Safety and adherence to medications and self-care advice in oncology (SAMSON): pilot randomised controlled trial protocol

Abstract

Introduction

With the increasing use of oral anti-cancer medicines (OAMs), research demonstrating the magnitude of the medication non-adherence problem and its consequences on treatments’ efficacy and toxicity is drawing more attention. Mobile phone interventions may be a practical solution to support patients taking OAMs at home, yet evidence to inform the efficacy of these interventions is lacking. The safety and adherence to medications and self-care advice in oncology (SAMSON) pilot randomised control trial (RCT) aims to evaluate the acceptability, feasibility and potential efficacy of a novel digital solution to improve medication adherence (MA) among people with cancer.

Methods and analysis

This is a two-arm, 12-week, pilot RCT aiming to enrol 50 adults with haematological, lung or melanoma cancers at an Australian metropolitan specialised oncology hospital, who are taking oral anti-cancer medicines. Participants will be randomised (1:1 allocation ratio) to either the intervention group (SAMSON solution) or the control group (usual care). The primary outcomes are the acceptability and feasibility of SAMSON. The secondary outcomes are MA, toxicity self-management, anxiety and depressive symptoms, health-related quality of life, and parameters relating to optimal intervention strategy. Quantitative data will be analysed on a modified intention-to-treat basis.

Summary

While multicomponent interventions are increasingly introduced, SAMSON incorporates novel approaches to the solution. SAMSON provides a comprehensive, patient-centred, digital MA intervention solution with seamless integration of a mobile platform with clinical consultations that are evidence-based, theory-based, co-designed and rigorously tested. The pilot trial will determine whether this type of intervention is feasible and acceptable in oncology and will provide a foundation for a future full-scale RCT.

Ethics and dissemination

Primary ethics approvals were received from Peter MacCallum Cancer Centre and Swinburne University of Technology Human Research Ethics Committees (HREC/95332/PMCC and 20237273–15836). Results will be disseminated via peer-reviewed publications and presentations at international and national conferences.

Trial registration number

The protocol has been prospectively registered on the Australian New Zealand Clinical Trials Registry with trial registration number (ACTRN12623000472673).

Strengths and limitation of this study.

• This pilot trial will address the knowledge gap in the use of technology, ongoing adherence assessments, follow-ups, coaching and motivational interviewing for patients on anti-cancer medications.

• The intervention solution co-design and development follows the design science research methodology and is based on cognitive and behavioural theories and evidence.

• Individual components of the intervention solution have previously been tested rigorously.

• This is a pilot study with primary aims of acceptability and feasibility.

• This is a study conducted in one specialised oncology hospital only.

Introduction

The increasing use of oral anti-cancer medicines is drawing attention to medicine adherence and the safety of treatment.1,4 Data show that the variability in oral medication adherence (MA) rates in cancer is very broad, ranging from 14% to 100%.5,7 MA is subjected to variable influences that can be categorised into five groups of factors: socioeconomic, health system, condition-related, therapy-related and patient-related.⁸ Therefore, multicomponent solutions tailored to patient barriers to MA are likely more effective than single-component interventions.⁹ Given the known negative impacts of poor adherence to the treatment efficacy and toxicity,710,12 and the explosion of and rapid uptake of information technologies in healthcare,^{3 13 14} mobile phone solutions may deliver multicomponent MA interventions more effectively and efficiently,^{9 14 15} and empowering patients to self-manage their therapies at home.^{8 13 16}

An increasing number of studies report on the use of technology to deliver multicomponent MA interventions in cancer,317,19 yet there is a paucity of evidence to inform best practice for these interventions.²⁰ Research shows that to be effective in improving MA, mobile phone interventions not only need to be comprehensive and address multidimensional aspects of non-adherence but also, theory-based and evidence-based, rigorously developed and tested.921,23 The SAMSON (safety and adherence to medication and self-care advice in oncology) project addresses the gaps in healthcare needs and research knowledge by (1) using co-design to develop a patient-centred, comprehensive, digital solution to improve MA in cancer, named SAMSON, comprising two synergetic components: a mobile application (app) and an online motivational interviewing training platform (MITP); and (2) evaluating the acceptability, feasibility and potential efficacy of the developed solution. This paper reports the protocol of a pilot randomised control trial (RCT) to evaluate the SAMSON solution. The trial protocol complies with the Standard Protocol Items: Recommendations for Interventional Trials 2013²⁴ (see online supplemental file 1).

