical and mental sensations; and (7) relinquishing attachment to the past and future to fully embrace the present. ²⁷

S-MBSR comprises 14 days of mindfulness meditation exercises. To accommodate the physical and psychological needs of cancer patients, the exercises draw from standard MBSR practices, including body scanning, raisin meditation, silent meditation, walking meditation, mountain meditation, lake meditation, and loving-kindness meditation. These exercises are recorded by a credentialed mindfulness trainer with no music background and each exercise ranges from 5 to 10 min.

Online interventions platform. We will use a self-developed app called Mind Habit as the platform to provide both interventions. It was developed by researchers since 2020. This platform encompasses a data management system, smartphone interactive interfaces, and compatibility with wearable devices. Moreover, the system can provide personalized user management, enabling tailored assessment and intervention for each participant. In this study, A researcher will upload intervention contents to the data management platform, another researcher who is blind to the randomization and has no contact with participants will create user accounts for participants, and manage their interventions according to their assigned groups. When participants log in to the app, they will access the assigned assessments and interventions. There is no limit to the number of times the subject can practice the exercises that have been completed that day and before.

Measures

All participants will fill in the assessments for primary, secondary, and exploratory outcomes at pre-test, mid-test (1 week), post-test (2 weeks), and follow-up (4 weeks after intervention). Demographic variables including sex, age, education, marital status, ethnicity, and occupation, will be assessed at baseline. All the questionnaires will be filled out online in the app. Physiological parameters will be collected by the nurses at pre- and post-test. Additionally, participants will report their mood and psychosomatic symptoms before and after each day's exercise in the app. Compliance will be measured at the post-test and follow-up.

Primary outcome

Anxiety. Anxiety will be assessed using the 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), which scores from 0 to 21. A higher score indicates a higher level of anxiety. ⁶⁰ The Chinese version of GAD-7 showed an excellent internal consistency (Cronbach α = 0.859) and a good validity. ⁶⁶ For mid-test and post-test, the time frame will be adjusted to 1 week. ⁶⁷

Secondary outcomes

Depression. Depression will be measured using the Patient Health Questionnaire-9 (PHQ-9), consisting of 9 items with scores ranging from 0 to 27. A higher score indicates a higher level of depression. The PHQ-9 is a validated scale and has been widely used. ⁶⁸ The Chinese version of PHQ-9 demonstrates excellent internal consistency (Cronbach α = 0.852) and a great validity. ⁶⁶

Sleep quality. The Pittsburgh Sleep Quality Index (PSQI) will be employed to evaluate sleep quality. This index comprises 19 self-rated items, with scores ranging from 0 to 21. A total score >5 indicates poor sleep quality. A lower score indicates a better sleep quality. ⁶⁹ The Cronbach α of the Chinese version PSQI was 0.84, both construct validity and empirical validity were verified. ⁷⁰

Psychological perceived harmony. Psychological perceived harmony refers to an individual's interest and ability to reflect on psychological states and processes. It will be assessed using the Chinese version of the Balanced Index of Psychological Mindedness (BIPM). It consists of 13 items divided into two-factor structures: insight and interest. The scores range from 0 to 52, with a higher score indicates a higher psychological perceived harmony. The Cronbach α is 0.748. The factor analysis supports that the scale has good structural validity. ⁷¹

Emotional regulation self-efficacy. Emotional regulation self-efficacy refers to an individual's level of confidence in their ability to effectively regulate their emotional state. ⁷² It will be measured using the Regulatory Emotional Self-Efficacy Scale (RESE), which includes 12 items divided into three dimensions: expressing positive emotional efficacy (POS), regulating depression/pain emotional efficacy (DES), and regulating anger/anger emotional efficacy (ANG). A higher score reflects a greater self-efficacy in emotional regulation. ⁷³ The Chinese version of RESE showed a high reliability (α = 0.85) and structural validity. ⁷²

Exploratory outcomes

Performance status. Performance status will be assessed using Zubrod/ECOG/WHO (ZPS), with 1 item for rating performance status on a scale of 0–5. A higher score indicates worse health status and treatment tolerance. ⁷⁴

