Lifestyle and Empowerment Techniques in Survivorship of Gynaecologic Oncology (LETSGO study): a study protocol for a multicentre longitudinal interventional study using mobile health technology and biobanking

Abstract

Introduction

The number of gynaecological cancer survivors is increasing and there is a need for a more sustainable model of follow-up care. Today’s follow-up model is time-consuming and patients have reported unmet needs regarding information about their cancer and strategies for managing the consequences of treatment. The main aim of this study is to assess health-related empowerment—in terms of patient education, psychosocial support, and promotion of physical activity—in a new follow-up model by comparing it to standard follow-up in a quasi-randomised study involving intervention hospitals and control hospitals.

Methods and analysis

At the intervention hospitals, patients will be stratified by risk of recurrence and late effects to either 1 or 3 years’ follow-up. Nurses will replace doctors in half of the follow-up visits and focus in particular on patient education, self-management and physical activity. They will provide patients with information and guide them in goal setting and action planning. These measures will be reinforced by a smartphone application for monitoring symptoms and promoting physical activity. At the control hospitals, patients will be included in the standard follow-up programme. All patients will be asked to complete questionnaires at baseline and after 3, 6, 12, 24 and 36 months. Blood samples will be collected for biobanking at 3, 12 and 36 months. The primary outcome is health-related empowerment. Secondary outcomes include health-related quality of life, adherence to physical activity recommendations, time to recurrence, healthcare costs and changes in biomarkers. Changes in these outcomes will be analysed using generalised linear mixed models for repeated measures. Type of hospital (intervention or control), time (measurement point), and possible confounders will be included as fixed factors.

Ethics and dissemination

The study is approved by the Regional Committee for Medical Research Ethics (2019/11093). Dissemination of findings will occur at the local, national and international levels.

Trial registration number

NCT04122235.

Strengths and limitations of this study.

• Lifestyle and Self-Management Techniques in Survivorship of Gynaecologic Oncology is the first multisite, comprehensive clinical study to investigate nurse-led patient education reinforced with a smartphone application compared with traditional follow-up after gynaecological cancer assessed with validated questionnaires.

• The longitudinal quasi-randomised design reflects daily clinical practice and allows us to estimate possible changes over time defining the temporal sequence of changes and providing stronger evidence for causality.

• The study has a translational approach with the establishment of a longitudinal biobank of samples of blood and blood components.

• A health economic evaluation will explore if the new follow-up programme results in fewer scheduled appointments at the intervention hospitals, which may have an effect on resource utilisation.

• The primary limitation of this study is the quasi-randomised design, which may lead to imbalances in prognostic factors between the groups.

Introduction

The current global yearly incidence of gynaecological cancer is almost 1.3 million cases and is expected to increase by 44.6% by 2040.¹ The increase in prevalence will pose challenges for post-treatment follow-up models, which are currently time-consuming, expensive, and lack evidence of efficacy regarding survival and quality of life (QoL).² Traditional hospital-based follow-up has been criticised for being too focused on the detection of recurrences and less attentive to physical and psychological rehabilitation after cancer treatment.^{3 4} Consequently, survivors report unmet needs relating to their cancer treatment, comorbidities, and economic and family concerns.⁵ A small number of clinical and economic evaluations of alternative approaches to survivorship care after gynaecological cancer have been reported to date,³ including three small randomised controlled trials (RTCs).^6–8 Theses RTCs evaluate nurse-led telephone follow-up and comparisons between more intensive and less intensive follow-up procedures.^{3 6–8} Another alternative model for delivering care in cancer survivorship is the risk-stratification model, whereby patients are stratified according to their risk of developing late effects of treatment or cancer recurrence.⁹

