Background
With approximately 14.1 million new cases in 2014, cancer is one of the leading causes of morbidity worldwide [
1]. Europe alone accounts for 24.4 % (approximately 3.44 million cases) of the worldwide incidence. The prostate (22.8 %), lung (15.9 %), and colorectum (13.2 %) are the most prominent cancer sites among men in Europe. Among women, the breast (28.8 %), colorectum (12.7 %), and lung (7.4 %) are the most frequently affected sites [
1]. These numbers also mirror the current situation in Germany where 477,300 incident cases were reported for 2010 [
2].
Due to better screening and treatment of cancer, survival rates in cancer patients have improved steadily over the last few years in most developed countries. Five-year survival rates for cancer improved for patients diagnosed between 2005 and 2009 in most developed countries when compared to 5-year survival rates between 1995 and 1999 (e.g. Germany: 48.7 to 64.6 % for colon cancer, 51.9 to 62.1 % for rectal cancer, 81.2 to 85.3 % for breast cancer) [
3]. As a result, the life situation of cancer survivors and their participation in different life domains received increasing attention from patients, clinicians, and researchers [
4]. One of these important life domains is work. Work not only provides income to afford living, it also helps to structure time, enables social contacts, and develops skills and personality [
5,
6]. The presence or absence of work has an impact on various facets of health and quality of life [
7,
8]. Work also has a positive influence on coping with a disease (e.g. stroke [
9,
10]; psychiatric disorders [
11]; multiple sclerosis [
12]). For cancer survivors, returning to work after cancer diagnosis and subsequent treatment may support their ability to cope with this critical life event and represents a major step in restoring normality [
13‐
16].
Although up to 75 % of cancer survivors previously working in a job return to it after treatment [
17], returning to work is often easier said than done. Cancer survivors are 1.4 times more likely to be unemployed compared to healthy controls [
18]. They also have an increased risk of early retirement and are less likely to be re-employed [
18,
19]. Reviews showed that a multitude of parameters influence the process of returning to work in cancer survivors, including health, well-being and symptoms, and different domains of functioning, as well as self-rated work ability and work-related factors such as job demands and the working environment [
18‐
22]. In line with general return-to-work (RTW) research [
23], RTW in cancer survivors can therefore be described as a multifaceted bio-psycho-socially moderated process. Consequently, comprehensive multidisciplinary rehabilitation strategies are favored for supporting RTW. A Cochrane review by de Boer et al. [
19] confirmed that only diverse, multidisciplinary interventions show moderate evidence of higher RTW rates for cancer survivors when compared to usual care (for a comprehensive review across several health conditions, please see Hoefsmit et al. [
24]). Established programs, however, are not necessarily multidisciplinary and often lack a specific focus on RTW [
25]. In Germany, the German Pension Insurance (GPI) provides medical rehabilitation (MR) for working-age patients with chronic diseases to improve and restore their work ability, and support returning to or staying at work, and thus tries to sustainably avoid health-related early retirement. In Germany, about one fifth of all rehabilitation measures are provided due to cancer [
26]. However, though improvement and restoration of work ability are the primary aims of German MR programs, conventional MR does not seem to address work-related issues sufficiently [
27,
28]. The evidence considering the effects of these programs on work-related outcome measures in cancer patients is mixed at best. Most studies that are available did not use a control group and focused only on generic health-related outcome measures. These studies showed that MR can increase health-related quality of life, physical functioning, and general mental well-being [
29‐
32], and decrease anxiety and depression [
33]. Several studies, however, showed that, in particular, persons with a poor self-rated RTW prognosis did not benefit from conventional MR [
34,
35]. Moreover, Weis and colleagues [
32], who investigated the work-related impact of inpatient rehabilitation in female breast cancer patients in a controlled study, found no sustainable effects on health- or work-related outcomes [
36]. Obviously, conventional MR as practiced in Germany is not a sufficient treatment to address the multifaceted factors of RTW in cancer survivors.
