European Journal of Oncology Nursing 17 (2013) 204e213

Contents lists available at SciVerse ScienceDirect

European Journal of Oncology Nursing

journal homepage: www.elsevier.com/locate/ejon

A patient education program is effective in reducing cancer-related fatigue: A

multi-centre randomised two-group waiting-list controlled intervention trial
Karl Reif a, Ulrike de Vries b, *, Franz Petermann b, Stefan Grres a
a
b

Institute for Public Health and Nursing Research, University of Bremen, Germany
Centre for Clinical Psychology and Rehabilitation, University of Bremen, Germany

a b s t r a c t
Keywords:
Cancer-related fatigue
Patient education
Nonpharmacologic interventions

Objective: To evaluate a patient education program that aims at reducing perceived fatigue in cancer
survivors.
Methods: In ten German centres, 261 patients with cancer-related fatigue were randomly assigned to
a patient education program consisting of 6 sessions 90 min or standard care. The primary outcome
measure was cancer-related fatigue. Data were analysed using analysis of variance (ANOVA) with
repeated measures.
Results: Patients in the intervention group showed statistically signicant reduction in cancer-related
fatigue (F 76.510, p < 0.001, h2 0.248). Secondary outcomes also showed signicant improvements in all measures, including quality of life (F 29.607, p < 0.001, h2 0.113), general self-efcacy
(F 27.680, p < 0.001, h2 0.107), exercise self-efcacy (F 49.230, p < 0.001, h2 0.175), physical
activity (F 8.036, p < 0.001, h2 0.033), anxiety (F 33.194, p < 0.001, h2 0.125), depression
(F 24.604, p < 0.001, h2 0.096), and fatigue knowledge (F 55.157, p < 0.001, h2 0.192).
Conclusion: The program was effective in reducing perceived fatigue as well as further outcomes.
Practice implications: This newly developed education program has the potential to ll a gap in the care of
cancer survivors. The program needs further evaluation in other countries employing a control group of
patients receiving equal time and attention as the intervention group.
2012 Elsevier Ltd. All rights reserved.

Introduction
Cancer-related fatigue (CRF) is dened as a distressing persistent sense of tiredness or exhaustion related to cancer that is not
proportional to recent activity and interferes with usual functioning (National Comprehensive Cancer Network, 2011). CRF is
seen as a multidimensional symptom as it encompasses physical,
mental and emotional aspects (Glaus et al., 1996). CRF is highly
prevalent across the cancer continuum from diagnosis and treatment through survivorship and end of life. The prevalence of
cancer-related fatigue ranged from 4% to 91%, depending on the
population studied and the methods of assessment (Lawrence et al.,
2004). Advances in diagnosis and treatment of malignancies have
resulted in a growth of the number of cancer survivors. Thus,
clinicians are being faced with a growing number of patients with
CRF, even years after treatment.
* Corresponding author. Present address: Centre for Clinical Psychology and
Rehabilitation, University of Bremen, Grazer Str. 6, D-28359 Bremen, Germany.
Tel.: 49 421 218 68612; fax: 49 421 218 68629.
E-mail address: udevries@uni-bremen.de (U. de Vries).
1462-3889/$ e see front matter 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejon.2012.07.002

There is a wide range of treatment options for CRF which can be

classied into pharmacologic and nonpharmacologic interventions.
Drug therapy for CRF is not well established yet. Hemopoietic
growth factors have been suggested to treat CRF but can no longer
be recommended due to safety issues (Minton et al., 2010). There is
evidence for the use of psychostimulants to treat CRF (Minton et al.,
2011). However, large scale trials to conrm these results are
required.
Nonpharmacologic interventions focus on exercise and
psychosocial interventions. In a meta-analysis, these interventions
achieved an overall effect size of 0.341 (p < 0.001) (Kangas et al.,
2008), with negative indices indicating less fatigue postintervention. Exercise has been studied extensively, yielding an
effect size in survivors of 0.31 (Brown et al., 2011). Psychosocial
interventions may comprise psychoeducation, psychotherapy or
social support; in a meta-analysis the pooled effect size was 0.313
(Kangas et al., 2008), whereas single trials resulted in effect sizes
from 0.17 to 1.07 (Goedendorp et al., 2009).
Psychoeducation is common in psychosocial interventions and
is recommended as a key strategy in CRF management (National
Comprehensive Cancer Network, 2011). However, the efcacy of

Table 1
Topics and methods of FIBS sessions.
Title of session

Topics

Methods

Materials

Duration

Dimensions of fatigue

Short lectures, moderated group

discussions.

Etiology and treatment

of fatigue

Overhead projector and transparencies,

ip chart, materials for metaplan method,
mailbox for anonymous communication,
specialized patient diary, summary of the session.
Overhead projector and transparencies, ip chart,
worksheets, mailbox, sports brochures and
training DVD, summary of the session.