Gynaecological cancer survivors report a high prevalence of treatment-related symptoms that can affect their QoL. The most frequently reported symptoms are fatigue, neuropathy, lymphoedema, sexual dysfunction, cognitive dysfunction, anxiety and depression.^10–17 Some of these symptoms may also be signs of disease recurrence.¹⁸ Despite having symptoms at recurrence, it is shown that many patients fail to make an appointment earlier than scheduled.¹⁸ This underlines the importance of providing education on alarm symptoms and motivating patients to actively manage their condition after gynaecological cancer treatment.^{2 19} In a cancer survivorship context, health-related empowerment refers to an individual’s feelings of being able to manage the challenges of the cancer experience and of having a sense of control over their own life.²⁰ The facilitation of empowerment through education and self-management strategies to enhance problem-solving skills, action planning and self-efficacy are components of the chronic care model developed by the MacColl Institute for Healthcare Innovation.^{2 19 21}

A follow-up model designed to increase health-related empowerment provides opportunities for highlighting patients’ lifestyle in terms of health behaviours, such as physical activity. It is well known that physical activity provides multiple psychological and physiological benefits after a cancer diagnosis and is associated with increased health-related QoL, as well as a reduced risk of cancer morbidity.^{22 23} International health authorities recommend that all adults, including cancer survivors, should engage in moderate-intensity physical activity for a minimum of 150 min per week or vigorous-intensity physical activity for at least 75 min per week.²⁴ Although patients often request information about health-promoting strategies, many gynaecological cancer survivors find it difficult to alter their lifestyles without external motivation.²⁵ In this context, research has consistently shown that interventions targeting patient autonomy and self-regulation (the ability to act in one’s own long-term best interest) can promote physical activity behavioural changes.²⁶

mHealth is a subset of the broader concept of electronic health and refers to the use of mobile devices to support the delivery of medical and public healthcare to individuals and populations. In recent years, mobile web applications (apps) have increasingly been used to promote chronic disease management, including patients with cancer.^27–29 Regular reporting of a limited set of symptoms has been found to be an accurate and cost-effective way of detecting recurrences and treatment-related late effects in patients with cancer in the lungs and breasts.^{30 31} Smartphone apps have also been used as tools to enhance physical function and physical activity in cancer patients.^{32 33}

Studies indicate that proinflammatory cytokines are important in the pathophysiology of cancer symptoms, including psychobehavioural symptoms³⁴ and that chronic inflammation increases the risk of cancer-related comorbidity and mortality.^34–36 Furthermore, inflammation and metabolic status have been linked to metabolic syndrome, which is closely related to the incidence of endometrial cancer.³⁷ Despite growing evidence of the role of biomarkers in cancer-related morbidity and QoL, studies investigating the contribution of biomarkers to gynaecological cancer survivorship are limited.

The aim of the Lifestyle and Self-Management Techniques in Survivorship of Gynecologic Oncology (LETSGO) study is to evaluate a new programme for follow-up after gynaecological cancer. The programme is based on risk stratification and patient self-management and includes nurse-led coaching, mHealth technology, and promotion of physical activity. It will be compared with the standard follow-up programme, which follows Norwegian guidelines.

The objectives are to

1. Compare patient empowerment (primary outcome) in patients attending intervention hospitals and those attending control hospitals at 12 months.

2. Compare health-related QoL between the intervention group and the control group.

3. Compare physical activity between the intervention group and the control group.

4. Compare time to detection of recurrence between the intervention group and the control group.

5. Assess whether the intervention is cost-effective compared with current practice.

6. Identify relationships between self-management, physical activity and various biomarkers.

Methods

The study follows the Standard Protocol Items: Recommendations for clinical trials checklist (online supplemental file 1)³⁸ and WHO Trial Registration Data Set (online supplemental file 2).

Design

The LETSGO study is a longitudinal, quasi-experimental multicentre clinical study comparing a new follow-up programme at intervention hospitals with the standard follow-up programme at control hospitals.

The LETSGO follow-up model

Our research group has developed a follow-up programme based on the principles of the risk-stratification model and the chronic care model comprising a 1-year hospital follow-up for low-risk gynaecological cancer patients or a 3-year follow-up for medium/high-risk patients. For half of the consultations, nurses will replace the doctors and will use evidence-based behavioural change techniques to coach the cancer patients on how to take a more active role in managing their health conditions.^39–41 The nurses will focus on information on symptoms of recurrence, management of late effects, goal setting for physical activity, action planning, review of goal setting and monitoring of physical activity. The techniques will be reinforced with the multifunctional LETSGO app with several modules (figure 1). The LETSGO follow-up model has been pilot-tested in 12 gynaecological cancer patients (NCT03453788).

