STUDY PROTOCOLOpen Access
Stepped care targeting psychological distress in
head and neck and lung cancer patients: a
randomized clinical trial
Anne-Marie H Krebber1, C René Leemans1, Remco de Bree1, Annemieke van Straten2, Filip Smit6,7, Egbert F Smit3,
Annemarie Becker3, Guus M Eeckhout4, Aartjan TF Beekman4, Pim Cuijpers2
and Irma M Verdonck-de Leeuw1,2,5*
Background: Psychological distress is common in cancer survivors. Although there is some evidence on
effectiveness of psychosocial care in distressed cancer patients, referral rate is low. Lack of adequate screening
instruments in oncology settings and insufficient availability of traditional models of psychosocial care are the main
barriers. A stepped care approach has the potential to improve the efficiency of psychosocial care. The aim of the
study described herein is to evaluate efficacy of a stepped care strategy targeting psychological distress in cancer
Methods/design: The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care
intervention programme versus care as usual. Patients treated for head and neck cancer (HNC) or lung cancer (LC)
are screened for distress using OncoQuest, a computerized touchscreen system. After stratification for tumour (HNC
vs. LC) and stage (stage I/II vs. III/IV), 176 distressed patients are randomly assigned to the intervention or control
group. Patients in the intervention group will follow a stepped care model with 4 evidence based steps: 1. Watchful
waiting, 2. Guided self-help via Internet or a booklet, 3. Problem Solving Treatment administered by a specialized
nurse, and 4. Specialized psychological intervention or antidepressant medication. In the control group, patients
receive care as usual which most often is a single interview or referral to specialized intervention. Primary outcome
is the Hospital Anxiety and Depression Scale (HADS). Secondary outcome measures are a clinical level of depression
or anxiety (CIDI), quality of life (EQ-5D, EORTC QLQ-C30, QLQ-HN35, QLQ-LC13), patient satisfaction with care
(EORTC QLQ-PATSAT), and costs (health care utilization and work loss (TIC-P and PRODISQ modules)). Outcomes are
evaluated before and after intervention and at 3, 6, 9 and 12 months after intervention.
Discussion: Stepped care is a system of delivering and monitoring treatments, such that effective, yet least
resource-intensive, treatment is delivered to patients first. The main aim of a stepped care approach is to simplify
the patient pathway, provide access to more patients and to improve patient well-being and cost reduction by
directing, where appropriate, patients to low cost (self-)management before high cost specialist services.
Trial registration: NTR1868
Keywords: Cancer, Distress, Anxiety, Depression, Psychosocial care, Stepped care, Screening, Quality of life, Efficacy
* Correspondence: email@example.com
1Department of Otolaryngology/Head and Neck Surgery, VU University
Medical Center, Amsterdam, the Netherlands
2Department of Clinical Psychology, VU University, Amsterdam, the
Full list of author information is available at the end of the article
© 2012 Krebber et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Krebber et al. BMC Cancer 2012, 12:173
Every year more than 14,000 patients are diagnosed with
cancer, of whom 11,470 with lung cancer (LC) and 2,870
with head and neck cancer (HNC) in the Netherlands
. Five-year survival rates are estimated at 13% in LC
and 50% in HNC. Approximately 80% of the LC patients
are male compared to 65% of the HNC patients. Patients
often have to deal with devastating side effects of initial
treatment (surgery, radiotherapy, and/or chemotherapy),
such as pain, fatigue, and respiratory, speech and swal-
lowing problems, negatively affecting health-related
quality of life and associated with increased levels of psy-
chological distress. Co-morbid anxiety or depression is
present in 20-30% of LC and HNC patients [2-4]. During
the first year after treatment there is a gradual improve-
ment of psychological functioning [5,6] but many
patients continue to suffer from or develop anxiety or
Because of the overwhelming evidence of psycho-
logical distress in LC and HNC patients, intervention is
recommended in national guidelines. Some recent
reviews have shown evidence on efficacy of psychosocial
intervention in cancer patients in general [10,11]. Others
question evidence mainly because randomized trials are
scarce [12,13] and because most studies included all
patients even those without symptoms of depression and
anxiety. Furthermore, it appears that most intervention
studies are applied in patients with breast cancer.
