Primary objective

1. To compare the efficacy of ACT in enhancing disease acceptance compared with the waitlist control group across three-time points (T0 = baseline assessment, T1 = 4 weeks, immediately after completion of the intervention, T2 = 6 months after commencement of the intervention, and T3 = 12 months after commencement of the intervention).

Secondary objectives

1. To compare the efficacy of ACT in reducing psychological inflexibility with the waitlist control group across three-time points (T0 = baseline assessment, T1 = 4 weeks, immediately after completion of the intervention, T2 = 6 months after commencement of the intervention, and T3 = 12 months after commencement of the intervention).
2. To compare the efficacy of ACT in reducing depression and anxiety compared with the waitlist control group across three-time points (T0 = baseline assessment, T1 = 4 weeks immediately after completion of the intervention, T2 = 6 months after commencement of the intervention, and T3 = 12 months after commencement of the intervention).
3. To compare the efficacy of ACT in enhancing QoL compared with the waitlist control group across three-time points (T0 = baseline assessment, T1 = 4 weeks, immediately after completion of the intervention, T2 = 6 months after commencement of the intervention, and T3 = 12 months after commencement of the intervention).
4. To compare the efficacy of ACT in enhancing social support compared with the waitlist control group across three-time points (T0 = baseline assessment, T1 = 4 weeks, immediately after completion of the intervention, T2 = 6 months after commencement of the intervention, and T3 = 12 months after commencement of the intervention).
5. To evaluate the mediating role of psychological inflexibility and disease acceptance in the relationship between ACT and QoL in breast cancer patients following ACT intervention.
6. To assess the moderating role of social support in the relationship between ACT and Psychological inflexibility in breast cancer patients.

Ethic

Ethical approval for this study was obtained from the Jawatankuasa Etika Penyelidikan Manusia, Universiti Sains Malaysia (JEPeM-USM), with approval granted on 19th December 2022 (JEPeM Code: USM/JEPeM/22080569). The approval was subsequently extended from 19th December 2023 to 18th December 2024. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Regarding the consent process for our study, we will obtain written consent from all participants. Participants will receive a Subject Information and Consent Form detailing the study’s purpose, procedures, risks, benefits, and their rights as participants. Additionally, participants were given a Participant’s Material Publication Consent Form to provide explicit consent for the publication of anonymized data or materials derived from their participation in the study. They will be given sufficient time to review the document and ask any questions before providing their signature indicating their voluntary participation. As our study did not involve minors, we did not need to obtain consent from parents or guardians.

Trial registration

This study is registered in ClinicalTrials.gov under the registration number NCT05327153.

Study design

This study will employ a double-blind, parallel-group randomized controlled trial to evaluate ACT’s effectiveness in promoting disease acceptance among breast cancer patients. This research protocol was developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines.

Randomization and allocation concealment

Permuted block randomization with an allocation ratio of 1:1 is carried out. Participants will be randomly assigned based on odd (Group A) and even (Group B) rows using a computer-generated randomisation sequence. The randomization sequence, informing participant assignment to either intervention (Group A) or waitlist control (Group B) condition, is provided in opaque envelopes by one investigator not involved in participant recruitment or assessment. Blinded to the study assignment, participants will be allotted to either group in a 1:1 ratio. Participants will be randomly assigned to two groups: the intervention group receiving ACT intervention or the control group receiving standard treatment with non-therapeutic intervention.

Blinding

Participants will be unaware of the study’s randomization into the designated groups, which will be carried out by a research assistant who is not otherwise involved. As a result, participants will not be informed of the group to which they are allocated.

Additionally, to minimize bias, the ACT intervention group and the control group will receive a 4-session program (with one hour per session, one session per week for 4 weeks). Participants in the control group will also receive equal attention (attentive listening) and time from the professional figure administering the program with non-therapeutic intervention(the participants in the control group are given equal duration of the session, number of sessions, duration of intervention and attended by the same therapists who conducted the ACT group. The participants will also be attended to with active listening by the therapists in the control group).

To maintain blinding throughout the study, the researchers will be blinded to participants’ randomized assignments into the groups. This process will be carried out by a research assistant who is not involved in the study. Additionally, data collection for this study will be conducted by the same research assistant, ensuring impartiality. The research assistant will remain unknown to the study’s hypotheses. Furthermore, data analysis for the study will be performed by statisticians who are not involved. The statistician will utilize a statistical analysis plan to conduct data analysis before the final unblinding of the data lock.

