An Open Trial of Group Metacognitive Therapy for Anxiety and Depression in Cancer Survivors
Phase: NA
Conditions: Cancer, Anxiety, Depression, Quality of Life
Sponsor: University of Liverpool

AN OPEN TRIAL OF GROUP METACOGNITIVE THERAPY FOR ANXIETY AND 
DEPRESSION IN CANCER SURVIVORS (GMAC Study) 
 
 
19/07/2017 
 
MAIN SPONSOR: 
University of Liverpool 
Protocol number:  
2 
IRAS project ID:  
227681 
 
Study Team 
Chief Investigator: 
Dr Peter Fisher, University of Liverpool 
Co‐investigators: 
Dr Gemma Cherry, University of Liverpool  
Dr Angela Byrne, Royal Liverpool University Hospital/University of 
Liverpool  
Professor Adrian Wells, University of Manchester  
 
Sponsor 
The University of Liverpool is the research Sponsor for this Study.  
 
For further information regarding the sponsorship conditions, please contact: 
 
Alex Astor 
Head of Research Support – Health and Life Sciences 
University of Liverpool 
Research Support Office 
2nd Floor Block D Waterhouse Building 
3 Brownlow Street 
Liverpool L69 3GL 
sponsor@liv.ac.uk  
Telephone: 0151 7948739 
 
 
 
 
 

Page 2 of 15 
 
CONTENTS 
 
1. PROTOCOL APPROVAL/SIGNATURES  
 
 
 
 
 
4 
1.1 Chief Investigator 
 
 
 
 
 
 
 
 
 
4 
1.2 Protocol Authorised  
 
 
 
 
 
 
 
 
4 
 
2. STUDY SUMMARY 
 
 
 
 
 
 
 
 
4 
 
3. BACKGROUND 
 
 
 
 
 
 
 
 
 
5 
 
4. RATIONALE FOR CURRENT STUDY 
 
 
 
 
 
 
6 
 
5. STUDY OBJECTIVES 
 
 
 
 
 
 
 
 
7 
 
6. STUDY DESIGN 
 
 
 
 
 
 
 
 
 
7 
6.1. Design 
 
 
 
 
 
 
 
 
 
 
7 
6.2. Study Measures 
 
 
 
 
 
 
 
 
 
7 
6.3. Intervention 
 
 
 
 
 
 
 
 
 
8 
6.4. Study Duration 
 
 
 
 
 
 
 
 
 
8 
 
7. PARTICPANT ENTRY 
 
 
 
 
 
 
 
 
9 
7.1. Inclusion Criteria  
 
 
 
 
 
 
 
 
9 
7.2. Exclusion Criteria  
 
 
 
 
 
 
 
 
9 
7.3 Ineligible and non-recruited participants 
 
 
 
 
 
 
9 
7.4 Discontinuation of participants 
 
 
 
 
 
 
 
9 
 
8. ADVERSE EVENTS 
 
 
 
 
 
 
 
 
10 
8.1. Definitions  
 
 
 
 
 
 
 
 
 
10 
8.2. Reporting Procedures 
 
 
 
 
 
 
 
 
10 
 
9. STATISTICS AND DATA ANALYSIS 
 
 
 
 
 
 
10 
9.1. Sample size  
 
 
 
 
 
 
 
 
 
10 
9.2 Power calculation   
 
 
 
 
 
 
 
 
11 
9.3 Analysis plan  
 
 
 
 
 
 
 
 
 
11 
 
10. ETHICAL AND REGULATORY REQUIREMENTS 
 
 
 
 
11 
10.1. Ethical Approval  
 
 
 
 
 
 
 
 
11 
  10.2. Sponsorship and Indemnity  
 
 
 
 
 
  
 
11 
  10.3. Participant Information and Informed Consent 
 
 
 
 
 
12 
  10.4. Participant Confidentiality and Data Protection 
 
 
 
 
 
12 
  10.5. Protocol Amendments 
 
 
 
 
 
 
 
 
12 
10.6. Audit 
 
 
 
 
 
 
 
 
 
 
13 
10.7 Funding 
 
 
 
 
 
 
 
 
 
 
13 
 
11. STUDY MANAGEMENT  
 
 
 
 
 
 
 
13 
 
12. END OF STUDY  
 
 
 