Physiological parameters. Several physiological parameters may be associated with the growth of certain cancers.^19–22 To explore any potential connections between physiological parameters with emotional and psychosomatic symptoms of patients with hematological malignancy, cortisol hormone, angiotensin, thyroid function, interleukin-6,^21,75 as well as immunity index such as immunoglobulin + complement and lymphocyte subsets will be collected at the pre- and post-test.^28,51 A nurse will collect the specimen of participants for assessing physiological parameters. In terms of the type of sample used, cortisol hormone, thyroid function, interleukin-6, and immunoglobulin will be measured in serum, while angiotensin is measured in plasma. On the other hand, lymphocyte subset analysis will utilize whole blood samples. The biochemical tests will be performed on a HITA CHI 7600 Automatic Biochemical Analyzer (Hitachi, Ltd) and a Tellgen Super Multiplex Immunoassay System TESMI-F4000 (Tellgen Corporation), respectively. All of the examinations will be conducted and analyzed by the Clinical Laboratory of Lishui Central Hospital.

Daily self-assessment. Daily self-assessment consists of 5 questions rated on a scale of 0–10, assessing mood, fatigue, pain, sleep quality, and emotional fluctuations. Participants will complete daily assessment twice before and after the exercise except sleep quality and emotional fluctuation (only one time a day). The daily assessment will record a dynamic continuous change of participants’ emotions and psychosomatic symptoms.

Compliance. We will evaluate the frequencies of participants’ app login, duration of app use, dropout rate as the compliance assessment. We will assess the participants’ adherence during the study at the post-test. It will help to identify any compliance issues they may have influenced the results. We will also evaluate long-term compliance at the follow-up to see if the adherence patterns changed over time.

Data collection

All self-reported data will be collected and stored in the data management system of the app. The blinded research assistant will download the data for analysis. Once the RCT is completed, data analysis will be conducted by a statistician blind to treatment group.

Adverse events

The adverse events include experiencing worsen emotional or physiological conditions. The researcher will inform participants about the possible adverse effect of interventions that may worsen existing conditions. The informed consent will provide the contact number of a researcher. If such situation occurs, the participant can contact the researcher, and then be referred to the supervising physician and the psychiatrist in the research team for consultation or necessary treatment when needed. The Principal Investigator will follow up on all reported cases when necessary.

Sample size

We referred to a previous study in calculating the sample size of this study. In the previous study, after receiving MSBR, 224 cancer survivors decreased the level of anxiety (Mean = 4.26, SD = 3.76) in GAD-7. ⁷⁶ Then we chose a reasonable a non-inferiority margin of 2.13 for anxiety and an equal group allocation (N1 = N2). As this is a single-center, parallel-designed, positive-control non-inferior clinical trial, we assumed a one-sided α = 0.025 and β = 0.2. ⁷⁷ The analysis resulted a need for 100 participants. Accounting for a dropout rate of 20%, the final estimation necessitates 120 participants with 60 participants in each group. This sample size will provide enough power to detect whether S-MI is truly non-inferior to S-MBSR in respect to effect on anxiety. Moreover, we adjusted p-value using the Bonferroni correction, and it showed that 120 participants are sufficient to meet the needs of multiple comparisons. The sample size differs from the one in the trial registration due to the adaptation of statistical methodologies.

The incorporation of repeated measures over time boosts the statistical power by increasing the “effective sample size,” which depends on the number of participants and the total number of measurements (0, 1, 2, and 6 weeks). In the event of high dropout rates, we will continue to enroll participants until we achieve the desired level of statistical power.

Randomization and blinding

Participants will be randomly assigned to either the S-MI or the S-MBRS using a computer-generated sequence of random numbers. To ensure concealment of allocation, a researcher has no contact with participants will print the randomization numbers and sealed in opaque envelopes. The researcher responsible for participant enrollment will open the envelopes sequentially to determine group assignment. The datasets are numbered with assigned numbers to ensure confidentiality.

Due to the nature of the intervention, it was not possible to blind participants to their group allocation. To minimize potential bias, the researcher administering the questionnaires will be blinded to participants’ group assignments. The statistician will also be blinded to group allocations until the completion of data collection.