90 min

2 (1 week
after session 1)

3 (1 week
after session 2)

Time and energy

management

Against the background of their own symptom

experiences, patients learn to differentiate
between the physical, cognitive and emotional
dimensions of fatigue.
Patients gain insight into the etiology of
fatigue. Information about treatment options
is given and discussed with the patients, taking
into account the strength of evidence. The
patients subjective theories of disease are
integrated into the discussion. Patients are
encouraged to establish an exercise program.
Patients learn to review their daily routines and
structure their activities according to their
energy levels, utilizing a patient diary.

4 (1 week
after session 3)

Healthy sleep and

enjoyment

5 (1 week
after session 4)

Coping with emotions

6 (1 week
after session 5)

Implementing new
strategies

Additional session 1
(3 months after
session 6)
Additional
session 2 (6 months
after session 6)

Exchanging experiences

Exchanging experiences

In the rst part of the session, patients are

informed about rules of sleep hygiene in order
to establish healthy sleep-wake rhythms. In the
second part, patients are trained positive
self-reinforcement techniques to enhance
enjoyment of life.
Patients learn strategies to overcome depressive
periods. Negative experiences in everyday life
are reviewed and strategies to activate positive
emotions are trained.
Patients discuss the use of resources to
overcome barriers that may occur when
implementing new strategies into everyday life.
Patients share their experiences with the
program in everyday life.
Patients share their experiences with the
program in everyday life.

Short lectures, moderated group

discussions, home exercises.

90 min

Short lectures, moderated group

discussions, individual tasks,
behavioural training, home
exercises.
Short lectures, moderated
group discussions,
individual tasks,
behavioural training,
home exercises.

Overhead projector and transparencies, ip chart,

worksheets, mailbox, specialized patient diary,
summary of the session.

90 min

Overhead projector and transparencies, ip chart,

worksheets, mailbox, summary of the session.

90 min

Short lectures, moderated

group discussions, individual
tasks, behavioral training,
home exercises.
Short lectures, moderated
group discussions.

Overhead projector and transparencies, ip chart,

worksheets, mailbox, summary of the session.

90 min

Overhead projector and transparencies, ip chart,

worksheets, summary of the session.

90 min

Moderated group discussion.

90 min

Moderated group discussion.

90 min

K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

Session

IG intervention group.
CG wait-list control group.
SD standard deviation.

205

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K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

Table 2
Topics and methods of the train-the-trainer seminar.
Session

Topics

Methods

Materials

Duration

Information about
cancer-related fatigue.
Principles of
communication, adult
education and lifelong
learning.
Principles of communication
and adult education. Group
leadership, group pedagogy
and group therapy.

Lectures and discussions,

training in communication
skills and strategies.

Notebook, projector, ip
chart, materials
for metaplan method,
FIBS materials.

1 day

Training in
communication
skills and strategies,
individual and group
exercises, role plays.

FIBS materials.

1 day

IG intervention group.
CG wait-list control group.
SD standard deviation.

psychoeducational interventions in cancer survivors has not been

established. Therefore, a patient education program was developed
by multidisciplinary collaboration using formative evaluation
methods. The program is named FIBS, Fatigue individuell bewltigen e ein Selbstmanagementprogramm fr Krebspatienten
(Coping with fatigue individually e a self-management program for
cancer patients). In this study, the aim was to determine whether
FIBS could improve the patients CRF management.

Enrollment

Methods
A multi-centre randomised two-group waiting-list controlled
intervention trial was carried out. Our main hypothesis was:
Participation in the patient education program signicantly
changes the level of CRF in disease-free cancer survivors with
a follow-up period of 6 months. The study was approved by the
Ethics Committee of the University of Bremen.

Assessed for eligibility (n=327)

Excluded (n=66)
Not meeting inclusion criteria (n=37)
Declined to participate (n=24)
Other reasons (n=5)

Randomized (n=261)

Allocation
Allocated to intervention (n=129)
Received allocated intervention (n=120)
Did not receive allocated intervention (n=9)
Declined to participate (n=3)
Died (n=1)
Other reasons (n=5)

Allocated to intervention (n=132)

Received allocated intervention (n=114)
Did not receive allocated intervention (n=18)
Declined to participate (n=3)
Rehabilitation (n=1)
Other reasons (n=14)

Follow-Up
Lost to follow-up (n=0)

Lost to follow-up (n=0)

Discontinued intervention (n=0)

Discontinued intervention (n=0)

Analysis
Analysed (n=120)
Excluded from analysis (n=9)

Analysed (n=114)
Excluded from analysis (n=18)

Fig. 1. Flow diagram of the FIBS study.

K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

207

Table 3
Demographic and clinical characteristics of patients in intervention group (IG) and wait-list control group (CG). All data in n (%) unless otherwise stated. There were no
signicant differences between groups on any of the demographic/clinical variables at baseline.

