A Multimodal Intervention to Address Sexual Dysfunction in Hematopoietic Stem Cell Transplant Survivors
Phase: NA
Conditions: Sexual Dysfunction
Sponsor: Massachusetts General Hospital

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SECTION 1: Protocol Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Using NCCN Sexual 
Dysfunction Questions: 
Patients in remission > 3 months 
after allogeneic HCT 
 
1. Do you have problems with your 
sexual function? 
2. Are these problems causing you 
distress?
Exclude: 
• 
No sexual dysfunction 
causing distress 
Patient Enrollment and Baseline 
Data Collection: 
• 
Complete questionnaires 
• 
Schedule first intervention visit. 
First Intervention Visit: 
• 
Interventionist rescreens patient 
for positive sexual dysfunction 
• 
Comprehensive assessment of 
sexual dysfunction 
• 
Normalization & Education 
• 
Therapeutic interventions 
Follow-Up Intervention Visit  
• 
Assess response to therapy 
6-Month Data Collection  
• 
Complete questionnaires 
Referral to 
Sexual Health 
Clinic 
• Suspected 
psychological etiology 
• Vaginal symptoms 
requiring internal 
examination 
• Complex sexual needs 
Did not respond to 
therapy 
Exclude: 
• 
No sexual dysfunction 
causing distress 

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SECTION 2:  BODY OF PROTOCOL 
 
 
TABLE OF CONTENTS 
 
1 
Introduction ................................................................................................................................................................. 3 
1.1 
Overview ..................................................................................................................................................................... 3 
1.2 
Background and Significance ..................................................................................................................................... 3 
1.3 
Preliminary Studies ..................................................................................................................................................... 5 
2 
Objectives ................................................................................................................................................................... 5 
3 
Research Subject Selection ......................................................................................................................................... 6 
3.1 
Study Subject Selection: .............................................................................................................................................. 6 
4 
Research Subject Entry ............................................................................................................................................... 6 
4.1 
Study Research Subject Entry ..................................................................................................................................... 6 
4.2 
REGISTRATION AND RANDOMIZATION PROCEDURES ..................................................................................... 7 
5 
Study Design and Methods ......................................................................................................................................... 7 
5.1 
Design/ Study Type ...................................................................................................................................................... 7 
5.2 
Study Procedures: ....................................................................................................................................................... 8 
5.5 
Description of Intervention ....................................................................................................................................... 10 
5.8 
Adverse Reactions and Their Management ............................................................................................................... 13 
5.8.1 Reporting Adverse or Unanticipated Events ............................................................................................................. 13 
5.8.2 Anticipated Reactions ............................................................................................................................................... 13 
5.8.3 Reaction Management ............................................................................................................................................... 13 
6 
Ethical and Legal Issues ........................................................................................................................................... 14 
6.1 
Confidentiality ........................................................................................................................................................... 14 
7 
Statistical Analysis .................................................................................................................................................... 14 
7.1 
Primary and secondary endpoints: ........................................................................................................................... 14 
7.1.2 Secondary endpoint: ................................................................................................................................................. 14 
7.2 
Sample Size Calculation: .......................................................................................................................................... 15 
7.3 
Stratification factors and intervention allocation plan for randomized studies ....................................................... 15 
7.4 
Definition of an allowance in design for unevaluable/ineligible participants .......................................................... 15 
7.5 
Analysis Plan: ........................................................................................................................................................... 15 
8 
References: ................................................................................................................................................................ 16 
9 
Appendices ................................................................................................................ Error! Bookmark not defined. 
 

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1 Introduction 
1.1 
Overview 
The goal of this project is to develop and evaluate a multimodal sexual dysfunction intervention for survivors of 
allogeneic hematopoietic stem cell transplantation (HCT). The National Comprehensive Cancer Network 
(NCCN) identifies sexual dysfunction as a major issue facing cancer survivors that negatively impacts their 
quality of life (QOL) and mood. Allogeneic HCT survivors, like many cancer survivors, experience a 
significant and drastic deterioration in their sexual function that persists for many years following their therapy.  
In fact, sexual dysfunction is the most common and persistent long-term complication of HCT, adversely 
affecting patients’ QOL, mood, and intimacy. Nearly half of HCT survivors are dissatisfied with the quality of 
their sexual life. Moreover, studies have clearly demonstrated that sexual dysfunction is associated with worse 
QOL, fatigue, emotional well-being, relationship satisfaction, and psychological distress.  Thus, many 
allogeneic HCT survivors endure a significant deterioration in their sexual function, which adversely impacts 
their QOL and mood, and increases the overall morbidity of their treatment. 
 
The etiology of sexual dysfunction post-transplant is multifactorial and includes problems with sexual desire 
and pleasure, hormonal deficiencies, vaginal and penile alterations secondary to graft-versus-host-disease 
(GHVD), delayed or absent orgasm and/or ejaculation, pain with intercourse, erectile dysfunction, and 
psychological problems such as anxiety, depression, and changes in body-image. Thus, an intervention that 
assesses a wide range of physical and psychological conditions is needed to address the range of sexual 
problems seen in this population.   
 
