Comparative Effectiveness of a Decision Aid for Therapeutic Options in Sickle Cell Disease
Phase: NA
Conditions: Sickle Cell Disease, Sickle Cell Anemia, Hemoglobin SS, Hemoglobin SC, Hemoglobin Beta Thalassemia
Sponsor: Emory University

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Krishnamurti – Decision Aid 
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Comparative Effectiveness of a Decision Aid for Therapeutic Options in Sickle Cell 
Disease 
NCT02326597 
5-17-2017 
  
 

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Krishnamurti – Decision Aid 
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Title: Comparative Effectiveness of a Decision Aid for Therapeutic Options in Sickle Cell 
Disease 
 
Grant: Patient-Centered Outcomes Research Institute 
 
PI: Dr. Lakshmanan Krishnamurti 
 
Coordinator: Diana Ross, MSN, RN 
 
Abstract: 
Background: Sickle cell disease (SCD) is an inherited disorder with chronic multi-system 
manifestations affecting 100,000 individuals in the US, largely of minority origin and associated 
with substantial morbidity, premature mortality, individual suffering, healthcare costs and loss of 
productivity. Disease modifying treatments such as Hydroxyurea, chronic blood transfusion and 
curative bone marrow transplantation are offered to patients based on physician preference and 
current practice informed by clinical trials. Decision aids are tools that could help translate 
evidence from these sources into practice by helping clinicians involve patients in making 
deliberate choices based on accessible information about the options available and their 
outcomes and to help them make decisions based on their values and preferences. 
 
Objective: The overarching goal of this project is to develop and implement a web based 
decision aid individualized to patient characteristics to help patients with SCD achieve more 
accurate perception of risks and benefits of treatment options and make decisions in 
congruence with their values and preferences. 
 
Methods: We will conduct needs assessments interviews as indicated by the data for saturation 
and validation of findings. We will conduct beta testing of the web-based decision aid to clarify 
development and validate findings. We will use a randomized controlled trial of the effectiveness 
of a web based decision aid to give patients accurate information about risks and benefits of 
therapies and enable them to make decisions based on their individual values and preferences. 
 
Outcomes: To provide accurate information to patients and caregivers about the risks and 
benefits of various treatments sore sickle cell disease and to enable them to make informed and 
involved therapeutic decisions based on their values, preferences and stated goals. 
 
 
 
Background: 
Sickle cell disease (SCD) is a major public health problem in the United States with an 
estimated 100, 000 individuals living with this disease 1. It is associated with significant 
morbidity caused by pain crises, acute chest syndrome, stroke, pulmonary hypertension, leg 
ulcers and irreversible organ damage 2. Quality of life is impaired in children and adults with this 
disease 3-6 and productivity is impaired, with a 40-60% unemployment rate in adult patients 7. 
The disease results in premature mortality, with a median age of death of 38 years 2, 8, 9. In 
2010 there were approximately 100, 000 hospital discharges in the United States for which SCD 
was the principal diagnosis. Mean hospital charges per admission were $15, 000, with the total 
annual charges in the US exceeding $1.5 billion 12. Approximately 70% of the patients were on 

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government sponsored medical insurance, predominantly Medicaid and Medicare. Sickle cell 
disease is thus the archetype of the chronic multisystem disease predominantly affecting a 
minority, disadvantaged population. 
 
Hydroxyurea (HU) has been demonstrated in placebo controlled multi-center clinical trials to be 
efficacious in reducing complications such as vasocclusive pain crises and acute chest 
syndrome in children and adults with SCD and in improving survival in adults 13-17. It is the only 
disease-modifying therapy and the only drug approved by the FDA for use in patients with SCD. 
While early studies demonstrated the benefit of HU therapy in adults with SCD 17, recent safety 
and efficacy data from the BABY-HUG study support the consideration of this therapy even in 
very young children 13. Patients who are adherent to treatment have been shown to have 
reduced health care utilization 18-21. Significant barriers remain, however, in the effectiveness of 
HU in real world circumstances 18. It is under prescribed, and when prescribed, underutilized by 
patients. Approximately 85% of SCD patients who receive an HU prescription never fill it 22-25, 
and the average refill prescription rate is reported as being as low as 58% 26. Patient-related 
barriers to adherence include time and transportation to a clinic and to pharmacy to obtain refills 
20. Over 20% of families refuse Hydroxyurea because of reasons such as fear of cancer or other 
side effects, concern about lack of efficacy, and unwillingness to take the medicine or come to 
clinic or pharmacy 22,23. 
 