 
 
 
 
 
13 
 
13. ARCHIVING 
 
 
 
 
 
 
 
 
 
13 
 
14. PUBLICATION POLICY  
 
 
 
 
 
 
 
13 
 
15. REFERENCES 
 
 
 
 
 
 
 
 
 
13 
 
 

Page 3 of 15 
 
GLOSSARY OF ABBREVIATIONS 
 
BCa 
 
Breast Cancer 
CBT 
 
Cognitive Behaviour Therapy 
CIC 
 
Confidence in Concept Scheme 
CRCa   
Colorectal Cancer 
MCT 
 
Metacognitive Therapy 
HADS  
Hospital Anxiety and Depression Scale 
NHS 
 
National Health Service 
CHPS  
Clinical Health Psychology Service  
MRC  
Medical Research Council 
PCa 
 
Prostate Cancer 
PTSD  
Posttraumatic Stress Disorder 
RLBUHT 
Royal Liverpool and Broadgreen University Hospital NHS Trust 
 

Page 4 of 15 
 
1. PROTOCOL APPROVAL/SIGNATURES  
 
This protocol describes the GMAC study and provides information about procedures for entering 
participants. Every care was taken in its drafting, but corrections or amendments may be 
necessary. These will be circulated to investigators in the Study. Problems relating to this Study 
should be referred, in the first instance, to the Chief Investigator. 
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for 
Health and Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data 
Protection Act and other regulatory requirements as appropriate. 
 
 
1.1 Chief Investigator  
 
I, Dr Peter Fisher as Chief Investigator for the GMAC study confirm that I will be responsible to 
ensure that all members of the study team are appropriately trained on the study protocol and have the 
relevant qualifications and experience to carry out their role in accordance with the study protocol. 
 
1.2 Protocol Authorised by: 
 
Name  
Site 
Signature 
Date 
Dr Peter Fisher 
(Chief Investigator) 
Psychological Sciences. 
University of Liverpool 
 
 
 
10/05/17 
 
 
2. STUDY SUMMARY 
 
Survival rates in cancer continue to improve, with over 2 million adult cancer survivors in the UK, 
projected to increase to 4 million by 2030. Around 25% of these survivors require treatment for 
clinical levels of emotional distress. Current pharmacological treatments are not very effective and are 
not well tolerated by patients, who prefer psychological treatments. However, meta-analyses of well-
controlled studies of psychological treatments indicate that these achieve only small effect sizes. 
Reflecting this limited efficacy in the face of the need for psychological treatment, the National 
Cancer Survivorship Research Initiative highlighted development and evaluation of practically 
feasible interventions for depression and anxiety in cancer survivors as an urgent research priority. It 
is recognised that current influential psychotherapeutic approaches need to be modified to meet the 
specific needs associated with cancer. However modifications have been pragmatic rather than theory-
driven and have not improved efficacy.  
 
Our study addresses the stages of ‘development’ and ‘piloting and feasibility’ in MRC guidance on 
intervention development, albeit with a relatively well-defined starting point given existing evidence 
for efficacy of MCT in other settings and promising preliminary evidence of applicability in cancer. 
We will conduct a phase I open trial to test the potential efficacy of group MCT in cancer survivors 
and the hypothesised causal metacognitive mechanisms underpinning treatment response. The 
evidence from this open trial will therefore allow us to progress to the next step in translating group 
MCT for cancer survivors: a randomised phase II controlled trial against the current gold standard 
approach, namely cognitive behaviour therapy. 
 
KEYWORDS: Group Metacognitive Therapy; Cancer Survivors; Open Trial; Anxiety; Depression 
 
 
 

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Title:  
An Open Trial of Group Metacognitive Therapy for Anxiety and Depression 
in Cancer Survivors (GMAC Study) 
 
 
Design:  
 
An open trial (single arm, single site) with follow-up at 3 and 6 months.  
 
Aim:  
To conduct an open trial of group MCT for cancer survivors experiencing 
clinically significant emotional distress. 
 
