Effectiveness and cost-effectiveness of meaning-centered group psychotherapy in cancer survivors: protocol of a randomized controlled trial

This study is a prospective randomized controlled trial with three study arms: MCGP-CS, SGP and CAU. Cancer survivors are recruited in two different ways: via several hospitals in the Netherlands (region Leiden and Amsterdam) and via public media (i.e. advertisement on websites of patient societies, and in magazines and local newspapers). All cancer survivors who meet in- and exclusion criteria are asked to participate. Survivors are assigned through cluster randomisation to one of the three study arms. The baseline assessment takes place before randomisation, with follow up assessments one week post-intervention and at 3, 6 and 12 months follow-up. Reasons for dropout are registered. The study protocol, information brochure, questionnaires and informed consent form are approved as a multicenter study by the Medical Ethics Committee of the Leiden University Medical Center. The design is illustrated in Figure 1.

The criteria are ascertained during a telephonic interview by a trained psychologist.

A study specific questionnaire comprises questions about sociodemographic (age, gender, religious background, marital status, family situation, education level, other important life events in the past 2 years) and clinical characteristics (type of cancer, cancer treatment, time since treatment) and will be filled out by participants at the first assessment, at baseline. Participants are asked which study-condition has their preference; this will not influence the assignment to the conditions.

Cancer survivors who meet the inclusion criteria and sign the informed consent, are allocated to a group. When the group counts 8 survivors, the group is randomly assigned by an independent researcher, through blocked randomization with randomly selected block sizes, to one of the three study arms.

Cancer survivors in the experimental study arm participate in MCGP-CS. The main purpose of the MCGP-CS is to sustain or enhance a sense of meaning or purpose in the patient’s life, in order to cope better with the consequences of cancer. MCGP-CS is a manualized 8-week intervention that makes us of didactics, group discussion and experiental exercises that focus around themes related to meaning and cancer survivorship. The sessions take two hours each and are held weekly. The participants use a workbook (called Life lessons portfolio) and get homework assignments every week. MCGP-CS is led by one psychotherapist with experience in treating patients with cancer. Each session addresses a specific theme that is related to the concepts and sources of meaning. The themes of the sessions are: 1. Concept and sources of meaning, 2. Meaning before and after cancer, 3. The story of our life as a source of meaning: what made us who we are today, 4. The story of our life as a source of meaning: things we have done and want to do in the future, 5. Attitudinal sources of meaning: encountering life’s limitations, 6. Creative sources of meaning: responsibility, courage and creativity, 7. Experiental sources of meaning, 8. Termination: presentations of our life lessons and goodbyes. Table 1 gives an overview of the themes of each session.

The control condition is an 8-week social support group following Payne et al. [24]. The sessions take two hours and are held weekly. Each group is supervised by a psychotherapist with experience in treating patients with cancer. The psychotherapist has an unconditionally positive regard and empathetic understanding, stimulates patients to actively share their experiences, and focuses on positive emotions, and expression of feelings.

Each of the 8 sessions has a different theme, which is mentioned at the beginning of the session. The themes of the sessions are: 1. group members’ introductions, 2. need for support, 3. coping with medical tests and communicating with physicians, 4. coping with family and friends, 5. coping with work issues, 6. coping with body image and physical functioning, 7. coping with the future, 8. termination: where do we go from here? Table 1 gives an overview of the themes of each session.

Cancer survivors assigned to the CAU study arm do not participate in one of the group interventions. If a patient in the CAU study arm asks the researcher for psychological help, he or she is referred to their General Practitioner (GP). Health care uptake is closely monitored, to enable detailed post-hoc description of what CAU entailed exactly.

In the MCGP-CS and the SGP study arms, after each session, the psychotherapist writes a short summary of the session where he/she notes whether the protocol was followed. All group sessions are audio taped and randomly selected audio fragments will be analysed by the researchers to establish whether the therapy protocol was followed correctly.

Outcomes measures include questionnaires on meaning, quality of life, anxiety and depression, hopelessness, optimism, mental adjustment to cancer, satisfaction with the intervention, and sociodemographic and clinical characteristics. Furthermore, a cost-evaluation will be carried out. Patients can choose to complete questionnaires online or via pen and paper. Primary outcomes are collected at all time points (baseline, after one week, 3, 6, and 12 months). Secondary outcome measures are collected at baseline, after one week, 3 and 6 months. Cost evaluation outcomes are collected at baseline, after 3, 6, and 12 months). A complete overview of the outcome measures is presented in Table 2 .