Hematopoietic stem cell transplantation has been demonstrated to be curative in patients with 
SCD 27, 28. Only a minority of patients who meet eligibility criteria for transplantation, however, 
proceed with the treatment even when a matched sibling donor is available 29. The low 
utilization of curative strategies for SCD appears to be partly attributable to a lack of information 
about the technologies available to facilitate transplantation 30. Thus, the low uptake by patients 
of therapeutic interventions proven in clinical trials suggests, on the one hand, a lack of 
awareness of therapeutic options and, on the other, a potential discordance between endpoints 
in clinical trials and outcomes that are considered important by patients. 
 
There are minimal data about patient-related barriers to, and attitudes towards, the use of 
curative therapies in SCD. A systematic review of the research on barriers to care in patients 
with SCD did not identify any studies that specifically addressed patient-related barriers to the 
use of Hydroxyurea 31. The attitudes of patients with SCD toward the use of hydroxyurea (HU) 
therapy may contribute to the underutilization of HU in the United States, yet our understanding 
of these attitudes is limited 32. Of patients who have never taken HU, half reported receiving no 
information about HU, and 85% report believing that they would receive no improvement if they 
were to take HU 32. In making choices regarding transfusion, transplantation or HU, families are 
most influenced by perceived efficacy and safety 33. Thus significant gaps remain in the 
understanding of patient perspectives, in the provision of accurate information about risks and 
benefits of therapies and of incorporating patients’ values and preferences in offering treatment 
options. Thus, there is a need for research that helps to understand patient values and 
preferences and determines how to help patients make informed treatment decision in 
congruence with their values and preferences. 
 
Significance: 
The Salzburg statement 34 recognizes that clinicians have an ethical imperative to share 
important decisions with patients. Much of the care patients receive is based on the ability and 
readiness of individual clinicians to provide it, rather than on widely agreed standards of best 
practice or patients preferences for treatment. There is thus, a need to stimulate a two-way flow 
of information that encourages patients to ask questions, explain their circumstances, and 
express their personal preferences, and prompts clinicians to provide accurate information 

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about options and the uncertainties, benefits, and harms of treatment in line with best practice 
for risk communication. Further, information must be tailored to individual patient needs, it must 
be acknowledged that most decisions do not have to be taken immediately, and patients and 
their families should be given the resources, time and help to reach decisions. 
 
Decision aids are designed to help patients improve their knowledge of the options, achieve a 
more accurate perception of risk and benefits of treatment, participate actively in decision 
making, and make choices more in keeping with their values and preferences. In randomized 
controlled trials (RCTs) evaluating the efficacy of decision aids for people facing difficult 
treatment or screening decisions, decision aids performed better than usual care interventions 
in terms of: greater knowledge; lower decisional conflict related to feeling uninformed, c) lower 
decisional conflict related to feeling unclear about personal values; d) reduced the proportion of 
people who were passive in decision making ; and e) reduced proportion of people who 
remained undecided post-intervention11. When simpler decision aids were compared to more 
detailed decision aids, the relative improvement was significant in knowledge and there was 
some evidence of greater agreement between values and choice. 
 
The proposed study will create and pilot test, for the first time, a web based decision aid for 
therapeutic options in sickle cell disease and test in a randomized clinical trial the comparative 
effectiveness of a decision aid and standard clinical care in patients with SCD facing treatment 
decisions. Thus, this decision aid has the potential to helping patients make decisions on their 
treatment based upon high quality information according to their values and in accordance with 
their preferences, thus producing improvement in their health, wellbeing and quality of care in a 
manner which is meaningful to them. 
 
There exists a significant a gap between results of clinical trials and patient uptake and 
adherence with disease modifying therapies for SCD. An effective decision aid is likely to 
empower patients with accurate information tailored to their clinical condition and their values 
and preferences. We anticipate this is likely to help them better navigate treatment choices. 
Further, the web based decision aid is also likely to serve as a tool for clarification of patient 
values to themselves and to their healthcare providers. This is likely to influence the course of 
research in the direction of development of therapies that are in line with the values and 
preferences important to patients. 
 
 
Hypothesis:  
Our overarching hypothesis is that a web based decision aid individualized to patient 
characteristics can improve knowledge and help patients with SCD achieve more accurate 
perception of risks and benefits of treatment options and is associated with lower decisional 
conflict than standard care. To test our hypothesis we propose the following specific aims: 
 
Aim 1: Develop a health literacy sensitive, web based, decision aid to help patients with 
sickle cell disease make informed choices about treatment options such as hydroxyurea, 
chronic blood transfusion, bone marrow transplantation and standard comprehensive 
care. 
 