Objectives:  
1. To obtain evidence of potential efficacy of group MCT in alleviating 
emotional distress in cancer survivors.  
2. To assess the acceptability of the intervention to patients.  
3. To obtain data to inform sample size calculations for a subsequent Phase II 
trial 
4. Determine whether group MCT for cancer survivors can be easily 
delivered in routine clinical practice 
 
 
Measures: 
 
Primary endpoint: Severity of depression and/or anxiety symptoms at post-
 
 
 
treatment, and at 3 and 6 months follow-up, measured by the full  
 
 
 
scale score on the Hospital Anxiety and Depression Scale (HADS; [33]).  
 
Secondary endpoints: Cognitive Attentional Syndrome-1 [19]; Fear of 
Cancer Recurrence Inventory [35]; Impact of Events Scale-Revised (IES-R) 
[36]; Metacognitions Questionnaire-30 (MCQ-30) [37]; Functional 
Assessment of Cancer Therapy-General (FACT-G) [38]. 
 
Population:   
 
Patients who are referred to the Clinical Health Psychology Service  
 
 
 
experiencing clinically significant distress, operationally defined as a score of 
 
 
 
≥ 15 on the full scale score on the HADS [32]. 
Intervention: 
The intervention will constitute 6 sessions of group MCT. Clinical 
psychologists trained in group MCT will deliver the therapy to groups of 4-8          
patients referred to the Liverpool psycho-oncology service, who meet study 
criteria and consent to participate. 
 
 
 
Study duration:  
15 months maximum 
 
 
 
 
3. BACKGROUND 
 
There are over 2 million adult survivors of cancer in the UK, projected to increase to 4 million by 
2030 [1]. Survivors are at increased risk of clinically significant distress. A population-based survey 
[2] reported 6% prevalence of psychiatric disorders in survivors; double that in the non-cancer 
comparison group, even when socio-demographic and clinical correlates were controlled. 
Furthermore, although not meeting specific diagnostic criteria, 25% of patients report clinically 
significant anxiety and depression [3]. Therefore, around 500,000 people have cancer-related distress 
warranting intervention. Our proposal addresses the need for effective help for this large population. 
We will study patients from tumour groups that provide the main populations of survivors including, 
but not limited to breast (BCa), prostate (PCa) and colorectal (CRCa). In each, distress is more 
prevalent than in the normal population. In PCa, incidence of anxiety and depression 3 years post-
diagnosis is 23% and 26%, respectively [4]. In BCa, incidence of depression, anxiety or both, defined 
by meeting full or borderline diagnostic criteria, is 25% 4 years post-diagnosis [5]. Although 
neglected in other cancers, post-traumatic stress disorder (PTSD) affects 5% of BCa patients [6], with 

Page 6 of 15 
 
troubling symptoms of PTSD affecting 34% of patients 5 years post-diagnosis [7]. Emotional distress 
has been less explored in CRCa, but evidence indicates clinical depression or anxiety in 22% 5 years 
post-surgery [7]. Emotional distress reduces quality of life and, in the context of cancer survivorship, 
causes wider damage, increasing pain and fatigue[8, 9], reducing treatment adherence and impairing 
treatment decision-making[10], and increasing demand for, and cost of, physical health care[11, 12]. 
Given the wide-reaching implications of emotional distress in cancer survivors, and patients’ 
preference for psychological over pharmacological treatments, highly efficacious treatments are 
needed.  
4. RATIONALE FOR CURRENT STUDY 
 
Meta-analyses of well-controlled studies indicate that current “gold standard” psychological and 
pharmacological treatments achieve only modest effect sizes [14-17). Cancer survivors therefore need 
researchers to develop and evaluate psychological treatments that potentially have a better 'fit' with 
the cancer context, and are linked to theoretical models applicable to diverse forms of distress. 
Specifically, an intervention which identifies and modifies core psychological processes underpinning 
multiple forms of distress would offer the most promise to cancer survivors. 
 