Research context

The SAMSON solution has been co-designed and developed based on evidence from literature and behavioural, cognitive and design sciences theories.25,30 The SAMSON mobile app comprises a smart phone-based application to remotely prompt MA, monitor the patient’s side-effects and provide self-care advice; and a web-based application for healthcare professionals (HCPs) to programme the patient’s daily drug reminders, side-effect surveys and relevant drugs’ information. The app was co-designed with stakeholders and users and developed following the four-cycle model³¹ and the six-stage³² of the Design Sciences Research Methodology (DSRM) (see online supplemental file 2). After development, the SAMSON app beta-version was tested by 30 people with haematological cancer at an Australian metropolitan specialised oncology hospital, using a mixed-methods design. The SAMSON beta-testing aimed to assess the quality of the app to ensure it is fit for purpose and user-friendly, and provides appropriate supporting MA education and information; as well as gain information on the patient experience, expectation and perception of the app. Results of this study demonstrated that patients highly rated the usability (78%), appeal (67%), visual design (70%) and adequacy of information (66%) of the app. About two-thirds of patients believed the app improved their adherence to oral treatment and would recommend it to their peers (63%). Feedback from the patient interviews revealed some functional errors and desire for new features which have been incorporated into the new version of SAMSON (manuscript is under review).³³

The MITP is an online training platform, which was created to provide general training on communication skills, share decision making (SDM)³⁴ and motivational interviewing (MI).³⁵ SDM and MI are evidence-based approaches to behavioural change and patient-centred care^{36 37} that have been proven to be effective in various health settings, including MA.³⁸ The MITP targets upskilling oncology HCPs in promoting MA and changing patients’ non-adherence behaviour. It was co-designed with HCPs, stakeholders and consumer representatives, then developed and tested based on the same principles of DSRM (see online supplemental file 2). Results from the user-testing study with 33 HCPs show that the MITP was perceived as useful (94%), easy to use (79%), improved MI knowledge and skills among HCPs (97%), and helpful (94%). Most participating HCPs (91%) wanted to use MI skills in their daily clinical practice and over two-third of them would refer this course to their colleagues (manuscript is under review).

In the present study, both components work synergistically in one intervention solution. Patients’ data on adherence and drug toxicity collected by the mobile app will allow HCPs to tailor teleconsultation conversations and apply motivational communication skills to provide ongoing support to maintain patients’ long-term adherence and to promote self-management behaviour for toxicities.

We hypothesise that the SAMSON is an acceptable and feasible MA digital intervention solution with the potential to help patients with cancer increase adherence to their oral medications when being treated at home.

Aims

This study aims to evaluate the acceptability, feasibility and potential efficacy of the SAMSON intervention solution.

Methods and analysis

Trial design

The study is a two-arm pilot RCT comparing an intervention group (SAMSON solution) with a control group (usual care) among 50 patients with cancer. After completion of baseline questionnaires, participants will be randomised to either intervention or control groups (1:1 ratio), using a computer-generated randomisation chart. Participants in the intervention group will receive the SAMSON intervention solution, while those in the control group will receive usual care, for 12 weeks immediately following the randomisation. Assessments will occur at different timepoints throughout the 12 weeks.

Setting

Participants will be recruited from the Haematology, Lung and Melanoma departments at Peter MacCallum Cancer Centre (Peter Mac), a metropolitan specialised oncology hospital in Victoria, Australia.

Patient and public involvement

A patient and a consumer representative will be involved in the design and conduct of this research as co-investigators (CIs). During the conception stage, the protocol, participant information statement and methods of recruitment were informed by discussions with these CIs. During the trial, the study progress will be regularly updated to the CIs. The patient-CI is a member of the trial steering committee (SC), which will be formed to provide guidance throughout the study. Once the trial has been published, the CIs will receive the study’s report.