Patients with less prevalent tumours such as HNC or
poor survival rates as in LC are often not involved, while
LC and HNC patients are among the most distressed
patients compared to cancer patients in general .
In clinical practice at present, many cancer patients
who report high levels of psychological distress are not
taking advantage of psychosocial care [14,15]. Barriers to
admission to adequate psychosocial care are a lack of ad-
equate screening of anxiety and depression in the often
very busy oncology settings, reluctance by patients to be
referred because of the already long treatment period,
and that traditional models of the delivery of psycho-
social care cannot meet current demand. Other forms of
delivery, such as brief therapies, group treatments and
self-help, and a stepped care approach may provide
useful alternatives. Studies regarding cost-effectiveness
of psychosocial intervention in cancer patients are
Stepped care algorithms are based on clinically proven,
best-practice pathways to care over a series of steps,
while taking into account patients’ preference . The
steps involve watchful waiting, guided self-help and
other brief therapies, followed by more intensive psycho-
logical interventions or medication. In stepped care, more
intensive treatments are generally reserved for people who
do not benefit from simpler first-line treatments, or for
those who can be accurately predicted not to benefit from
such treatments. The results of treatments and decisions
about treatment provision are monitored systematically,
and changes are made (‘stepping up’) if current treatments
are not achieving a significant health gain . Stepped
care models have been developed for several health
problems, including smoking, back pain, alcohol treat-
ment, migraine, anxiety, eating disorders, methadone
maintenance, and depression .
The main goal of the proposed study is to assess effi-
cacy of a stepped care strategy compared to care as
usual in patients with psychological distress after treat-
ment for LC or HNC to improve psychological distress
and thereby quality of life.
In this prospective randomized controlled trial in two
parallel groups, patients are recruited by screening all
LC and HNC patients, who visit the Department of Pul-
monary Diseases or the Department of Otolaryngology
and Head and Neck Surgery of the VU University Med-
ical Center in Amsterdam, the Netherlands, for follow-
up consultation at least one month after treatment, for
distress using a computerized touch screen data collec-
tion system (OncoQuest) or by telephone using the Hos-
pital Anxiety and Depression Scale (HADS). All patients
who fulfil the in- and exclusion criteria are asked to par-
ticipate. After stratification for tumour site (LC vs.
HNC) and stage (stage I-II versus III-IV), 176 participat-
ing patients are randomly assigned to the intervention
or control group. In order to assess efficacy, assessment
before and after intervention takes place and at 3, 6, 9,
and 12 months follow up.
Inclusion criteria are: treatment for UICC stage I-IV
lung or head and neck carcinoma: ICD-10 C00-C14 (lip,
oral cavity and pharynx), C32 (larynx), C33 (trachea), C34
(lung); psychological distress or possible or probable cases
of depression or anxiety as assessed by the Hospital
Anxiety and Depression Scale (HADS; HADS-D>7
or HADS-A>7 or HADS-total>14).
Exclusion criteria are: other (neurological) diseases
causing cognitive dysfunction; no motivation to undergo
psychological therapy; current treatment for a depressive
or anxiety disorder; end of treatment for a psychiatric
disorder less than two months ago; high suicide risk;
psychotic and/or manic signs; too little knowledge of the
Dutch language to fill out the questionnaires.
Randomization is conducted centrally by an independent
statistician, in blocks of two, stratified for tumour site
Krebber et al. BMC Cancer 2012, 12:173
Page 2 of 8
(LC vs. HNC) and stage (stage I-II vs. III-IV), because
these variables have prognostic relevance and need to be
distributed evenly across both conditions.
Patients in the experimental study arm enter a stepped
care programme including 1) watchful waiting, 2) guided
self-help via Internet or a booklet, 3) face-to-face prob-
lem solving treatment, 4) specialised psychological inter-
ventions such as cognitive behavioural therapy and/or
The basic proposition of stepped care is that all
patients are offered the same low intensity (evidence-
based) treatment as a first step. Only those patients, who
do not recover, step up to a more intensive treatment.