As a result, rehabilitation programs with a stronger focus on work, work ability, and RTW have been developed in recent years. By addressing the individual job demands and necessary skills to meet them, these programs aim to increase the chances of a sustainable participation in the labor market, especially for patients with more severe restrictions of their work ability (e.g. long or repeated periods of sick leave, unemployment, poor self-rated RTW prognosis). To provide a framework for these diverse programs and activities, the GPI published guidelines for the implementation of work-related medical rehabilitation (WMR) [
37]. These guidelines define the target group, describe specific work-related diagnostic measures, and explain the core therapeutic modules that complement WMR programs as compared to conventional MR. The definition of the target group, i.e. patients on long-term sick leave and patients with a poor self-rated RTW prognosis, also includes recommendations for the identification of these patients by naming several screening instruments that assess an elevated risk of permanent work disability. The diagnostic process in WMR is described as demand-oriented, meaning that it should assess physical and psycho-social work ability against the background of the individual work-related demands. This also includes the identification of individual and environmental risk factors and resources that might be related to coping with these demands. Additionally, a functional capacity evaluation should be part of the diagnostic procedure [
38,
39]. Finally, the core therapeutic modules of WMR as described by the guidelines are a) work-related functional capacity training, b) work-related psychological groups, and c) intensified social counseling [
37].
Randomized controlled trials in patients with musculoskeletal [
40,
41], cardiac [
42], neurological [
43], and psychosomatic disorders [
44,
45] showed that patients who received WMR reported significantly higher RTW rates than patients who received a conventional MR program. Though WMR is well established for several disorders, there are currently only a few WMR programs for cancer patients. One non-randomized clinical trial in cancer patients showed no differences in RTW rates, work-related stress, and job satisfaction between a WMR group and a conventional MR group [
46]. A major methodological shortcoming of this study was the imbalance of both groups regarding several baseline measures. Moreover, the description of the program indicates that it was not a comparably comprehensive strategy as described in the current guidelines for WMR. Therefore, we designed a study to determine the effects of well-implemented WMR programs on work-related and quality-of-life outcomes in cancer survivors.
Methods
Design
The study is designed as a cluster-randomized multicenter trial which is realized in four German rehabilitation centers: the Klinik Bavaria in Freyung, the Paracelsus-Klinik am See in Bad Gandersheim, the MediClin Rose Klinik Horn-Bad Meinberg, and the Röpersbergklinik in Ratzeburg. The control group receives conventional MR as prescribed by the German Pension Insurance, whereas the intervention group receives a WMR program. Patients are randomized in clusters. These clusters are defined by a shared start of the rehabilitation program. Randomization is stratified by centers.
Recruitment
Patients are informed about the study by a study nurse or a physician in charge and have to provide written informed consent prior to study participation. Participants can withdraw their consent at any time without any consequences. No modifications to the intervention are planned. All rehabilitation centers were provided with a process description for recruitment prior to the study start and follow the same procedure.
When giving informed consent to participate in the study, the name and address will be listed by the rehabilitation center and a study number will be assigned. This study number will be entered in a field on each questionnaire. The study number will be also added to the medical discharge letter while all information on name and address will be removed to ensure that research data and confidential data cannot be linked. The study list with personal data and the study number will be destructed at the end of the study (12/31/2017) by each rehabilitation center to ensure that names and addresses of study participants are no longer available.
The researchers receive a copy of this study list only for mailing the questionnaires 3 and 12 months after discharge. Use of these data is not allowed for any other purpose but sending out the questionnaires. The study list will be secured with a password, stored separately from the collected research data, and erased after sending out the last questionnaires. The time schedule of enrolment and interventions is displayed in Table
1.
Table 1
Time schedule of enrolment and interventions
Enrolment: | | | | | | | |
Eligibility screen | X | | | | | | |
Informed consent | X | | | | | | |
Allocation | | X | | | | | |
Interventions: | | | | | | | |
Work-related medical rehabilitation | | | | | | X |
Conventional medical rehabilitation | | | | | | X |
Treatment
Control
Participants in the control group receive a conventional MR as provided by rehabilitation centers in Germany. Conventional MR is usually a 3-week program with an overall amount of 60–75 h of therapy [
26]. This includes exercise therapy, physiotherapy, social counseling, occupational therapy, psychological seminars and counseling, and dieting. Participants in the control group do not receive intensified work-related therapies. However, social counseling as an obligatory part of conventional MR informs on social law and provides basic knowledge about the rights of persons with disabilities. This also includes work-related issues.
Intervention
Participants in the intervention group receive a WMR program. In addition to the conventional MR, the WMR includes additional work-related therapies as defined by the WMR guideline (see above) [
37]. This guideline prescribes at least 11–25 h of additional work-related content for WMR patients [
37]. The complete treatment dose of a WMR program contains up to 100 h of therapy.