Sex
Age
Marital status

Education (school leaving certicate)

Vocational training/professional education

Current occupation

Certied unt for work because of fatigue

Rehabilitation
Most prevalent initial diagnoses

Comorbidities
Most prevalent comorbidities

Duration of fatigue
Fatigue interventions

Female
Mean (SD)
Unmarried
Married
Divorced/separated
Widowed
Secondary school
Polytechnic secondary school
Advanced technical college certicate
A-level-exam
None
Apprenticeship
Trade and technical schools
University of applied science
University
Other
Working
Parental leave
Housewife/househusband
On apprenticeship
Unemployed
Invalidity pension
Retired
Other
Yes
Duration: mean weeks (SD)
Yes

Yes
Depression
Hypertension
Diabetes
<6 months
>6 months
None
Information brochures
Internet
Self-help group
Psychotherapy
Sports
Other

IG n 120

CG n 114

97 (80.8%)
57.78 (10.32)
10 (8.3%)
86 (71.7%)
14 (11.7%)
10 (8.3%)
71 (59.2%)
9 (7.5%)
14 (11.7%)
24 (20.0%)
6 (5.0%)
68 (56.7%)
16 (13.3%)
7 (5.8%)
21 (17.5%)
2 (1.7%)
49 (40.8%)
1 (0.8%)
9 (7.5%)
1 (0.8%)
1 (0.8%)
16 (13.3%)
40 (33.3%)
3 (2.5%)
30 (25.0%)
21.57 (22.96)
92 (76.7%)
Breast cancer
76 (63.3%)
Colon cancer
8 (6.7%)
Prostate cancer
5 (4.2%)
72 (60.0%)
34 (28.3%)
12 (10.0%)
8 (6.7%)
8 (6.7%)
112 (93.3%)
37 (30.8%)
29 (24.2%)
19 (15.8%)
11 (9.2%)
9 (7.5%)
13 (10.8%)
2 (1.7%)

90 (78.9%)
57.52 (11.90)
11 (9.6%)
71 (62.3%)
23 (20.2%)
9 (7.9%)
61 (53.5%)
10 (8.8%)
14 (12.3%)
29 (25.4%)
6 (5.3%)
57 (50.0%)
10 (8.8%)
10 (8.8%)
22 (19.3%)
9 (7.9%)
48 (42.1%)
0 (0%)
8 (7.0%)
0 (0%)
4 (3.5%)
17 (14.9%)
36 (31.5%)
0 (0%)
25 (21.9%)
29.2 (24.9)
87 (76.3%)
Breast cancer
61 (53.5%)
Leukaemia
6 (5.3%)
Lymphoma
6 (5.3%)
78 (68.4%)
33 (28.9%)
30 (26.3%)
4 (3.5%)
4 (3.5%)
107 (93.9%)
28 (24.6%)
23 (20.2%)
18 (15.8%)
7 (6.1%)
7 (6.1%)
23 (20.2%)
4 (3.5%)

IG intervention group.
CG wait-list control group.
SD standard deviation.

Participants

Procedures

Patients were eligible if they were 18 years or older and diagnosed with malignant tumours. They had to be in a stable condition
(ECOG Performance Status 0e2) (Oken et al., 1982) at any time
point following active treatment and remission of acute toxic side
effects. The patients CRF level had to be rated as moderate (4e6) or
severe (7e10) on a scale from 0 to 10 (National Comprehensive
Cancer Network, 2011). Patients were excluded if their life expectancy was less than 12 months, if they had brain tumours or brain
metastases, cognitive disorders or psychiatric conditions. Patients
with depression were not excluded. Crucial inclusion factors were
a sufcient level of functioning and motivation to be able to
participate in a multi-part seminar.
Patients were recruited by their physicians who checked the
inclusion and exclusion criteria from July 2008 to March 2010 in 10
German centres covering urban and rural areas. All participants
received personal and written information about the study and
gave written informed consent.

Computer-generated randomisation lists were used for concealed allocation by central telephone calls. Data collection was
scheduled at baseline (t0), post-treatment (t1) and at a follow-up of
6 months (t2).Baseline measures (t0) were obtained prior to randomisation. Although the data entry and analysis was performed by
blinded researchers, patients and tutors could not be blinded to
treatment allocation for practical reasons.
Intervention
The intervention was a structured patient education program
consisting of six weekly sessions 90 min designed for groups of 8
cancer survivors. The topics and methods of each session are presented in Table 1. FIBS aims at impacting on health-related selfefcacy as it is known that knowledge by itself hasnt proved to
achieve behaviour modications. This was realized by implementing a training of problem solving, including goal setting and

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Table 4
Changes in Fatigue Assessment Questionnaire (FAQ) (primary outcome).
Group

Total scale (range: 0e60)

Physical subscale (range: 0e33)
Cognitive subscale (range: 0e9)
Affective subscale (range: 0e15)
Insomnia (range: 0e3)
Visual analogue scales (range: 0e9)

IG
CG
IG
CG
IG
CG
IG
CG
IG
CG
IG
CG

Pre-intervention

Post-intervention

Follow-up at 6 months

Group  time

Partial eta-squared

Mean (SD)

Mean (SD)

Mean (SD)

Group  time

42.42
41.68
24.77
24.38
6.16
3.15
9.45
9.22
2.05
1.94
8.03
8.09

27.88
41.35
16.32
24.10
4.07
6.15
6.12
9.10
1.37
2.00
5.94
8.06

22.85
42.65
13.35
24.53
3.34
6.21
4.89
9.83
1.27
2.08
5.01
7.80

76.510

<0.001

0.248

72.610

<0.001

0.238

41.638

<0.001

0.152

49.904

<0.001

0.177

23.019

<0.001

0.090

48.790

<0.001

0.174

(9.17)
(10.13)
(5.16)
(5.88)
(2.08)
(2.09)
(3.55)
(3.75)
(0.98)
(1.01)
(1.57)
(1.34)