The HADS score is used to determine stepped-up levels
of care. Stepping up to the next treatment level is indi-
cated when a participant’s HADS-A or HADS-D score
exceeds 7. The care coordinator controls the process,
monitors the symptoms, and makes sure the patient
steps up if necessary.
The stepped care programme in the present project
includes the following four steps.
Step 1: Watchful waiting
In the first step it is agreed on not to start intervention
yet, but to wait for further development of symptoms.
Because part of the patients recovers spontaneously 
‘watchful waiting’ is included in the multidisciplinary
guideline on depression as first treatment step. Duration
of the watchful waiting period in the present project in-
cluding cancer patients is set on 2 weeks.
Step 2: Guided self-help via Internet or a booklet
If there is no spontaneous recovery after 2 weeks, the
care coordinator contacts the patient for one counselling
session in which the self-help programme is introduced.
As intervention the existing programme “Allesondercon-
trole” or the web based programme “Allesondercontrole”
(http://allesondercontrole.psy.vu.nl) is used. “Allesonder-
controle” is a brief intervention for problem-solving based
on self-examination. “Allesondercontrole” is already avail-
able. The website is currently only used for research pur-
poses and both international and national research has
shown that this intervention is effective in depression and
anxiety . The intervention is based on problem-
solving therapy, which has been proven to be effective in
several randomized controlled studies , also when
delivered via the Internet. A recent meta-analysis by
our group found that the effects of Internet-based
treatments of depression and anxiety disorders are as
large as those of face-to-face treatments . The inter-
vention “Allesondercontrole” takes 5 weeks. In that period
respondents describe what they think is important in their
lives, make a list of their problems and concerns, and
divide these into three categories: unimportant problems
(problems which are not related to what is important in
their life), important and amenable problems (these are
solved through a six-step procedure of problem-solving),
and important but unsolvable problems (such as having a
serious disease like cancer); for each of the amenable pro-
blems the respondent makes a plan). Trained coaches
guide the patients through this process. The coaching
consists of brief, weekly contacts by email or by telephone,
which takes about 10 to 15 minutes per week. The total
coaching time is 1 to 1.5 hours per patient (estimation
based on our previous trial). Coaching is not aimed at
developing a patient-therapist relation but is only meant
to give support in working through the self-help method.
Step 3: Face-to-face problem solving treatment
When the patient has not recovered from the guided
self-help programme, a nurse from the department of
Psychiatry offers a brief intervention: Problem Solving
Treatment (PST). Earlier studies revealed that PST can
be delivered by psychologists as well as nurses [22-24].
PST identifies problems that interfere with everyday
functioning and that contribute to depression and anxiety.
The treatment provides compensatory strategies that
are designed to bypass the person's cognitive limitations
and to improve adaptive functioning. PST comprises a
short 6-session protocolled intervention. The first session
takes 1 hour, the other sessions 45 minutes. PST is an
evidence-based intervention for major depression and
for psychological distress characterised by symptoms of
depression and anxiety [22,23,25-28].
Step 4: Specialised psychological interventions such as
cognitive behavioural therapy and/or antidepressant
In case all previous steps have not induced recovery, the
patient chooses in close cooperation with the care co-
ordinator between medication and psychotherapy. To
ease this decision, the patient is offered the patient
information letter of the Dutch College of General
Practitioners on antidepressant medication. (A) If the pa-
tient chooses medication, the care coordinator contacts
the patients’ physician who prescribes antidepressant
medication and monitors outcomes. (B) If the patient
chooses psychotherapy, the patient is referred to a psych-
ologist or a psychiatrist. The stepped care programme is
illustrated in Figure 1.
Care as usual
Control group patients receive care as usual, which
often means a single interview by a nurse or specialised
intervention delivered by a social worker, psychologist
or psychiatrist. In the context of the health economic
Krebber et al. BMC Cancer 2012, 12:173
Page 3 of 8
evaluation, health care uptake is closely monitored, thus
allowing for detailed post-hoc description of what usual
care entailed exactly.