The intervention content is guided by the WMR guidelines [
37]. Further specifications of the diagnostic and therapeutic procedures are achieved in collaboration with the rehabilitation centers, based on an implementation phase before the start of the initial trial. This implementation phase is aimed at increasing the feasibility and fidelity of therapies across all participating rehabilitation centers. This phase is also used to check whether centers prescribe WMR therapies in addition to conventional MR therapies for the intervention groups and that control groups only receive conventional MR. The additional content of WMR and work-specific therapies as well as their minimum amount of time are described below (see Table
2 for a brief overview).
Table 2
Brief overview of the WMR program
Additional work-related diagnostics | During admission to rehabilitation Total: at least 60 minutes Medical assessment: 15 minutes Psychological assessment: 15 minutes Test of functional capacity and performance: 30 minutes | Personal interaction with the patient | Physician Psychologist, psychotherapist Occupational therapist, physiotherapist | Assessment of work functioning and its restrictions related to body functions and structures as well as activities and participation Assessment of environmental and personal factors that impact work functioning positively as resources and skills or negatively as barriers Use of structured patient interviews and/or standardized assessment instruments as well as standardized tests of functional capacity evaluation, structured observations of non-standardized job tasks |
Multi-professional team meetings | After admission During the course of rehabilitation Before discharge | N/A | All professions associated with the WMR program | Individual case conference for each patient After admission: results of the work-related diagnostics, joint development of a treatment plan During the course of rehabilitation: development of the patient, adjustment of the treatment plan if needed Before discharge: evaluation of rehabilitation outcomes, return-to-work prognosis, additional measures to support return to work if needed |
Introductory session | After admission | Presentation in front of all WMR patients | Physician | Description of the aims of WMR, explanation of the program structure and each module, introduction of the rehabilitation team Inform, motivate and prepare the patient for the subsequent program Establish treatment collaboration |
Work-related functional capacity training | At least 360 minutes | Training in small groups or personal training | Occupational therapist, physiotherapist | Complex and multidimensional tasks to simulate realistic work-related demands and situations Integrated ergonomic and cognitive training |
Work-related psychological groups | At least 240 minutes | Seminars with small groups | Psychologist, psychotherapist | Seminars focusing on work-related stress and coping, work-related social competencies in communication, and planning the concrete return to work |
Intensified social counseling | At least 90 minutes: 60 minutes seminars 30 minutes personal counseling | Seminars with small groups or personal counseling | Social worker | Clarification of the problematic work-related situations and perspectives, information and consultation on social law-related topics as well as measures and benefits to support return to work, establish contact with employer and request further measures and benefits from the social or health services agencies if needed |
Participants
Cancer patients (ICD-10: C00-D48) aged 18 to 60 years are included in the study if they have a score of ≥70 % on the Karnofsky Performance Status Scale [
50,
51] and a preliminary positive social-medical prognosis of employability for at least 3 h/day within the next 6 months as assessed by the rehabilitation physician in the initial examination after starting the rehabilitation program. Moreover, patients are only eligible to participate if they have an elevated risk of not returning to work. This risk is assessed by the Screening Instrument Work and Occupation (German: Screening-Instrument Beruf und Arbeit in der Rehabilitation, SIBAR) [
52‐
54]. This screening consists of three subscales. The first subscale is a 9-item scale and assesses the risk of health-related early retirement on the basis of a weighted sum score of several risk indicators (e.g. sick leave duration and the patients’ belief of time to return to work). A score of more than 7 out of 19 possible points indicates an elevated risk of early retirement and thus a need for a WMR program. The second subscale is a 1-item score and assesses the amount of perceived job strain. The third scale is also a 1-item score and assesses the subjective need for work-related therapies during the rehabilitation program. If patients indicate a very stressful job situation or assume that work-related therapies will be very helpful, this is also taken as a marker of the need for a WMR program. In brief, patients are included if one of the three scales indicates a need for a WMR program. Previous studies estimated that this is the case for about half of the patients. Moreover, about a quarter of the patients has an elevated risk of early retirement based on the first scale of the SIBAR [
52‐
54]. No exclusion criteria were defined.
Randomization
The study is designed as a cluster-randomized multicenter trial. Patients are recruited from four inpatient rehabilitation centers. Patients of a rehabilitation center who start their rehabilitation in the same week represent a cluster. These patients jointly receive either the intervention or the control treatment. Cluster-randomization was chosen to avoid spillover effects between therapy groups. Each of the four rehabilitation centers receives its own randomization schedule. The randomization lists are created by the last author using computer-generated random numbers and blocks of 4. The administrative employees who assign the patients to their date of rehabilitation are blinded to the randomization schedule.