Aim 2: To estimate in a randomized clinical trial the effectiveness of the decision aid 
tailored to individual patient characteristics on patient knowledge, patient involvement in 
decision-making and decision-making quality, when compared with usual care. 
 
Aim 3: To validate decision aid in Hindi language 

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Research Questions:  
1. What are the needs of patients with sickle cell disease and their parents/caregivers 
when considering treatment options for sickle cell disease?  
2. Does the use of a decision aid result in improvement of patient knowledge, patient 
involvement in the decision, the congruence of their decision with their values and 
preferences? 
 
3. Is the Hindi version understandable and useable by patients? 
 
 
Expected Outcomes: 
1. Collection and analysis of qualitative interviews using an open-ended semi-structure 
interview guide will provide understanding of patient and parent/caregiver knowledge, 
expectations, values, barriers and needed support that needs to be provided in a 
decision aid tool. 
 
2. Based on the goals of the decision aid to provide accurate information to patients and 
caregivers about the risks and benefits of various treatments and to enable them to 
make informed and involved therapeutic decisions based on their values, preferences 
and stated goals we propose the following outcomes: 
 
a) Impact on patient knowledge and understanding of treatment risks and benefits. 
Patient knowledge will be tested by using a knowledge questionnaire. Since 
knowledge is different from understanding we will design questions that test 
understanding e.g., if they understand the concepts and meaning for e. g., of an 
80% survival by using different scenarios. 
 
b) Impact of the decision aid on the decision making process and on the treatment 
decision, including the extent of patient involvement, the specific decision made, 
satisfaction with the decision-making process and with the decision. Patient 
involvement in decision making will be tested using a Patients' Perceived 
Involvement in Care Scale38,39. 
 
c) Psychological impact of decision aids on decisional burden, decisional conflict 
and decisional regret. Decisional conflict will be measured using a decisional 
conflict scale. Decisional conflict is evaluated using a validated decisional conflict 
scale 40,41. Decisional regret will be evaluated by using a validated decision regret 
scale42. Decisional burden will be evaluated using a validated decision burden 
scale43. 
 
d) Uptake, adherence and satisfaction with therapeutic option discussed. Within 4 
months following discussion with the physician/healthcare provider we will also 
survey patients to determine their uptake, adherence with, and satisfaction with, 
the therapeutic option discussed. 
 
3. The Hindi version of the decision aid will be comprehensible and useable as 
demonstrated by beta testing. 
 
 
 

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Methods 
 
Study Design for Qualitative Interviews Decisional Needs Assessment 
After consenting by a research team member via telephone or in-person, an in-depth needs 
assessment of participants age =>8 years with sickle cell disease and parents/legal 
guardians/caregivers of individuals (of any age) with sickle cell disease and will be scheduled 
for an interview within 6 weeks of consent. Additionally, stakeholders and healthcare providers 
may be recruited for participation. Interviews will be completed via in-person or telephone 
interaction. Interviewers will use a semi-structured open-ended question guide developed based 
on the Ottawa Decisions Support Framework workbook, Decisional Needs Assessment in 
Populations. Interviews may also be based on a need to expand knowledge of previous 
interviews. Using qualitative iterative process, questions design will be analyzed after every 3 to 
5 interviews, allowing for increased focus of questions based on themes and issues identified 
during ongoing analysis. Per qualitative data collection and analysis methods, this process 
allows for greater clarification of emerging themes and concepts. Interviews will take up to 45 to 
60 minutes. Interviews will be audio recorded and transcribed verbatim for later analysis. 
Interviews will be conducted in a private setting, away from parents, family, caregivers and 
clinical staff. Research staff may visit the clinic for observation and to collect field notes related 
to clinic management prior to and during recruitment. These field notes will allow the research 
team to better understand current practice related to clinical practice and allow for better 
refinement of the decision aid. No patients will be identified in the field notes and identifiable 
incidents will not be recorded. There will be no audio recording of these clinic observational 
visits. 
 
Demographic information will be collected including but not limited to age, gender, marital 
status, education level and role in sickle cell disease (patient, caregiver, stakeholder, provider). 
Additionally patients and parents/legal guardians of patients will be asked to self-report 
information regarding themselves or the patient they care for  including but not limited to patient 
age, gender, education level, marital status, genotype, insurance type, history of HLA typing, 
number of hospitalizations for sickle cell related complications in the past 2 years. No PHI will 
be accessed for these qualitative interviews. 
 
