Study design and setting
The study was carried out as an explorative interventional study in the period from February 2017 to January 2019 including patients with advanced cancer. In current study, advanced cancer was considered as metastases to the peritoneum originating from intraabdominal organs (i.e. colon, rectum, appendix, and ovaries) and pseudomyxoma peritonei with or without limited spread to organs such as liver or lungs. In case of metastases to the liver and/or lungs, all metastases were deemed treatable with curative intent). Patients with peritoneal metastases were treated with curative intent with complex cancer surgery at two different departments at Aarhus University Hospital. Both departments were national treatment centers for CRS + HIPEC. At Department of Surgery, the procedure was offered as standard treatment, whereas the treatment was performed as a part of a clinical trial at Department of Gynecology[24].
As depicted in Fig. 1, the routine follow-up was scheduled according to specific cancer disease of interest, and thus, unequal at the two departments.
At Department of Surgery, according to national guidelines, the routine follow-up included a consultation in the outpatient clinic at 3, 6, 12, 18, 24, 36, 48, and 60 months postoperatively. The standard follow-up included blood samples and a Computer Tomography (CT) of the thorax, abdomen and pelvis, with a subsequently physical follow-up visit containing results of the CT and a clinical examination.
At Department of Gynecology, the standard follow-up included blood samples (tumor marker), a physical follow-up with a clinical examination and a pelvic examination with a vaginal ultrasound. Imaging was only performed if recurrence was suspected.
Participants
Patients from the two departments (Department of Surgery and Department of Gynecology) who had undergone CRS + HIPEC with curative intent were considered eligible for study inclusion. Inclusion were consecutively performed in the period from January 2017 to October 2019, irrespective of time since the complex surgery (i.e. patients could be included at any visit during the follow-up). Patients were included in the outpatient clinic or by telephone prior to each follow-up consultation. Informed written consent was signed on-site or sent by e-mail and returned either personally or by mail.
A follow-up for patients surviving peritoneal metastases can be dynamic due to several reasons. First, in the initial period after CRS + HIPC most patients receive systemic chemotherapy. Second, though beneficial survival effects have been demonstrated with CRS + HIPEC, recurrence still occur in a large part of the patients, which impacts the follow-up [25, 26].
Patients were not included in case of the following: (1) unable to speak and read Danish, (2) the forthcoming consultation would be the last (i.e., 60 months postoperatively), (3) no digital e-mail solution reached by public authorities and/or e-mail, (4) informed of recurrence at the consultation subjected to inclusion and (5) in a diagnostic process of recurrence.
Intervention
An ePRO supported consultation was considered as the intervention. The ePRO included the validated questionnaires The European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QlQ) C30 [27], C29 [28] and OV28 [29], and item 6 and 11 from the Hospital and Anxiety Depression scale [30]. Further, the ePRO provided opportunity for patients to state three concerns to be prioritized in the consultation.
The ePRO supported consultations were performed in the period from February 2018 to January 2019. The ePRO was sent out to the patient one week prior to a follow-up consultation. Each patient response was flagged with colors illustrating the severity according to the original response algorithm developed for each questionnaire [31]. The patient’s ePRO response was graphically presented to the clinician. After the consultation, clinicians were required to document the use of the e-PRO, either technically in the electronic system or with a comment in the Electronic Medical Record. All clinicians were provided with a one-page manual of how to prepare for, undergo and document an e-PRO-based consultation, supplied by a one-hour training session.
The ePRO was developed in collaboration with Ambuflex [32], which is an electronic system that uses PRO measures as the basis of follow-up to improve quality of care. Furthermore, the ePRO was developed and tested in co-operation between a small selected group of patients and clinicians. The development of the e-PRO is described in details elsewhere [31].
Outcomes measurements
The primary outcome was PA and PI. These outcomes were evaluated with an electronic questionnaire (i.e. evaluation) sent out 2–4 days after each follow-up consultation to all study patients, before and during the intervention (Fig. 1).
PA was measured by the Danish validated 13-item Patient Activation measurement (PAM) questionnaire[33], which was developed and validated by Hibbard et al. to evaluate the patient’s ability to self-manage [16, 34]. The PAM scores from 0 to 100, where a higher score indicates a higher level of activation.
PI was described by five questions, which validity and reliability of these questions as indicators of PI had been tested among 3000 Danish patients [35]. The questions were as followed:
-
(I)
The health care provider asked about my own experiences with my illness / condition
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(II)
I talked to the health care provider about the questions or concerns I had
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(III)
The health care professional encouraged me to ask questions or talk about concerns
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(IV)
I was on advice when deciding what was to happen
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(V)
I have had appropriate conversations with healthcare professionals about how to best manage my illness/condition.
Patients had following response categories “Not at all”, “Less”, “Some”, “Much” and “very much”.
Statistical methods
Apart from the disease characteristics, which were retrieved from a local database, patient characteristics were collected with an online questionnaire at inclusion. Patient and disease characteristics are presented as frequencies and percentages for categorical variables, while continuous variables are presented as median with ranges. Patient characteristics are described according to following grouping: Patients only completed routine follow-up without ePRO were referred to as ‘− ePRO’. Patients who completed a routine follow-up (− ePRO) and an ePRO supported follow-up were referred to as ‘− /+ ePRO’. Patients who participated in an interventional follow-up with ePRO consultations were referred to as the ‘+ ePRO group’.
The PAM score ranges from 0 to 100 introducing ceiling and floor effects that affect the normal distribution of data. Currently, no guidelines exist on the presentation of PAM, and PAM is often presented as means with 95% confidence intervals despite its distribution. The Danish validated version of the 13-item PAM does not recommend the presentation of four levels [33], thus we restrained from this. Raw PAM scores were presented as group means with 95% confidence intervals. The PAM-score was analysed using a linear mixed effect regression model with ePRO as an intervention (yes/no) and time since surgery along with the interaction between them as categorical fixed effects. Patient was included as a random effect. In order to take into account that some patients had observations corresponding to both interventions, also a random treatment within patient effect was included. Model validation was performed by comparing observed and expected within subject standard deviations and correlations and by inspecting QQ-plots.
PI data were presented according to ePRO as an intervention (yes/no), yet multiple responses for each patient could occur in both groups (− ePRO/+ ePRO).
As this type of data can be analysed in several ways, we have presented them in a simple method as well. A mean PAM score was estimated for each patient, and presented according to group − ePRO, + ePRO and ‘− /+ ePRO.
All analyses were performed as complete case analyses, thus only patients who answered outcome measurements were included in the analysis. The statistical analyses were performed using STATA statistical software (STATA, release IC15, STATACorp, Texas, USA).