Figure 1.

The LETSGO-app (Anette Gjoerv). LETSGO, Lifestyle and Self-Management Techniques in Survivorship of Gynaecologic Oncology.

Study population

We have begun to recruit a cohort of women who have completed treatment for gynaecological cancer. The study is being conducted at 10 Norwegian hospitals (five intervention and five reference hospitals). University hospitals, regional hospitals and all Norwegian health regions are equally distributed in both groups, and their standard follow-up routines do not differ.⁴² Participating hospitals are listed at wwwclinicaltrialsgov. Medical specialists and study nurses will inform eligible patients about the study before the first follow-up visit after primary treatment has been completed.

Inclusion criteria

Eligible participants (1) have histologically verified cervical cancer (restricted to squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), endometrial cancer, ovarian cancer (restricted to epithelial type) or vulvar cancer; (2) have completed primary standard treatment and are scheduled for follow-up; (3) are able (both physically and cognitively) to complete patient-reported outcome measures independently in Norwegian; (4) are ≥18 years and (5) are able to provide informed consent.

Exclusion criteria

Patients are ineligible if they (1) are participating in a clinical treatment trial; (2) are on intravenous maintenance treatment (eg, bevacizumab) and (3) are cervical cancer patients who have been treated with trachelectomy.

Study timeline

Enrolment of participants started in November 2019 and is due to close in December 2024 or after accrual and the last patient visit is completed

Intervention hospitals

Nurse-led consultations

The low-risk group will be followed up for 1 year and the medium/high-risk group for 3 years (table 1). Before entering the follow-up programme, the participants will be assigned to either the low-risk group or the medium/high-risk group according to predefined risk criteria. The low-risk group includes patients with (1) cervical cancer International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 with negative cytology and human papilloma virus status at 9 months after treatment; (2) endometrial cancer FIGO stage IA or B with endometrioid adenocarcinoma grade 1 and no adjuvant therapy or (3) ovarian cancer FIGO stage IA and no adjuvant therapy. The medium/high-risk group includes patients with (1) cervical cancer FIGO stage IA1 with positive cytology and human papilloma virus status at 9 months after treatment or any other FIGO stage; (2) endometrial cancer at any stage except FIGO stage IA/B with endometrioid adenocarcinoma grade 1; (3) ovarian cancer FIGO stage IA with adjuvant chemotherapy or FIGO stage IB to IVB; or (4) vulvar cancer at any stage.

Table 1.

Overview of all outcome measures and assessment times of the LETSGO study

Outcomes	Measurement instrument	Intervention hospitals											Control hospitals
		B1	3w2	6w	3m3	6m	9m	12 m	15 m	18 m	21/30 m	24/30 m	B	3m4	6m	9m	12 m	15 m	18 m	21/30 m	24/30 m
Questionnaires
Psychosocial outcomes
Patient empowerment	heiQ6	X			X	X		X				X	X	X	X		X				X
Generic QOL5	EQ-5D7	X			X	X		X				X	X	X	X		X				X
Disease specific QOL	EORTC QLQ-C308	X			X	X		X				X	X	X	X		X				X
Tumour specific QOL	EORTC QLQ modules9	X			X	X		X				X	X	X	X		X				X
	CX24, EN24, OV28 and VU34	X			X	X		X				X	X	X	X		X				X
Cancer worry	IOC10 worry subscale	X			X	X		X				X	X	X	X		X				X
Sexuality	SQOL-f11 selected items	X			X	X		X				X	X	X	X		X				X
Follow-up care	Study-specific questions	X			X	X		X				X	X	X	X		X				X
Personal factors
Demographic variables	Standard questions	X			X	X		X				X	X	X	X		X				X
Comorbidity	SCQ12	X			X	X		X				X	X	X	X		X				X
Lifestyle factors
Physical activity	IPAQ-SF13, ESAI14	X			X	X		X				X	X	X	X		X				X
Alcohol use	Standard questions	X			X	X		X				X	X	X	X		X				X
Smoking	Standard questions	X			X	X		X				X	X	X	X		X				X
Clinical factors
Medical history	eCRF15	X											X
Medication	eCRF	X											X
Vital signs	Blood pressure, pulse, weight	X		X		X		X		X		X
Performance status	ECOG16 status	X		X		X		X		X		X
Gynaecological examination	NA17				X		X		X		X			X	X	X	X	X	X	X	X
LETSGO intervention (nurse)
Introduction to LETSGO-app	NA			X		X		X		X		X
Assessment of rehabilitation needs	NA			X		X		X		X		X
Set goals for physical activity	NA			X
Follow-up goals for physical activity	NA					X		X		X		X
Motivating interview	NA	X		X		X		X		X		X
Assessment of late-effects	Study-specific chart					X		X		X		X
Visits at out-patient clinic	NA
Low-risk group intervention		X	X		X		X
Medium/high-risk group intervention		X	X		X		X		X		X	X
Control group (all)														X	X	X	X	X	X	X	X
Biological factors
General laboratory	Blood	X			X	X		X				X	X	X	X		X				X
Biomarkers	Blood				X			X				X18	X	X			X				X18

