Authors: Cho Lee Wong, Huiyuan Li, Chi Kong Li, Carmen Wing Han Chan, Yin Ting Cheung, Kai Chow Choi, Winnie Kwok Wei So
Categories: Paediatrics, CHEMOTHERAPY, Nursing Care, Paediatric oncology, Virtual Reality, 1506, 1719
Source: BMJ Open
Effects of immersive virtual reality for alleviating anxiety, nausea and vomiting among patients with paediatric cancer receiving their first protocol for a randomised controlled trial
Authors: Cho Lee Wong, Huiyuan Li, Chi Kong Li, Carmen Wing Han Chan, Yin Ting Cheung, Kai Chow Choi, Winnie Kwok Wei So
Abstract
Introduction
Anxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on improving anxiety and distress symptoms including nausea and vomiting in this vulnerable group. This trial aims to evaluate the effects of IVR intervention on anxiety, chemotherapy-induced nausea and vomiting and anticipatory nausea and vomiting in patients with paediatric cancer receiving first chemotherapy.
Method and analysis
An assessor-blinded, randomised controlled trial with a mixed methods evaluation approach. On the basis of our pilot results, 128 chemotherapy-naive patients with paediatric cancer scheduled to receive their first intravenous chemotherapy will be recruited from a public hospital and randomly allocated to intervention (n=64) or control groups (n=64). The intervention group will receive the IVR intervention for three 2 hours before the first chemotherapy, 5 min before and during their first chemotherapy and 5 min before and during their second chemotherapy, respectively. The control group will receive standard care only. A subsample of 30 participants in the intervention group will be invited for a qualitative interview. Study instruments (1) short form of the Chinese version of the State Anxiety Scale for Children, (2) visual analogue scale for anticipatory nausea and vomiting, (3) Chinese version of the Multinational Association of Supportive Care in Cancer Antiemesis Tool and (4) individual face-to-face semistructured interviews to explore intervention participants’ perceptions of the IVR intervention.
Ethics and dissemination
This study has been approved by the Hong Kong Children’s Hospital Research Ethics Committee (HKCH-REC-2021-009). The findings will be disseminated in peer-reviewed journals and through local or interventional conference presentations.
Trial registration number
ChiCTR2100048732.
Introduction
Chemotherapy can provoke anxiety in patients, especially those receiving chemotherapy for the first time.1 An observational study has shown that pre-chemotherapy anxiety is reported by 89% of chemotherapy-naive patients.1 Patients with paediatric cancer with heightened anxiety early in therapy are four times more likely to have elevated anxiety after the therapy.2 Moreover, pre-chemotherapy anxiety and anxiety experienced after receiving chemotherapy predispose patients to a higher risk of chemotherapy-induced nausea and vomiting (CINV).3
CINV remains the most aversive side effect in paediatric patients undergoing chemotherapy.4 Acute CINV refers to symptoms occurring within 24 hours of chemotherapy administration, whereas delayed CINV occurs 24 hours and up to 5 days after chemotherapy.5 Chemotherapy emetogenicity is the strongest known determinant of CINV in paediatric patients.5 Without prophylaxis, the incidence of emesis varies from 30% to 90% and >90% with moderately and highly emetogenic chemotherapy, respectively.5 Current guidelines recommend a 5-HT3 antagonist, dexamethasone and aprepitant for children receiving highly emetogenic chemotherapy and aprepitant as an alternative to be used together with 5-HT3 antagonist for children who cannot take dexamethasone but are receiving moderately emetogenic chemotherapy.5 However, the management of CINV in paediatric patients remains suboptimal.6 A retrospective review of Canadian patients with paediatric cancer found that only 30% of patients have complete CINV control despite pharmacological management.6 Without proper initial management, CINV may trigger the development of anticipatory nausea and vomiting. This conditioned response is linked to previous experience of CINV that occurs prior to a subsequent encounter with stimuli reminiscent of chemotherapy infusion.6 A study has shown that anticipatory nausea and vomiting is reported by up to 59% of paediatric patients.7 Furthermore, once conditioned anticipatory nausea and vomiting has been established, it is unresponsive to antiemetics.8
Poorly managed anxiety and CINV can lead to detrimental physical and psychological consequences, such as dehydration and electrolyte disturbances. The patients’ ability to cope with subsequent chemotherapy is also hindered.4 The results are dose reduction and delay or discontinuation of treatment, thereby reducing patients’ chances of recovery and survival.4 Therefore, international guidelines and expert consensus strongly recommend that optimal psychological interventions be offered to patients with paediatric cancer to manage anxiety and CINV, especially during their first chemotherapy.8 9
A systematic review has suggested that distraction is among the most effective psychological interventions in reducing anxiety and distress, especially in paediatric patients younger than 12 years.10 Our team has previously examined distraction play for paediatric patients who undergo a cast-removal procedure,11 as well as nurse-led distraction and relaxation exercises, to elicit a relaxing response as counter condition for patients with paediatric cancer prior to chemotherapy commencement.12 However, these interventions require specialised training before implementation and are labour intensive, thereby limiting their clinical feasibility and applications.