Unfortunately, interventions to improve sexual function in HCT survivors are lacking. Additionally, clinicians 
are reluctant to address sexual function with their patients due to their lack of training and discomfort in 
engaging in these conversations. Given the well-documented burden of sexual dysfunction that allogeneic HCT 
survivors face, there is a compelling need to develop interventions that encourage clinicians to discuss sexual 
health issues with their patients, using a comprehensive and multimodal approach to address their diverse sexual 
needs.   
 
In this project, we will develop and evaluate the efficacy of a multimodal sexual dysfunction intervention for 
allogeneic HCT survivors. The proposed project will proceed in two phases. During phase 1, we will conduct a 
prospective pilot study assessing the feasibility and preliminary efficacy of the intervention in improving 
patients’ sexual function, QOL, and mood. During phase 2, we will conduct qualitative interviews with patients 
who completed the intervention to explore their perceptions of its acceptability, content, and efficacy, and the 
optimal timing for its delivery during their survivorship course. Data from this work will help inform a large-
scale randomized study of a sexual dysfunction intervention for allogeneic HCT survivors. 
 
The proposed project will assess an innovative and sexual dysfunction intervention that has the potential to 
substantially enhance the care of survivors of hematologic malignancies. Moreover, such an intervention can be 
adapted for use with other cancer survivors struggling with sexual dysfunction after their treatment. By 
implementing a multimodal intervention to improve sexual function, we aim to enhance the QOL, mood, and 
intimacy of cancer survivors. 
1.2 
Background and Significance 
The NCCN identifies sexual dysfunction as a major issue affecting many cancer survivors.1 For allogeneic 
HCT survivors, sexual dysfunction is the most common and persistent long-term complication affecting 
patients’ QOL, mood, and intimacy.2-5 Nearly half of HCT survivors are dissatisfied with the quality of their 

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sexual life.6 Studies have clearly documented worse psychosexual functioning in HCT survivors compared to 
healthy subjects and to those treated with chemotherapy alone.2,3 Notably, 45% of men reported a significant 
decline in quality and quantity of sexual function at 6 months, 1, 2, and 3 years after HCT compared to prior to 
transplant.5 Moreover, 40% of women are not sexually active at any time point post-HCT. 5 Thus, many 
allogeneic HCT survivors endure a significant and rapid deterioration in sexual function, which persists 
for many years after their treatment. 
 
Sexual health plays a central role in one’s identity, QOL, and self-esteem;2 thus it is not surprising that sexual 
dysfunction causes increased distress and negatively impacts the QOL of cancer survivors.7-10 Research has 
shown that sexual function is associated with QOL, fatigue, relationship satisfaction, emotional well-being, 
anxiety, and depression.3,11 Therefore, improving patient’s sexual function post-transplant may have 
significant effects on their QOL and psychological distress, and decrease the overall morbidity of 
allogeneic HCT.  
 
Allogeneic HCT survivors experience diverse problems affecting their sexual function.2 Sexual 
complications include decreased libido, decreased pleasure, vaginal alterations, erectile and ejaculatory 
dysfunction, delay or absence of orgasm/ejaculation, premature menopause, sex hormonal deficiencies, 
dyspareunia, and infertility.3,12-17 Moreover, GVHD can affect the genital tract leading to vaginal stenosis and 
scarring.  It can also cause scarring, adhesions and long-term injury to blood vessels with resulting arterial 
insufficiency, which manifests as erectile dysfunction in men and potentially anorgasmia in women. Finally, 
transplant itself can result in dermatologic changes and increased skin sensitivity affecting the genital 
tract.14,17,18 Lastly, problems with body-image, self-confidence, fear of disease recurrence, anxiety, depression, 
and concerns about infertility all play a major psychological role in affecting sexual function in transplant 
survivors.19-22 Sexual dysfunction post-transplant is multi-factorial and requires a multimodal approach 
to care. 
 
Despite its prevalence, health care providers are reluctant to address sexual dysfunction with cancer 
survivors.4,16,23,24 In addition to insufficient time during an outpatient clinic visit, clinicians also site lack of 
training and discomfort as barriers to discussing sexual dysfunction with their patients.1,25 Interestingly, patients 
who participated in a discussion with their health care provider about sexuality reported fewer sexual 
functioning problems at 3 years post-transplant compared to those who did not have any discussions.4 
Interventions are critically needed to improve the rate and content of conversations between clinicians 
and patients about sexual functioning post-HCT.  
 
In addition to encouraging clinicians to discuss sexual health issues with their patients, we must develop 
interventions to improve patients’ sexual function. Despite the tremendous well-documented burden of 
sexual dysfunction on allogeneic HCT survivors, interventions to improve sexual function are lacking.2 
Importantly, given the diversity of problems affecting sexuality in allogeneic HCT survivors, interventions must 
include a comprehensive assessment and a multimodal approach to address the diverse needs of this 
population.2 While effective strategies exist to treat both female and male sexual dysfunction, 
interventions are critically needed to integrate these strategies into the care of allogeneic HCT survivors 
with an emphasis on their specialized needs. 
 