Participants

Patients receiving treatment in oncology clinics at Universiti Sains Malaysia and Hospital Seberang Jaya will be recruited for the study. The criteria for study participation include: (1) diagnosed with breast cancer, (2) aged 18 years or older, (3) currently receiving treatment, (4) able to understand and communicate in the study language, and (5) willing to participate in the intervention and follow-up assessments. Patients are deemed ineligible for the study if they: (1) have severe cognitive impairment or significant psychiatric comorbidities (e.g., psychosis, substance abuse) that could hinder their participation in the study, (2) are diagnosed with malignant tumors, and (3) currently receiving any other form of psychological therapy intervention.

Sample size calculations will be based on power analysis using established effect sizes from previous studies on ACT interventions and disease acceptance among similar populations. We conducted an a priori power analysis using GPower 3.1.9.7 to calculate the estimated sample size needed for mixed ANOVA with control of three covariates: the type I error was 0.05, with a power of 0.95, three covariates, with two intervention groups and an effect size of 0.46 by referring to an RCT on the efficacy of ACT on illness cognition among breast cancer patients [28], Hence, the estimated sample size needed is 80 (with the inclusion of a 20% dropout rate). Hence, 40 subjects are required per group.

Procedure

This research used a consecutive sampling technique for subject recruitment before randomly assigning them to the intervention and control groups. Potential participants will first be screened to determine their eligibility for study participation. Invitations to take part in this trial will follow. The investigator will ensure that participants receive a thorough explanation of the study goals and methods before agreeing to join the study. Participants will sign the Subject Information and Consent Form and Participant’s Material Publication Consent Form before enrolling in the research to indicate their agreement. We will ensure the participants’ anonymity and inform them about their right to withdraw from the study at any point, guaranteeing their confidentiality and autonomy. To ensure participants receive similar intervention, the trial adapts a brief ACT module by Shari et al. [31]. The therapist will administer the intervention when patients are in the hospital for treatment. The assessment batteries will be issued at three specific time points: before the intervention, immediately after the intervention, and three months following the intervention.

Participants in the control group will receive the non-therapeutic approaches, such as reassurance, to allow patients to ventilate their problems and to conduct relaxation techniques such as deep breathing. The intervention and the control groups will receive a 4-session program to ensure ethical considerations and participant access to the intervention. The enrolment, interventions, and assessments of the study are summarized in Fig 1. Fig 2 shows the flow of the research procedures and outcome measures.

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Fig 1. Scheduled assessment of the randomized control trial’s outcome measures.

https://doi.org/10.1371/journal.pone.0312669.g001

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Fig 2. The flow of the research procedures and outcome measures.

https://doi.org/10.1371/journal.pone.0312669.g002

ACT intervention

ACT is one of the most representative experiential behavior therapies in the third wave of cognitive and behavior therapy, called “contextual cognitive-behavioral therapy.” ACT aims to increase psychological flexibility so that people may dedicate themselves to a worthwhile and meaningful life via flexible therapeutic methods, as well as mindfulness, acceptance, defusion, self as context, value, and committed action. The interventions include evaluating cognitive fusion and values, accepting negative emotions and experiences, dissociating from personal experience, contact with the present and meditation training, determining importance, making behavior plans, etc. The ACT intervention is scheduled for 1 session per week for 4 weeks. Each session lasts for 1 hour. The activities in each session are summarized in Table 1. A detailed description of the activities in each session is presented in the S1 Appendix.

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Table 1. Summary of content of ACT treatment sessions.

https://doi.org/10.1371/journal.pone.0312669.t001

Control group

The control group participants will receive treatment as usual, including nonspecific and nontherapeutic approaches such as providing psychological understanding, identifying current problems, and practising deep breathing exercises. They will receive the same amount of time and attention from the same therapist as the intervention groups and participate in a one-session weekly program for four weeks.

Treatment fidelity

The ACT intervention group will receive therapy administered by a therapist specifically trained in ACT. This therapist, a PhD student in psychiatry, is not otherwise involved in the study. They have received training from a licensed clinical psychologist with six years of experience in practising ACT. To ensure treatment integrity, independent monitoring will be conducted by a psychiatrist and a clinical psychologist trained in ACT, who will evaluate the delivery of interventions by the therapists in the ACT group. About 15% audio recordings of the psychotherapy sessions will be randomly selected and stratified according to the intervention phase (early, middle, or end). Then, treatment integrity assessments will be performed using (1) the Drexel University CT/ACT Therapist Adherence and (2) the Competence Rating Scale for the selected ACT session recording. Each treatment integrity assessor will assess half of the selected sessions. Then, the inter-rater reliability between the two treatment integrity assessors is computed to assess the treatment integrity of the therapists who are delivering the interventions. If the therapist is inconsistent in delivering some sessions, the therapist will discuss this issue with the principal investigator to solve any shortcomings during the interventions.