(13.99)
(11.52)
(8.23)
(6.17)
(2.53)
(2.41)
(3.90)
(4.09)
(1.12)
(1.03)
(2.27)
(1.52)

(15.73)
(12.02)
(9.32)
(6.60)
(2.67)
(2.23)
(4.12)
(4.13)
(1.12)
(1.01)
(2.44)
(1.64)

IG intervention group.
CG wait-list control group.
SD standard deviation.

evaluation, and other cognitive techniques into the program. We

utilized behaviour therapy-oriented strategies and techniques and
designed the program to be effective in the cognitive, emotional,
and behavioural aspect. The structure of the sessions was scheduled so that short periods of lecture activity by the trainer and
longer periods of controlled participant activity alternated. In that
way all patients could express their thoughts and feelings on any
topic and the individual needs of patients could be taken into
account. Also, the subject matter could be easier kept in mind as it
was worked out by the patients themselves.
Between sessions, the patients were encouraged to keep
a diary, perform exercises and implement lifestyle changes. Two
additional meetings after 3 and 6 months were offered to patients
to share their experiences in daily life. The program was administered by nurses and psychologists but can also be carried out by
other health care professionals. The manual is published in
German (de Vries et al., 2011). Patients in the intervention group
(IG) were highly satised with the program (Reif et al., 2010). The
trainers were mostly nurses, but also psychologists worked as
trainers. All trainers attended a specialized train-the-trainer
workshop held by the authors to ensure that the program is
conducted in each centre in the same way. The topics and methods
of this seminar are shown in Table 2.

Patients in the control group (CG) were put on a waiting-list.

They participated in the program after the IG had completed
their follow-up.
All patients received standard information on fatigue as
a lecture. For all patients medical care, e.g. routine follow-up,
continued as usual and no additional intervention was provided.
Outcome measures
CRF was measured by the Fatigue Assessment Questionnaire
(FAQ). The scale consists of 20 items: 11 items represent physical, 5
items affective and 3 cognitive fatigue; one item is about insomnia.
In addition, there are three visual analogue scales about fatigue
intensity and burden. Cronbachs alpha of the total scale was 0.90,
physical subscale 0.95, affective subscale 0.83 and cognitive
subscale 0.86 (Glaus and Mller, 2001).
Quality of life was measured with the EORTC QLQ-C30 questionnaire. It is a 30-item questionnaire that reects the multidimensionality of the construct. It includes 5 functional scales, 3
symptom scales and a global health status scale. 6 single item side
effects scales are added. The questionnaire showed satisfactory
psychometric properties and was found to be useful for detecting
changes over time (Aaronson et al., 1993). The reliability

Table 5
Changes in EORTC Quality of Life Questionnaire QLQ-C30 (version 3.0).
Group

Global Health Status (range: 0e100)

Physical functioning (range: 0e100)
Role functioning (range: 0e100)
Emotional functioning (range: 0e100)
Cognitive functioning (range: 0e100)
Social functioning (range: 0e100)
Fatigue (range: 0e100)
Insomnia (range: 0e100)
IG intervention group.
CG wait-list control group.
SD standard deviation.

IG
CG
IG
CG
IG
CG
IG
CG
IG
CG
IG
CG
IG
CG
IG
CG

Pre-intervention

Post-intervention

Follow-up at 6 months

Group  time

Partial eta-squared

Mean (SD)

Mean (SD)

Mean (SD)

Group  time

44.17
43.06
59.28
58.60
41.39
39.18
37.64
37.28
41.25
42.25
37.08
39.62
75.37
73.29
64.44
61.11

57.08
40.35
72.33
57.48
59.58
37.86
58.82
36.77
60.97
39.77
58.33
37.86
48.70
72.71
45.83
64.33

63.82
39.91
78.55
56.78
69.58
38.16
68.96
33.77
68.61
36.70
66.11
35.09
40.74
74.27
38.89
66.67

29.607

<0.001

0.113

32.432

<0.001

0.123

33.906

<0.001

0.128

51.826

<0.001

0.183

48.974

<0.001

0.174

31.282

<0.001

0.119

57.837

<0.001

0.200

22.727

<0.001

0.089

(18.32)
(18.97)
(20.92)
(19.92)
(25.20)
(23.46)
(24.89)
(24.92)
(24.82)
(26.16)
(28.04)
(31.39)
(19.39)
(22.01)
(33.12)
(36.28)

(22.93)
(19.16)
(19.28)
(22.74)
(29.36)
(26.17)
(26.42)
(25.81)
(28.21)
(27.20)
(31.53)
(31.14)
(30.76)
(20.75)
(37.44)
(34.84)

(21.67)
(18.57)
(20.55)
(24.15)
(28.96)
(27.93)
(27.14)
(25.37)
(28.92)
(27.17)
(32.40)
(28.60)
(30.60)
(22.53)
(36.24)
(33.77)