Main outcome measure
The primary outcome measure is the Hospital Anxiety
and Depression Scale (HADS). The Hospital Anxiety and
Depression Scale (HADS) is a 14-item self-assessment
scale for measuring symptoms of anxiety and depression
and has been specifically designed for use in the medical
ill. This scale has been proven to have adequate psycho-
metrical properties and the total HADS score has been
recommended for routine monitoring of psychological
distress in cancer patients [29-32].
Secondary outcome measures are health related qual-
ity of life questionnaires (EORTC QLQ-C30), EORTC
QLQ-HN35, EORTC QLQ-LC13), general patient satisfac-
tion (EORTC QLQ-PATSAT), and economic evaluation.
The EORTC QLQ-C30 is a tumour-specific, patient-
based questionnaire. The questionnaire includes a global
HRQOL scale (2 items) and comprises 5 functional
scales: physical functioning (5 items), role functioning
(2 items), emotional functioning (4 items), cognitive
functioning (2 items) and social functioning (2 items).
There are three symptom scales (fatigue (3 items), nausea,
vomiting (2 items) and pain (2 items) and 6 single items
relating to dyspnoea, insomnia, loss of appetite, constipa-
tion, diarrhoea and financial difficulties .
The EORTC QLQ-LC13 module covers specific issues
on lung cancer. The questionnaire comprises 12 symptom
scales: a 3 item scale on dyspnoea, and 1 item scales on
coughing, haemoptysis, sore mouth, dysphagia, peripheral
neuropathy, alopecia, pain in chest, pain in arm or shoul-
der, pain in other parts .
The EORTC QLQ-HN35 module covers specific issues
on head and neck cancer. It has been used previously in
studies. The questionnaire comprises 7 subscales: pain
(4 items), swallowing (5 items), senses (2 items), speech
(3 items), social eating (4 items), social contact (5 items)
and sexuality (2 items). There are 10 single items cover-
ing problems with teeth, dry mouth, sticky saliva, cough,
opening the mouth wide, weight loss, weight gain, use of
nutritional supplements, feeding tubes, and painkillers
The EORTC QLQ-PATSAT32 module is a patient sat-
isfaction with care measure. The questionnaire com-
prises 4 scales on interpersonal skills (3 items), technical
skills (3 items), information provision (3 items), and avail-
ability (2 items) of doctors, the same 4 scales regarding
Figure 1 Overview of the stepped care programme.
Krebber et al. BMC Cancer 2012, 12:173
Page 4 of 8
nurses, 1 scale on other hospital personnel kindness and
helpfulness, and information giving (3 items), 1 scale on
waiting time (2 items), 1 scale on access (2 items), and
3 single items on exchange of information, comfort/
cleanness, and general satisfaction .
The economic evaluation will be conducted as a cost-
utility analysis were outcomes are (changes in) health-
related quality of life at patient level. Health-related
quality of life is assessed with the EQ-5D [36,37] at base-
line and 12 months follow-up. Direct medical and direct
non-medical cost data are collected with the TIC-P ,
a widely used health service receipt interview in eco-
nomic evaluations. Unit resource use (GP visits, hospital
days, etc.) will be multiplied by their appropriate integral
cost prices . Indirect non-medical cost data related
to production losses through work loss days and work
cutback days will be sampled with the appropriate PRO-
DISQ modules .
Sociodemographic and medical data
Next to the outcome measures, a case record form is
developed including sociodemography (age, gender, social
economic status), cancer and cancer treatment (TNM and
ICD-10 classification, documentation of surgery and
(chemo)radiation), and co-morbidity (Adult Comorbidity
Evaluation 27 (ACE-27) test). The ACE-27 was designed
specifically for cancer patients and classifies patients
into 1 of 4 grades of comorbidity (none, mild, moderate,
The presence of a major depression or an anxiety disorder
is assessed according to the Composite International
Diagnostic Interview (CIDI). The CIDI is a comprehen-
sive, fully structured interview designed to be used by
trained lay interviewers for the assessment of mental dis-
orders according to the definitions and criteria of ICD-10
and DSM-IV. The diagnostic section of the interview is
based on the World Health Organization's Composite
International Diagnostic Interview [41-43].