Primary outcome: Disease acceptance

Disease acceptance will be assessed using the Malay version of the Illness Cognition Questionnaire (ICQ-M) for breast cancer patients. Evers created ICQ in 2001, and it assesses disease cognition from both positive and negative viewpoints, with three dimensions of helplessness, acceptance, and perception benefit. The better the condition of the related dimensions, the higher the score [32]. ICQ-M demonstrates strong psychometric properties, making it a reliable and acceptable tool for assessing disease acceptance among breast cancer patients. The ICQ-M exhibited good internal consistency, with Cronbach’s alpha values ranging from 0.742 to 0.927, indicating high reliability across its domains. Content validity was evaluated by a panel of experts who rated the relevance of each item, resulting in high item-level and scale-level content validity indices (I-CVI and S-CVI), affirming the appropriateness of the ICQ-M items. Construct validity was supported by factor analysis, which confirmed the structural integrity of the questionnaire, comprising 17 items distributed across two domains with good convergent and discriminant validity. Additionally, concurrent validity was evidenced by moderate correlations with the Acceptance and Action Questionnaire II (AAQ-II), indicating that the ICQ-M effectively measures the intended constructs in relation to similar tools. The ICQ-M’s reliability and validity make it suitable for measuring disease acceptance in Malay-speaking breast cancer patients [33].

Secondary outcome

Descriptive analysis

Statistical software for social sciences (SPSS version 27) will be used to conduct data analysis. The study of sociodemographic data will make use of descriptive statistics. Race, age, marital status, educational background, work position, and illness state, including the stage at diagnosis, chemotherapy regimen, and time since diagnosis, are all described using frequency and percentage. Before implementing the ACT intervention, inference analysis will examine the significant differences between the waiting and intervention groups. The study’s primary analysis will adhere to the intention-to-treat (ITT) principle. Furthermore, the main effect will be accompanied by a 95% confidence interval. Statistical significance will be determined using a two-tailed approach and set at p<0.05.

To address any instances of missing data, the approach will be as follows: If missing data accounts for less than 5% of the total collected data, they will be disregarded. In cases where missing data exceed 5% but fall below 40% of the total collected data and are assumed to occur randomly, multiple imputations using restricted maximum likelihood estimation will be conducted using Stata 15. However, if missing data surpass 40% of the total collected data or are presumed to be non-random or entirely random, only the available data will be utilized for analysis in the study, and any absence of data will be acknowledged as a limitation in subsequent publications of the study’s findings [41].

Mixed ANOVA analysis

The comparison of mean differences before and post-intervention will be examined to see whether any changes in illness cognition, anxiety, depression, psychological inflexibility, QoL, and social support among breast cancer patients in response to ACT intervention. Then, while controlling for confounders, mixed ANCOVA will be used to look at any significant changes in the measured variables between the waiting and intervention groups, with the group as the between-group factor and time as the within-group factor. A few confounding factors that may affect disease acceptance in cancer will be taken into account and controlled by using mixed ANCOVA, such as the level of pain and fatigue and monthly income [42, 43]. Age is also included as a covariance.

The effect sizes will be determined to evaluate how much patients’ perceptions of the measured variables changed with and without an ACT intervention. The formula of Cohen’s d (Rosnow Rosenthal, 1996) [44] is used to calculate the effect size. According to Cohen (1988), the effect size will be considered small if (d = 0.2), medium (d = 0.5), and large (d = 0.8).

Mediators and moderators

The mediation analysis will be conducted using the PROCESS macro-Version 3.5 developed by Andrew F. Hayes. This research uses a single mediator model to examine the total, direct, and indirect effects. The independent variables will be the groups in the RCT study (ACT intervention group and control group). At the same time, the dependent outcomes will be the change scores of illness cognition and QoL from pre-treatment to post-assessment. The change score is chosen as the dependent variable to assess the improvement of scores between pre-and post-treatment. Proposed mediator variables include psychological inflexibilities, anxiety, depression and social support. PROCESS will be used to validate the mediating effect of psychological inflexibility and disease cognition on the relationship between the ACT intervention and QoL. The Bootstrap program will confirm the direct and indirect effects. Additionally, social support will be introduced as a moderating variable in the coping path to create a final model that verifies the overall mediating product.