 
Study Design for Beta Testing 
After consenting by a research team member in person or via telephone, review of the web-
based Sickle Cell Decision Aid will be reviewed with participants, age =>8 years with sickle cell 
disease and parents/legal guardians/caregivers of individuals (of any age) with sickle cell 
disease will be scheduled for an interview and review of the website within 6 weeks of consent. 
Additionally, stakeholders and healthcare providers may be recruited for participation.  
Interviewers will demonstrate in-person or describe over the telephone use of the website, 
including navigation and the elements of the site. Participants will then be asked to navigate the 
site. As the participant navigates the site, the interviewer will ask the participants to describe 
thoughts about the site, including but not limited to ease of navigation, content and construction.  
Beta testing may be performed in-person or via telephone. Using qualitative iterative process, 
questions design will be analyzed after every 15-30 interviews, allowing for increased focus of 
questions based on themes and issues identified during ongoing analysis. Per qualitative data 
collection and analysis methods, this process allows for greater clarification of emerging themes 
and concepts. Interviews will take up to 60 to 90 minutes to complete. Interviews will be audio 
recorded and transcribed verbatim for later analysis. Interviews will be conducted in a private 
setting, away from parents, family, caregivers and clinical staff. 

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Demographic information will be collected including but not limited to age, gender, marital 
status, education level and role in sickle cell disease (patient, caregiver, stakeholder, provider). 
Additionally patients and parents/legal guardians of patients will be asked to self-report 
information regarding themselves or the patient they care for  including but not limited to patient 
age, gender, education level, marital status, genotype, insurance type, history of HLA typing, 
number of hospitalizations for sickle cell related complications in the past 2 years. No PHI will 
be accessed for these qualitative interviews. 
 
Hindi Beta Testing 
After consenting by a research team member review of the web-based Sickle Cell Decision Aid 
will be completed with the participant (physician, parent/caregiver, or patient) using a computer 
or smart phone. Participants who are patients will be 16 years or older. Physicians will be 
hematologists, general practice physicians or bone marrow transplant specialists who provide 
health care services for patient with sickle cell disease. Research interviewers will record the 
interaction for later transcription and analysis. The interviewer will demonstrate logging onto the 
website then will ask the participant to navigate the site, reading and commenting on the various 
pages of the site. Interviewers will keep track of which pages were viewed by participants to 
ensure that the majority of, if not all, web pages are viewed during beta testing. The participant 
will be asked to discuss ease of navigation and the various educational elements and features 
of the site, including content and construction. Interviews will take up to 60 to 90 minutes to 
complete. Interviews will then be transcribed and analyzed for like themes. Interviews will be 
conducted in a private setting, away from parents, family, caregivers, and medical staff. 
 
Demographic information will be collected, including but not limited to age, gender, marital 
status, education level and role in sickle cell disease (patient, parent/caregiver or health care 
provider. Additionally, Parents/caregivers of patients and patients will be asked to self-report 
information regarding the person they care for with sickle cell disease or themselves, including 
but not limited to patient age, gender, education level, marital status, type of sickle cell disease, 
number of hospitalizations or emergency room visits in past year due to sickle cell pain. No 
medical records will be accessed for the purpose of collecting private health information. 
 
Study Design for Testing of Decision Aid 
For Cohort A, we will use a randomized controlled trial for the use of a web based decision aid 
to give patients with sickle cell disease and parent/legal guardian of children with sickle cell 
disease accurate information about risks and benefits of therapies and enable them to make 
decisions based on their individual values and preferences. Participants will complete surveys 
before, soon after and within 4 months following their discussion with their health care provider 
to determine impact of the decision aid on knowledge, involvement in the decision and on 
decisional conflict, quality and uptake and adherence with the therapies.  
 
For Cohort B we will use a mixed methods descriptive study design to determine the impact of 
the decision aid on quality and comprehension of information, and impact on daily life relating to 
management of sickle cell disease in patients <18 years of age.  
 
Cohort C - To better understand the effect of the decision aid in decision making and patient 
involvement as reported by the physicians consenting these patients (child and adult) for 
treatment will be asked to participate in the study. Health care providers will not be randomized. 
 