Virtual reality (VR), a novel and interactive form of distraction that can be delivered without training, is being increasingly studied. VR allows users to become active participants in a three-dimensional (3D) computer-generated virtual environment.13 It ranges from non-immersive to immersive depending on the degree of the user’s isolation from physical surroundings. Immersive VR (IVR) is advantageous over non-IVR in that IVR completely isolates users visually and acoustically from an anxiety-inducing clinical environment and helps users focus on relaxing stimuli through a head-mounted display.13 Moreover, the efficacy of IVR does not decrease after 8 weeks of repeated exposures in a controlled laboratory environment.14 Considering these unique features, IVR is used in cancer centres in Australia15 and the USA16 to relax patients during treatments.
Our previous works have also supported the use of IVR as a distraction and relaxation intervention for paediatric patients undergoing distressing procedures. A randomised controlled trial (RCT) examining the effect of IVR on 108 patients with paediatric cancer who had undergone repeated peripheral intravenous cannulation has revealed that patients in the IVR group reported significantly less pain immediately after the procedure than their control counterparts.17 Preliminary data from another funded trial extended to younger general paediatric patients (aged 4–12 years) undergoing venipuncture have also yielded similar results.
Recent reviews have suggested that IVR intervention can be applied to reducing anxiety and symptom distress in both adults and paediatric patients undergoing chemotherapy sessions.13 18 19 Both commercial or tailored-made VR modules have been used in the included studies with at least 20 min of intervention time.13 For instance, a pretest and post-test study involving 12 children receiving chemotherapy has reported improved distress symptoms, including nausea and vomiting, after one session of IVR intervention.20 IVR has also helped patients underestimate their time perception, and the chemotherapy duration seems shortened for them.21 However, previous studies are limited by methodological weaknesses, such as the use of pretest and post-test design, small sample size, lack of blinding of outcome assessors and use of only a single IVR session.13 18–21 Future studies that will address these limitations are warranted.13 18 19
The research team led by the principal investigator (PI) is conducting an exploratory trial funded by Health and Medical Research Fund to assess the feasibility, acceptability and preliminary effects of IVR on patients with paediatric cancer receiving chemotherapy for the first time. In total, 16 paediatric patients were recruited and randomly assigned to either an intervention (receiving IVR intervention) or a control (receiving standard care) group. Preliminary results showed 100% recruitment and retention rates. A significant reduction in anxiety level was also noted in the IVR group. The qualitative data collected from patients, parents and healthcare providers supported the acceptability and feasibility of integrating IVR intervention into routine clinical practice, with few potential modifications related to the VR system suggested by the participants. These results offered insights to optimise the development of a definitive trial.
Extended and built on our previous works of IVR on distressing procedures for patients with paediatric cancer, the current proposed trial is a pioneer in adopting a robust design for examining the effects of IVR to establish relaxation as counter conditioning and distraction in the intervention package for patients with paediatric cancer undergoing their first chemotherapy. With encouraging results from our exploratory trial, the next step is to conduct a full-scale RCT to provide greater confidence in our conclusions regarding the intervention effects using a quantitative and qualitative evaluation approach.
Theoretical framework underpinning the IVR intervention
Pavlovian classical conditioning is used to guide this trial.22 It suggests that an unconditioned stimulus (chemotherapy) that produces an unconditioned response (ie, anxiety/nausea/vomiting) is paired with a conditioned stimulus. Potentially conditioned stimuli related to chemotherapy treatments may include sights of the clinic, nurses or chemotherapy infusion devices. Exposure to the conditioned stimuli alone can sufficiently elicit the conditioned response by pairing the unconditioned stimulus with conditioned stimuli in the acquisition phase.22
Patients with paediatric cancer often experience substantial anxiety before initiation of chemotherapy, which may further enhance the conditioned response to anticipatory CINV. In contrast, optimisation of acute CINV control for children undergoing the first chemotherapy may help minimise patients’ exposure to the negative stimuli required for conditioning.7 9 IVR functions by establishing a relaxing and playful response as counter conditioning before chemotherapy commences. It also provides multisensory inputs to distract the patients from their anxiety and focus on the pleasant VR environment during chemotherapy. Therefore, IVR helps block the conscious attention of patients away from the conditioned and unconditioned stimuli. As a result, patient’s anxiety and CINV would likely be alleviated, and the satisfaction of the patients will be improved by the intervention.