Statistical analysis

To assess the balance of baseline demographic and clinical characteristics between the S-MI and S-MBSR groups, we will employ appropriate statistical tests, such as t-tests for continuous variables and chi-square tests for categorical variables. We anticipate that randomization will result in comparable groups with respect to key demographic variables. Any significant imbalances will be explored as potential confounders. ⁷⁸

The RCT will employ a 2 × 4 design (S-MI vs. S-MBSR × pre-test, mid-test, post-test, and 1-month follow-up) for each outcome measure. Both Intent-to-Treat (ITT) and Per Protocol Set (PPS) analyses will be conducted for primary outcomes. Given the non-inferiority design, both ITT and PPS results are essential for drawing valid conclusions. Mean change in primary outcome scores from pre-test to follow-up will be compared between groups using 95% confidence intervals and one-sided t-tests (α = 0.025). ⁷⁷ T-tests or repeated measures analysis of variance will be used for secondary and exploratory outcomes. Generalized estimating equations will analyze daily self-report outcomes to assess treatment effects over time.

Discussion

Music intervention has demonstrated efficacy in ameliorating cognitive decline, mood disturbances, sleep disruptions, and pain in cancer patients.^12,43,44 Given the widespread accessibility of smartphones, smartphone-based music intervention (S-MI) offers a promising avenue to expand access and delivery of this therapeutic modality. However, the specific impact of S-MI on hematological malignancies remains unexplored. This study aims to bridge this knowledge gap by comparing S-MI with smartphone-based mindfulness-based stress reduction (S-MBSR) on emotional and psychosomatic symptoms in this patient population. Given the established benefits of music therapy and the potential of smartphone technology, we hypothesize that S-MI will demonstrate non-inferiority to S-MBSR in reducing negative affect and psychosomatic symptoms among patients with hematological malignancies.

This study protocol has several limitations. First, the single-center design involving a specific patient population may restrict the generalizability of findings to other healthcare settings and patient cohorts. Second, the two-week intervention period exceeds typical hospitalization (i.e., one week) for hematological malignancies in China, potentially complicating participant adherence and support. Third, given the nature of the interventions, blinding participants to treatment allocation is not feasible, which could introduce bias.

Despite these limitations, this study represents a significant step toward evaluating the efficacy of smartphone-based music intervention (S-MI) in managing emotional and psychosomatic symptoms among patients with hematological malignancies. By comparing S-MI to S-MBSR, this research will contribute valuable insights into the potential of these accessible interventions. If found to be effective, S-MI could offer a cost-effective and widely implementable approach to improving the quality of life for cancer patients.

Conclusion

This study protocol outlines a non-inferiority randomized controlled trial designed to evaluate the comparative efficacy of smartphone-based music intervention (S-MI) and smartphone-based mindfulness-based stress reduction (S-MBSR) in mitigating emotional and psychosomatic symptoms among patients with hematological malignancies. By directly comparing these widely accessible interventions, this trial aims to provide robust evidence regarding their potential to alleviate psychological distress in this vulnerable population. The study will also assess the feasibility and acceptability of these smartphone-delivered interventions, with a particular focus on their potential for widespread implementation. Given the high smartphone penetration in regions such as China, this study has the potential to inform the development of scalable and accessible interventions for a broad patient population.

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Supplemental material, sj-docx-1-dhj-10.1177_20552076241286941 for Effects of smartphone-based music intervention on improving emotional and psychosomatic symptoms of patients with hematological malignancy: A study protocol for a non-inferiority randomized controlled trial by Weifen Zhang, Lo-Ting Chen, Nengwen Xu, Feifei Ke, Liming Lan, Linjie Li, Wei’e Liu and Xijing Chen in DIGITAL HEALTH

Supplemental Material

sj-doc-2-dhj-10.1177_20552076241286941 - Supplemental material for Effects of smartphone-based music intervention on improving emotional and psychosomatic symptoms of patients with hematological malignancy: A study protocol for a non-inferiority randomized controlled trial

Supplemental material, sj-doc-2-dhj-10.1177_20552076241286941 for Effects of smartphone-based music intervention on improving emotional and psychosomatic symptoms of patients with hematological malignancy: A study protocol for a non-inferiority randomized controlled trial by Weifen Zhang, Lo-Ting Chen, Nengwen Xu, Feifei Ke, Liming Lan, Linjie Li, Wei’e Liu and Xijing Chen in DIGITAL HEALTH