In this project, we aim to develop and evaluate a multimodal sexual dysfunction intervention for 
allogeneic HCT survivors. We will assess the feasibility and preliminary efficacy of the intervention in 
improving sexual function, QOL, and mood in transplant survivors. We will also use qualitative methods to 
explore patient’s perception of the acceptability, content, and efficacy of the intervention and their preferences 

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for the timing of its delivery in the survivorship course. Data from this work will help inform a large-scale 
randomized study of a sexual dysfunction intervention for allogeneic HCT survivors. 
1.3 
Preliminary Studies 
Quality of Life and Mood of Patients and Family Caregivers During Hospitalization for HCT26 
We conducted a prospective longitudinal study of patients undergoing HCT to assess the impact of transplant 
hospitalization on patients’ QOL and mood. We enrolled 97% of potentially eligible patients undergoing HCT. 
We administered patient reported measures to assess QOL and mood both weekly during their transplant 
hospitalization and at a follow up outpatient clinic visits, with a missing data rate of only 20%. Of note, we did 
not have any missing data from the outpatient clinic visits. This work demonstrates our research team’s success 
in conducting longitudinal studies on patients undergoing HCT. Additionally, the findings from this work were 
used to develop a palliative care intervention specifically addressing the needs of patients undergoing HCT, 
which is currently being tested in a randomized clinical trial. Therefore, our team has prior experience 
developing innovative interventions targeting the needs of a particular population.  
 
Randomized Study of a Targeted Palliative Care Intervention in Patients Hospitalized for HCT 
We are currently conducting a randomized trial to evaluate the impact of a palliative care intervention on 
patients’ QOL, mood, and symptom burden during hospitalization for HCT. The study opened for enrollment in 
August 2014 and to date we have enrolled 57 of 60 (95%) eligible participants. Only one participant (2.5%) 
withdrew and did not complete all patient reported measures. This work highlights our research team’s 
experience conducting supportive care interventions in patients undergoing HCT. Moreover, it demonstrates our 
ability to successfully recruit and enroll transplant patients in intervention studies. 
2 Objectives 
Quantitative Objectives and Hypotheses: 
 
1. To evaluate the feasibility of implementing a multi-modality sexual dysfunction intervention for 
allogeneic HCT survivors. 
 
Hypothesis: We will be able to recruit 75% of patients who screen positive for sexual dysfunction causing 
distress to participate in a sexual dysfunction intervention, and 80% of participants will attend at least one 
additional follow-up or referral visit. 
 
2. To determine the preliminary efficacy of the intervention in improving sexual function, QOL, and 
mood. 
 
Hypothesis: Participants will have improved sexual function, QOL, and mood at 6 months post-intervention 
compared to baseline. 
 
Qualitative Objective: 
1. To explore patients’ perception of the acceptability, content, and efficacy of the intervention, as well 
as the optimal timing for intervention delivery during the survivorship course. 

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3 Research Subject Selection 
3.1 
Study Subject Selection: 
We will recruit 53 allogeneic HCT survivors who are at least 3 months post-HCT and without evidence of 
disease from Massachusetts General Hospital bone marrow transplant clinic to participate in this prospective 
pilot study.   
 
Patients Eligibility criteria: 
1. Adult patients (≥18 years) with hematologic malignancy who underwent an allogeneic HCT at least 3 
months prior to study enrollment. 
2. Ability to speak English or able to complete questionnaires with assistance required from an interpreter or 
family member. 
3. Positive screen for sexual dysfunction that is causing distress based on the NCCN survivorship guidelines. 
 
Patient Exclusion criteria: 
1. Patients with relapsed disease post-HCT. 
2. Significant psychiatric or other co-morbid disease, which the treating clinician believes prohibits the 
patient’s ability to participate in the informed consent procedures. 
4 Research Subject Entry 
4.1 
Study Research Subject Entry 
A total of 53 patients with hematologic malignancies who are 3 months after allogeniec HCT will participate in 
this study. All MGH transplant oncologists and nurse practitioners have agreed to participate in the study.   
 
The research team will screen the weekly transplant clinic schedule to identify potentially eligible patients. The 
research staff will then inform the transplant clinician that the patient is eligible and inquire about any concerns 
regarding his or her study participation. If the transplant clinician has any objections regarding the patients’ 
participation, we will document the reasons and not approach those individuals. If there are no concerns 
regarding study participation, the research team will attach a notification form to the patient’s check-in sheet 
upon arrival to the transplant clinic. The form will instruct the transplant clinician to screen the patient for 
sexual dysfunction using the two-question approach based on the updated 2015 NCCN survivorship guidelines: 
1) do you have problems with sexual function?; and 2) Are these problems causing you distress? The transplant 
clinician will then offer study participation for those individuals who screen positive for sexual dysfunction 
causing distress.  If patients are interested in study participation, a member of the research team will then will 
review the consent form with potential participants, which will clearly detail the nature of the study procedures, 
the time requirements, and frequency of the self-report questionnaires.  The research team member will obtain 
written informed consent from participants and provide them with a copy of the signed consent form.   
 
Study participants will complete baseline self-report assessments at the time of obtaining informed consent for 
the study or within the 72 hour window from study enrollment.  Patients who provide informed consent and 
complete baseline questionnaires will then be registered with QACT and scheduled for their first study 
intervention visit on the same day as their regularly scheduled subsequent follow-up visit.  

