(Cost-)effectiveness of an internet-based physical activity support program (with and without physiotherapy counselling) on physical activity levels of breast and prostate cancer survivors: design of the PABLO trial

Patients with histologically confirmed primary breast or prostate cancer (stages: T1 – T4, N0 – N3 and M0), who may currently be receiving adjuvant endocrine treatment (breast and prostate cancer) or Trastuzumab (breast cancer) will be included in the study. Primary treatment should have been completed a minimum of 3 months and a maximum of 12 months prior to study entry. All patients need to provide written informed consent.

Main exclusion criteria are a lack of basic proficiency in Dutch, serious cognitive or psychiatric problems that would preclude following the intervention or completing the study questionnaires, and lack of internet access. Patients without a digital ID (DigID), which is a Dutch digital authentication code based on one’s social security number (mostly used for governmental services) will be excluded. DigID is one of the most frequently used authentication methods in the Netherlands. Also, patients participating in concurrent studies or rehabilitation programs containing psychosocial and/or exercise interventions will be excluded, as well as patients who are unable to perform unsupervised exercise at the recommended levels or who cannot safely perform such exercise according to the pre-exercise screening recommendations of the American College of Sports Medicine [23]. Patients who have (signs of) cardiovascular, metabolic, or renal disease, can only participate after approval by the treating physician. Lastly, because our aim is to increase PA-levels of cancer survivors, we will a-priori determine, by a short interview, who already meets the PA guideline of > 150 min MVPA/week of moderate to vigorous PA for more than 6 months. To take into account a ~ 30% overestimation of self-reported PA [24], we will be excluding patients who report > 200 min/week MVPA for longer than 6 months.

Many trials on PA behaviour change interventions show recruitment rates of around 30% [25]. We expect that, in the current trial, a substantial percentage of eligible patients will also decline the invitation to participate. To gain more insight into the characteristics of this group, the non-participants will be invited to complete a one-time online questionnaire similar to the baseline questionnaire completed by study participants. In addition, we will ask them if they are willing to report their reason(s) for not participating.

The Internet-based Physical Activity Support intervention is structured according to the Transtheoretical model (TTM) [27] and uses aspects from the Theory of Planned behaviour [28] and Social Cognitive theory [29] (Table 1). The TTM postulates that subjects can be classified into one of five stages of behavioural change related to the desired behaviour, in this case, meeting physical activity guidelines [27]. The five stages identified are [1] precontemplation (not sufficiently active and not intending to change), [2] contemplation (not sufficiently active but willing to change within next 6 months), [3] preparation (not sufficiently active but planning to change within 1 month), action (sufficiently active but for less than 6 months) or maintenance (sufficiently active for longer than 6 months). Patients can move through the stages during the intervention. In every stage, patients receive information that matches the particular stage. This approach is essentially the same as in the pilot intervention described previously [17], but has been improved in several ways to make it more attractive by adding more and more appealing information, images, interactive assignments and video’s.

During the six months of the intervention, patients will be invited by email to fill out an online questionnaire a month after completing the previous questionnaire. Questions will be posed on current PA levels (last 7 days) and motivation to become more physically active (see Additional file 1). Based on their responses, patients will be classified into one of the TTM stages, using the behaviour of ≥150 min per week of moderate to vigorous PA as target behaviour [30]. If patients forget to complete the questionnaire, a reminder will be sent after one week. After patients have completed their questionnaire, they will be directed to a content page that provides feedback on current PA levels via a graph and a table related to cancer survivorship guidelines (i.e. ≥150 min moderate to vigorous physical activity per week and two days a week of muscle strengthening exercises) [30]. Additionally, information is provided on several topics (e.g. “benefits of exercise”, “fatigue”, “start exercising”) in writing and through videos. The videos show breast or prostate survivors (depending on the participant’s diagnosis), who explain perceived benefits from exercise, or how they have overcome barriers to exercise. Other videos show physiotherapists or a physician explaining exercise principles and benefits. Also, there are several homework assignments (e.g., setting realistic goals, seeking social support, and identifying barriers and facilitators for being (more) physically active). Although not included in the criterion for target behaviour of ≥150 min of MVPA per week, throughout the program we also encourage patients to do muscle strengthening exercises at least 2 days a week, in accordance with current guidelines for physical activity for cancer survivors [31]. Table 1 presents an overview of the approach per stage of change, and examples of content are provided in Tables 2 and 3. Additional file 2 shows an example of the advice page that will be provided to the patients. New material will be provided monthly, tailored to the patients’ current stage of change. We have developed three content sets for every stage except for the maintenance stage for which we developed two content sets. Most of the content is the same for breast and prostate cancer survivors, but texts and videos are tailored to the specific population.

Apart from some obvious differences, e.g. showing a female patient as a role model for breast cancer survivors and a male role model prostate cancer survivors in the videos, we tailored information texts on the benefits of exercise to the available evidence for that group. Also, information on exercising with (risk of) lymphedema is only provided to breast cancer patients.

In total, the intervention lasts for 6 months. To facilitate and stimulate use of the IPAS, the intervention is embedded in the hospitals’ patient portal. Via this portal, patients can, for example, also access their medical record and see their clinical appointments. Patients receive two positively worded reminders via email in the first two months to stimulate their participation.

In the second intervention group, the IPAS intervention will be complemented with additional monthly support provided by a physiotherapist (IPAS+TS). With the exception of the first appointment, which will be a face to face intake, consultations will be done by phone.

