Personalising Psychotherapy for Chronic Primary Pain Using Network Analysis

Study Overview
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Brief Summary
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The goal of this single case experimental design study with multiple baselines is to use network analysis to personalise cognitive behaviour therapy for chronic primary pain (CPP) and base the selection of individual treatment targets and interventions on data to avoid cognitive biases of the clinicians. The main questions it aims to answer are: Is the study procedure accepted by and feasible for CPP patients as well as their therapists? Does the personalised psychotherapy with databased clinical decisionmaking lead to significant improvement? Participants will go through several study phases: Pretest and informational meeting with study management Baseline 1: answering a questionnaire six times a day for 21 days in daily life on their mobilephone (EMA); this data will be used for the calculation of a network for each participant, that in turn will be used to select the treatment target and according treatment intervention as suggested by an algorithmic decisiontool Probatory therapy phase: three weekly sessions with therapist; questionnaire three times a week Baseline 2: questionnaire three times a week Therapy phase: up to ten sessions with therapist; questionnaire three times a week Post phase: posttest, two weeks of three weekly assessments, then another 21 days EMA; two monthly booster sessions with therapist Follow-up: posttest and meeting with study management

Detailed Description
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Background and aims: The treatment of chronic primary pain (CPP) with Cognitive Behaviour Therapy (CBT) is effective, yet effects remain small to moderate. New approaches to the treatment of CPP are needed. They should include an orientation toward processes instead of symptoms and strategies for personalisation. This paradigm shift requests precisce, testable models that allow to link treatment procedures to psychological changes. Unfortunately, current models are rather vague about specific, especially temporal pathways by which its elements interact, or the pathways are not as simplistic as proposed. Therefore, multiple variables and pathways related to the development and persistence of pain-related disabilities should be considered. One approach to individualisation makes use of repeated measures in the daily lives of patients, which enable the usage of network analysis to investigate interactions between symptoms/processes of a patient. Process-oriented, individualised, network-based therapy for CPP (POINT Pain) combines process-oriented measurements to individualise therapy with network-based analysis approaches for target and treatment selection. We propose the following hypotheses: In line with previous research, we assume that the implementation of POINT Pain is feasible for and accepted by patients as well as therapists. Feasibility and acceptance are indicated by mean ratings of at least 3.5 out of 5 across all items of one scale (each rated on 1-5 Likert scales) on a feedback form developed for this study and by positive comments to open ended questions. Furthermore, we expect POINT Pain to lead to clinically significant improvements as compared to baseline, i.e. decreasing scores in the outcome measures. According to current recommendations, the improvement will be operationalised as effect-size estimated with Hedge's g, the significance with Tau-z. Procedure: Before participants are enrolled in the study, they will have two sessions with the study management for diagnostics, pretest, and individualisation of and instructions to the questionnaire. An ABA'C Multiple Baseline design is chosen to evaluate the effect of individually selected therapy interventions: Firstly, a baseline assessment (A) is conducted over the period of 21 days six times per day using EMA. In the EMA, a previously validated and piloted questionnaire with items on treatment relevant pain processes is implemented. It contains processes derived from the most prominent psychological models of chronic pain, as there is no overarching theoretical framework adressing the interaction of multi-dimensional pain processes yet. For the EMA, the waking hours of the participants will be divided into six equal time intervals within which the signals for the questionnaires will be randomised (semi randomisation). After completion of phase A, an individual network will be computed. Secondly, the probatory phase (B) is initiated after completion of phase A. After this phase, an application for psychotherapy is sent to the patient's insurance agency. As much information is already available from phase A, phase B will comprise three sessions. Participants will switch from EMA to SCED assessment in phase B, which means they will answer the same questionnaire as before three times a week, two of which during the week and one on the weekend. The timepoints for the questionnaires will again be semi-randomised during the waking hours of the participants. This procedure stays the same for the remaining phases. As there is often a natural break between the probatory and the treatment phases due to the psychotherapy application, another baseline (A') is implemented after phase B. The duration of this second baseline will be semi-randomised between one and three weeks. There are several possibilities for the selection of the most relevant or central variable in a network. The clinical decision regarding treatment target and module will be based on an algorithmic decision-tool which will is programmed based on experts' ratings (see preregistration: https://doi.org/10.17605/OSF.IO/BNFWY). Possible interventions will be limited to a pre-defined intervention pool that was developed based on common therapy manuals for chronic pain. Therapist and supervisor can only rule out the module suggested by the algorithmic decision-tool if there are serious concerns regarding potential harms (e.g. red flags rule out exposure in vivo). At last, the treatment phase (C) is realised. The selected intervention is carried out until clinically significant improvement is reached or until a maximum of ten sessions has been conducted. For all assessments using the EMA questionnaire (i.e. phases A to C), the software m-Path (https://m-path.io/landing/) published by KU Leuven will be used. In addition to the aforementioned assessments, participants will complete traditional outcome measures at three timepoints, i.e. before phase A (pretest), after phase C (posttest), and three months after finishing phase C (follow-up). After phase C, participants will have two more weeks of SCED, after which they will undergo another EMA phase of 21 days with a frequency of six assessments per day in order to calculate a post-therapy network. During this study phase, two monthly booster-sessions with their therapist will take place, but there will not be any further intervention, only monitoring. The results of the weekly SCED assessments will be analysed in a timely manner and discussed with the participants regularly. Feasibility and acceptance will be evaluated post-treatment and at follow-up. A feedback form developed for this study will be used for quantitative and qualitative assessment. Participants: Patients will be recruited via the waiting list of the university's outpatient clinic, in cooperation with other currently running studies at the same university recruiting chronic pain patients, and via various media (e.g. newspaper articles) and doctors' offices. Study therapists will be recruited in the university's outpatient clinic as well. Inclusion criteria for patients are at least 18 years of age, having access to a smartphone, and the main diagnosis of chronic pain. The diagnosis will be checked using the brief version of the Diagnostic Interview for Mental Disorders (Mini-DIPS). For patients recruited via the waiting list, screening for suitability will take place during the first consultation at the university psychotherapy training centre's outpatient clinic. Suitable participants will be informed about the study and referred if they agree to be contacted. Furthermore, patients that had to be excluded from other currently running studies will be referred if they agreed to be contacted as well. Analysis: In the context of SCEDs, each individual can be analysed separately. Especially regarding the qualitative measurements (acceptance, feasibility), it can be assumed that a sample of twelve will lead to a saturation in obtainable answers. Thus, all hypotheses can be answered with a sample of twelve: (1) We can evaluate whether the study procedure is feasible and accepted by patients and therapists, and (2) within SCED clinically significant change can be evaluated per individual. Of course, SCED results will not be generalizable to other individuals.