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4.2 
Registration and randomization procedures 
4.2.1 General Guidelines for DF/HCC and DF/PCC Institutions 
  
Institutions will register eligible participants with the DF/HCC Quality Assurance Office for Clinical Trials 
(QACT) central registration system. 
  
An investigator will confirm eligibility criteria and a member of the study team will complete the QACT 
protocol-specific eligibility checklist. 
4.2.2 Registration Process for DF/HCC and DF/PCC Institutions 
  
The QACT registration staff is accessible on Monday through Friday, from 8:00 AM to 5:00 PM Eastern 
Standard Time. 
  
The registration procedures are as follows: 
  
• Obtain written informed consent from the participant prior to the performance of any protocol specific 
procedures or assessments. 
 
• Complete the QACT protocol-specific eligibility checklist using the eligibility assessment documented 
in the participant’s medical record and/or research chart. To be eligible for registration to the protocol, 
the participant must meet all inclusion and exclusion criterion as described in the protocol and reflected 
on the eligibility checklist. 
 
• Fax the eligibility checklist(s) and all pages of the consent form(s) to the QACT at 617-632-2295.  
 
• The QACT Registrar will (a) review the eligibility checklist, (b) register the participant on the protocol, 
and (c) randomize the participant when applicable. 
 
• An email confirmation of the registration and/or randomization will be sent to the Overall PI, study 
coordinator(s) from the Lead Site, treating investigator and registering person immediately following the 
registration and/or randomization.  
4.2.3 General Guidelines for Other Investigative Sites: Not applicable 
  
4.2.4 Registration Process for Other Investigative Sites: Not applicable 
5 
Study Design and Methods  
5.1 
Design/ Study Type 
The proposed project will proceed in two phases. During phase 1, we will conduct a prospective pilot study 
assessing the feasibility and preliminary efficacy of the intervention in improving patients’ sexual function, 
QOL, and mood (quantitative objectives). During phase 2, we will conduct qualitative interviews with patients 
who completed the intervention to explore their perceptions of its acceptability, content, and efficacy, and the 
optimal timing for its delivery during their survivorship course (qualitative objective). 

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5.2 
 Study Procedures:  
We will recruit 53 patients with hematologic malignancies 3 months after allogeneic HCT who report having 
sexual dysfunction causing distress for this study.  Once written informed consent is obtained, patients will 
receive an outpatient multimodal sexual dysfunction intervention . The interventionist will rescreen the patients 
at the beginning of their initial visit. If patients no longer experiences sexual dysfunction before their initial 
study visit, they will considered ineligible for the study as they are no longer experiencing distress relating to 
sexual dysfunction. Because these patients have already signed consent, they will count towards accrual, but 
will no longer be eligible to participate in the intervention.  
 
Prior to patients’ enrollment on this study, we will train a total of two transplant clinicians regarding how to 
assess and address sexual dysfunction in the transplant clinic. Dr. Don Dizon is the Director of the MGH Cancer 
Center Sexual Health Clinic and a world-renown expert on sexual dysfunction in cancer survivors. He will first 
provide transplant clinicians with reading materials regarding how to assess and address sexual dysfunction.  
The transplant clinicians will review this literature prior to their didactic training sessions with Dr. Dizon. Dr. 
Dizon will then conduct two training sessions with the same two transplant clinicians prior to study enrollment 
to ensure they acquire the necessary skills to implement the sexual dysfunction intervention in the transplant 
clinic. One transplant MD and one experienced transplant nurse practitioner (NP) will be responsible for 
implementing the intervention in the transplant clinic.  
 
Dr. Dizon will first conduct a two-hour didactic training session with the transplant clinicians, focusing on the 
following areas: 
1) How to perform a comprehensive sexual function assessment: This includes a comprehensive assessment of 
prior and current sexual history with an emphasis on identifying the causes of sexual dysfunction. Dr. Dizon 
will review the sexual function questionnaires that he utilizes in the Sexual Health Clinic to identify causes of 
sexual dysfunction. These questionnaires will be completed by all study participants at baseline and will be 
available to the transplant clinicians to review prior to seeing the patients for an intervention visit. Dr. Dizon 
will review how to assess various aspects of sexual function including  libido, pleasure, orgasm/ejaculation, 
vaginal symptoms (for women), painful intercourse, erectile and ejaculatory function, premature menopausal 
symptoms, signs and symptoms of hormonal deficiencies, and psychological barriers to intimacy including 
body-image issues, self-confidence, anxiety, depression. 
 
2) Normalization of the topic and patient empowerment and education: Dr. Dizon will also train transplant 
clinicians regarding the optimal ways to discuss this sensitive topic.  He will review strategies to normalize the 
topic, create a comfortable environment for patients to ask questions, and empower them to become an active 
part of addressing their sexual health needs.  Dr. Dizon will focus on the language he utilizes in his clinic when 
speaking to patients regarding their sexual function. 
 
3) Therapeutic interventions for sexual dysfunction in men and women: Dr. Dizon will also outline therapeutic 
strategies to address the various causes of sexual dysfunction in men and women.  For full details regarding 
these interventions, please see section 5.5 (therapeutic interventions). 
 
4) When to refer patients for additional expertise: Dr. Dizon will teach transplant clinicians to identify patients 
with more complex sexual dysfunction needs including suspected psychological etiology for sexual 
dysfunction, relationship or intimacy problems, and women with significant vaginal symptoms requiring a 
vaginal examination.  
 

