RCT of an Internet-based CBT Program for Sexuality and Intimacy Problems in Women Treated for Breast Cancer
Condition: Sexual Dysfunction; Intimacy Problems; Breast Cancer Survivors
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the efficacy and cost-effectiveness of an
      internet-based cognitive behavioural therapy program in alleviating problems with intimacy
      and sexuality in women treated for breast cancer.
    

Detailed description: 
      Background. Breast cancer is the most common cancer among women in the Netherlands, with an
      incidence of 71 per 100.000 person-years, and a lifetime risk of 10%. Currently, 85% of women
      with breast cancer live longer than 5 years, and 75% 10 years or longer(1,2). As a result,
      more interest and research has focused on the health-related quality of life (HRQL) of breast
      cancer survivors, including issues of sexuality and intimacy. Compelling evidence has
      established that sexual dysfunction is a prevalent, long term complication of breast cancer
      and its treatment (3,4-11). Overall, approximately 50% of breast cancer survivors report some
      form of sexual dysfunction as a result of treatment(6,10,13-15). Frequently reported problems
      regarding intimacy and sexuality include decreased sexual desire (23-64%), decreased arousal
      or lubrication (20-48%), anorgasmia (16-36%) and dyspareunia (35-38%)(10). Hill et al. report
      that over 40% of the breast cancer and gynaecological cancer survivors in their study
      expressed interest in receiving professional sexual health care(15). However, there is a
      significant discrepancy between the self-reported need for professional sexual health care
      and the actual uptake of care(16). Hill et al.(15) reported that, although over 40% of their
      sample expressed interest in receiving professional care, only 7% had ever actually sought
      such care. Although sexual functioning is an important issue, it may be difficult for women
      to initiate discussion with their general practitioner or medical specialist. Health care
      professionals may also be reluctant to query about sexual problems, due to time constraints,
      embarrassment, and/or lack of experience and communication skills in this area(16,17). Many
      women consider face-to-face sexual counselling to be confronting, and see internet-based
      interventions as a less threatening and more acceptable approach(18,19). There is growing
      evidence that internet-based cognitive behavioural therapy (CBT) can effectively treat a
      range of psychosocial problems, including anxiety, depression and PTSD(20,21). More recently,
      internet-based cognitive behavioural therapy programs for sexual dysfunction have been
      developed, typically paralleling the content of face-to-face therapy, with studies showing
      the efficacy of these internet-based programs in improving sexual functioning(22-25).

      Design. This pragmatic clinical trial will employ a prospective, randomized design with one
      intervention group and a control group. Potentially eligible patients will be identified
      through the hospital registries. These patients will be sent a letter signed by their
      treating/former surgeon, together with an informational brochure about the study and possible
      cancer-related intimacy and sexuality problems. Women who are potentially interested in
      participating in the study will be asked to indicate this on the enclosed response card.
      Women who are not interested in participation will be requested to return the response card
      to indicate their motive(s) for not being able to participate. Women who are not interested
      in participation or who do not respond to the invitation to participate in the study will not
      be contacted again. If interested, women are asked to write down their contact information.
      Those women who return the questionnaire will be contacted by telephone by one of the members
      of the study staff to inform them more thoroughly about the study purpose and procedures. At
      this time, additional questions will be posed regarding current treatment of
      sexuality/intimacy problems, current participation in a research trial with a focus on
      alleviating sexuality/intimacy problems, access to internet, date of breast cancer diagnosis,
      and completion/continuation of the different parts of treatment of breast cancer
      (chemotherapy, radiation therapy, endocrine treatment).

      Those women who remain interested in the study and who appear to be eligible will undergo an
      intake evaluation by telephone with a sexologist who will carry out a more extensive
      diagnostic interview in order to determine final eligibility of the woman for the
      internet-based cognitive behavioral therapy program. Questions will be asked about problems
      with sexuality and intimacy and relationship/marriage.