Descriptive statistics will be generated for the range
of outcome variables, in particular to gauge whether
randomization resulted in a balanced distribution of
patients characteristics across the experimental conditions.
Repeated measures ANOVA will be used to determine
the efficacy of intervention for continuous outcomes
such as changes in HADS depression/anxiety symptom
severity. Longitudinal changes over time in these vari-
ables will also be evaluation over all time points simul-
taneously using generalized estimating equations (GEEs).
Analyses will be conducted in agreement with the
The economic data will be collected at baseline and
follow-up and conducted as a cost utility analysis that is
with health-related quality of life as the clinical end-
point. For the economic evaluation use will be made of
the pertinent guidelines [39,44-46]. In other words, ana-
lyses will be conducted in agreement with the intention-
to-treat principle; the societal perspective will be taken
encompassing intervention costs, direct non-medical
costs and indirect costs. Production losses will be eco-
nomically valued using the friction cost method .
The time horizon will be set at one year, and therefore
we will neither discount costs nor effects. Costs and
effects will be analysed simultaneously, incremental
cost-effectiveness ratios (ICERs) will be calculated and
placed within 95% confidence intervals, 2,500 boot-
strap replications of the ICERs will be projected on a
cost-effectiveness plane, ICER acceptability curves will be
plotted against different willingness-to-pay ceilings ,
and sensitivity analysis will be conducted as a matter of
course focussing on uncertainty in the main cost-drivers.
This will be done for the costs per QALY gained in a cost
Sample size calculation
To demonstrate an effect size of 0.50 (based on a meta-
analysis on psychological treatment in mild depression),
66 patients are needed in each group (power 80%, sig-
nificance level 5%) . Taking into account a dropout
of 25%, in total 176 patients will be included. With an
annual intake of 450 LC and HNC patients, 30% having
psychological distress, and 50% willing to cooperate, and
an inclusion period of 2.5 years, feasibility of the study is
There is a rising need towards screening for physical
and psychosocial problems and the need for supportive
care in routine clinical practice through patient-reported
outcomes (PRO’s) [50-54]. The use of PRO’s has proven
to facilitate communication concerning quality of life be-
tween patients and health care professionals [55-57]. Evi-
dence that this approach may influence patient outcome
or improve quality of life is scarce. Luckett and collea-
gues  recommend additional efforts to strengthen
the effects of screening, such as using more tumour
specific (instead of generic) PRO’s, improving the inter-
pretability of feedback for both medical staff and patients,
and training patients in self-efficacy. Organising support-
ive care according to the chronic care model  and pro-
viding evidence based supportive care can also improve
disease management in cancer patients.
Disease management refers to a system of coordinated
comprehensive care along the continuum of the disease
across health care delivery systems, with a specific focus on
Krebber et al. BMC Cancer 2012, 12:173
Page 5 of 8
self-management. Other forms of providing supportive care
comprise integrated care, transmural care, collaborative
care, case management, and stepped care. In oncological
settings, recent projects as “Supporting transmural onco-
logical care”  and “Integrated care”  revealed that
supportive care coordination improves supportive care de-
livery in cancer patients. A review on professional patient
navigation in head and neck cancer patients showed that
the presence of a professional care navigator leads to higher
patient satisfaction, shorter duration of hospitalization,
fewer cancer-related problems, better emotional quality of
life, and patient empowerment .
At present, in VU University Medical Center in
Amsterdam, The Netherlands, efficient structured moni-
toring of quality of life by a touchscreen computer-based
data collection system “OncoQuest” is implemented in
routine clinical practice [15,62]. Patients can independ-
ently fill in the EORTC QLQ-C30, and tumour specific
modules, and the Hospital Anxiety and Depression Scale
(HADS) on a touchscreen. It takes on average 9 minutes
to complete the questionnaires. Data are processed in
real-time and care providers can watch the results by clear
charts (the well-being profile) on a computer in their con-
sulting rooms and, if indicated, set up a custom-made
supportive care plan. Nurses are trained as care navigators
to arrange the supportive care according to the disease
From an economic perspective and in an age of increas-
ing numbers of cancer survivors and increasing shortages
of health care personnel, it is relevant to integrate cost-
effective health care options including e-health applica-
tions into a stepped care approach, as in the presented
RCT. This fits right in with the importance that patient
organizations, policy makers and researchers currently
attach to e-health self-management tools.