Our solution lies in recent developments of the area of ‘metacognitive’ theory and metacognitive 
therapy in mental health. Metacognitive therapy is derived from a trans-diagnostic model of 
metacognitive processes in psychopathology, the Self-Regulatory Executive Function (S-REF) model 
[18]. According to this model, emotional disorders are maintained by the cognitive-attentional 
syndrome (CAS) which comprises three processes: (i) perseverative thinking (worry and rumination); 
(ii) attentional strategies (monitoring for signs of potential threat); and (iii) counterproductive coping 
strategies (e.g. thought suppression and avoidance). Applying this to cancer survivors, multiple 
factors can temporarily activate the CAS, such as fears of recurrence or rumination about implications 
of cancer on work and family roles. For most patients, resulting worry and rumination are transient 
but, in those who will become depressed or anxious, sustained rumination (e.g. about current impact 
on family) or worry (e.g. about what will happen in future) occurs. The S-REF model specifies that 
such perseverative thinking is activated by metacognitive beliefs about the usefulness of worry and 
rumination: e.g. “worry will help me cope”. Unfortunately, worry and rumination achieve the 
opposite, because they increase negative thoughts and broaden the sense of threat. The individual 
repeatedly acts as if the negative thought is valid and important, preventing the development of a 
more flexible relationship with thoughts that can reduce worry and rumination. Similarly, the S-REF 
model explains how threat monitoring (e.g. scanning for symptoms or for negative thoughts) is driven 
by metacognitive beliefs that this strategy will be helpful, whereas it has the opposite effect by 
maintaining the sense of threat and personal vulnerability so that emotional distress persists or 
escalates.  
 
Metacognitive therapy (MCT) modifies the beliefs and cognitive processes that maintain distress 
using a range of well-specified strategies and techniques outlined in a treatment manual [19]. Clinical 
application of MCT differs in important ways from Cognitive Behaviour Therapy (CBT) – the current 
gold standard treatment for anxiety and depression in cancer patients. CBT focuses on reality-testing 
negative thoughts or core beliefs, whereas MCT targets cognitive processes (worry/rumination) rather 
than challenging cognitive content. For example, common concerns in cancer patients are fear of 
recurrence or functional limitations associated with the disease and treatment. By contrast with CBT, 
MCT would not challenge the content of these potentially accurate thoughts or explore their 
‘meaning’. Instead patients would be helped to understand the deleterious and counterproductive 
effects of worry and rumination, therefore enhancing motivation to suspend worry. Simultaneously, 
metacognitive beliefs about the uncontrollability of worry, which sustain worry, would be challenged 
using established MCT techniques, helping patients to suspend worry and rumination. Modifying 
negative metacognitive beliefs is centrally important in the S-REF model because, as long as patients 
believe that worry is uncontrollable, they will not attempt to control it. Therefore, in targeting 
cognitive processes rather than cognitive content, MCT offers a particularly close ‘fit’ with the needs 
of cancer survivors indicating potential for greater efficacy.  
  

Page 7 of 15 
 
 
The evidence base for MCT is firmly established, with well over 150 empirical studies supporting the 
underpinning theory [19]. Metacognitive beliefs and processes have been implicated in emotional 
distress in diverse conditions including coronary heart disease, chronic obstructive pulmonary disease, 
chronic fatigue syndrome, Parkinson’s disease, diabetes, and in cancer patients at all stages of the 
treatment trajectory [20-27]. Moreover, in terms of treatment outcomes, MCT is more effective than 
both wait-list control (Hedge’s g=1.18) and CBT (Hedge’s g=0.97) for anxiety and depression in 
mental health settings [28].  
 
Translation of metacognitive theory and therapy to cancer is under way, with encouraging evidence 
for the explanatory and therapeutic utility of MCT in cancer. In patients with recently diagnosed 
breast cancer and prostate cancer, metacognitive beliefs predicted anxiety, after controlling for 
severity of worry and negative health beliefs [29]. In the first prospective study on the role of 
metacognition in breast and prostate cancer patients (n=206), metacognitive beliefs around the time of 
diagnosis predicted anxiety, depression and trauma symptoms 12 months later, after controlling for 
symptoms and cognitive beliefs at baseline [30]. We have conducted one open trial in young adult 
survivors of paediatric cancer (12 patients aged 18-24). MCT was highly acceptable and reduced 
anxiety, trauma symptoms and depression, with treatment gains maintained though to six months 
follow-up [31]. We are currently analysing data from a second open trial of MCT in a broader 
population of cancer survivors; preliminary data corroborate previous findings and indicate the 
effectiveness and acceptability of MCT to adult cancer survivors.   
 
Given the growing evidence of its efficacy across a range of emotional disorders in mental health 
settings and potential efficacy in a range of cancer survivors, it is important now to further develop 
MCT for the broader cancer population, to evaluate its efficacy, and to determine the most effective 
form of delivery.  
 