¹Baseline; ²Weeks; ³Months; ⁴At reference hospitals, first questionnaire/blood tests may be collected at 3 months; ⁵Quality of Life; ⁶Health Education Impact Questionnaire; ⁷EuroQol five dimensions questionnaire; ⁸The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; ⁹Modules: cervix, endometrium, ovarian, vulvar; ¹⁰The Impact of Cancer Questionnaire; ¹¹Sexual Quality of Life-Female Questionnaire; ¹²Self-Administered Comorbidity Questionnaire; ¹³Physical Activity Questionnaire Short-Form ¹⁴Exercise Stage Assessment Instrument; ¹⁵Electronic Case Report Form; ¹⁶Eastern Cooperative Oncology Group; ¹⁷Not applicable; ¹⁸Biomarkers at 3, 12 and 36 months.

LETSGO, Lifestyle and Self-Management Techniques in Survivorship of Gynaecologic Oncology; NA, not available.

The first visit will take place 3–5 weeks after treatment ends (chemotherapy, radiotherapy or surgery completion). A second nurse-led visit will take place 7–8 weeks after treatment. Thereafter, patients will alternate between nurse-led and doctor-led consultations. At the 3–5 weeks visit, the nurse will assess the women’s physical and emotional status, as well as aspects of her lifestyle and family environment. Patients with smartphones or tablets will be introduced to the LETSGO app (see below), and patients without smartphones or tablets will be provided with an information booklet containing identical information to that contained in the app. At the second nurse-led visit, the nurse will explore the patient’s previous physical activity and their motivation for future physical activity, using an autonomous supportive communication style inspired by motivational interviewing.⁴³ In addition, the nurse will work with the patient to set individualised goals for physical activity in line with the patients’ motivation and barriers. To encourage physical activity, the patients will receive a Garmin activity tracker and will be instructed to wear it all day through the entire study period. The step count is displayed in the LETSGO app when the patient’s mobile phone is connected to the activity tracker. Goals will be reviewed and adapted accordingly at subsequent nurse-led visits.

The patients at the intervention hospitals will have access to the LETSGO app throughout the 3-year study period, irrespective of their risk group (except cervical cancer patients in the low-risk group who have been treated with conisation only, to avoid unnecessary fear of cancer recurrence in this low-risk population). At the final follow-up visit (at 12 months or 36 months, depending on the risk group), the nurse will emphasise the importance of being attentive to symptoms as signs of recurrence and of a healthy lifestyle for well-being. The patients will receive written information on whom to contact if they experience treatment-related side effects or suspect disease recurrence. A summary of the patient’s treatment, potential side effects, and symptoms of potential recurrence will be sent to the patient’s responsible general practitioner (GP). The nurses involved in the study are familiar with gynaecological cancer patients. They have participated in a 2-day intensive course covering relevant subjects, including gynaecological cancer treatment, physical and mental treatment-related symptoms, symptoms of recurrence, benefits of physical activity, autonomous supportive communication style, and motivation and individualised goal setting for physical activity. The nurses’ education was reinforced by an electronic learning programme with modules covering these subjects, which they were required to complete before the course.