Sample size calculation
Sample size calculation was done to detect a standardized mean difference (SMD) of SMD = 0.3 in the primary outcome with 80 % power and a two-sided alpha error of 5 %. Using a t-test, a sample size of 352 participants would be needed. The planned regression modeling of treatment effects, which includes the baseline measurement of the primary outcome as a covariate, needs a sample size that is reduced by the factor 1 - r
2 [
55]. The correlation r represents the correlation between baseline and follow-up measurement. The approximation of the sample size based on a t-test represents a conservative proxy, even when considering the design effects induced by the cluster-randomization or missing values. Based on expected sample attrition due to nonresponse to the 1-year follow-up questionnaire of 30 %, we aim to recruit at least 504 patients.
Outcome measures
Primary and secondary outcomes are assessed by questionnaires at the beginning of the inpatient rehabilitation program, at discharge from the rehabilitation program, and 3 and 12 months after discharge. Questionnaires at the beginning and discharge of the program are delivered and collected by study nurses in the rehabilitation centers. These nurses are not blinded to the treatment allocation. Questionnaires at 3- and 12-month follow-up are sent by mail to the first author who is also not blinded to the treatment allocation. Table
3 shows all variables and their corresponding measurement point.
Table 3
Time schedule of assessments and instruments
Role functioning (EORTC QLQ-C30) [ 56] | X | | X | X |
Physical functioning (EORTC QLQ-C30) [ 56] | X | X | X | X |
Emotional functioning (EORTC QLQ-C30) [ 56] | X | X | X | X |
Social functioning (EORTC QLQ-C30) [ 56] | X | | X | X |
Pain (EORTC QLQ-C30) [ 56] | X | X | X | X |
Global health (EORTC QLQ-C30) [ 56] | X | X | X | X |
Fatigue (EORTC QLQ-FA13) | X | X | X | X |
Coping with illness (FCQI) [ 60] | X | X | X | X |
Implementation of work-related therapies [ 63] | | X | | |
Consistency of work-related rehabilitation strategy [ 63] | | X | | |
Benefit from work-related therapies [ 63] | | X | | |
| X | X | X | X |
Employment status | X | | X | X |
Time of return to work | | | X | X |
Sick leave duration | X | | X | X |
Disability days during the last 3 months [ 61] | X | | X | X |
Patient satisfaction [ 64] | | X | | |
Sociodemographic data | X | | | |
Discrete choice experiment | X | | | |
Screening Instrument Work and Occupation [ 67] | X | | | |
In the case of nonresponse to the follow-up questionnaires at 3 and 12 months after discharge, participants receive three additional reminders. The first reminder consists of a letter and is sent one week after the initial follow-up questionnaire; the second reminder includes the questionnaire again and is sent three weeks after the initial follow-up questionnaire; the third reminder also includes the questionnaire again and is sent six weeks after the initial follow-up questionnaire.
Main study outcome
The primary outcome of the study is the role functioning scale of the 30-item quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-30). The role functioning scale comprises two items that relate to a) work and other daily activities and b) hobbies and leisure time activities. Response categories are “not at all,” “a little,” “quite a bit,” and “very much.” Single-item scores will be averaged and transformed to a score from 0 to 100 points. Higher scores represent better functioning [
56].
Secondary study outcome
Secondary outcome measures are additional scales of the EORTC QLQ-30. These scales measure physical functioning, emotional functioning, social functioning, pain, and global health [
56,
57]. Additionally, we use the 13-item fatigue module (EORTC QLQ-FA13) [
58]. All scales range from 0 to 100 points. Higher scores indicate a better health-related quality of life.
Self-rated work ability is measured with the Work Ability Score. Ten points represent the best work ability ever achieved; 0 points indicate total work disability [
59].
Disease coping is measured with three scales of the Freiburg Questionnaire of Coping with Illness (FCQI; depressive coping, active coping, distraction, and self-encouragement) with 5-point scaled items [
60]. Raw item scores will be added up to a sum score for each scale. These will be used to calculate a mean scale score, resulting in values ranging from 1 to 5 points [
60].
Participation in working life is measured with an assessment of the current employment status, current sick leave status, and disability days during the last 3 months [
61,
62]. The assessment after 12 months also includes a question regarding the date of initial return to work.