5. STUDY OBJECTIVES 
 
The primary aim is to conduct an open trial of group MCT for cancer survivors experiencing   
clinically significant emotional distress.  
 
Specific objectives are to: 
 
1. Obtain evidence of potential efficacy of group MCT in alleviating emotional distress in 
cancer survivors. 
 
2. Assess the acceptability of the intervention to patients.  
 
3. Obtain data to inform sample size calculations for a subsequent Phase II trial 
 
4. Determine whether group MCT for cancer survivors can be easily delivered in routine 
clinical practice 
 
 
6. STUDY DESIGN  
 
6.1. Design 
 
An open trial (single arm, single site) with follow-up at 3 and 6 months.  
 
6.2. Study Measures  
 
All outcome measures will be administered pre-treatment, post treatment and at 3- and 6-months 
follow-up. 

Page 8 of 15 
 
 
(i) Primary outcome:  
 
Hospital Anxiety Depression Scale (HADS) [32] total was chosen because: 1) it has proven 
 
construct validity for measuring emotional distress in cancer patients [33], and 2) it is the 
 
optimal measure of general distress for evaluating treatment efficacy in heterogeneous 
 
cancer populations [34]. 
 
(ii) Secondary outcomes:  
 
Cognitive Attentional Syndrome-1 [19] will assess rumination and worry. A single 
 
measure rather than separate measures of rumination and worry will reduce patient burden.  
 
 
Fear of Cancer Recurrence Inventory [35] will assess fear of recurrence 
 
 
Impact of Events Scale-Revised (IES-R) [36] will assess trauma related symptoms. 
 
Metacognitions Questionnaire-30 (MCQ-30) [37]  will assess metacognitive beliefs. 
 
 
Functional Assessment of Cancer Therapy-General (FACT-G) [38], will assess cancer-
 
specific quality of life.  
 
(iii) Sample characteristics and potential covariates: We will record socio-demographic 
characteristics, time and nature of cancer diagnosis, psychiatric history, and previous and current 
treatment including any psychotropic medication. 
 
6.3. Intervention 
 
Group metacognitive therapy (MCT) is a brief psychological intervention designed to be delivered in 
small groups of 4-8 patients over a course of six, 90 minute sessions conducted on a weekly basis. 
Treatment is based on a manualised protocol [19] and is structured in the following way. In session 1, 
idiosyncratic case formulations based on the generic metacognitive model are developed for each 
participant. Socialization proceeds by Socratic Questioning to help the patients understand that 
worry/rumination and unhelpful coping strategies are maintaining emotional distress. Patients are then 
introduced to, and practice, the Spatial Attention Control Exercise (SPACE), which is designed to 
illustrate patients’ control over their attention. The remaining sessions focus on modifying negative 
beliefs about uncontrollability of rumination/worry through training in detached mindfulness (DM) 
and in rumination/worry postponement. Patients will be helped to differentiate spontaneously 
occurring negative thoughts and images (e.g. “I’m useless”, “What if my cancer returns?”, or an 
image of the intensive care unit) from subsequent perseverative thinking (rumination and/or worry). 
They will be encouraged to regularly practice SPACE to demonstrate their control over their attention 
and thoughts. Rumination/worry postponement will be used as an experiment to challenge the 
metacognitive belief that perseverative thinking is uncontrollable. The final session addresses relapse 
prevention and involves modifying remaining use of the ‘cognitive attentional syndrome’, reviewing 
residual conviction in positive and negative beliefs and consolidating and strengthening alternative 
ways of responding to negative thoughts. All treatment sessions will be audio-recorded; individual 
supervision will be weekly by PF, who has internationally recognised expertise in developing and 
evaluating psychological therapies, particularly MCT and led the first evaluation of MCT for 
adolescent survivors of cancer [31]. MCT will be provided by MGC and AB, both of whom hold 
clinical contracts with RLBUHT and work clinically within the Clinical Health Psychology Service 
(CHPS).  
 
6.4. Study Duration 
 
Each participant will be involved in the study for 9 months and the total duration of the study will be 
15 months. 
 