Aim and hypothesis
This trial aims to examine the effects of IVR as a distraction and relaxation intervention for reducing anxiety, CINV and anticipatory nausea and vomiting among patients with paediatric cancer receiving their first chemotherapy.
We hypothesise that, compared with standard care, IVR intervention significantly reduces anxiety, CINV and anticipatory nausea and vomiting in patients with paediatric cancer receiving chemotherapy 5 min before and immediately after the first and second chemotherapy.
Methods and analysis
Design
An assessor-blind, two-arm RCT with a mixed methods evaluation approach will be conducted. Figure 1 shows the study procedure. The protocol is registered on the Chinese Clinical Trial Registry (ChiCTR2100048732).
Participants
Participants will be recruited in the Oncology Department of Hong Kong Children’s Hospital using convenience sampling. The unit admits children and adolescents with cancer who are under 18 years of age. It is the only hospital in Hong Kong that provides diagnosis and treatment for all children with cancer in the public healthcare system.
Inclusion criteria
Patients who are (1) aged between 6 and 12 years, (2) chemotherapy naive, (3) scheduled to receive moderately or highly emetogenic intravenous chemotherapy,5 (4) received antiemetic prophylaxis (eg, 5-HT3 antagonist, aprepitant and/or dexamethasone)5 and (5) can understand Chinese and follow instructions.
Exclusion criteria
Patients who have (1) identified cognitive problems arising due to brain injuries, neurodegenerative disorders or developmental disorders, that is, had difficulty understanding the study procedures, following instructions or providing informed consent, in their medical record, (2) brain tumours or metastases, (3) identified contact precautions and (4) previous history of seizures or motion sickness.
The rationale for recruiting patients aged 6–12 years is that younger patients are more vulnerable to anxiety when undergoing medical procedures as compared with older ones (>12 years).10–12 Meanwhile, this homogenous age group is in the concrete operational developmental stage which is more responsive to VR interventions as reported in a systematic review.19
Sample size
Sample size estimation was based on the effects estimated from our pilot trial,23 indicating that the effect sizes of Cohen’s d on the primary outcome of anxiety level immediately after the first and second chemotherapy ranged from 0.52 to 0.62. By using power analysis software G*Power 3.1 and considering the smallest effect size of 0.52 and an attrition rate of 5%, we estimated that a sample size of 64 participants per group would be adequate for a two-group RCT with 80% power at two-sided with 5% level of significance. As emetogenicity of chemotherapy can be a main confounder for the trial,5 the participants will be recruited with stratification by the level of emetogenicity of chemotherapy (moderate or high). A total of 128 eligible participants with 64 scheduled to receive moderately and another 64 scheduled to receive highly emetogenic intravenous chemotherapy will be recruited into the trial.
As approximately 50 eligible patients with paediatric cancer aged between 6 and 12 years were admitted to the study institution for their first chemotherapy, with an estimated number of four eligible patients admitted per month, we anticipate that the recruitment of a total of 128 subjects will be completed within 36 months of the proposed study period.
In addition, a maximum variation sample of 30 participants from the intervention group will be purposively invited for a qualitative interview post intervention. Participants will be selected according to changes in their post‐intervention anxiety, nausea or vomiting scores.
Randomisation and blinding
This trial comprises two an intervention group that receives the IVR intervention and standard care and a control group that receives standard care only. A computer-based stratified randomisation will be used to allocate patients into the intervention or control groups with stratification by moderately (eg, vincristine, methotrexate and/or doxorubicin) or highly (eg, cyclophosphamide and/or cisplatin) emetogenic chemotherapy, an approach commonly adopted in previous studies.5
Eligible participants in each of the two strata of emetogenicity of chemotherapy (moderate and high) will be randomly assigned in a 1 ratio to either the control group or the intervention group, using permuted block randomisation with varying block sizes ranging from 4 to 8 to optimise allocation concealment and maintain a good balance of participants between the two groups and levels of emetogenicity of chemotherapy throughout the subject recruitment period.24
The sequence of grouping identifiers (I=intervention group or C=control group) will be prepared in advance by an independent statistician using computer-generated random codes. The group identifiers for each stratum of emetogenicity of chemotherapy will then be placed in serially numbered sealed opaque envelopes according to the random sequence list generated by the statistician. The patient’s group allocation will be assigned according to the sequence of enrolment in the study and the group identifier contained in the corresponding numbered envelopes.