The realization of work-related goals and therapies during rehabilitation is assessed with a slightly modified version of a previously used set of items from a study that investigated the implementation of the WMR guidelines [
63]. Participants report on 12 dichotomized items whether they received WMR contents throughout their rehabilitation program. Scores are aggregated to a total score ranging from 0 to 12 points. This score reflects the implementation of the work-related therapies. Additionally, 6 items assess the perceived diagnostic and therapeutic focus on issues of return to work and work ability, e.g. the experience of a consistent RTW strategy. These items are 5-point scaled. Scores will be summed to a total score ranging from 0 to 24 points. Finally, the subjective work-related benefit from participating in the rehabilitation program is assessed with 8 items using 5-point scales. Scores are aggregated to a total score ranging from 0 to 32 points.
Treatment satisfaction is assessed using the German version of the Client Satisfaction Questionnaire (CSQ-8) [
64]. This questionnaire uses 8 items to assess various aspects of the patient’s satisfaction with the treatment. Items are 4-point scaled. The sum score ranges from 8 to 32 points.
Supplemental data
The sociodemographic data that are assessed include age, sex, employment status, native language, partnership, number of children, educational level, and job qualification. Additionally, a discrete choice experiment is attached to the baseline questionnaire to assess patients’ treatment preferences [
65].
Data management
Questionnaires will be scanned and verified by an electronic data capture system and exported to statistical software packages for further analysis. Scanning and verifying is done by trained research assistants. Research assistants check electronically processed data item by item and compare imported data with the original questionnaire data.
If available, standard syntaxes are used to calculate scales (e.g. symptom scales of the EORTC QLQ-30) for further analyses. Each data set is checked for errors or inconsistencies before merging them with data from the other data sources or time points via the assigned study number to create a comprehensive data set. Data access is limited to the authors and the research assistants of the research team at the University of Lübeck.
Statistical analysis
Treatment effects are tested using regression analyses. In the case of binary study outcomes, logistic regression will be used (e.g. effects on employment status or sick leave at follow-up). For analysis of time to return to work, we will use proportional hazard models. Baseline parameters will be considered as covariates [
66]. Due to the cluster-randomization, the induced correlation of error terms for patients with the same arrival week will be taken into account by a random effect [
67‐
69]. Rehabilitation centers will be considered using a fixed effect.
To calculate a SMD of the between-group difference, the unstandardized regression coefficient estimate of the treatment effect will be used [
70]. This estimate will be standardized using the pooled standard deviation of the observed follow-up scores [
71]. In the case of binary study outcomes, estimated odds ratios will be transformed into SMDs using a logit-transformation [
71,
72]. SMDs will be interpreted as suggested by Cohen [
73]: small effect: SMD ≥0.2, medium effect: SMD ≥0.5, large effect: SMD ≥0.8.
Furthermore, to test whether the treatment effect on the primary outcome is moderated by other variables we will include two-way interaction terms in the regression model. Potential moderators that will be tested are the remaining EORTC QLQ-30 scales, fatigue, the Work Ability Score, disease coping, and the type of rehabilitation (rehabilitation following primary cancer treatment vs. follow-up rehabilitation) as well as sociodemographic variables. Continuous moderators will be standardized using a z-transformation. The parameter estimate of the interaction between the z-standardized continuous score and the treatment indicator then represents the additional treatment effects when increasing the potential moderator by about one standard deviation [
74‐
76]. Patients will be included in our analyses if they have completed the corresponding follow-up questionnaire and will be analyzed as randomized, i.e. as intended to treat [
77]. Differences will be regarded as significant if the two-sided p-value of a test is less than 0.05.
Missing observations are excluded from the primary analysis. Supplementary analyses will impute missing observation by using the last observation carried forward method, in which the last observed value is used in place of the missing endpoint. No stopping guidelines are applied and no adverse health events are expected.
Abbreviations
CSQ, Client Satisfaction Questionnaire; EORTC QLQ-30, 30-item quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer; EORTC QLQ-FA13, 13-item fatigue questionnaire of the European Organization for Research and Treatment of Cancer; FCQI, Freiburg Questionnaire of Coping with Illness; GPI, German Pension Insurance; ICD, International Statistical Classification of Diseases and Related Health Problems; MR, medical rehabilitation; RTW, return to work; SIBAR, Screening Instrument Work and Occupation (German: Screening-Instrument Beruf und Arbeit in der Rehabilitation); SMD, standardized mean difference; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials; WMR, work-related medical rehabilitation
Acknowledgements
We would like to thank the Klinik Bavaria in Freyung, the Paracelsus-Klinik am See in Bad Gandersheim, the MediClin Rose Klinik Horn-Bad Meinberg, and the Röpersbergklinik in Ratzeburg for their support. This study protocol was written according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. The SPIRIT checklist is presented in Additional file
2.