Official Title
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Personalising Cognitive Behaviour Therapy for Chronic Primary Pain Using Network Analysis - A Single Case Experimental Design Study With Multiple Baselines

Conditions
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Chronic Primary Pain

Intervention / Treatment
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* Behavioral: Cognitive Behaviour Therapy including third-wave


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: main diagnosis of chronic pain (i.e. pain persists for at least 6 months and is the most prominent/most burdensome symptom) subjective impairment/disability (yes-no) access to a smartphone compatible with the app mPath Exclusion Criteria: acute hazard due to suicidality, substance abuse, and/or psychosis only migraine/headache or migraine/headache are the focus of pain analphabetism insufficient German knowledge current psychotherapy current participation in another intervention study physical inability to take part in therapy and study sessions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be allocated to one out of ten treatment modules according to their most relevant pain process. The same module will be used for the whole therapy phase if no adverse effects or long lasting non-response is observed. Only then can the participant be allocated to another treatment module.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exposure in vivo<br>The goal of the exposure in vivo treatment module is the correction of irrational, fearful beliefs regarding movements, a reduction of avoidance behaviours and hence a facilitation of activity levels. This will be done by carrying out feared, avoided movements and seeking out avoided situations and places. Exemplary units are the development of a movement hierarchy and protocols for exposure exercises. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Relaxation<br>Goal of the relaxation treatment module is the reduction of stress and tension, which will be achieved applying relaxation techniques such as Progressive Muscle Relaxation (PMR), breathing techniques, and imaginary methods. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Activity and Rest<br>The treatment module activity and rest is based on pacing and pursues the goal to balance active and resting phases. For overly active patients, the module will consist of implementing breaks and resting phases, while for overly resting patients the module will consist of graduated activity build-up. Acitivity protocols, plans, and exercises will be used. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Cognitive Coping with Pain<br>Goal of the treatment module cognitive coping with pain is the reduction of rigid, dysfunctional thought patterns by flexibilising them and implement functional thought patterns instead. It includes classical methods such as cognitive restructuring as well as meta-cognitive or defusion techniques. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Attention Control<br>The goal of the treatment module attention control is to enable patients to willingly draw their attention towards other entities as their pain or perceive their pain in a non-judgmental way, thus improve their coping strategies and enhance functioning levels. Exemplary units are the anti-pain diary or the distraction alphabet. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Activating Resources<br>The goal of the activating resources module is relief and a balance between unpleasant perceptions as pain and pleasent experiences. This will be achieved by reactivating lost resources and implementing new ones, e.g. social networks or hobbies. Exemplary units are the positive diary or focusing on healthy bodyparts. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Acceptance<br>Goal of the acceptance module is the flexibilisation of thought patterns by regaining mental resources through givign up inner resistance against the pain. Patients will be supported in developing an accepting attitude towards their suffering using working units like the monster by the wayside or concluding a peace treaty with oneself. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Values and Values-based Action<br>Goal of the treatment module values and values-based action is enhancing satisfaction with life and regaining action control. Patients will learn about their personal values and how they can align their actions with them. Exemplary units are sorting values, a value diary, or looking back on one's life. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Sleep<br>Goal of the treatment module sleep is enhancing the subjective sleep quality and increase the feeling of recovery. Patients will learn about sleep hygiene, stimulus control, and imaginary techniques such as the inner feel-good place. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|