 
Randomization 

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After the consenting process is completed, adult participants will be assigned to Cohort A and 
will be randomized to the clinical trial control or intervention group. Further subdivision will be 
done by age, to include three age groups:  
1. Parent/legal guardian of children (age group of child < 18 years) 
2. Individuals with sickle cell disease =>18 years to <28 years 
3. Individuals with sickle cell disease =>28 years 
 
Participants <18 years will be assigned to Cohort B and will not be randomized.  
 
Health care providers will be assigned to Cohort C and will not be randomized. 
 
 
 
Cohort A 
 
Consenting/Visit 1 
After consenting in-person or via telephone, we will collect demographic information from adults 
with sickle cell disease including but not limited to age, gender, race, education, marital status, 
employment, religion, number of full and half siblings, as well as relationship, age and education 
of individual(s) who assists with sickle cell related healthcare decision making.  
 
We will collect demographic information from parent/legal guardian of children (<18 years of 
age) including but not limited to age, gender, race, education, marital status, employment and 
religion. Additionally we will collect demographic information about the child including but not 
limited to age, gender, race, education, number of full and half siblings). Additionally patients 
and parents/legal guardians of patients will be asked to self-report information regarding 
themselves or the patient they care for  including but not limited to patient age, gender, 
education level, marital status, genotype, insurance type, history of HLA typing, number of 
hospitalizations for sickle cell related complications in the past 2 years. No PHI will be 
accessed. 
 
Participants will be asked to complete the following study surveys at within 2 weeks following 
their office/clinic visit, questionnaires will be available in paper version and electronically: 
 
Acceptability of education (8 multiple choice, 2 short answer)  
 
Decision Self-Efficacy Scale (11 multiple choice) 
 
Decisional Conflict Scale (16 multiple choice) 
 
Values survey (14 multiple choice, 6 fill in the blank) 
 
Realistic Expectations (multiple choice) 
 
Preparation for Decision Making Scale (10 multiple choice) 
 
Knowledge Survey (25 multiple choice) 
 
Choice Predisposition and Decision (1 multiple choice and 4 fill in the blank) 
 
Stage of Decision Making (10 multiple choice) 
 
Participants => 18 years of age will complete: 
 
Emotional distress Anxiety  – short form 6a – participant version 
 
Depression – short form 6a – participant version 
 
Fatigue – short form 6a – participant version 
 
Pain interference  – short form 6a – participant version 
 
Physical Function – short form 8b – participant version 

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 
Ability to participate in social roles and activities – short form 6a – participant version 
 
 
Participants of children <18 years of age will complete: 
 
 Fatigue – short form 10 – parent proxy 
 
Mobility – short form 8 – parent proxy 
 
Peer relations  – short form 7 – parent proxy 
 
Anxiety  – short form 8b – parent proxy 
 
Depressive symptoms – short form 6b – parent proxy  
 
It is anticipated that these surveys will take 20-30 minutes to complete within 2 weeks following 
each visit. Surveys may be available via paper version and electronically. 
 
Participants in Cohort A who are assigned to the control group will receive education regarding 
treatment consideration from their healthcare provider/team as per standard practice (usual 
care). 
Participants in Cohort A who are assigned to the intervention group will receive education 
regarding treatment consideration from their healthcare provider/team as per standard practice. 
Additionally, they will be provided access to the decisional aid and will be provided with a unique 
access ID and password for purposes of this study. Participants will receive follow-up monthly 
via telephone call and/or e-mail to verify ability to access and navigate through website. 
 
 
Visit 2 
Participants will be scheduled for the second research visit to coincide with the completion of 
education presented by the healthcare provider/team. Participants will be asked to complete the 
study surveys within 2 weeks following the office/clinic visit via paper version or on-line. Self-
report information regarding themselves or the patient they care for will be updated relating to 
sickle cell disease management and complications since Consent/Visit 1. Participants will 
receive follow-up monthly via telephone call and/or e-mail to verify ability to access and navigate 
through website. 
 
 
 
 
 
Visit 3 
Participants will be scheduled for the final research visit within 4 months of the completion of 
education and discussion with their healthcare provider/team. Participants will be asked to 
complete the study surveys as well as either via paper versions or online within 2 weeks 
following this office/clinic visit: 
 
Decision Regret Scale (5 multiple choice) 
 
 
Additionally, a qualitative interview will be conducted with the participants within 4 weeks 
of visit 3 to evaluate the extent to which the method of educational tools (standard 
practice or decision aid) helped the participant to recognized that a decision needs to be 
made regarding treatment of sickle cell disease, to understand the values that affect the 
decision, and understand if and how these values were addressed with the health care 
provider. Interviews will take approximately 30-45 minutes for completion. Interviews will 

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be audio recorded and transcribed verbatim for later analysis. Interviews will be 
conducted in a private setting, away from family members and clinical staff. 
 