Eligibility

Inclusion criteria. Each participant must meet the following criteria:

• age over 18 years;

• diagnosed with haematological, lung or melanoma cancer;

• scheduled to commence oral anti-cancer medicines or commenced the medication for less than 12 months;

• willing to have oral anti-cancer medicines dispensed at Peter Mac;

• able to communicate in English; and

• have access to the internet, a smartphone (and/or a computer), and/or telehealth.

Exclusion criteria. Participants will be excluded if they meet any of the following:

• remaining oral anti-cancer treatment is less than 12 weeks;

• too unwell to participate in the study or demonstrated cognitive or psychological difficulties that would preclude study participation as defined by the treatment team.

Intervention

SAMSON includes two components:

1. SAMSON mobile app, including a mobile version for patients and a web-based version for HCPs. Participants’ clinical data (diagnosis and treatment details) extracted from the hospital’s electronic medical record system will be imported to the SAMSON mobile app to remotely prompt MA, monitor drug side-effects and deliver tailored self-care advice. Medicine information, such as cautions, and side-effects were developed by hospital’s pharmacy department Medicines Information Service. Self-care advice was developed based on available reliable resources, such as the hospital patient information portal³⁹ and eviQ,⁴⁰ and reviewed by Peter Mac Human Research Ethics Committees (HREC).

   Participants will receive SAMSON mobile app user manual, log in details and assistance to instal and access the app on their mobile phone. They will receive and be asked to respond to daily individualised medication self-administration reminders and weekly side-effects surveys via the smartphone app. They will also be encouraged to access side-effects self-care advice in the app. Data on patients’ adherence and drug toxicity collected in the SAMSON system will be stored centrally on a secure server, then aggregated and uploaded onto a dashboard on SAMSON webpage. On the dashboard, HCPs can track patients’ adherence to individual medicine and symptoms, their personal and clinical details, as well as previous communication and consultation notes. This data will assist HCPs to tailor their teleconsultations with patients.

2. HCP teleconsultations, using MI skills, delivered by oncology HCPs. HCPs were enrolled in the MITP, available in the hospital’s learning management system, and trained on MI skills to promote patient’s adherence and side-effects self-management. The structured counselling sessions will be either in person, via phone or online (telehealth). The initial consultation (30–60 min) will be delivered by a clinical pharmacist within 3 days of enrollment. Follow-up consultations (15–30 min) will be delivered by a clinical nurse at weeks 1, 4, 8 and 12. The quantity and length of consultations will be tailored to the individual patient’s need and adherence status, assessed by the consultant. Intervention nurses and pharmacists will be eligible for the role if they have at least 1 year of clinical experience in providing oncology care and successfully complete the MITP training to conduct the structured counselling sessions with participants. They will be provided instruction manuals to guide them for each consultation and to use SAMSON mobile app. At the end of each consultation, they will need to complete a session checklist on hospital’s electronic medical records system (EPIC) and send a summary to patients’ SAMSON app from the dashboard.

Usual care

Usual care at this hospital consists of a clinician consultation, an initial pharmacist consultation and a nurse-phone-call follow-up within 1–2 weeks after commencing medication as routine practice within the Haematology, Lung, and Melanoma departments at Peter Mac.

All participants will be provided contact details of the study HCPs and be informed of standard care processes if any urgent care enquiries arise.

Measures

Overview

All participants will complete the demographics survey at baseline, followed by Patient Activation Measure-Short Form (PAM-SF),⁴¹ Patient-Reported Outcomes Measurement Information System (PROMIS),⁴² Functional Assessment of Cancer Therapy–General (FACT-G)⁴³ and Self-report Adherence (ASK-12)⁴⁴ at week 1 (t₀) and week 12 (t₁). Intervention participants will complete the adapted Unified Theory of Acceptance and Use of Technology (UTAUT)^{45 46} for patients at the end of week 12. Study HCPs will complete the adapted UTAUT for HCPs at the end of the trial. Data collection will be via REDCap, a secure online data collection tool.^{47 48}

Primary outcome measures

Acceptability

HCPs’ and patients’ acceptability will be assessed by UTAUT questionnaires. The questionnaire will be adapted to assess determinants of clinicians’ and patients’ acceptance and use of the SAMSON solution, including (1) performance expectancy (the degree to which clinicians believe that using the solution will increase their ability to support patient adherence, while patients believe that using the solution will increase their knowledge, ability and confidence in medication treatment management); (2) effort expectancy (the degree of ease associated with using the solution); (3) social influence (the extent to which clinicians and patients perceive that the solution is considered socially acceptable); (4) facilitating conditions (the degree to which the organisational resources and support are available for clinicians and patients to use the solution); and (5) behavioural intention (the degree to which clinicians and patients plan to use solution in real life). Reliability metrics and validity analysis showed that UTAUT is a useful tool to assess the likelihood of success and to understand the drivers of acceptance of a new technology intervention.^{45 46} The questionnaire also includes some open questions for participants to provide more feedback and suggestions on the solution.