| Experimental: Selfcompassion<br>Goal of the selfcompassion treatment module is the development of a benevolent, loving, and kind attitude towards oneself and one's suffering in order to enhance wellbeing and feelings of self-worth. Exemplary units are the selfcompassion break, writing a letter to oneself, or changing perspective. | Behavioral: Cognitive Behaviour Therapy including third-wave<br>* All treatment modules are based on evaluated treatment manuals and contain methods from Cognitive Behaviour Therapy including methods from the third wave like Acceptance and Commitment Therapy or Mindful Selfcompassion.<br>* Other names: Mindful Selfcompassion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ecological Momentary Assessment questionnaire | Throughout the whole study, the same questionnaire developed and in-evaluation for the use in Ecological Momentary Assessment will be applied. It assesses several therapy-relevant pain processes derived from common psychological models of chronic pain: catastrophising, avoidance, depression (Fear-Avoidance model, Avoidance-Endurance model); thought supression, task persistence, positive affect (Avoidance-Endurance model); acceptance, values (Psychological Flexibility); expectations (Predictive Coding); pain instenisty, pain-related disability (Pain Experience); pain self-efficacy, sleep disturbance, self-compassion. The individual primary outcome will be the most relevant process for each participant according to the network from the first baseline. | pre-intervention (two baselines), during intervention (on average 10 weeks + 3 weeks probatory phase), directly after intervention (2 weeks + 21 days) | 
| Pain Disability Index (PDI) | The Pain Disability Index assesses the daily disability caused by pain in seven areas: family/domestic duties, recovery, social activities, work, sexuality, self-care, and life-sustaining activities. It has shown to be a valid instrument, displaying moderate test-retest reliability. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 
| Quebec Back Pain Disability Scale (QBPDS) | The Quebec Back Pain Disability Scale will be adapted for chronic pain in general in this study. It assesses disability caused by pain in 20 activities relevant to everyday life. It displays sufficient validity and reliability. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity | Pain Intensity will be measured on an 11-point numerical analogue scale over a period of 24 hours. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 
| Short-Form McGill Pain Questionnaire (SF-MPQ) | The Short-Form McGill Pain Questionnaire contains of 15 items assessing different pain qualities on a 4-point scale: 11 items assess sensory pain experience, 4 affective pain experience. It also contains a measure of present pain. It is an instrument sensitive enough to detect treatment effects. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 
| German Pain Solutions Questionnaire (PaSol) | The German version of the Pain Solutions Questionnaire assesses different coping strategies for pain with 14 items on a 7-point scale: solving pain, meaningfulness of life despite pain, acceptance of the insolubility of pain, and belief in a solution. It displays good reliability and validity and is sensistive for change. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 
| Patient Global Impression of Change (PGIC) | One item will be used to assess subjective treatment effects with the Patient Global Impression of Change. It will be answered on a 7-point scale, ranging from no change to very much better. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 
| Pain Self-Efficacy Questionnaire | The Pain Self-Efficacy Questionnaire contains on 10 items using a 7-point scale. It was tested regarding comprehensibility and displays high reliability and validity. It also is sensitive to change. | Pre-intervention, Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 
| Acceptance and feasibility of study procedures (Feedback form developed for this study) | Acceptance of the study phases and feasibility will be measured with a feedback form developed for this study, using a 5-point Likert scale. | Post-intervention (directly after intervention), Follow-up (on average three months after intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Pain, Single Case Experimental Design, Ecological Momentary Assessment, Network analysis, Cognitive Behaviour Therapy