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Dr. Dizon will then conduct an additional 1-hour didactic session with the transplant clinicians.  This additional 
training session will involve case presentations to augment the clinicians’ understanding of the various causes 
and treatments of sexual dysfunction.   
 
Finally, the transplant clinicians will also attend two sexual health clinic sessions with Dr. Dizon to obtain 
clinical experience in evaluating and treating patients with sexual dysfunction. 
 
5.3 
Selection of study instruments 
• Demographics:  
Patients will complete a demographic questionnaire at baseline detailing their age, sex, race, ethnicity, religion, 
relationship status (FC will specify their relationship with patients), educational level, annual household 
income, and living situation [appendix A].  
 
• Participant-reported measures: We will administer the following questionnaires at baseline and 6 months 
after enrollment: 
• Male sexual function: We will utilize the PROMIS Sexual Function and Satisfaction measures for men 
including the following domains: Global satisfaction with sex life, interest in sexual activity, erectile 
function, and orgasm [Appendix B].27 
 
• Female sexual function: We will utilize the Female Sexual Function Index (FSFI), which identifies 
problems with sexual desire and interest, sexual arousal, lubrication, reaching orgasm, pain with intercourse, 
and emotional closeness during sexual activity [Appendix C].28 
 
• Patient-QOL: We will use the Functional assessment of Cancer Therapy-Bone Marrow Transplant (FACT-
BMT) to assess QOL, which has been validated for use in patients undergoing HCT [Appendix D].29 
 
• Mood: We will use the Hospital Anxiety and Depression Scale (HADS)30 to assess symptoms of 
psychological distress (depression and anxiety) [Appendix E], and the PHQ-931 to assess major depressive 
syndrome [Appendix F]. 
 
• Qualitative Data Collection: We will also conduct qualitative interviews with approximately 8 male and 8 
female patients from the phase I participant pool to participate in the second phase. Participants must 
complete the 6-month post intervention assessment in phase I prior to enrolling in phase II. We will use a 
semi-structured interview guide to 1) explore patients’ perception of the acceptability and content of the 
sexual dysfunction intervention; 2) explore patients’ perception of the efficacy; and 3) identify the optimal 
timing of intervention delivery during the survivorship course. We will audi-record the interviews, 
transcribe them by Audio Transcription Center in Boston, MA, and code and analyze them using NVivo 10 
software. 
 
 
5.4 
Administration and timing of self-reported measures: 
We will collect and enter all patient-reported data electronically using Research Electronic Data Capture 
(REDCap). The REDCap Survey is a tool for building and managing online surveys. Vanderbilt University, in 
collaboration with a consortium of institutional partners, has developed this software and workflow 
methodology for electronic collection and management of research and clinical trial data. Our research team has 
extensive experience using REDCap and will create and design the surveys in a web browser, with institutional 
information technology support. The REDCap Survey system offers secure, HIPAA compliant, web-based 

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applications that provide an intuitive interface for participants to enter data, with real-time validation rules at the 
time of entry. 
   
Participants will use tablet computers to complete questionnaires in clinic. If any participants refuse or are 
unable to complete the questionnaires on the computer, they will be permitted to use hard-copy paper versions. 
Participants who do not have a regularly scheduled clinic visit will be provided with remote access to REDCap 
system or paper-based questionnaire for home administration. The research team will contact patients twice to 
remind them to complete and return the surveys. If study participants fail to complete the surveys within the 
expected time point, we will report the data as missing and document the reason for incompletion. Table 1 
details the schedule for administering the self-report measures.  All participants will complete baseline 
evaluation within 72 hours of study enrollment.  All participants will then have a second evaluation at 6 months 
(+/- 2 weeks).  
 
Table 1 
 
Participant Measures 
Baseline (within 72 hours 
of informed consent) 
6 months from 
enrollment (+/- 2 weeks) 
 
Demographics 
X 
 
Male sexual function 
X 
X 
Female sexual function 
X 
X 
QOL (FACT-BMT) 
X 
X 
Depression/Anxiety (HADS) 
X 
X 
Depression (PHQ-9) 
X 
X 
5.5 
Description of Intervention 
The intervention will include the following two components: 1) assessing and treating sexual dysfunction in the 
transplant clinic; and 2) referring patients with more complicated needs to the sexual health clinic. During the 
first component, patients will attend up to two intervention visits with the trained transplant clinicians to assess 
and address sexual dysfunction.  If patients do not respond to the intervention delivered in the transplant clinic 
and/or they are deemed to have more complex sexual health needs, they will be referred to the sexual health 
clinic for additional expertise (second component). Therefore, the intervention entails both the intervention 
visits in the transplant clinic as well as any additional visits in the sexual health clinic. 
 
1. Primary sexual dysfunction intervention in the transplant clinic: We developed this multimodal 
intervention in collaboration with Dr. Don Dizon based upon 1) a comprehensive review of the NCCN 
guidelines on survivorship; and 2) a systematic review of the literature on sexual dysfunction affecting men 
and women. 
 