Given the nature of IVR intervention, conducting a double-blinded trial will be difficult. Nevertheless, a single-blinded trial with the group allocation conceals from the research assistant who will perform the pre-outcome and post-outcome assessments will be conducted.25
Control: standard care
Participants in the control group will receive standard care only with no IVR intervention during their chemotherapy. Standard care consists of pre-chemotherapy instruction and antiemetic prophylaxis administration.
Intervention: IVR
In addition to standard care, participants will receive IVR for three separate sessions during their first and second (1) 2 hours prior to chemotherapy commencement, (2) 5 min before and during the first chemotherapy and (3) 5 min before and during the second chemotherapy. Each IVR session will last for 20 min. A total of 20 min is selected based on previous studies suggesting that such duration is effective in reducing chemotherapy-induced anxiety and distress symptom.13 Additionally, it also reduces the risk of developing transient dizziness, which may occur in patients with paediatric cancer who are exposed to VR for a long time.
Considering that unconditioned stimulus–conditioned stimulus pairings are sufficient even for one course of chemotherapy exposure, conducting additional sessions may result in missing data despite enhancing the intervention effect. Therefore, three sessions of IVR that involve the first and second chemotherapy are feasible.22
The first IVR session is used to establish a relaxation and playful response as counter conditioning before the chemotherapy commenced. Based on our pilot, patients usually admitted in the morning to prepare for chemotherapy infusion that is commenced in the afternoon, the first IVR session is held 2 hours before commencement of chemotherapy for practical reason.
The second IVR session is used to establish IVR as counter conditioning and distraction intervention during chemotherapy infusion to reduce the anxiety and CINV of patients.
The third session aims to reinforce the IVR effects on reducing anxiety and CINV.
During the intervention, the patients will experience the sense of immersion with a first-generation all-in-one headset (Oculus Go) delivering IVR sounds and images. We have previously used a low-tech VR system (Google cardboard goggles) but received comments from patients such as limited field of view, lack of durability and difficulty in holding the phone. Accordingly, we changed the VR system to be used, and this change is also consistent with a recent review recommending the use of high-tech VR systems (such as Oculus Go) to provide participants with higher resolution and wider field of view.19 To minimise the risk of contact infection, a removable face pad will be applied. The headset and the controller will also be disinfected with alcohol-based sanitary wipes before and after use according to the manufacturer’s recommendation.
Previous studies have used commercially available VR modules or specially developed modules for distracting and relaxing paediatric patients during medical procedures.13 18 However, a meta-analysis has found no difference between the two.19 Our pilot work used 3D cartoon modules, such as Minions and Disney, which provide wide-ranging visual and auditory stimuli and can be freely downloaded for the patients. These modules were considered as appropriate after consultation with oncologists, nurses in paediatric cancer units and an IT specialist. We received comments from patients in pilot that these modules were interesting, interactive and can capture their attention for an extended period of time, and they preferred to have both interactive and non-interactive modules in a session. Therefore, we modified each session with a combination of two modules (table 1).
Implementation
A trained research assistant (RA1) provides the patients with standard instructions on how to use the IVR equipment in the first session. The VR headset will then be placed and adjusted on the patient’s head to ensure comfort and secure fit. For the first session, patients are given 5 min to use and familiarise themselves with the headset.17 18
For the second and third sessions, RA1 provides IVR to patients 5 min before the chemotherapy commences.2 19 RA1 asks the oncology nurse to start the administration once the patients are ready for the chemotherapy treatment. The nurse first disinfects outlets of the intravenous site, connects the device and starts infusion, during which patients will be allowed to view their selected VR modules. The headset will be removed by RA1 after each session.