The LETSGO app

The app is available for smartphones and tablets. It contains information on the different gynaecological cancers, as well as lifestyle information and advice. It is distributed through Apple Store and Google Play, and a personal code is required to open the study version.

The app consists of the following modules (figure 1):

1. Disease-specific information (written and audiovisual) on ovarian, uterine, cervical or vulvar cancer, signs of recurrence, and late effects after treatment.

2. General lifestyle information.

3. Physical activity exercises and programmes with instructions (written and audiovisual) for both beginners and experienced persons.

4. Physical activity goal setting: Participants will be asked to define a goal for the week (eg, a 30 min walk twice a week or strength exercise in a health studio three times a week).

5. Monitoring of symptoms of recurrence: Once monthly, the participants will be asked to rate 10 symptoms that may indicate recurrence.

Patient-reported outcome studies have shown that the most frequent symptoms of recurrence are pain and fatigue for all gynaecological cancers and bleeding for endometrial and cervical cancer.¹⁸ To cover these symptoms, we have selected relevant items from the European Organisation of Research and Treatment of Cancer (EORTC) item library,⁴⁴ adjusted to each cancer type. The 10 EORTC items in the app refer to the preceding week. For instance, patients treated for endometrial or cervical cancer will be asked, ‘Have you had abnormal bleeding from your vagina?’ Each participant will rate the severity of their symptoms in the preceding week from 0 (not at all) to 3 (very much). If a predefined threshold is reached, the participant will receive an alert on their phone or tablet informing her that the answer given may indicate recurrence and advising her to phone the presaved telephone number of the gynaecological outpatient clinic. We anticipate that some participants may refrain from making contact. Therefore, the database will be checked for flags at regular time points by the project data manager. Patient visits and imaging will be brought forward if recurrence is suspected.

Control hospitals

Patients will receive standard follow-up according to current guidelines. Standard follow-up in Norway consists of clinical examination with vaginal ultrasound three to four times a year during the first 2 years, twice a year for the next 3 years, and annually thereafter, depending on the recommendations of the patient’s doctor.

Data collection

Data will be collected using medical records, patient registries, validated questionnaires (electronic or written), and blood samples. Primary and secondary outcomes will be measured for all participants at enrollment (for baseline data) and again at 3, 6, 12, 24 and 36 months. Biobank samples will be collected at 3, 12, and 36 months and at time of recurrence, if applicable). At each time point, a reminder will be sent within 3 weeks to any participant who does not return the questionnaire. For the intervention group, data will also be abstracted from the app and the activity tracker.

Discontinuation

Participants will be withdrawn from the study if a recurrence occur.

Primary outcome

Patient empowerment

The Health Education Impact Questionnaire (heiQ), a well validated, widely used measurement system for comprehensively assessing the effects of health education programmes on self-management.^{20 45} It consists of 40 questions grouped into eight domains. Responses are given on four-point Likert scales ranging from ‘strongly agree’ to ‘strongly disagree’. The heiQ has been translated into several languages and has been validated in a Norwegian population.⁴⁶

Secondary outcomes

Health-related QoL

Health-related QoL will be measured using the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)⁴⁷ and the EuroQol 5 Dimensions Questionnaire (EQ-5D).⁴⁸ Regarding the EORTC QLQ-C30, the scores of the five functional scales and one global QoL scale are converted to a 0–100 scale.⁴⁷ A higher score reflects a better level of functioning and better QoL. Tumour-specific complaints are measured using the disease-specific supplements EORTC QLQ-EN24⁴⁹ for endometrial cancer, EORTC QLQ-OV28⁵⁰ for ovarian cancer, EORTC QLQ-CX24⁵¹ for cervical cancer and EORTC VU-34 (under development, phase 4) for vulvar cancer. The EORTC instruments (except EORTC VU-34) have been used in studies of gynaecological cancer survivors, some of which were conducted in Norway.^{14 15 52} The EQ-5D consists of two components: A descriptive system, which defines health-related QoL in terms of five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and a visual analogue scale.⁴⁸