Feasibility

The feasibility of the SAMSON intervention will be assessed at every stage of the trial, including recruitment, randomisation, retention, intervention adherence and assessment processes.^{49 50} Recruitment feasibility will be assessed based on the number of patients recruited divided by the number of patients offered to join the study. Retention feasibility will be assessed based on the proportion of participants who remain at the end of the study divided by the total patients who consent to join the study. We will track intervention adherence, that is, the rate of responding to medication reminders and side-effects surveys. We will also assess the feasibility of data collection compliance, that is, study outcomes assessments, in terms of the percentage of the assessments completed at different timepoints and the completeness of the collected data. The criteria for determining feasibility success will be assessed quantitatively using a traffic light approach (table 1). Any outcome above the upper threshold will be deemed feasible. Outcome(s) between the two thresholds will be considered for protocol changes to raise the measure above the upper threshold. Any outcome below the lower threshold will be deemed as infeasible. In this case, information collected from study HCPs on issues/challenges will be used to explain the reason for failures. Discussions with study personnel and the SC will be made on the possibility of making changes to the trial protocol, for example, extending the number of study sites if the recruitment rate is unmet.

Table 1. Thresholds for traffic light approach to feasibility.

Measures of feasibility	% lower threshold	% upper threshold
Recruitment rate	30	60
Retention rate of study	70	80
Intervention adherence – patients:
Responding to medication reminders	70	90
Responding to symptoms surveys	70	90
Data collection compliance:
ASK-12	50	70
PAM-SF	50	70
PROMIS	50	70
FACT-G	50	70
UTAUT	50	70

ASK-12Self-report AdherenceFACT-GFunctional Assessment of Cancer Therapy–GeneralPAM-SFPatient Activation Measure-Short FormPROMISPatient-Reported Outcomes Measurement Information SystemUTAUTUnified Theory of Acceptance and Use of Technology

Secondary outcome measures

Medication adherence will be assessed by medication refill adherence (MRA)⁵¹ in week 16. The MRA is recommended as the preferred measure of adherence because of its convenience while still producing equivalent results compared with other measures.⁵¹ Pharmacy dispensing data will be used to determine MRA, defined as the total days’ supply divided by the number of days of study participation and multiplied by 100. In this study, the patient will be considered as optimal adherence if their MRA is ≥90%.

Self-report adherence will be measured by ASK-12, which includes 12 items in three subscales: adherence behaviour, health beliefs and inconvenience or forgetfulness. The tool has good internal consistency reliability (Cronbach alpha=0.75) and test-retest reliability (intraclass correlation=0.79). This tool was found to be practical and useful for the clinical setting for predicting risk of non-adherence as well as measuring rates of adherence.^{44 52}

Toxicity self-management will be assessed by PAM-SF, which is a 13-item self-report measure assessing the patient’s knowledge, skills and confidence in the self-management of their disease and related symptoms. Responses to the survey categorise patients into one of four possible groups¹: disengaged and overwhelmed,² becoming aware but still struggling,³ taking action and⁴ maintaining behaviours and pushing further. This scale has good internal consistency, α=0.81.⁵³

Anxiety, depression and symptoms: PROMIS adult short form (26 items) will be used to assess depression, anxiety, pain interference, fatigue, sleep disturbance and physical function. These self-report scales have excellent test-retest reliability (≥0.86) and acceptable convergent and discriminative validity in people with cancer.⁴²

Quality of life will be assessed by FACT-G, which is a 27-item self-report scale measuring quality of life of patients currently undergoing cancer treatment. Questions are categorised into four domains: physical, social/family, emotional and functional well-being. The scale has shown internal consistency of α≥0.90 overall and α≥0.70 for each subscale, and acceptable convergent validity when assessed in patients with non-Hodgkin’s lymphoma.⁵⁴

Optimal intervention strategy will be measured by qualitative questions in the UTAUT surveys to identify the optimal dose of delivering MI teleconsultations.