We will schedule all consented participants for a clinic visit with one of the three trained transplant 
clinicians specifically addressing sexual dysfunction, including the following elements: 
  
A. In-depth sexual function assessment: The trained transplant clinicians will conduct a comprehensive 
sexual function assessment based on the NCCN survivorship guidelines. They will utilize the baseline 
questionnaires completed by participants to identify factors contributing to sexual dysfunction.  Female 
participants will complete the Female Sexual Function Index (FSFI) and male participants will complete 
the PROMIS Sexual Function and Satisfaction measures for men. Additionally, the transplant clinicians 
will evaluate psychological causes for sexual dysfunction including self-confidence, body image issues, 
anxiety, and depression. Lastly, the transplant clinicians will evaluate patients for hormonal deficiencies, 

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GVHD affecting the skin and genitals, medication side-effects or substance abuse, and other 
comorbidities that may affect sexual function in men and women. 
 
B. Normalization, Empowerment, and Education: The transplant clinicians will provide information about 
sexuality in order to normalize these issues and affirm the importance of the topic. In addition, the 
transplant clinicians will educate patients on issues relevant to sexual health, including but not limited to 
the prevalence of sexual dysfunction post HCT. They will also elicit participants’ concerns regarding 
engaging in such a conversation. They will provide participants with educational materials focusing on 
sexual dysfunction in cancer survivors including the potential etiologies and contributing factors as well 
as helpful suggestions for management. The transplant clinicians will empower patients to ask questions 
and utilize these resources. 
 
C. Therapeutic Interventions: Additional interventions instituted in the transplant clinic will be directed 
towards the various etiologies affecting sexual function. Additional intervention visits may also be 
conducted over the phone to minimize the stress and travel of participants. Specifically: 
 
For men with: 
o Signs and symptoms suggestive of testosterone deficiency32: These include erectile dysfunction, low 
sexual desire, and delayed ejaculation, as well as other signs such as visceral obesity, reduced 
muscle mass, and low bone mineral density. Transplant clinicians will screen for testosterone 
deficiency. If total testosterone <230 ng/dL, they will start testosterone supplementation.  
o Erectile dysfunction32: Transplant clinicians will counsel male participants regarding risk factor 
modification including smoking cessation, weight loss, increasing physical activity, and avoiding 
access alcohol consumption. In addition, the transplant clinicians will prescribe and titrate 
phosphodiesterase inhibitors for the treatment of erectile dysfunction. 
  
For women with: 
o Signs and symptoms suggestive of menopause or treatment-induced amenorrhea25: These include 
vaginal symptoms, including dryness and dyspareunia, as well as more systemic signs, such as hot 
flushes and irritability. If present, transplant clinicians will offer participants hormone replacement 
therapy. However, acknowledging that some patients will not be interested in hormone replacement 
therapy, transplant clinicians will offer non-estrogenic therapies including gabapentin and/or 
selective serotonin inhibitors. 
  
o Dyspareunia: Patients will require a pelvic examination for complaints of dyspareunia and they will 
be referred to the sexual health clinic. 
 
For men and women with: 
• Skin GVHD: Transplant clinicians will treat signs of genitopelvic GVHD with local corticosteroid 
and/or tacrolimus creams. 
• Medication-induced sexual dysfunction: Transplant clinicians will identify potential offending 
agents and discontinue them if possible. When medications causing sexual dysfunction are 
necessary, the clinicians will prescribe treatment to enhance sexual function such as 
phosphodiesterase inhibitors. 
• Low desire secondary to depression treatment: Patients on antidepressant medication may 
experience a lack of desire. For these patients, transplant clinicians will offer the use of 
phosphodiesterase inhibitors. 

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We will schedule all participants for a 4-week follow-up intervention visit and/or referral to the MGH 
Cancer Center sexual health clinic (see specialty referral to the sexual health clinic). The objective of the 
4-week follow-up visit is to assess participants’ responses to specific therapies. 4-week follow-up visits 
can be conducted over the phone or in clinic at MGH. If participants do not report any improvement in 
their sexual dysfunction during the follow-up visit based on the transplant clinician’s assessment, they 
will be considered non-responders.  The transplant clinicians will then refer them to the sexual health 
clinic within 30 days. 
 
2. Specialty referral to the sexual health clinic: During the first transplant clinic visit, the transplant clinicians 
will refer the following participants directly to the MGH Cancer Center sexual health clinic: 
 
o Suspected psychological etiology for sexual dysfunction (self-confidence, body-image issues, 
depression, anxiety, and/or fear of disease recurrence). 
o Suspected relationship and intimacy problems. 
o Women participants with vaginal dryness, itching, and/or pain with intercourse: These women 
will require a vaginal examination to differentiate atrophic vaginitis from GVHD.  
o Participants with complex sexual needs as determined by the transplant clinicians.  
 
Dr. Don Dizon will evaluate all participants referred to the sexual health clinic at the MGH Cancer Center. He 
will conduct a comprehensive sexual assessment and individualize his treatment approach based on the needs of 
the study participants. Possible interventions will include: the use of lubricants, vaginal moisturizers, topical 
lidocaine, estrogen creams for atrophic vaginitis, local corticosteroid therapy for GVHD, dilators, testosterone 
to enhance male/female sexual desire, continuous and intermittent phosphodiesterase inhibitors, vacuum-
assisted erection devices, penile self-injections, intraurethral prostaglandins, and referrals for penile 
prosthesis.25  Moreover, Dr. Dizon will triage and refer participants with psychological causes of sexual 
dysfunction to psychiatry, cognitive behavioral therapy, and/or couples or sex therapy as appropriate. 
 