A validated Dutch version of the Hospital Anxiety and Depression Scale (HADS) is used to assess emotional distress. The HADS is a 14-item self-assessment scale for measuring distress with two subscales, anxiety and depression. The HADS was specifically designed for use in the medically ill. The total HADS score ranges from 0 to 42, the subscales from 0 to 21. A score of >15 is used as an indicator of a high level of psychological distress [30].

The Dutch Beck Hopelessness Scale (BHS) is a 20 item self-assessment scale for measuring hopelessness. The scale consists of 20 statements about oneself which are endorsed as true or false. The content of 11 statements is hopeless, the content of 9 statements is hopeful [31, 32].

The Dutch Life Orientation Test (LOT-R), is a 10-item self-assessment scale for measuring optimism. The scale consists of 10 statements about oneself which are endorsed on a 5-point likert scale (from 1 totally disagree to 5 totally agree) [33, 34].

Cognitive and behavioural response to cancer diagnosis and treatment is determined by the Mental Adjustment to Cancer (MAC) questionnaire. The MAC scale comprises five subscales: Fighting Spirit, Helplessness/Hopelessness, Anxious Preoccupation, Fatalism and Avoidance [20].

At T1, cancer survivors in both the MCGP-CS and SGP study arms are asked to evaluate the strengths and weaknesses of the group training that they received and rate their satisfaction with the content, duration, and quality of the training and the trainers on a 15 item likert-scaled questionnaire and on free text responses. Participants in the MCGP-CS condition are asked three additional evaluation questions about the specific content of the MCGP-CS protocol (their opinion on talking about meaning, the homework assignments and the workbook).

Direct medical and direct non-medical cost data are collected with the Trimbos and iMTA questionnaire on Costs associated with Psychiatric illness (TiC-P) [35, 36]. Unit resource use (GP visits, hospital days, etc.) will be multiplied by their appropriate integral cost prices.

An economic evaluation regarding work (loss) and health care use will be conducted as a cost-utility analysis for (changes in) health-related quality of life as assessed with the EQ-5D [37].

Indirect non-medical cost data related to production losses through work loss days and work cutback days will be sampled with the appropriate PRODISQ modules [38]. Indicators of return to work (RTW) are: Time to partial and to full RTW, meaning number of calendar days between end of treatment and first day at work; Time to full RTW corrected for partial RTW.

Based on a priori power analyses for hierarchical multiple regression, assuming a power of .80, Cohen’s d of .80 and alpha of .05, each study condition will need at least 43 cancer survivors. We will anticipate for loss to follow-up of 30%, and will therefore need 56 cancer survivors per condition at baseline. In total, we will recruit 168 cancer survivors during an inclusion period of 2.5 years.

Descriptive statistics, t-tests and Chi² tests will be used to determine whether patient characteristics are similar across experimental conditions. Results will be reported on an intention-to-treat basis. The Linear Mixed Modeling (LMM) procedure will be used to estimate missing values. This procedure includes incomplete cases in the analysis and employs restricted maximum likelihood estimation to calculate parameter estimates. LMM assumes that missing data are missing at random. LMM will be used to investigate the longitudinal development of meaning making in the three groups. The effect of study condition will be tested using contrasts within the LMM. Mediation analyses [39, 40] will be used to test as whether development in the patients’ meaning making explains/mediates the expected improvement in psychological functioning in the MCGP condition.

For the economic evaluation we will make use of the pertinent guidelines [36, 41‐43]. The societal perspective will be taken encompassing intervention costs, direct non-medical costs and indirect costs. The latter is not expected to be very important in the studied population, which is characterised by unemployment, but the data on production losses will be collected anyway. Production losses will be economically valuated using the friction cost method [44]. Costs and effects will be analysed simultaneously, incremental cost-effectiveness ratios (ICERs) will be calculated and placed within 95% confidence intervals, 2,500 bootstrap replications of the ICERs will be projected on a cost-effectiveness plane, ICER acceptability curves will be plotted against different willingness-to-pay ceilings [45], 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 utility analysis.

This study is conducted in accordance with local laws and regulations. Eligible patients are fully informed about the study and asked to participate. The patients receive a patient information sheet and flyer and they are also informed by telephone about the implications of participation. Patients have ample opportunity to ask questions and to consider the implications of the study before deciding to participate. Patients provide written informed consent, compliant with the local and ethical regulations, before participation. Patients are allowed to withdraw from the study without giving a reason, at any time. The study protocol has been approved by the Medical Ethical Committee of Leiden University Medical Center, Leiden, The Netherlands.