K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

209

Table 6
Changes in General Self-Efcacy Scale (GSE).
Group

GSE total score (range: 10e40)

IG
CG

Pre-intervention

Post-intervention

Follow-up at 6 months

Group  time

Mean (SD)

Mean (SD)

Mean (SD)

Group  time

26.35 (6.23)
25.54 (6.04)

29.61 (7.32)
24.99 (6.24)

31.12 (7.18)
27.73 (6.74)

27.680

<0.001

0.107

Partial eta-squared

IG intervention group.
CG wait-list control group.
SD standard deviation.

coefcients for the multi-item scales in a German population

ranged from 0.65 to 0.89 (Schwarz and Hinz, 2001). For this study,
the questionnaire was adapted to the survivors conditions and thus
reduced to 21 items, omitting acute disease specic items like
dyspnoea and nausea/vomiting.
General self-efcacy was assessed by using the General SelfEfcacy Scale (Schwarzer and Jerusalem, 1995). It is a 10-item
questionnaire designed to assess optimistic self-belief that one
can perform on novel or difcult tasks or cope with adversity in
various domains of functioning. The scale has proved reliable and
valid. Cronbachs alpha ranged from 0.76 to 0.90. Criterion-related
validity is documented in numerous correlation studies (Scholz
et al., 2002).
Exercise self-efcacy was measured with the Physical Exercise
Self-Efcacy Scale. This 20-item instrument was developed to
assess efcacy beliefs in initiating and maintaining a regular
program of physical exercise even under unfavourable circumstances. Cronbachs alpha was 0.89 (Fuchs and Schwarzer, 1994).
The instrument was positively correlated with generalized selfefcacy. Further evidence of validity is provided by the correlation between the scale and the intention towards physical exercise
(Fuchs and Schwarzer, 1994).
Physical activity was measured by the Freiburg Questionnaire on
Physical Activity (FFKA) (Frey et al., 1999). Originally, the questionnaire consisted of 12 items. In consultation with the authors
those 4 items which measure the quality of sleep were omitted. An
estimate of energy expenditure was derived by multiplying hours
of reported activity by the average intensity expressed in metabolic
equivalent values for activities (MET) (Ainsworth et al., 2000). The
scale has satisfactory psychometric properties and allows a calculation of weighted MET hours per week. The test-retest-reliability
of subscales ranged between 0.751 and 0.998. Maximum oxygen
uptake correlated with sport activities, thus showing a good validity (Frey et al., 1999).
Anxiety and depression were measured by the German version
of the Hospital Anxiety and Depression Scale (HADS-D) (Hinz and

Schwarz, 2002), consisting of 7 items on both subscales. Cronbachs alpha varied from 0.67 to 0.90 (Bjelland et al., 2002). The
sensitivity and specicity was approximately 0.80. Correlations
between HADS and other commonly used questionnaires ranged
from 0.49 to 0.83 (Hinz and Schwarz, 2002; Bjelland et al., 2002).
Since there were no scales for measuring CRF knowledge the
Fatigue Knowledge Test (F-WT) was developed. The concepts were
drawn from clinical recommendations with emphasis on self-care.
The items are based on a systematic review (de Vries et al., 2009).
The F-WT is a 34-item instrument with true/false questions containing 9 items about etiology and signs of CRF, 6 items about
treatment, 3 items about exercise, 6 items about exercise motivation, 5 items about scheduling daily activities and 5 items about
improvement of the sleep-wake rhythm. Cronbachs alpha calculated from our study was 0.82.
A questionnaire to measure the patients satisfaction was
developed, the Fatigue education satisfaction scale, based on
a scale for asthma education. The original scale contained 28 items.
Cronbachs alpha for the total scale was 0.92 and ranged from 0.47
to 0.91 for subscales (de Vries et al., 2008). This questionnaire was
modied for use in FIBS.
Statistical analysis
The sample size estimation was based on the FAQ. To detect
a clinically relevant difference of 4 points in the mean with 80%
power and a two-sided 0.05 signicance, 120 patients were needed
in each group. Data for the sample size estimation was determined
by research (Geinitz et al., 2004). We anticipated an attrition of 20%,
giving a total n of 150 per group or n of 120 per group being analysed at t2.
We used a group-by-time two-way analysis of variance
(ANOVA) statistics with time as the repeated factor. Group-by-time
effects on changes in patients outcomes and partial eta-squared
(h2) values were calculated. The primary outcome measure was
CRF, all other outcomes were secondary. We considered results to

Table 7
Changes in Physical Exercise Self-Efcacy Scale.
Group

Planning phase (range: 1e4)

Implementation phase (range: 5e20)
Habituation phase (range: 1e4)
Maintenance (range: 11e44)
Recidivism (range: 2e8)
Total score (range: 20e80)
IG intervention group.
CG wait-list control group.
SD standard deviation.