Fidelity of the intervention
The fidelity of the intervention is ensured by recruiting two part-time research assistants (RA1 and RA2) with at least 1 year of experience in paediatric care. The principal investigator will provide 1.5 days of training to RAs in (1) evidence of the benefits of IVR to paediatric patients; (2) application and basic knowledge about IVR; and (3) procedures of implementing the intervention. A standardised manual will be developed to guide the delivery of IVR intervention. Moreover, at least one session conducted by the RAs each month will be randomly selected to assess compliance with the data collection and protocol implementation by the principal investigator.
Outcome measurements
The following outcome measures will be collected by research assistant (RA2) who is blinded to the participants’ allocation.
Primary outcome
Anxiety
The short form of the Chinese version of the State Anxiety Scale for Children (CSAS-C) will be used to measure the anxiety levels of the participants.26 It is a 3-point Likert scale with 10 items and scores ranging from 10 to 30, with higher scores indicating higher anxiety levels.26 The State Anxiety Scale has been used in our previous study and pilot to measure anxiety among children undergoing needle-related procedures or chemotherapy, with a Cronbach’s alpha coefficient of 0.82–0.93.18
Secondary outcomes
Heart rate
The physiological responses of anxiety will be measured by heart rate using a standard automatic blood pressure monitoring machine (available in the study institution). This indicator is considered to be objective and definitive in assessing physiological responses of anxiety.11 17
Anticipatory nausea and vomiting
A visual analogue scale will be used to assess the severity of nausea and vomiting before the chemotherapy.4 Children will be asked to indicate their severity of nausea and vomiting on a 0–100 mm horizontal line, with ‘0’ indicating the absence of nausea and vomiting, while ‘100’ indicates the most severe form of nausea and vomiting.
Acute nausea and vomiting
The Multinational Association of Supportive Care in Cancer Antiemesis Tool will be adopted to assess the incidence, duration and frequency of CINV. The Chinese version has good reliability and validity with a Cronbach’s alpha coefficient of 0.73–0.81 in previous and our pilot trial.27 The four items assessing acute CINV will be used in this trial.
Qualitative interviews
Individual face-to-face semistructured interviews will be conducted using an interview guide (online supplemental material 1) with a subsample of 30 patients in the intervention group. The interviews aim to gain an in-depth understanding of patients’ experiences of IVR intervention during chemotherapy. These unique perspectives can help to enrich our understanding of why and how the IVR intervention works, as well as ways to improve the effectiveness of the intervention.
RA 1, who also has considerable experience in qualitative interviews, will conduct the interviews. Each interview will be audiotape recorded and conducted in a quiet room provided at the study institution.
Sociodemographic and clinical characteristics
The following clinical characteristics will be collected from the participant’s medical age, sex, year of study, medical diagnosis, time since diagnosis, stage of disease, type of cancer treatment received, chemotherapy regimen, types and dosage of antiemetic and other concomitant medications prescribed and intake.
Data collection procedures
A nurse working in the paediatric oncology unit will screen for eligibility for all patients who are admitted to receive their first intravenous chemotherapy during pre-chemotherapy assessment. If children meet the inclusion criteria, the nurse will refer them and their accompanying parents to RA1, who will provide them with an information sheet, explain the trial and show the IVR equipment. If they agree to participate, RA1 will obtain written informed consent from the accompanying parent(s) and assent from the patients. RA1 will then acquire the sociodemographics and clinical characteristics of the patients from medical records before randomisation. According to the subject allocation, children in the control group will receive standard care, while those in the intervention group will additionally receive the IVR intervention. The outcome assessments will be conducted by a blinded assessor (RA2) at five time points (T0–T4).
Two hours prior to (T0), immediately before the first (T1) and second chemotherapy begins (T3), a set of data (ie, anxiety, HR and anticipatory nausea and vomiting) will be collected from the patients.
Immediately after the first (T2) and second chemotherapy (T4), the anxiety, HR and acute CINV will be collected. In the intervention group, the IVR modules selected will also be recorded.
Individual face-to-face semistructured interviews will be conducted at T4 with patients in the interventional group. The frequency of vomiting and antiemetics used will be obtained from medical records (T0–T4). All children will be given VR goggles after the completion of the trial. The data collection plan is shown in table 2.
Data management
The data from participants will be kept strictly confidential and used for research purpose only. All research data will be stored in a computer that only research personnel can access. All data will also be destroyed 5 years after the completion of the study.
Patient and public involvement
Patients and their accompanying parents were involved in the development of the intervention. Before the start of the study, patients and their accompanying parents were first invited to participate in the main sessions of the study to ensure clarity and comprehension. After the intervention delivery, semistructured interviews will be carried out in participants in the intervention group to explore their experiences on the intervention’s usefulness and acceptability.