Beside assessing overall efficacy of a stepped care ap-
proach targeting psychological distress in cancer patients,
also insight will be obtained into possible determinants
of the need for psychosocial care and success of a
stepped care approach. These possible determinants in-
clude sociodemographic and disease and treatment related
parameters, comorbidity, and quality of life.
Knowledge transfer of the results of the project on
efficacy of stepped care targeting psychological distress
in cancer patients into the scientific community includes
submitting papers to (inter)national peer-reviewed jour-
nals, proceedings, and news letters and presenting papers
at national and international conferences, both in early
pilot stages and after conclusion of the project.
In case of positive results of this RCT on effectiveness,
a second step aims at adaptation and maintenance of the
stepped care approach to bring the evidence-based
practice regarding improving distress in cancer patients
into consistent and appropriate use in all oncological
centers in the Netherlands. A sharing mechanism will be
designed to facilitate adaptation and maintenance such as
informing the Dutch Lung Cancer Study Group, Dutch
Society of Pulmonologists (NVALT), Netherlands Society of
Otorhinolaryngology and Cervico-Facial Surgery, Dutch
Head and Neck Oncology Cooperative Group (NWHHT),
Dutch Society of Psychosocial Oncology, oncological and
psychiatric nursing societies and patient societies, to struc-
ture the results of this project into implementation projects
in all oncological centers throughout The Netherlands.
Guideline committees will be informed and advised to
adapt the Nation-wide Guidelines on Laryngeal (2010,
version 3.0), Lung (2004, version 1.0), Oral Cavity and
Oropharyngeal (2004, version 1.4) and Hypopharyngeal
(2010, version 2.0) Cancer [63-66].
The bottom line of the stepped care approach is
healthier patients, more satisfied care providers, and cost
savings by empowering both professionals and patients.
This study is conducted in accordance with the Declaration
of Helsinki and in accordance with local laws and regula-
tions. Eligible patients are fully informed about the study
and asked to participate. The patients receive a patient in-
formation sheet and have ample opportunity to ask ques-
tions and to consider the implications of the study before
deciding to participate. Patients consent is noted on an
informed consent form compliant with the local and
ethical regulations. If during the study the patient for
whatever reason no longer wishes to participate, the pa-
tient is allowed to withdraw his consent at any time. The
study protocol has been approved by the Medical Ethical
Committee of VU University Medical Center, Amsterdam,
The authors declare that they have no competing interests.
CRL, RB, AS, FS, PC, and IMVL contributed to the design of the study. The
study is being coordinated by AMHK and IMVL. The present manuscript was
drafted by AMHK en IMVL. All authors contributed to critical revision of the
manuscript. All authors read and approved the final manuscript.
The study is funded by The Netherlands Organisation for Health Research
and Development, grant-number 300020012.
1Department of Otolaryngology/Head and Neck Surgery, VU University
Medical Center, Amsterdam, the Netherlands.2Department of Clinical
Psychology, VU University, Amsterdam, the Netherlands.3Department of
Pulmonary Diseases, VU University Medical Center, Amsterdam, the
Netherlands.4Department of Psychiatry, VU University Medical Center,
Amsterdam, the Netherlands.5Department of Otolaryngology / Head and
Neck Surgery, VU University Medical Center, PO BOX 70571007 MB,
Amsterdam, The Netherlands.6Trimbos Institute, Netherlands Institute of
Mental Health and Addiction, Utrecht, The Netherlands.7Department of
Epidemiology and Biostatistics, EMGO Institute for Health and Care Research,
VU University Medical Center, Amsterdam, The Netherlands.
Krebber et al. BMC Cancer 2012, 12:173
Page 6 of 8
Received: 31 January 2012 Accepted: 3 May 2012
Published: 10 May 2012
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Cite this article as: Krebber et al.: Stepped care targeting psychological
distress in head and neck and lung cancer patients: a randomized
clinical trial. BMC Cancer 2012 12:173.
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