      If the woman meets final eligibility criteria, she will receive a baseline questionnaire,
      together with an informed consent form. The questionnaire will assess sociodemographic and
      medical background variables, and the primary (sexuality and intimacy problems) and secondary
      study outcomes (body image, menopausal symptoms, marital functioning, psychological distress
      and health-related quality of life). In total, 160 consenting women will be randomized to
      either the intervention group (n = 80), or to a control group (n = 80) using the minimization
      technique, with primary surgery (breast conserving treatment; mastectomy without
      reconstructive surgery; mastectomy with reconstructive surgery), menopausal status
      (premenopausal; postmenopausal), current endocrine treatment for breast cancer (yes; no), and
      time since breast cancer diagnosis (<1 year; 1-3 yrs; 3-5 yrs) as stratification variables.
      Women allocated to the intervention group will be asked to complete a battery of
      questionnaires assessing primary and secondary outcomes at four points in time: ten weeks
      after the start of the CBT program (T1), and at post-treatment (T2; to achieve an equivalent
      average assessment time for both study groups, women in the intervention group complete T2
      post-treatment, but always between 20 and 24 weeks after start of therapy. Women who finish
      the CBT prior to 20 weeks complete T2 20 weeks after start of therapy). The last two
      questionnaires are completed 3-months after completion of therapy (T3) and 6 months after T3
      (T4). The control group is not asked to complete T3 or T4, but rather is given the
      opportunity to undergo the intervention following completion of T2. This was done because it
      was not deemed ethically acceptable to withhold the intervention from women in the control
      group for the prolonged period of time that would be required if they were to be first asked
      to complete all follow-up sessions (i.e., approximately one year after study enrollment). To
      minimize respondent burden, the T4 questionnaire only includes questionnaires assessing the
      primary outcome measures.

      Control group. Women who are assigned to the control group will be contacted by telephone by
      a member of the study staff to inform them about this allocation. These women will receive a
      booklet per mail that addresses 80 questions about sexuality and cancer. Six weeks later,
      women in the control group will receive an empathetic phone call from one of the sexologists,
      during which there is also time available to discuss further questions the participants may
      have concerning sexuality and cancer. The purpose of keeping in contact with the control
      group, as opposed to a pure waiting list control group, is creating the opportunity to
      provide some control for a possible attention placebo-effect. Ten weeks post study entry,
      women in the control group will be asked to complete the first follow-up questionnaire. After
      completion of the questionnaire, women in the control group will be telephoned by a member of
      the study staff for another empathetic conversation. Women in the control group will complete
      a final questionnaire twenty weeks post study entry, after which they will be given the
      opportunity to undergo the internet-based cognitive behavioral program.

      Intervention group. For women allocated to the intervention group, the sexologist will
      develop a tailored treatment plan, consisting of a maximum of 10 treatment modules (see below
      for a more detailed description of the intervention). The therapist has received specialized
      training in the nature of breast cancer and its treatment, in general, and more specifically
      sexuality and intimacy issues associated with breast cancer and its treatment. Each woman is
      assigned a personal sexologist (therapist) who guides her through the internet-based CBT
      program and provides feedback on the homework assignments. Contact with the therapist is
      fully web-based, via a secured website. The CBT program comprises a maximum of ten treatment
      modules that can be used in varying order. The choice of modules to be used by any given
      woman is based on the information obtained via the screening by telephone and the intake
      evaluation by the therapist. Each module contains three interventions and a personal
      evaluation form to report on the intervention. Each intervention comprises the following
      elements: 1) introduction, 2) psycho-education about symptoms, 3) "homework" assignments
      (e.g. relaxation techniques (pelvis); discuss intimacy with partner; sensate focus) and 4)
      reporting back to the therapist and receiving feedback on the "homework" assignments. Each
      week there are two "practice" sessions of 30 minutes each and one hour per week to report
      on/evaluate the intervention. The therapy has a mean duration of 20 weeks.The modules
      include: (1) "Put your problem into words" where the client describes her problems, is asked
      to distinguish between feelings, thoughts, and behaviors, and learns about what intimacy is
      and how it interplays with sexuality, the sexual response curve and the most common
      (psycho)sexual problems; (2) "How is my relationship doing?" in which the client explores how
      intimate the relationship actually is, becomes aware of the amount of quality time spent with
      the partner, receives psycho-education about sex and intimacy, the importance of open
      communication with the partner, and advice on how to improve open communication; (3) "Sex and
      my body" during which the client first experiences sensate focus therapy (targeted at
      becoming more comfortable with one's own body and achieving (non) sexual intimacy with one's
      partner physically and emotionally); (4) "Focus my attention" in which the client receives
      task concentration training to learn to focus her attention on sexual experiences; (5)
      "Explore my body" in which sensate focus therapy is further used, and the client writes about
      her experiences with the homework exercises within a cognitive behavioral framework (with
      particular focus on inhibiting thoughts); (6 & 7) "Discovering my sexual arousal feelings
      (versions for the woman and for her partner) in which psycho-education is provided about
      genital stimulation, sexual techniques, etc., and how to discuss sexual feelings with the
      partner; (8) "Change my thoughts" that involves cognitive restructuring to promote adaptive
      thoughts; (9) "My sexual preferences" in which the client talks about her sexual preferences
      with her partner, and makes an action plan for behavior change; and (10) "Relapse prevention"
      in which the client writes about her former automatic behavior and the risk factors for
      relapse, after which a plan of action is made in case of a relapse.