Page 9 of 15 
 
 
7. PARTICPANT ENTRY 
 
The participants will be consecutive consenting patients referred to the CHPS. At their initial 
assessment appointment with a psychologist, patients routinely complete the Hospital and Anxiety 
Depression Scale (HADS) [32]. Those patients scoring ≥15 on the HADS total scale and deemed 
potentially eligible1 for the study will be given a GMAC invitation and Patient Information Sheet 
(PIS). The CHPS psychologist will explain the study and seek expression of interest. If the patient is 
interested, the psychologist will record their details on a form (name, address, gender, contact 
telephone number and HADS score). This form will be securely passed onto MGC and AB, who will 
enter these details into a secure database. MGC/AB will contact patients by telephone one week later 
to confirm that they have read and understood the PIS, answer any questions, and confirm interest and 
eligibility. Patients will be informed of the dates and times of the next available group MCT sessions. 
Prior to attendance at the first group session, MGC and AB will seek informed written consent for 
participation and will administer the baseline questionnaires. The original, signed copy of the consent 
form(s) will be retained by the University of Liverpool, a copy given to the patient and a copy placed 
in the patient’s clinical notes. 
 
7.1. Inclusion Criteria 
 
(i) Cancer diagnosis at least 6 months previously  
(ii) Scoring >15 on the full scale score of the Hospital Anxiety and Depression Scale (HADS) [32] 
(iii) Sufficient understanding of English to consent and engage in therapy 
(iv) Stable on, or free from, psychotropic medication 
(v) Minimum of 18 years old  
 
7.2. Exclusion Criteria 
 
(i)  History of psychotic disorder, learning disability, or organic mental disorder 
(ii) Risk of self-harm or suicide warranting immediate intervention 
(iii) In palliative phase of treatment 
(iv) Being considered for risk-reducing or reconstructive surgery within 1 year 
(v) Concurrent psychological intervention for emotional distress  
(vi) Cognitive impairment precluding informed consent or participation  
(vii) Undergoing acute medical treatment (e.g. chemotherapy, radiotherapy) 
(viii) Current drug/alcohol abuse 
 
7.3 Ineligible and non-recruited participants 
 
Patients who are ineligible or decline to participate at any point will continue to be offered usual care 
by CHPS. 
 
7.4 Discontinuation of participants 
 
Participants may withdraw from the trial at their own request at any time, without any consequences 
to themselves, their healthcare or their ability to take part in future research.  
 
 
 
 
                                                 
1 All psychologists within the Clinical Health Psychology Service will be fully briefed about the study and its 
eligibility criteria by members of the research team prior to study commencement. To aid determination of 
eligibility during assessment appointments, each psychologist within the service will also be provided with a 
checklist of inclusion and exclusion criteria, against which they can screen patients during their assessment 
appointment. Please see enclosure.   

Page 10 of 15 
 
8. ADVERSE EVENTS 
 
8.1. Definitions  
 
Adverse Event (AE): An AE is any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product or study-specific intervention and which does not 
necessarily have a causal relationship with this intervention. Note: An AE may therefore be any 
unfavourable and unintended sign (including abnormal findings), symptom or disease concurrently 
associated with the use of the study intervention, regardless of any relation to the intervention. 
 
8.2. Reporting Procedures 
 
The Clinical Psychologists delivering group MCT will monitor patient’s mental and physical health in 
accordance with good clinical practice guidelines. Any adverse events identified as likely to be caused 
by the intervention during the period of recruitment or intervention on the GMAC study will be 
recorded at the study site using a AEs/SAE record form which will be completed by the health 
professionals. The study CI, Dr Peter Fisher will be informed and information inputted onto a secure 
database. The CI will also assess whether the nature of the event suggests that it is likely to have been 
induced as a result of the study intervention or processes.  
 
One hypothesised adverse event which could occur due to the study intervention is as follows: 
 
• 
Lowered mood and suicidality – a patient could become lower in mood or suicidal as a result 
of discussing their current health status.  
 
Our proposed intervention does not withhold or significantly alter patient’s usual medical care. The 
group MCT intervention is designed to improve patient’s mood. However it is acknowledged that 
thinking or talking about distress can worsen mood or anxieties for some patients although this effect 
is rare and usually transient and is no more likely to occur with group MCT than with any other form 
of psychological treatment. However, in the event that patients feel more distressed following the 
intervention these patients will have access to continuing assessment and treatment by the CHPS. 
 