Data analysis
IBM SPSS (V.24) will be used for statistical analyses. Continuous demographic (eg, age) and clinical variables (eg, scores on CSAS-C) will be presented by their means and SD or medians and IQRs, as appropriate, whereas categorical data (eg, sex) will be presented in frequencies and percentages. Pearson’s χ^2^ test (or Fisher’s exact test) and independent t-test (or Mann-Whitney test for highly skewed data) will be used as appropriate for assessing the homogeneity of the baseline characteristics of the two groups. The intention-to-treat principle will be adopted in the outcome evaluation between the two groups. A generalised estimating equation (GEE) model will be used to compare each of the outcome measures across the time points between the two groups with adjustment for the stratification factor of emetogenicity of chemotherapy and other potential confounding factors, including age, cancer diagnosis, antiemetic agents used and chemotherapy regimen to improve the precision of the effect estimates. The GEE model can account for intra-correlated repeated measures data and produce unbiased estimates even in the presence of missing data, provided they are missing at completely random. Cohen’s d values will also be calculated to estimate the effect sizes of the IVR intervention on the outcome variables. All statistical analyses are two-sided, and the level of significance will be set at 0.05.
For the qualitative interviews, all interviews will be transcribed verbatim into written Chinese before conventional content analysis is conducted. The researcher will first familiarise herself with the data by reading the transcribed verbatim several times. Starting with line-by-line coding, statements that are related to (1) the experiences of the IVR intervention and (2) views and perceptions of the IVR intervention will be coded and categorised. Once the categories have ample data, they will be broken down into subcategories. The categories and subcategories will be reviewed by two coinvestigators to ensure participants’ points of view are accurately reflected.
Appropriate strategies will be undertaken to ensure the trustworthiness of the study, including credibility, dependability, confirmability and transferability.28 Credibility will be ensured by peer debriefing during the data analysis process. Dependability will also be ensured, as interviews will be conducted by a single RA to maintain consistency in data collection. All the interview transcripts will be checked for accuracy to ensure a complete account of the participant’s responses. For confirmability, the researcher will critically examine her own assumptions and actions by being self-aware of the research process, bracketing her preconceived ideas and experience. To facilitate transferability, a thick description of the study will be provided.25
Ethics and dissemination
Ethical approval has been sought from the Hong Kong Children’s Hospital Research Ethics Committee with reference number HKCH-REC-2021-009. We will protect the participants’ rights and safety by adhering to local laws, the Hong Kong Personal Data (Privacy) Ordinance, the Declaration of Helsinki, institutional policies and the International Conference on Harmonization-Good Clinical Practice. A nurse working in the paediatric oncology unit will screen for eligibility for all patients who are admitted to receive their first intravenous chemotherapy during pre-chemotherapy assessment. If children meet the inclusion criteria, the nurse will refer them and their accompanying parents to RA1, who will provide them with an information sheet, explain the trial and show the IVR equipment. If they agree to participate, RA1 will obtain written informed consent from the accompanying parent(s) and assent from the patients. Written consent will be obtained from each participant by the researcher conducting recruitment (online supplemental material 2). All data collected from participants will only be used for research. Potential participants will be informed that they may withdraw from the study at any time during the research period, with or without providing a reason, and it will not affect their child’s current or future medical and care services. The findings will be disseminated in peer-reviewed journals and through local or interventional conference presentations.
Discussion
Given the negative consequences of unmanaged anxiety and CINV, identifying an effective intervention that can alleviate these symptoms is crucial to improving patients’ coping with chemotherapy treatments and thus enhancing their chances of recovery. This novel study aims to generate new knowledge related to the effects of IVR, an innovative, convenient and attractive intervention that can be used by paediatric patients undergoing their first chemotherapy virtually at any time and place. The results will advance the understanding of the use of IVR in intervention delivery. It may positively contribute to improvements in patient outcomes. As the health-delivery system includes important quality benchmarks for patient outcomes, this study will also provide knowledge on the optimisation of care provided to patients with paediatric cancer and thus help strengthen the healthcare system. This innovation has far-reaching implications and is likely to extend to other patients with cancer. These impacts will be achieved through the provision of high-quality research results and knowledge-exchange activities involving the engagement of different stakeholders, including local and national health agencies, universities, cancer organisations, patient groups and media groups.