During the 45-min intake, a physiotherapist will briefly introduce the study and the IPAS intervention, and discuss current PA level and motivation and barriers to PA. Subsequently, the patient will be asked to exercise on a stationary bike or treadmill, to experience the desired moderate intensity. The workload on the bike/treadmill will be determined by the physiotherapist based on heart rate and clinical signs (breathing frequency, etc.) and confirmed by ratings of perceived exertion (RPE 11–13 on a 6 to 20-point Borg scale) [32]. The intake session is concluded by making an agreement with the patient on the intended behaviour change, and by establishing the most convenient time at which the patient can be reached by telephone. Telephone calls will be scheduled as soon as patients have filled out the monthly questionnaire in IPAS, and additional calls can be made on an ad-hoc basis, when desired. Prior to the telephone call, the physiotherapist will look-up the current stage of change by reviewing the last completed online questionnaire. During the monthly call, the physiotherapist first confirms the stage of change by discussing current PA levels. Next, the physiotherapist provides feedback on the stage of change and restates the agreed behaviour from the previous (intake- or telephone-) consultation. The patient is asked to comment on her or his experiences with respect to exercise behaviour in the past period. The physiotherapist will help the patient reflect on these experiences and accompanying thoughts, and will normalize, reinforce or explain physical activity behavior whenever relevant. The telephone consultation concludes with an agreement on a behavioural goal (related to physical activity) for the next month. Physiotherapists take notes of each discussion in standardized forms (see Additional file 3).

All physiotherapists receive a two-hour-training and detailed guidelines for the intake and telephone calls. Physiotherapists are instructed to choose their words carefully so as to avoid coming across as being judgmental or directive. Also, they are instructed to support patients in finding their own solutions to experienced barriers, to normalize negative experiences and to reinforce positive experiences, whenever possible.

The control group will receive usual care and a leaflet with current physical activity guidelines for cancer survivors [31]. Both intervention groups will have access to the same leaflet via IPAS. The leaflet explains the physical activity guidelines and provides information on how the intensity of moderate to vigorous PA can be monitored by Borg rating of perceived exertion, a “talk-test” (when it becomes more difficult to talk in whole sentences) and heartrate self-monitoring. Although they are not actively referred, participants are not prohibited from participating in a rehabilitation or exercise programs with a physiotherapist in primary care, if they so wish. At 6 months, questions about participation in such programs will be included in the questionnaire.

The main study parameter is objectively measured PA, using the Actigraph GT3X+ activity monitor (Actigraph, Pensacola, Florida, USA) and a BT-Q1000XT GPS-device (QStarz International Co). The Actigraph is a small tri-axial accelerometer that can measure accelerations from 0.05 to 2.00 G [34]. An instruction leaflet will be provided to explain how both devices should be worn on the right hip. The accelerometers and GPS devices will be initialized to collect data at 5 s intervals during 7 consecutive days. After each period of data collection (at baseline, 6 and 12 months) the devices will be sent back by patients to the research institute via mail. Output (activity counts and GPS data) will be downloaded to a PC after the monitoring period. Weekly time spent in MVPA will be calculated by standard cut-points [35, 36]. GPS-data will be used to better classify PA behaviour, e.g. if the speed of GPS data- points is < 12 km/h, the modality will be set to ‘walking & jogging’, and if the speed of the GPS data-points is ≥12 and < 25 km/h, modality will be set to ‘cycling’. Change in weekly time spent in MVPA between baseline and 6 and 12 months will be used as the main outcome parameter. An overview of primary and secondary outcome measures is provided in Table 4.

Secondary outcomes are measured by questionnaires at baseline, 6 and 12 months follow-up. The cost questionnaires will be filled in after 6 and 12 months.

Data will be handled confidentially. A subject identification code list will be used to link the data to the subject. The key to the code will be safeguarded by the investigators (HvdW and WG) and will be saved on a computer in the work office at the AVL. The data will be coded using numbers in order enrolment, 1 / 2 / 3 etc., and the recruiting hospital will be added as a fixed code after that A / B / C. Only the investigators HvdW, WG, WvH and MS will have access to the source data. Data will be stored for at least 15 years in an office at the AVL and on a network folder especially made for research data storage.

Amendments are changes made to the research after a favourable opinion by the accredited Institutional Review Board (IRB) has been given. Substantial amendments will be notified to the IRB that gave a favourable opinion. Non-substantial amendments will not be notified to the accredited IRB and the competent authority, but will be recorded and filed by the sponsor.

In accordance to section 10, subsection 4, of the Dutch law of scientific research involving human subject (WMO), the sponsor will suspend the study if there is sufficient ground that continuation of the study will jeopardise subject health or safety. The sponsor will notify the accredited IRB without undue delay of a temporary halt including the reason for such an action. The study will be suspended pending a further positive decision by the accredited IRB. The investigator will take care that all subjects are kept informed.

Change in weekly time spent in MVPA, as measured with the accelerometer, between baseline and 6 months will be used as the main outcome parameter. We will evaluate differences over time between intervention (blended care and web-only) and usual care with a mixed-effects linear regression model adjusted for MVPA baseline scores and stratification factors.

We will evaluate between-group differences over time in self-reported level of PA, fatigue, mood, and HRQOL using mixed effects linear regression models. Scores for the IPAQ, MFI, POMS, SF-36 will be calculated according to existing algorithms. Differences in mean change scores over time between the combined intervention group and the control group (blended care and web-only) will be accompanied by effect sizes. Effect sizes, defined as standardized measures of the strength of the difference in improvement between groups over time, will be calculated by subtracting the mean change scores of the control group from those of the intervention group, and subsequently dividing this by the pooled standard deviation. Effect sizes of 0.2 are considered small, 0.5 moderate, and 0.8 large [54]. The p-value for overall model effects will be set at 0.05, and for specific contrasts to 0.01, lowering the risk of Type I errors due to multiple testing [55]. All analyses will be conducted on an intention-to-treat basis. In addition, per-protocol analyses will be performed on patients according to compliance levels.