Physical activity

Self-reported physical activity will be assessed using the short form of the International Physical Activity Questionnaire.⁵³ Exercise stage/readiness to change will be assessed using one item: ‘Please indicate which alternative corresponds with your current physical activity level or your interest in physical activity.’ Responses are given on a five-point ordinal scale from the exercise stages of change assessment instrument,⁵⁴ which is based on the trans-theoretical (stages of change) model.⁵⁵ The scale represents five different stages of change, ranging from 1 = ‘Not physically active and I do not intend to become more physically active during the next 6 months’ (precontemplation stage) to 5 = ‘Physically active and I have been so for more than 6 months’ (maintenance stage). Step count data imported from the Garmin activity tracker into the LETSGO app will be compared with self-reports of physical activity.

Fear of cancer recurrence

The Health Worries subscale of the Impact of Cancer (IOC) scale will be used to assess fear of cancer recurrence.⁵⁶ The module consists of seven questions, including questions on worry about the future, worry about health due to cancer, and worry about recurrence. Items are scored on a five-point intensity scale ranging from 1 (strongly disagree) to 5 (strongly agree). Higher scores reflect greater fear of cancer. The IOC has been validated in oncology patients in oncology settings.⁵⁶

Healthcare utilisation

Healthcare utilisation will be assessed by asking patients about the frequency of their contact with their gynaecologist and primary care physician and about how many healthcare visits were related to cancer. We will also assess how often the patients use additional care services (eg, psychologist, rehabilitation course, physical therapist).

Health economic evaluation

The EQ-5D is the generic measure preferred by the UK National Institute of Health and Care Excellence for cost-effectiveness and comparative purposes, which in turn has affected guidelines in several other countries, including Norway.⁴⁸ Quality-adjusted life-years (QALYs) will be calculated based on the area-under-the curve principle, taking into account both health-related QoL and survival of the patients during the 3-year follow-up period. Healthcare utilisation at participating hospitals during the trial will be gathered for both groups. Healthcare utilisation in other parts of the healthcare sector will be gathered from the following registry data sources: the Norwegian Prescription Database (www.reseptregisteret.no), which contains data on all medical prescriptions redeemed from Norwegian pharmacies; the Norwegian Patient Registry, which includes data on diagnostic information (International Classification of Diseases, 10th Revision), medical treatment, length of hospital stay and discharge data; the Municipal Patient and User Register; the individual-based care and care statistics registry (https://helsedirektoratet.no/iplos-registeret) for variables related to use of specialist and primary healthcare services; the Control and Payment of Health Reimbursement Database (https://helfo.no/) regarding GP visits, physiotherapy and health transportation; and the social security event database. The costs of the intervention will be considered along with differences in resource use during follow-up and differences in QALYs to assess the incremental cost-effectiveness of the intervention compared with the control.

Biobanking

Blood samples will be collected at defined time points, as described in table 1. Standard operating procedures (SOP) have been established for blood and sera collections. The blood samples will be processed in components and stored at −80°C. Three 6 mL EDTA samples will be collected and immediately centrifuged. From these, buffy coat (for isolation of genomic DNA) and plasma (for purification of circulating tumour DNA) will be isolated and stored in cryo tubes. Three5 mL serum separator vacutainer tubes will be collected and centrifuged after 30 min of coagulation time. Serum (for cytokine and metabolite analysis) will then be transferred to cryo tubes for storage. The consented SOP has been introduced at the participating hospitals, with an alternative protocol for the smaller hospitals without microcentrifuges.

Other measurements

Comorbidity will be assessed using the Self-Administered Comorbidity Questionnaire (SCQ) (59), which consists of 16 common and three optional medical conditions. Patients will be asked to indicate whether they have the condition, if they are receiving treatment for it, and if it limits their activities. For the present study, we will only ask whether the patients have any of the common conditions. The SCQ has well-established validity and reliability in Norwegian patients with chronic medical conditions.^{57 58} Demographic information such as age, education, marital status, and treatment will be obtained from baseline questionnaires and medical records.