Participant timelines

The trial was started in August 2023 and is expected to complete in June 2024. Participants will be recruited over an estimated 6-month period. After participants have consented and completed their t₀ measures, they will be randomised and followed over 12 weeks. At the end of the 12 weeks, participants will fill out end-of-study surveys. A visual summary of the timeline and assessment points can be found in figure 1.

Figure 1. SPIRIT schedule of enrolment, interventions and assessments. SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.

Sample size

In general, sample size calculations are not required for pilot studies, as long as numbers are large enough to provide useful information about the aspects being assessed for feasibility.⁵⁵ Some others may argue that a sample size between 20 and 100 participants is reasonable for similar trials assessing acceptability, feasibility and usability.^{56 57} For this trial, we anticipate recruiting up to 50 participants, within a 6 months’ time frame. As a pilot RCT, the trial is not powered to evaluate the effectiveness of the intervention compared with the control.

Recruitment

The study design, including recruitment and allocation, is summarised in figure 2.

Figure 2. CONSORT flow diagram—study design flowchart of the SAMSON trial. SAMSON, safety and adherence to medications and self-care advice in oncology; CONSORT, Consolidated Standards of Reporting Trials.

Potentially eligible patients will be identified by study site nurses, pharmacists or treating consultants, who are informed about the study and eligible criteria, through their clinic lists and pharmacy dispensing records. If the patient agrees, the study HCPs will then pass on the patient’s contact to the research coordinator (HD). After that, the research coordinator will meet the patient, either in person outside the clinic or online to discuss the study and go through a comprehensive informed consent process if the patient is interested in participating.

Assignment of interventions

Following written consent, participants will be randomised to either intervention or control group (1:1 ratio). A permuted block randomisation of size 4 will be used to ensure an even balance of patients in each group throughout the study period. The allocation schedule is generated by a statistician (SQ) who is not involved in the research process and is blinded to the participants. This will help prevent any predictability when randomising participants to intervention or control.⁵⁸

Withdrawing from the trial

Participants are free to withdraw from the trial at any time on request. A brief reason will be recorded on the participant master spreadsheet. Withdrawing from the trial will not affect their access to usual care at the hospital or their relationship with their care team. If participants in the intervention group withdraw, they will be asked to no longer access the SAMSON mobile app.

Data collection and management

Survey data will be collected using REDCap. Participants’ responses to medication reminders and side-effects surveys will be collected via the SAMSON smartphone app. The data management plan has been approved by HREC at Peter Mac. All essential study-related documentation will be collected, stored and maintained, with appropriate version control logs. All participants’ data collected via REDCap will be stored in the password-protected REDCap database while the study is being undertaken, then downloaded to a secure electronic file, and transferred to disk to be archived following analysis. Data collected via the SAMSON app will be stored in a password-protected secure server. All information provided will be de-identified. Only the research team will have access to the list that can link participants’ names with their individual data. All study data will remain confidential and will be kept securely for 7 years from the date of publication of the results, after which it will be destroyed as confidential waste. Only de-identified data will be reported.

Data analysis

Quantitative

Data will be analysed on a modified intention-to-treat basis, meaning that all randomised patients will be included in the outcome analyses where possible and analysed in the groups to which they are allocated. Missing data will be handled accordingly. Quantitative data will be analysed using STATA 18.⁵⁹ Given the relatively small sample size, and that this is a feasibility and acceptability study, analysis of outcome data will be mainly descriptive (eg, counts/percentages, means/SD or medians/IQR, CIs). These measures will be used to summarise the information to describe (1) sample demographics; (2) participants’ acceptability and intention to use the SAMSON; and (3) patients’ adherence, side-effects monitoring, toxicity self-management, anxiety, depression and symptoms and quality of life. Between-group and within-group comparisons on the outcomes of interest will be conducted using chi-squared tests, t-tests and linear regression. Results will be used to inform the selection of appropriate endpoints and sample size calculations for a larger RCT that may be conducted in the future.