Self-report information regarding themselves or the patient they care for will be updated relating 
to sickle cell disease management and complications since Visit 2.  
 
Cross-Over  
After completion of final study visits/surveys and data collection, participants in the control group 
for Cohort A will be offered opportunity to visit the Decision Aid website. Participants will be 
given 4 weeks to review this site, at which time they will be asked to complete a series of 
questionnaires via paper version or electronically:  
 
Acceptability of education (8 multiple choice, 2 short answer)  
 
Decision Self-Efficacy Scale (11 multiple choice) 
 
Decisional Conflict Scale (16 multiple choice) 
 
Stage of Decision Making (10 multiple choice) 
 
Values survey (14 multiple choice, 6 fill in the blank) 
 
Realistic Expectations (multiple choice) 
 
Preparation for Decision Making Scale (10 multiple choice) 
 
Knowledge Survey (25 multiple choice) 
 
Choice Predisposition and Decision (1 multiple choice and 4 fill in the blank  
 
Decision Regret Scale (5 multiple choice) 
 
Participants => 18 years of age will complete: 
 
 
 
Emotional distress Anxiety  – short form 6a – participant version 
 
Depression – short form 6a – participant version 
 
Fatigue – short form 6a – participant version 
 
Pain interference  – short form 6a – participant version 
 
Physical Function – short form 8b – participant version 
 
Ability to participate in social roles and activities – short form 6a – participant version 
 
 
Participants of children <18 years of age will complete: 
 
 
 
Fatigue – short form 10 – parent proxy 
 
Mobility – short form 8 – parent proxy 
 
Peer relations  – short form 7 – parent proxy 
 
Anxiety  – short form 8b – parent proxy 
 
Depressive symptoms – short form 6b – parent proxy  
 
 
A qualitative interview will be conducted within 4 weeks of completion of the questionnaires to 
understand participant-perceived comparison of supportive care in decision making versus use 
of the Decision Aid tool. Participants will be asked to discuss the affect, if any, on their treatment 
decision prior to use of the Decision Aid tool. Participants will receive follow-up monthly via 
telephone call and/or e-mail to verify ability to access and navigate through website after 
receiving access to the decision aid. 
 

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Cohort B 
 
Consenting/Visit 1 
After consenting in-person or via telephone, we will collect demographic information from 
children (<18 years of age) including but not limited to age, gender, race, education, number of 
full and half siblings as well as information about the parent/legal guardian of the child including 
but not limited to age, gender, race, education, marital status, employment, and religion. 
 
Participants will be asked to complete the following study surveys within 2 weeks following each 
clinic/office visit: 
 
Decision Self-Efficacy Scale (11 multiple choice) 
 
Pediatric fatigue –  short form 10a 
 
Pediatric mobility  – short form 8a 
 
Pediatric pain interference –  short form 8a 
 
Pediatric peer relationship  – short form 8a 
 
Pediatric anxiety –  short form 8b 
 
Pediatric depressive symptoms  – short for 8b 
 
 
Surveys may be available on-line for distant participation. 
 
 
 
 
 
Visit 2 
Participants will be scheduled for the second research visit to coincide with their next clinic 
appointment or within 4 months of Visit 1. Participants will be asked to complete the study 
surveys via paper version or online within 2 weeks following the office/clinic visit. 
Self-report information regarding themselves or the patient they care for will be updated relating 
to sickle cell disease management and complications since Consent/Visit 1.  
 
 
Visit 3 
Participants will be scheduled for the final research within 4 months of Visit 2. Participants will 
be asked to complete the study surveys via paper version or online within 2 weeks following 
clinic/office visit. 
 
Additionally, a qualitative interview will be conducted with the child within 4 weeks following visit 
3 to understand the implications of education regarding sickle cell disease using the web-based 
decision aid tool on their daily lives: implementation of learned information to manage sickle cell 
disease, discussion with parent/legal guardian and/or healthcare provider regarding information 
gleaned from the decision aid tool, including conversations about potential treatment options. 
Interviews will take approximately 30-45 minutes for completion. Interviews will be audio 
recorded and transcribed verbatim for later analysis. Interviews will be conducted in a private 
setting, away from parents and clinical staff. 
 