IG
CG
IG
CG
IG
CG
IG
CG
IG
CG
IG
CG

Pre-intervention

Post-intervention

Follow-up at 6 months

Group  time

Mean (SD)

Mean (SD)

Mean (SD)

Group  time

2.54
2.55
14.51
14.67
2.59
2.70
25.36
26.07
5.48
5.52
50.48
51.51

3.02
2.47
16.52
13.95
3.12
2.59
30.20
24.56
6.40
5.24
59.26
48.81

3.12
2.25
16.82
12.90
3.18
2.46
31.65
23.33
6.61
4.83
61.39
45.78

21.938

<0.001

0.086

27.83

<0.001

0.107

23.821

<0.001

0.093

46.803

<0.001

0.168

32.301

<0.001

0.122

49.230

<0.001

0.175

(0.81)
(0.89)
(3.66)
(4.26)
(0.85)
(0.91)
(5.63)
(6.34)
(1.49)
(1.70)
(10.73)
(12.40)

(0.86)
(0.94)
(3.48)
(4.11)
(0.82)
(0.90)
(8.13)
(6.28)
(1.53)
(1.64)
(13.37)
(12.13)

(0.84)
(0.95)
(3.41)
(4.68)
(0.84)
(0.91)
(8.49)
(7.48)
(1.44)
(1.72)
(13.83)
(13.88)

Partial eta-squared

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K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

Table 8
Changes in Freiburg Questionnaire on Physical Activity (FFKA).
Group

Basic activities (MET-hours per week)

Leisure activities (MET-hours per week)
Sports (MET-hours per week)
Total activity (MET-hours per week)

IG
CG
IG
CG
IG
CG
IG
CG

Pre-intervention

Post-intervention

Follow-up 6 months

Group  time

Mean (SD)

Mean (SD)

Mean (SD)

20.16
15.12
11.44
13.85
7.42
12.38
39.02
41.35

20.02
17.26
15.08
11.62
11.99
6.14
47.09
35.03

26.01
14.21
18.67
11.06
12.92
7.26
57.61
32.53

5.213

0.006

0.022

5.833

0.003

0.025

3.109

0.046

0.013

8.036

<0.001

0.033

(21.22)
(14.37)
(13.46)
(29.14)
(12.05)
(64.42)
(33.74)
(72.44)

(18.89)
(21.96)
(15.67)
(16.13)
(16.52)
(12.61)
(34.29)
(34.24)

(28.59)
(16.75)
(19.96)
(16.45)
(17.79)
(16.42)
(51.62)
(33.12

Partial eta-squared
Group  time

IG intervention group.
CG wait-list control group.
SD standard deviation.

be statistically signicant if the two-sided p-values were less than

0.05.
All patients who completed the questionnaires were included in
the analyses regardless of their participation in the sessions
(intention-to-treat analysis). No interim analyses for efcacy or
futility were carried out, no stopping rules applied. All statistical
analyses were carried out using SPSS for Windows Release 18.
Results
327 patients were assessed for eligibility; 261 were randomised,
129 allocated to the IG and 132 to the CG. 120 patients attended the
program. All of these and 114 patients in the CG were analysed at
follow-up. 27 patients couldnt be analysed as there were no data
available (Fig. 1). No patient discontinued the intervention, but
some didnt attend all modules for different reasons (e.g. illness or
scheduling conicts). The mean participation rate was 4.3 modules
(n 104).
Table 3 displays the baseline characteristics of the patients. All
characteristics were similar between groups. The patients were
predominantly women caused by numerous participation of
certied Breast Units at hospitals. This also explains the high
prevalence of breast cancer patients. However, in total patients
with 29 tumour entities participated in the study. The most prevalent comorbidity was depression. Most patients had already taken
measures against CRF like information or sports.
Primary outcome measure
Our ndings suggest that the study population was highly
fatigued at baseline, scoring 42.42 (SD 9.17) in the IG and 41.68
(10.13) in the CG on the FAQ scale ranging from 0 to 60 (Table 4).
Likewise, the mean visual analogue subscale values 8.03 (1.57) in
the IG and 8.09 (1.34) in the CG on a scale of 0e9 indicate severe
subjective CRF burden. The values of the fatigue subscale of the
QLQ-C30 conrm these results; they show a fatigue burden of 75.37