The time period for detecting and recording AEs and SAEs in participants will be from the point of 
study inclusion until the end of the intervention. 
 
9. STATISTICS AND DATA ANALYSIS 
 
9.1. Sample size and feasibility  
 
The study will require 40 patients to be recruited, allowing for attrition of 33% from baseline to 6-
month follow-up to leave a sample of 27 (see power calculation). The CHPS receives approximately 
400 new referrals annually. In a recently completed open trial of MCT hosted within the CHPS, 
approximately half of all referrals fulfilled eligibility criteria. Approximately 50% of eligible patients 
declined to participate. If we assume a more conservative 25% take-up, this will provide 50 patients, 
i.e. 25% more than needed. 
 
To date, we have completed two MCT training groups. To determine the feasibility of the proposed 
study, we followed the methodology outlined above. Six out of nine patients (i.e. 66%) were 
considered treatment completers (i.e. they attended the first and last sessions, and at least two of the 
four interim sessions offered to them). Reasons for non-completion included disengagement (n = 1), 
work commitments (n = 1) and change in personal circumstances (n = 1). These preliminary data 
indicate that the proposed attrition rate outlined above is feasible for this patient group.   
 
 
 

Page 11 of 15 
 
9.2 Power calculation  
 
The primary indicator of efficacy will be change in HADS total between pre-treatment and 6-months 
follow up. In a recently completed open trial of MCT, the estimated between-patient standard 
deviation was approximately 7. As this is based on a small number of patients (n=20), a between-
patient standard deviation of 12 will be used. No information on within-patient standard deviation is 
available so the between-patient standard deviation is used as a conservative measure. A trial with 
95% power to detect a reduction in HADS score of 8 points, which is the minimum reliable difference 
we seek to obtain between baseline and 6 months follow up, requires 24 patients (one-sided alpha = 
0.01). To account for clustering by group we will increase the sample size by a factor of 1.10 (1+ 
(average cluster size-1)) x intra-class correlation coefficient), therefore the required sample size will 
be 27.  
 
9.3 Analysis Plan  
 
Descriptive analysis will explore the acceptability of group MCT by examining the number of eligible 
participants who took up the offer of intervention and the retention rate. Analysis will test treatment 
effects across time (baseline, post-treatment, and 6-month follow-up) using repeated measure analysis 
of variance. Main effects will be followed by Bonferroni corrected pairwise comparisons for each 
outcome. Within-group effect size (Hedges’ g) will be calculated for ITT and completer samples and 
will be used to estimate the required sample size for a full randomised trial. Clinical significance of 
treatment effects will be assessed using the Jacobson method [39] to establish whether participants 
could be considered recovered as a result of treatment.  This method allocates each patient to one of 
four possible outcomes: (1) reliable deterioration; (2) no change; (3) reliable improvement; and (4) 
recovered. The first three outcomes are derived solely from a reliable change index (RCI) which 
compares treatment outcomes to normative data from non-clinical samples to determine whether the 
magnitude of change is statistically significant.  To be classified as ‘recovered’, patients need to 
demonstrate both a reliable change and a score that falls below the established clinical cut-
off.  Therefore patients will classified as ‘recovered’ where post-treatment HADS total <13, RCI will 
be 8 based on normative data from a large non-clinical sample [40].   
 
10. ETHICAL AND REGULATORY REQUIREMENTS 
 
10.1. Ethical Approval 
 
This study will be subject to NHS Research Ethics Approval and Health Research Authority (HRA) 
approval. The study will be submitted to the Royal Liverpool and Broadgreen University Hospital for 
Confirmation of Capacity and Capability. This study will not be initiated before the protocol, 
informed consent forms and participant information sheets have received approval/ favourable 
Research Ethics Approval and HRA approval. Should a protocol amendment be made that requires 
Research Ethics Committee (REC) approval, the changes in the protocol will not be implemented 
until the amendment and revised informed consent forms and participant and (if appropriate) have 
been reviewed and received favourable REC and HRA opinion. The Chief Investigator will have a 
copy of the HRA approval letter before accepting participants into the study. The study will be 
conducted in accordance with the recommendations for physicians involved in research on human 
subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
 
10.2. Sponsorship and Indemnity 
 
The University of Liverpool will act as Sponsor for this study. Delegated responsibilities will be 
assigned to the Royal Liverpool and Broadgreen NHS Trust which is taking part in this study. The 
University of Liverpool holds indemnity and insurance cover with Marsh UK LTD, which apply to 
this study. 
 