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Self-report information regarding themselves or the patient they care for will be updated relating 
to sickle cell disease management and complications since Visit 2.  
 
 
Cohort C 
After consenting to participate in the study in-person or via telephone demographic information 
will be collected from health care providers including but not limited to education, years of 
practice, age, and gender after Cohort A visit 3. Health care providers will be asked to complete 
one questionnaire after Cohort A visit 3 interview and again after Cohort A visit 4 interview. It is 
anticipated that this survey will take no more than 5 minutes to complete. 
 
 
Physician determination of patient readiness for treatment decision making in sickle cell 
disease 
 
 
 
 
 
 
Study Population 
Study population may be drawn from among sickle cell patients, any patient who is post-bone 
marrow transplant for sickle cell disease, and the caregivers of pediatric patients who receive 
care at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta 
(Egleston, Hughes Spalding, and Scottish Rite locations) and various sickle cell clinics across 
the United States. Contact will be made with physicians and sickle cell foundations through list-
serves, professional conferences, and seminars regarding this study. Recruitment flyers will be 
provided for placement in patient/parent/caregiver common areas to physicians, clinics, and 
sickle cell foundations known to the research team across the country after permission has 
been obtained from these entities. Recruitment flyers will request individuals to contact the 
research team if interested in participation. Discussion with physicians will occur prior to 
placement of flyers for Decision Aid website testing to obtain physician understanding of the 
study. 
 
Recruitment of Women and Minorities as Research Subjects. Equal number of women and men 
are likely to be recruited. Majority of the patients will be of minority ethnic origin because of the 
demographics of distribution of SCD. The racial, gender and ethnic characteristics of the 
proposed subject population reflects the demographics of the study sites. We shall attempt to 
recruit subjects in respective proportion to these demographics. No exclusion shall be based on 
race, ethnicity, or gender. 
 
 
There is a minimal risk of breach of confidentiality of health information even though no medical 
data will be collected from official medical records/charts and only self-reported information will 
be collected from participants. Participants have the right to refuse to answer self-reported 
questions regarding their health or the health of family members. Any private data reported by 
participants related to sickle cell disease will be maintained in a confidential file within the 
secure offices of the Hematology/Oncology Department. When collecting data from third parties 
(i.e. parents, caregivers, family) no names of patients with sickle cell disease, names of health 
care providers/medical facilities will be obtained. This is meant to decrease any possibility of 
patient identification. Participants in Cohort A and Cohort B will be informed that health care 

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providers will be made aware of their participation in Testing of Decision Aid due to the 
participation of health care providers in this study, Cohort C. 
 
 
Age range 
8 to 80 years, inclusive 
 
 
Inclusion Criteria 
 
Qualitative Needs Assessment Interviews and Beta Testing 
1. Individuals with sickle cell disease ages 8 to 80 years, inclusive 
2. Individuals who are post- bone marrow transplant for sickle cell disease 
3. Parents/legal guardians/caregivers (including significant others, family and friends) of 
individuals with sickle cell disease (newborn to 80 years) directly involved in decision 
making with/for that individual 
4. Parents/legal guardians/caregivers (including significant others) of individuals who are 
post-bone marrow transplant for sickle cell disease who are directly involved in decision 
making with/for that individual  
5. Stakeholders involved in any aspect of sickle cell disease 
6. Healthcare providers who are directly involved in sickle cell healthcare, including but not 
limited to physicians, nurse practitioners, physician assistants, social workers, and 
nurses. 
7. All participants will be able to comprehend English 
8. Patients <18 years may also participate in Testing of Decision Aid only if they complete 
the Needs Assessment Interview first. 
 
Beta Testing (additional) 
1. Access to the internet via smartphone, personal computer, tablet or other device 
allowing for access to the decision aid website for telephone interviews. (Computers may 
be provided for access during in-person interviews by the research team.)  
2. Patients will have sickle cell disease. 
3. Parents/caregivers will be directly responsible for care of child <18 years of age with 
sickle cell disease. 
4. Health care providers will provide direct care to patients with sickle cell disease. 
5. Participants will speak and read fluent Hindi for enrollment into the Hindi Beta testing 
portion of the study. 
 