5.6 
Data Collection 
As discussion previously in section 5.4 (Administration and timing of self-reported measures), we will collect 
and enter all patient-reported data electronically using Research Electronic Data Capture (REDCap).  Our 
research team has extensive experience using REDCap and will create and design the surveys in a web browser, 
with institutional information technology support.  The REDCap Survey system offers secure, HIPAA 
compliant, web-based applications that provide an intuitive interface for participants to enter data, with real-
time validation rules (automated data type and range checks) at the time of entry. 
 
5.7 
Description of Study Process 
 
5.7.1 Study Instrument Administration 
Patients will use tablet computers to complete baseline and 6-month questionnaires in clinic.  If participants 
refuse or are unable to complete the questionnaires on the computer, they will be permitted to use paper 
versions.  Participants who are not present in the cancer center during the period of data collection will be 
provided with remote access to the REDCap system or paper-based questionnaires for home administration.  
The research team will contact patients twice to remind them to complete and return the surveys.  If study 
participants fail to complete the surveys within the expected time point, we will report the data as missing and 
document the reason for incompletion.   
 
5.7.2 Intervention Administration 

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Patients will be scheduled to meet with the trained transplant clinician for the sexual dysfunction intervention 
on the same day as their regularly scheduled follow-up visit. After the initial intervention visit, the participants 
will be scheduled for a 4-week follow-up visit with the trained transplant clinician and/or referral to the sexual 
health clinic. The objective of the 4-week follow-up visit is to assess participants’ responses to specific 
therapies. If participants do not report any improvement in their sexual dysfunction during the follow-up visit 
based on the transplant clinician’s assessment, they will be considered non-responders.  The transplant 
clinicians will then refer them to the sexual health clinic within 30 days. Once referred to the sexual health 
clinic, patients and Dr. Dizon may schedule additional visits as needed.  
 
5.7.3 Special Concerns 
We do not anticipate any complications with this study.  We have administered questionnaires to over 100 
patients in previous studies and there have been no complications. 
 
5.7.4 Compensation 
We will provide no compensation for participating in this study. 
5.8 
Adverse Reactions and Their Management  
5.8.1 Reporting Adverse or Unanticipated Events  
This study is evaluating the feasibility and preliminary efficacy of a sexual dysfunction intervention with 
minimal chance of causing harm.  We have administered study questionnaires to over 100 patients in previous 
studies with no adverse events.  While some of the items on the questionnaires are sensitive in nature, no 
previous study participants have withdrawn from the study. 
5.8.2 Anticipated Reactions  
Should participants exhibit or express distress or anger, they will be reassured by the Research Assistant that 
they need not answer any questions which they find upsetting.  They will also be reminded that study 
participation is voluntary.  If participants remain distressed, both the Principal Investigator and the transplant 
oncology team will be notified.  Should several participants express distress over an individual item, the 
research team will review the questionnaire and contact the IRB to consider removing it from the study. 
 
If participants report severe distress or suicidal ideations during the interview or while completing any of the 
questionnaires, the research team will inform the participants that there is an obligation to report this to the 
patients’ primary oncology team and the transplant social worker.  The oncologist and social worker will then 
determine the need to involve psychiatry and take further action as deemed necessary. The research team will 
review sensitive items regarding suicidal ideations immediately at the time of survey administration and will 
report any suicidal ideations to the oncology provider and social worker promptly prior to participants’ 
departure from clinic. 
5.8.3 Reaction Management  
Should participants experience distress, the outpatient transplant social worker will be contacted to see the 
participant.  All staff are familiar with how to contact the social worker via pager.  The transplant social 
workers at MGH have all agreed to be available to respond and help with the management of any adverse 
reactions. 
 
If participants report suicidal ideations during the interview or while completing any of the questionnaires, the 
research team will inform study participants that there is an obligation to inform their oncologist and the 

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transplant social worker.  The oncologist and social worker will then determine the need to involve psychiatry 
and take further action as deemed necessary. 
6 
Ethical and Legal Issues  
6.1 
Confidentiality  
All patient information will remain confidential and stored on Partners computers and in REDCap.  Identifiers 
such as name will only be used during the initial data retrieval process and can be destroyed once all data 
records have been obtained and data analysis completed. 
 
