Title: SAFFRON: Developing a Stepped Approach to improving sexual Function aFteR treatment fOr gyNaecological cancer
Funder: Department of Health (England)

Abstract: Trial summaryA 2-stage study:Stage (1) developing a stepped care system of interventions for psycho sexual difficulties in women treated for gynaecological (GN) cancer; Stage (2) an exploratory trial of the stepped care approach to assess feasibility and acceptability of the interventions and collect data on sample and effect sizes to inform a larger definitive trial.Trial designFeasibility study: Two arm parallel group RCT.Setting: UCLH & University Hospitals Bristol Gynaecological Cancer Centres Eligibility: All women over age of 18 with adequate English attending either gynae-oncology clinic for follow-up at least 6 months after a course of treatment for any gynaecological malignancy and any stage Feasibility trial entry:All women attending either gynae-oncology clinic for follow-up 6 months or longer after a course of treatment will be approached by a clinical nurse specialist or their clinic doctor to raise the issue of sexual dysfunction. Initial approach to the patient will take place as an integral part of the follow-up appointment. Patients will be asked 3 questions within the clinical consultation. ‘Are you having any sexual difficulties? Is this a problem for you? Would you like to have some help with this?’ Those who agree will then be offered participation in the trial. Those who agree will give informed consent and be assessed using the new assessment algorithm developed within the trial and randomised to treatment as usual (TAU) to include dilators hormone creams and written and verbal information or the stepped care programme plus TAU. All other patients who refuse entry to the trial will be offered TAU.The stepped care programme: the stepped care programme will have 3 steps with clear entry criteria and treatment protocols. Most women will first be offered step 1 but based on the structured assessment and pre-determined criteria within the treatment algorithm a number of women will be referred directly to step 2 or 3. Women who do not benefit from step 1 or 2 interventions ( based on data from routine sessional measures) will be referred to step 3. All steps will use sessional outcome monitoring to assess progress. Step 1:Interventions offered at this stage will be psychoeducational materials collected for the trial about sexual problems after gynaecological cancer offering self-help.Step 2 the focus of this step will be on the provision of a range of manualised low intensity interventions delivered only by study trained CNSs with accompanying workbooks to be developed. They will be based on existing psychosexual interventions body image work and couple work with a mindfulness component (Brotto et al 2008).Mood and anxiety will be addressed if needed using adapted workbooks from the Camden IAPT programme. It is expected that the majority of women will be treated at step 1 or 2. Women who do not benefit from step 2 interventions (shown by routine outcome measures) will then be referred to step 3. The step 2 intervention will be delivered by study trained CNSs and will comprise from one to five 30 minutes sessions (some sessions could be delivered by telephone) with one follow up session at 12 weeks after the first session.Step 3 The third or high intensity intervention will be a newly devised adaptation of an evidence based treatment (InterPersonal Therapy-IPT) adapted for use with gynaecological cancer survivors. This will be offered to the minority of patients for whom steps 1 and 2 are insufficient and involves targeted use of more psychologically skilled therapists for patients with more complex problems The manual will be written by experienced team member (Lemma) a nationally accredited IPT trainer. The choice of adapted IPT for the step 3 intervention is based on strong evidence for its effectiveness on mood (NICE recommended therapy for depression) together with strong face validity because of its focus on social relationships role transitions such as those occasioned by serious illness loss of fertility and grief and loss generally. IPT has already been effectively adapted for other settings where body changes are central.Adherence to model of treatmentAdherence to the model of intervention and protocol for delivery will be monitored at all steps. CNS and clinical psychologist sessions will be taped and rated for adherence to the model using standard techniques as used in the IAPT programme and clinical psychologist sessions will be taped and rated for adherence to the model using standard techniques as used in the IAPT programme (Reachout Manual Richards and Whyte 2009 via www.iapt.nhs.ukMeasures of costs and outcomesPrimary endpoint: The primary outcome measure is psycho-sexual functioning using the Female Sexual Function Index (FSFI) a 19 item self-report measure with six domains (desire arousal lubrication orgasm satisfaction and pain) and an overall score. Secondary endpoints: Mood anxiety and self-esteem. Hospital Anxiety and Depression Scale (HADS) a 14 item measure designed for use in the physically ill[Zigmond and Snaith 1983]: PHQ-9 – assesses depression and used in primary care and IAPT (Spitzer R L 1999);GAD-7 (assesses anxiety used in primary care); Rosenberg’s self esteem scale. Other outcomes for economic evaluation: Quality of Life : EQ-5D to measure cost effectiveness and (EORTC QLQ-C30) [Aaronson 1993]: a 30 item cancer-specific questionnaire validated for Europe; Client Services Receipt Inventory(short form) to assess use of health and social services (Knapp and Beecham).Assessments: All measures will be completed at baseline 6 weeks and 3 6 and 12 months after joining the study. Qualitative investigation Semi-structured interviews will be conducted at 12 months with a purposive sample patients randomised to the stepped care arm of the trial throughout Part 2 to explore their experience of the process of recruitment to the trial and of receiving the interventions. We shall also interview clinical staff to understand their experiences of recruiting participants to the trial and with senior clinicians and managers about the operation of the SAFFRON intervention and stepped care model. These data will be analysed thematically using the Framework approach (Ritchie et al 2003 Pope et al 2000) with the aid of QSR NVivo qualitative data analysis software and will provide important information on acceptability and potential for harm as well as potential obstacles and facilitating elements for the intervention. Data analysis: Statistical Analysis Analysis of this feasibility trial will be mainly descriptive. We will measure rates of recruitment acceptance of randomisation attrition from treatment and trial and completion rates for the outcome measures (to gauge acceptability and appropriateness of the outcomes). We will also estimate differences (with 95% confidence intervals) for the main trial outcomes between the groups using appropriate regression methods adjusted for baseline values. Information required for the sample size calculation and analysis plan of the definitive trial will be obtained including estimates of standard deviation for the primary outcome and correlations between repeated measurements distributional properties of the data and possible clustering effects. We will investigate if attrition levels are similar across the trial arms and examine the characteristics of participants who drop out and reasons for attrition where available. This will help in understanding the pattern of missingness and to make appropriate plans to handle missing data in the larger randomised trial. Economic evaluation We will assess the feasibility of conducting an economic evaluation of a stepped care system of interventions for psychosexual difficulties in women treated for GN cancer compared to TAU and the feasibility and acceptability of collecting cost and outcome information for use in an economic evaluation. The anticipated analysis for a main trial would be an incremental cost per Quality Adjusted Life Year (QALY) gained of stepped care compared to TAU or a cost-utility analysis (CUA). As a CUA has never been conducted for a psychosexual intervention for GN cancer patients the reliablility and validity of the generic health related quality of life questionnaire required for a CUA the EQ-5D is unknown. To provide more information on how the EQ-5D responds to changes in outcomes of interest we will calculate the correlation between EQ-5D scores and other measures. We will conduct an initial CUA from a health and social care cost perspective. Patient health and social care resource use will be collected using a short version of the CSRI modified for cancer patients. Resource use will be costed using nationally published data sources.The cost of training and the intervention will also be calculated. Confidence intervals will be constructed using bootstrapping with replacement and one and two-way sensitivity analyses conducted to test key assumptions and areas of uncertainity. The EORTC QLQ 30 can also be used in a CUA as utility scores for this have been calculated and we will conduct an additional CUA analysis using these values. We will also assess the feasibility of conducting a CUA using a sexual function measure.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS;REPRODUCTIVE HEALTH AND CHILDBIRTH