      Study measures. The primary outcomes (sexuality and intimacy problems) are measured using the
      Sexual Activity Questionnaire, Female Sexual Functioning Scale, Female Sexual Distress Scale
      and the Personal Assessment of Intimacy in Relationships. Secondary outcomes measures include
      QLQ-BR23 (body image), FACT-ES (menopausal symptoms), Maudsley Marital Questionnaire (marital
      functioning), Hospital Anxiety and Depression Scale (psychological distress) and MOS SF-36
      (health-related quality of life).

      Program adherence. Women who do not complete their tailored internet-based therapy program
      will be asked to indicate the reason(s) for their discontinuation (e.g., illness, lack of
      motivation, burden, etc.). Every effort will be made to obtain a final, post-intervention
      assessment for all women, regardless of whether they do or do not complete their therapy.
      This will facilitate a maximum sample size for the primary, 'intention-to-treat' analysis of
      between-group differences over time. Additionally, all women, including those in the control
      group, will be asked if, during the period of the study, they pursued any (other) activities
      relating to their sexual and intimacy issues.

      Patients' evaluation of the intervention program. At the end of their treatment, women in the
      intervention group will be asked about their experience with the module, the homework
      assignments, and the feedback received from the therapist. Additionally, immediate
      post-treatment, these women will be asked whether they would suggest any changes to the
      program, and if they would recommend it to other women experiencing similar problems.

      Semi-structured interview. A subset of women (approximately 15 from the intervention group)
      will be asked to participate in a telephone interview. This semi-structured interview will
      cover the same topic areas as addressed by the self-report questionnaire, allowing women to
      provide feedback in a more narrative form about their sexual wellbeing and their experience
      with the CBT program. Women will also be asked if their partner would be willing to share
      his/her experience with the program (where applicable). The interview protocol has been
      developed and pilot-tested during the preparatory phase of the study.

      Sample size and statistical power calculations. The prospective study design will allow for
      testing of the main effect of the internet-based intervention program. The SAQ, FSFI, FSFS
      and PAIR Inventory are the primary outcome measures on which sample size calculations are
      based. Specifically, the difference between the SAQ, FSFI and FSDS scores at baseline,
      mid-treatment (e.g. after 10 weeks), post-treatment (e.g. after 20 weeks), at 3 months
      follow-up (T3) and at 9 months follow-up (T4) will be calculated for each patient, and these
      changes will be the primary endpoints of the study. The mean of these differences in scores
      will be compared with the minimal intervention control group.

      With a total sample of 130 women (65 per group), and under the assumption of no interaction,
      the study will have 80% power to detect an effect size of 0.5 for the main effects of the web
      based intervention program, with the p value set at 0.05.

      160 women will be recruited into the study, to allow for an attrition rate of approximately
      20% (i.e., women who discontinue participation in the study entirely, including failure to
      complete all follow-up questionnaires). Those women who discontinue participation in one of
      the groups but complete the follow-up assessments will be included in the intention-to-treat
      analysis.

      Statistical analyses. Analysis will first be performed to evaluate the comparability of the
      intervention and control group at baseline in terms of sociodemographic and clinical
      characteristics. Student's t-test or appropriate non-parametric statistics will be used,
      depending on the level of measurement. If, despite the stratified randomization procedures,
      the groups are found not to be comparable on one or more background variables, those
      variables will be employed routinely as covariates in subsequent analyses.

      Questionnaire scores will be calculated according to published scoring algorithms.
      Between-group differences over time in mean scores will be tested using multilevel analysis.
      Effect sizes will be calculated using standard statistical procedures. Effect sizes of 0.2
      will be considered as small, 0.5 moderate, and 0.8 large. Effect sizes of approximately 0.4
      will be considered as clinically relevant. All analysis will, to as great an extent as
      possible, be conducted on an intention-to-treat basis. The variables used in the minimization
      procedure will be employed as covariates. Per protocol analyses will also be carried out (as
      a secondary analysis), comparing women who meet minimal compliance levels (to be defined)
      with the program to the control group. We will also use correlation analyses to examine the
      relationship between degree of program adherence, partner involvement, and program effect. As
      indicated previously, the SAQ, FSFI, FSDS and PAIR inventory will be used as the primary
      study endpoints, and the remaining measures will be considered as secondary endpoints. For
      the analysis of these latter variables, appropriate statistical (p value) adjustments will be
      made for multiple testing. Since the sample size will not provide sufficient power to conduct
      subgroup analyses, an interaction term (group x time since diagnosis) will be added to the
      analyses. The semi-structured interview data will be transcribed and content analyzed to
      extract narrative, qualitative information about the women's sexual and intimacy problems
      and, where relevant, their experience with the intervention.
    

Intervention name(s): Internet-based cognitive behavioral therapy.
Intervention type(s): Behavioral
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sexual dysfunction; Intimacy problems; Breast cancer survivors; Internet-based; Cognitive behavioral therapy