Sample size calculation

Sample size calculations were based on the primary outcome of interest. From a review of the available literature,^{46 59} we anticipated that the change in mean value of the heiQ domain (self-monitoring and insight) from baseline to 12 months would be higher in the intervention group.⁶⁰ A 10% difference is considered clinically relevant.⁶¹ Assuming a common SD of 1.4 and using the customary significance level alpha of 5% and power of 80%, we determined that 343 individuals in each group would be needed to reveal a clinically relevant difference of 10% or more. Accounting for a drop-out rate of 10%, we determined that 377 would be needed in each group.

Statistical analyses

Data will be analysed after 1 and 3 years of follow-up. Data will be presented as counts and percentages (categorical variables) and mean and SD or median and range for continuous data following normal or skewed distribution, respectively. Pairs of categorical variables will be compared using a chi-square test or, for small numbers, Fisher’s exact test. Univariate analysis for comparison of continuous variables will be performed using a t-test for normally distributed data or the Mann-Whitney Wilcoxon test for variables with skewed distribution. Changes in the main outcome will be analysed using generalised linear mixed models (GLMM) for repeated measures, as the outcomes are all continuous. As all included individuals will be assessed at several time points (baseline, 3, 6, 12, 24 and 36 months), statistical dependencies will exist. We will adjust for these using an unstructured covariance matrix if the model converges; if the model does not converge, we will fit a more specified covariance matrix. Type of hospital (intervention or control), time (measurement point), and possible confounders identified when comparing patients at the intervention and control hospitals will be included as fixed factors. To account for added variation caused by enrolling participants at 10 different hospitals, we will include each hospital as a random factor. As GLMM models use all available observations, no imputation of missing data will be necessary. The results will be expressed as estimated means with 95% CIs for each time point and type of hospital (intervention vs control). Differences in means between the intervention and control groups for each assessment point will be estimated. Time to recurrence will be modelled using survival analysis methodologies. Specifically, we will use Kaplan-Meier curves to depict crude time to recurrence and a Cox model to estimate HRs for recurrence. The economic analyses will include controlling for enrolment differences and sensitivity analyses, according to international guidelines.⁶¹

Committees for the research

A scientific management group (consisting of the authors of the present protocol paper) has developed this protocol. A steering committee has been appointed to ensure that the trial is conducted in accordance with standard ethical principles. The committee provides an overall supervision of the study regarding the participants’ safety, as well the delivery of the project outputs and the achievement of project outcomes.

Data management

The database for clinical data and questionnaire data will be created using the Viedoc software. Data from the app will be stored at Services for sensitive data (University of Oslo). Access to databases will be secured and limited to the professionals involved in the study (personal ID and password required). The investigators in the scientific committee will be given access to the cleaned data set. Data monitoring will be provided by the trial steering committee. The research team will make regular reports to the trial steering committee. Interim analyses and stopping guidelines are not indicated because the intervention is not expected to have a significant risk of potential harm for the patients. The project management group will have close cooperation with project investigators at the participating hospitals. Research nurses at each hospital are responsible for the day-to-day data collection. Collection of data will be supervised by the project management group in close collaboration with the scientific management group.

Patient and public involvement

We appointed a user panel of three women who had been treated for gynaecological cancer and had no former experience with mHealth. The users have participated in several meetings since the initial planning of the study, and the resulting follow-up model has been adjusted based on their feedback and opinions. The users have read and commented on the protocol and have been involved in the development of the app. They have given their opinions on both the content of the app and the nurse-led consultations.

Ethics and dissemination

The LETSGO study has been approved by the Regional Committee for Medical and Health Research Ethics of South East Norway (2019/11093). The institutional review board and the data protection officer at each of the study sites have also approved the study. All patients will receive oral and written information about the study, and written informed consent will be collected prior to enrollment. An electronic case report form is used, and participants receive a unique subject number and subject identifier. Data are entered under this identification number onto a central database stored on secured servers. The servers are protected by firewalls and are patched and maintained according to best practice. The study investigators retain the right to access data. It is estimated that the study will be completed in 2024, after which the data analysis and the results will be disseminated.

Trial status

The trial started inclusion in November 2019. On 27 May 2021, 378 patients have been included.

Ethics statements

Patient consent for publication

Not required.