(19.39) in the IG and 73.29 (22.01) in the CG on a scale of 0e100

(Table 5).
In the IG, CRF was reduced to 22.85 (15.73) at t2. The CG showed
almost no change in CRF levels over time. In the repeated measures
ANOVA, this difference was statistically signicant for the group by
time interaction (F 76.51, p < 0.001). The partial h2 of 0.248
indicates a large effect. All subscales of the FAQ achieved statistically signicant effects with partial h2 ranging from 0.09 (the
smallest effect in insomnia) to 0.238 (the largest effect in physical
fatigue) (Table 4).
Secondary outcome measures
The changes in the quality of life questionnaire QLQ-C30 indicate a signicant improvement in the global health status in the IG
compared to the CG (Table 5). All functional and symptom scale
values as well as single items values increased signicantly. The
largest effect could be seen in the fatigue subscale: the IG showed
a reduction from 75.37 (19.39) to 40.74 (30.60) while the values in
the CG remained about the same (F 57.837, partial h2 0.2,
p < 0.001). This nding conrms the results of the FAQ.
Self-efcacy was improved signicantly by the intervention, in
the general scale (Table 6) as well as in the physical exercise scale
(Table 7). However, physical exercise self-efcacy declined in the
CG over time, in the total scale as well as in all subscales. A similar
effect was found in the changes in physical activity (Table 8). Total
activity improved in the IG but declined in the CG. The group
difference indicated a small effect (F 8.036, partial h2 0.033,
p < 0.001). All subscales of the FFKA showed signicant improvements. The largest effect could be seen in leisure activities, whereas
sports showed the smallest effect. The decline in self-efcacy and
physical activity in the CG might be explained by a lack of expectations that may have occurred in the CG while waiting for the
intervention.
Anxiety and depression could be reduced signicantly in the IG
(Table 9) while these parameters increased in the CG. The total

Table 9
Changes in Hospital Anxiety and Depression Scale (HADS).
Group

Anxiety scale (range: 0e21)

Depression scale (range: 0e21)
IG intervention group.
CG wait-list control group.
SD standard deviation.

IG
CG
IG
CG

Pre-intervention

Post-intervention

Follow-up at 6 months

Group  time

Mean (SD)

Mean (SD)

Mean (SD)

Group  time

9.16
9.51
8.32
8.71

6.73
9.47
6.09
8.77

5.32
9.81
5.04
8.86

33.194

<0.001

0.125

24.604

<0.001

0.096

(3.92)
(3.98)
(3.85)
(3.58)

(4.40)
(3.94)
(4.72)
(3.88)

(4.39)
(4.43)
(4.71)
(4.01)

Partial eta-squared

K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

211

Table 10
Changes in Fatigue knowledge test (F-WT).
Group

F-WT total score (range: 0e34)

IG
CG

Pre-intervention

Post-intervention

Follow-up at 6 months

Group  time

Partial eta-squared

Mean (SD)

Mean (SD)

Mean (SD)

Group  time

21.25 (5.12)
21.56 (5.79)

28.12 (4.77)
21.74 (5.95)

28.30 (4.89)
22.59 (6.12)

55.157

<0.001

0.192

IG intervention group.
CG wait-list control group.
SD standard deviation.

score of the Fatigue Knowledge Test showed an improvement in the

IG from t0 to t1 and remained roughly on this position until t2,
whereas the knowledge gain in the CG remained minimal, indicating a signicant difference (Table 10).
Discussion and conclusion
This trial, designed and reported to meet CONSORT requirements (Schulz et al., 2010), introduces an education program for
fatigued cancer patients following therapy completion. In the
evaluation, the newly developed program FIBS proved superior to
standard information and care for patients on a wait-list. At baseline, participating patients were suffering from severe symptom
burden, and the majority of patients had already made multiple
attempts to combat fatigue.
Strengths and limitations
The major strengths of this study were the well-balanced
distribution of demographic and clinical characteristics at baseline in both groups and the low dropout/withdrawal rate. All
patients who attended the sessions completed the questionnaires.
Moreover, patients with a wide range of educational backgrounds
participated in the study.
As a major limitation, the lack of blinding may have biased
estimated intervention effects, especially since the outcome variables were patient-reported. CRF is recognized as a subjective
experience. It can be described most accurately by patient selfreport, and there are no objective measures of this variable.
Therefore, the results were susceptible to bias based on changes in
perception of the symptom. However, additional objective data can
be useful in the assessment of subjective symptoms. The inclusion
of the MET calculation can thus be seen as a strength of the study.
Another limiting factor may be the wait-list control design. The
current study is not able to discern specic therapeutic factors
operating in the patient education from general factors like social
interaction. The inclusion of comparison groups receiving the same
time and attention in future studies may help tease apart these
factors. On the other hand, some authors state that the true benet
of the educational interventions may be difcult to detect when the
control group is getting aid beyond standard care (Lagger et al.,
2010).
For future research using behavioural measures to determine
compliance with the intervention could be helpful. Implementation
delity is dened as the degree to which an intervention was
implemented as it was prescribed by the program developers.
Fidelity could be measured through self-report, ratings, and direct
observation and coding of audio- and video-tapes of actual
encounters, or patient interaction in terms of adherence to the
curriculum, dose or amount of program delivered, and quality of
delivery.
Under health economical aspects it could further be interesting
if the programme needs to be the current length or could be
shortened. Few people dropped out of the intervention group