Page 12 of 15 
 
 
10.3. Participant Information and Informed Consent 
 
The patient’s consent to participate in the study will be obtained after a full explanation of the study 
has been given and the patient has been given sufficient time to discuss participation in the study with 
friends and family. A contact number will be given to the patient should they wish to discuss any 
aspect of the study.  
 
The right of the patient to refuse to participate in the study without giving reasons must be respected. 
Similarly, the patient must remain free to withdraw at any time from the protocol treatment without 
giving reasons and without prejudicing his/her further treatment. 
 
10.4. Participant Confidentiality and Data Protection 
 
All information collected during this study will be kept confidential in accordance with NHS Data 
Protection guidelines. Identifying information will be anonymised. Confidentiality will only be 
breached if a participant discloses information which may indicate harm to themselves or others. We 
will take every opportunity to discuss any possible breaches of confidentiality patients prior to 
informing any appropriate agencies e.g. oncology staff, GP or A&E services. 
 
Participants will be allocated a study identity code number by the study team for use on all study 
documents and the electronic database. The study team will make a separate confidential database for 
the participants name, date of birth and study identity code to permit identification of participants 
enrolled in the study e.g. for follow-up. All other information will be anonymised. All study 
documents (including participant’s written consent forms) which are to be held at the participating 
centre will be held in strictest confidence. 
 
Data will only be available through restricted, shared areas on the secure University of Liverpool 
computer systems (password and username secured). Participants will be informed of this on the 
participant information sheet and will be asked to consent to this at the time of consent to the study. 
All paper forms shall be filled in using black or blue ballpoint pen. Errors shall be lined out but not 
obliterated by using correction fluid and the correction inserted, initialled and dated. 
 
All member of staff involved with the study must comply with the requirements of the Data 
Protection Act 1998 with regard to the collection, storage, processing and disclosure of personal 
information and will uphold the Act’s core principles. 
 
Statistical analysis will be directed and supervised by Dr Peter Fisher. No information which may 
allow identification of individual participants will be included in publications or dissemination 
activities. 
Storage and use of data after the end of the study 
NHS patient data collected within RLBUHT will follow the standard operating procedure which states 
all information involving NHS patients, interventional or observational should be retained for a 
minimum of 10 years after completion of the study in a secure storage area with limited access. The 
University of Liverpool will arrange appropriate storage and archiving of data. 
 
  10.5. Protocol Amendments 
 
Any changes in research activity will be reviewed and approved by the Chief Investigator (CI) and 
submitted in writing to the appropriate REC and local research site for approval prior to being 
included in an amended protocol.  
 
 
 

Page 13 of 15 
 
10.6. Audit 
 
The study may be subject to inspection and audit by the University of Liverpool under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research Governance 
Framework for Health and Social Care (2nd edition).  
 
10.7 Funding  
 
This study is unfunded. 
 
11. STUDY MANAGEMENT 
 
The day to day management of the study will be coordinated through a study management team, 
which will be chaired by PF and will include the co-investigators (MGC; AB; AW). PF will supervise 
the clinical psychologists providing MCT (MGC; AB). 
 
12. END OF STUDY 
 
The study end date is deemed to be the date of the last data capture. The CI has the right at any time to 
terminate the study for clinical or administrative reasons. The end of the study will be reported to the 
REC within the required timeframe if the study is terminated prematurely. Investigators will inform 
patients of any premature termination of the study and ensure that the appropriate follow up is 
arranged for all involved. Following the end of the study a summary report of the study will be 
provided to the REC within the required timeframe 
 
13. ARCHIVING 
 
Documents will be stored by the University of Liverpool and at CHPS in a way that will facilitate the 
management of the study, audit and inspection. Study documentation will be securely stored and 
retained for a period of 10 years for possible audit or inspection. Access to these documents will be 
restricted to authorised persons. 
 
14. PUBLICATION POLICY 
 
The main findings will be published in open-access journals and secondary data will be reported in 
other peer reviewed journals.  
 
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