Qualitative

Qualitative data collected from the UTAUT questionnaire, feasibility data, and consultation checklists and summaries from the study HCPs will be summarised and analysed using thematic analysis.^{60 61}

Results will be reported in accordance with the Consolidated Standards of Reporting Trials statements for pilot RCTs⁶² and eHealth interventions.⁶³

Ethical considerations

This protocol (see online supplemental file 3), the informed consent documents (see online supplemental file 4) and any subsequent amendments were reviewed and approved prior to commencing the research. Ethics approvals granted by the HREC at Peter MacCallum Cancer Centre (Peter Mac) (HREC/95332/PMCC) and Swinburne University of Technology (Swinburne) (20237273–15836), and the Peter Mac Research Governance (SSA/95332/PMCC) (see online supplemental file 5). The protocol has been prospectively registered on the Australian New Zealand Clinical Trials Registry with trial registration number (ACTRN12623000472673).

Dissemination policy and results

Participant recruitment and data collection will commence in August 2023. Results are expected in June 2024. On completion of the study, results will be disseminated via peer-reviewed scholarly journal articles, presentations and conferences, and articles in media and health publications consistent with an open access policy.

Discussion

Considerable gaps remain in addressing the medication non-adherence (MNA) problem in chronic conditions, specifically cancer.^{5 8} Although many interventions have been developed to address this problem,^{13 14} there is a knowledge gap in the use of technology and limited evidence on ongoing adherence assessments, follow-ups, coaching and using MI in addition to usual care for patients on anti-cancer medications.²⁰ The SAMSON pilot RCT can address this gap by testing a technology-based solution that includes adherence assessment, side-effects monitoring, HCPs’ follow-ups and coaching using MI skills.

While multicomponent interventions are being increasingly introduced⁹ to tackle the complexity of MNA issues, the approach of SAMSON is novel in many ways. First, SAMSON was developed based on cognitive, behavioural and design sciences theories and evidence. Second, the individual components were rigorously tested before the pilot RCT was undertaken. These are important for the likelihood of success of MA interventions.⁹ Third, the SAMSON was co-designed with end-users and key stakeholders. Co-design is the ‘creativity of designers and people not trained in design working together in the design development process’.⁶⁴ Using co-design in developing mobile health systems could contribute to improved mobile health applications,⁶⁵ which helps to avoid the pitfalls in the adoption and effective use of the intervention.⁶⁶ Most importantly, the SAMSON solution is a seamless integration of a mobile platform with direct clinical consultations, using behavioural change approaches. By incorporating the SAMSON app with positive psychological skill development: SDM and MI, we hope to build patients’ motivation and self-efficacy for being active in disease and treatment self-management, which are crucial elements of MA.⁶⁷

This study has some limitations. First, as this is a pilot study, the primary aims of the trial are acceptability and feasibility assessments, and the sample size was not calculated. Thus, only preliminary results on the efficacy of SAMSON will be reported. Despite this, we acknowledge that the small number of participants in this study might hinder the ability to detect differences in device utilisation, especially considering the comprehensive primary and secondary outcome assessments. Also, no definitive conclusion on specificity or mechanism of intervention, for example, optimal intervention strategy, can be put forward. Second, we wanted to test whether the 12-week follow-up period is feasible in clinical oncology setting and sufficient to demonstrate adherence and anticipated outcomes. This observation period may not be long enough to detect the changes in outcomes. However, findings will help inform the design of a full RCT in the future. Third, most outcomes in the study will be measured via self-report. Therefore, we have tried to also include both subjective and objective MA measurements. Finally, participants enrolled in the study will be from a metropolitan specialised oncology hospital in Australia, which may not be representative of other oncology settings. Future research can extend the evaluation of SAMSON to patients in different healthcare settings.

Findings from this SAMSON pilot RCT can be used to inform larger studies to examine the efficacy or effectiveness of SAMSON solution in the future. Ultimately, a solution such as SAMSON could be integrated into usual oncology care as an add-on remotely delivered, long-term solution to promote MA for patients in homecare setting. Given the importance and prevalence of technologies in society today, the study represents a novel and impactful approach to provide potentially effective solution to address MA in cancer, thus improving the treatment efficacy and drug toxicity management.