Participants’ response to survey questions will remain confidential unless there are active suicidal ideations 
confirmed by the research team.  Under these circumstances, as clearly stated in the patient consent form, 
participants will be informed that the research team has a formal obligation to inform the oncologist and the 
transplant social worker due to concern for participants’ safety.  The oncologist and the social worker will then 
determine the need to involve psychiatry and/or take further action as deemed necessary. 
7 
Statistical Analysis  
7.1 
Primary and secondary endpoints: 
7.1.1 Primary endpoint:  The primary endpoint of the proposed study is feasibility. We chose the sample size 
for this study based on the feasibility of completing the project during the proposed timeframe. The 
proposed intervention will be deemed feasible if it meets the following criteria: 
• At least 75% (95% confidence interval +/- 12%) of patients screening positive for sexual 
dysfunction causing distress agree to participate in the study and attend the first scheduled 
intervention visit. 
• At least 80% of participants (95% confidence interval +/- 11%) attend at least two intervention 
visits (either in the transplant clinic or specialty referral). 
7.1.2 Secondary endpoint: The following secondary endpoints represent the preliminary efficacy endpoints 
1. Change in sexual function from baseline to 6 months 
2. Change in QOL from baseline to 6 months 
3. Change in psychological distress scores (HADs and PHQ-9) from baseline to 6 months 
4. To qualitatively 1) explore patients’ perception of the acceptability and content of the sexual dysfunction 
intervention; 2) explore patients’ perception of the efficacy; and 3) identify the optimal timing of 
intervention delivery during the survivorship course. 

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7.2 
Sample Size Calculation:  
As stated in section 7.1.1, the primary endpoint of the proposed study is feasibility. We chose the sample size 
for this study based on the feasibility of completing the project during the proposed timeframe. The proposed 
intervention will be deemed feasible if it meets the following criteria: 
• At least 75% (95% confidence interval +/- 12%) of patients screening positive for sexual 
dysfunction causing distress agree to participate in the study and attend the first scheduled 
intervention visit. 
• At least 80% (95% confidence interval +/- 11%) of participants who attend the first visit will also 
attend at least one additional follow-up visit and/or specialty referral. 
These estimates are informed by our prior supportive care trial in HCT patients. We are currently conducting a 
study evaluating a palliative care intervention for patients undergoing HCT. In this study, we have successfully 
enrolled 40/44 (90.9%) of potentially eligible participants. Only one participant withdrew and did not complete 
the longitudinal follow-up (2.5%). Given the sensitive nature of the topic, we are making a conservative 
estimate of feasibility that 60% (0.75 X 0.80) of patients screening positive for sexual dysfunction will attend 
the first scheduled intervention visit and at least one additional follow-up and/or specialty referral visit. 
 
We will also select approximately 8 male and 8 female patients from the phase I participant pool to participate 
in the qualitative phase of this study. We chose approximately 8 male and 8 female patients for the qualitative 
study to ensure that we have sufficient number of patients to achieve thematic saturation. Additionally, we will 
purposefully select participants with varying times from their HCT to capture participants throughout the 
survivorship trajectory. Therefore, we will select approximately 5-6 participants who enrolled in the study 
within each of the following timeframes: 1) less than one year after HCT; 2) greater than one year, but less than 
two years after HCT; and 3) more than two years after HCT. 
 
7.3 
Stratification factors and intervention allocation plan for randomized studies: not applicable 
 
7.4 
Definition of an allowance in design for unevaluable/ineligible participants: No applicable 
7.5 
Analysis Plan: 
We will report baseline demographic and clinical characteristics of all study participants. The primary endpoint 
of the proposed study is feasibility. The proposed intervention will be deemed feasible if it meets the following 
criteria: 
• At least 75% of patients screening positive for sexual dysfunction causing distress agree to 
participate in the study and attend the first scheduled intervention visit. 
• At least 80% of participants who attend the first visit will also attend at least one additional 
follow-up visit and/or specialty referral. 
 
The secondary endpoints will include determining the preliminary efficacy of the intervention in improving 
QOL, mood, and sexual dysfunction (objective 2). We will utilize the paired t-test to examine changes in QOL 
(FACT-BMT), depression and anxiety (HADS, PHQ-9), and sexual dysfunction (PROMIS for males, and FSFI 
for females) scores from baseline to 6 months after initial intervention visit. In addition to examining 

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participants’ mood scores continuously as described above, we will also transform scores into dichotomous 
outcomes reflecting the presence or absence of clinically significant depression and anxiety symptoms ((HADS-
subscale score > 7)) and major or other depressive syndromes (PHQ-9). For the PHQ-9, a major or other 
depressive syndrome is diagnosed if a patient reports at least two of the nine symptoms of depression, with one 
of the symptoms being anhedonia or depressed mood.31 We will use the McNemar test on paired proportion to 
examine the change in these dichotomous outcomes from baseline to 6 months.  We chose 6 months to assess 
the preliminary efficacy of the intervention as this would allow participants sufficient time to attend at least two 
intervention visits targeting their sexual dysfunction within a reasonable timeframe for project completion. 
 
We will analyze the qualitative data using qualitative methodologies described by the NIH Best Practices for 
Mixed Methods Research in Health Science by Miles and Huberman’s text, Qualitative Data Analysis.33 The 
analyses will entail a multi-step process using coding and content analysis to explore 1) patients’ perception of 
the acceptability and content of the sexual dysfunction intervention; 2) patients’ perception of intervention 
efficacy; and 3) the optimal timing of intervention delivery during the survivorship course. This will involve 
coding to structure data into categories and creating groups according to the broader issues or themes. We will 
identify major and minor themes within each content area and we will extract and highlight messages. Two 
independent coders will examine discrepant, unexpected, or unclear data until agreement is reached. To assure 
the trustworthiness of our findings, we will take steps to maximize reliability and credibility including: 
investigator triangulation (using a multidisciplinary team of investigator), and team debriefs of the interview 
content. 
8 
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