suggesting they were nding it benecial. However, we are not able

to make statements about which modules would be essential and
which redundant because the uctuation of the participants was
unsystematic. As far as possible we tried to nd out the reasons
why patients dropped out or did not attend all sessions. No patient
reported that the content, length or number of sessions were
negative. There were other reasons like personal problems with
time schedules. On the contrary, most patients found that the
seminar was too short.
Maybe answering the question of minimum effective dose of
patient education could be an interesting issue for further
research e and we already tried to evaluate this in asthmapatient-education (de Vries et al., 2008).
Discussion
Treatment options for fatigued patients offered in medical care
are often insufcient and especially the psychosocial components
are often not addressed adequately. Survivors suffering from CRF
are a largely unrecognized and undertreated group.
Other intervention trials specic for fatigue generated similar
effects like our trial but they were conducted during cancer treatment. In 5 studies identied by a systematic review (Goedendorp
et al., 2009), 4 trials achieved a signicant effect in CRF (Armes
et al., 2007; Barsevick et al., 2004; Ream et al., 2006; Yates et al.,
2005). However, in only 2 of these studies the effect could be
maintained to follow-up. In contrast to our study, they were brief
interventions (3 sessions) and were administered individually, but
the contents were similar (information, self-care, activity
management, balancing between activities and rest). The study
without a signicant effect was probably underpowered (Godino
et al., 2006).
Studies evaluating educational interventions in cancer survivors
are rare and often utilize a general approach for quality of life, not
including fatigue as an outcome variable (Meneses et al., 2007;
Owen et al., 2005). In a trial with a fatigue endpoint, the CG
received standard print material, IG group 1 an additional peermodelling videotape, and IG 2 an additional videotape, two
sessions with a trained cancer educator, and informational workbook. IG 1 improved in fatigue signicantly at 6 months compared
to the CG (Stanton et al., 2005). Another study applied a cognitivebehavioural therapy approach resulting in small to medium effects
on CRF (Dolbeault et al., 2009). Both interventions differed significantly from our study as they focused on different techniques.
Our study adds a patient education program for cancer survivors. The efcacy of the program can be explained by multiple
factors.
 FIBS was designed to reduce CRF in cancer patients. In studies
identied by a Cochrane review (Goedendorp et al., 2009),
specic interventions for CRF had a higher probability of being
effective compared to interventions not specic for CRF.
 FIBS was composed of CRF specic strategies that were
assumed effective as mentioned in the NCCN guideline

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K. Reif et al. / European Journal of Oncology Nursing 17 (2013) 204e213

(National Comprehensive Cancer Network, 2011) and in

recommendations from the Oncology Nursing Society
(Mitchell et al., 2007).
 Advice on social support and support from other patients can
be a helpful component of effective interventions for CRF (Fors
et al., 2010) and was therefore included in the FIBS program.
The sessions were designed so that patients could learn from
each other.
 As depression is a major factor frequently associated with CRF
(Jacobsen et al., 2003), advice on strategies to overcome
depressive periods may have helped to ameliorate depressive
symptoms as well as affective fatigue.

Study protocol
The study protocol has been published (Stuhldreher et al., 2008).
Registration
The trial was registered with ClinicalTrials.gov (Identier:
NCT00552552).
Statement

Conclusion

I conrm all patient/personal identiers have been removed or

disguised so the patient/person(s) described are not identiable
and cannot be identied through the details of the story.

Our education program designed for cancer survivors after

treatment had a positive impact on perceived fatigue and other
secondary variables. The effect could be maintained 6 months
following participation.

Acknowledgements

Practice implications
The program FIBS has aroused considerable interest by cancer
patients in Germany, since there is currently no other treatment
available. The results show that FIBS has the potential to ll this
gap. As the program was implemented for both sexes, for adults at
a wide range of ages, many cancer entities, and at levels of fatigue
from mild to severe, the results indicate that the entire range of
fatigued cancer survivors may benet from FIBS. Therefore, FIBS is
supposed to be a complementary intervention to individual counselling for fatigue.
Counselling centres, cancer centres or specialized clinics could
provide the program. In our opinion, the course can be best carried
out by experienced oncology nurses, but also other health professionals like psychologists, physiotherapists or doctors can be
perfect trainers. The qualications of trainers depends less on their
profession than on personal suitability in dealing with cancer
patients and management of patient groups.
We developed a train-the-trainer seminar which is a prerequisite for all FIBS trainers. In our study, usually one trainer held the
program, but also other options were allowed, such as one trainer
in charge and additional trainers for special themes.
FIBS should be translated and evaluated in other countries than
Germany, including a control group receiving the same time and
attention like the intervention group.
Ethical approval
The study has been approved by the ethics committee of the
University of Bremen (Germany).
Funding
The study was funded from 2007 to 2010 by the German Federal
Ministry of Education and Research (FKZ: 01GT0605). The sponsor
was not involved in decisions about the study design; the collection, analysis and interpretation of data; the writing of the report;
or in the decision to submit the paper for publication.
Competing interests
The authors KR, UdV, FP, and SG declare no conict of interest.
The authors disclose no nancial and personal relationships with
other people or organisations that could inappropriately inuence
(bias) our work.

The authors would like to thank the members of the Bremer

Krebsgesellschaft e.V. for their practical support in realizing the
initial idea and implementing the program. We would like to thank
all other participating centres as well: Brandenburgische Krebsgesellschaft, Bayerische Krebsgesellschaft, Universittsklinikum Jena,
Universittsklinikum Greifswald, Klinik fr Tumorbiologie in Freiburg, Klinikum Hanau, Klinikum Region Hannover, Krankenhaus
Ludmillenstift in Meppen, Praxis Phoenix in Neustadt am
Rbenberge.
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