Testing of Decision Aid 
1. Individuals with sickle cell disease ages 8 to 80 years, inclusive 
OR 
2. Parent/legal guardian of patients (age < 18 years) with sickle cell disease who are 
directly involved in decision making regarding sickle cell disease healthcare treatment 
OR 
3. Health care provider directly involved in care of individuals with sickle cell disease, 
including child of parent/legal guardian enrolled in study 
4. Patients/parents/caregivers who have made a past decision to not obtain treatment of 
the considered option or who have not obtained treatment of the chosen option in past 
12 months.  
5. All participants will be able to comprehend English 

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6. Patients/Parent/Legal guardian will have access to the internet from iPad, smart phone 
or personal computer 
7. Patients <18 years may participate in Testing of Decision Aid, Cohort B, if they have 
participated in the Qualitative Needs Assessment Interviews only if they complete the 
Needs Assessment Interview first. 
 
 
Exclusion Criteria 
 
Qualitative Needs Assessment Interviews 
1. Family members/Individuals/Caregivers not directly involved in decision-making 
regarding sickle cell disease healthcare. 
2. Family members/Individuals/Caregivers not directly involved in decision-making 
regarding healthcare for post-bone marrow transplant patients with sickle cell disease. 
3. Adult patient/parent/legal guardian participant in Testing of Decision Aid aspect of this 
study 
4. Healthcare providers who are not directly involved in care of sickle cell patients 
5. Stakeholders who are not involved in any aspect of sickle cell disease 
 
 
Testing of Decision Aid 
1. Family Members/Individuals/Caregivers not directly involved in decision-making 
regarding sickle cell disease healthcare.  
2. Patient/parent/legal guardian who has already made a decision to begin and has started 
the treatment option. 
3. Parent/legal guardian of child who is participating in Cohort B of this study. 
4. Child < 18 years of parent/legal guardian who is participating in Cohort A of this study 
and randomized to the control arm and not the decision aid arm. 
5. Spouse, significant other, or other family member involved in decision making for child 
<18 years if parent/legal guardian of child already enrolled into this study. 
 
 
 
Total number of subjects to be studied (including those screened for eligibility) in Qualitative 
Needs Assessment Interviews and Beta Testing: 
Up to 50. Sample size is dependent on data saturation during analysis and need for verification 
of findings. 
 
Total number of subjects to be studied in Hindi Beta Testing 
Up to 50 individuals will be consented for participation in the Hindi Beta Testing study. Sample 
size is dependent on data saturation during analysis and need for verification of findings. 
 
Total number of subjects to be studied (including those screened for eligibility) in Testing of 
Decision Aid: 
Cohort A: 120 
Cohort B: 25 
Cohort C: Up to 50 (depending on number of health care providers providing care to patient 
population in this study. 
 
 
 

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Sample Size Calculations for the Randomized Clinical Trial (Cohort A) 
We assume that patient involvement is 30% with standard care and we can double this with the 
intervention. Based on 90% power and 0.05 significance level we will require 110 patients, 55 in 
each group for comparing 2 binomial proportions44. To account for attrition we propose to recruit 
120 patients, 60 in each group treatment group with 20 in each of 3 age groups. 
 
 
 
Total Duration of Participation 
Qualitative Needs Assessment Interviews: 6 weeks 
 
Decision Aid Testing:  Up to 12 months 
 
 
 
Recruitment Methods 
Potential participants may be recruited from the Aflac Cancer and Blood Disorders Center of 
Children's Healthcare of Atlanta (Egleston, Hughes Spalding, and Scottish Rite locations) and 
the Georgia Comprehensive Sickle Cell Center at Grady Health System. Physicians will be 
notified via list-serves, at conferences and seminars of study recruitment. They will be asked to 
contact the study coordinator if interested in participating. We will provide patient recruitment 
flyers for placement in patient/parent/caregiver common areas in their office or clinic. 
Additionally, we will contact sickle cell foundations for assistance. We will ask that the 
recruitment flyers be placed on their websites. Recruitment flyers will request interested 
individuals to contact the research team if interested in participation. Discussion with physicians 
will occur prior to enrollment of subjects to obtain physician understanding of study. Patients 
and/or caregivers may be approached directly by research team members for participation in 
the needs assessment. 
 
Flyers with study information for study sections will be provided to the clinics and to the 
healthcare providers. 
 
Needs Assessment Interviews: Patients and/or caregivers may be approached directly by 
research team members for participation in the needs assessment. Physicians and other 
healthcare providers may also refer patients for possible participation. Potential participants may 
also contact the study coordinator directly using the contact information provided on the flyer if 
interested in hearing more about the study.  
 
Hindi Beta Testing Recruitment 
Health care providers will be notified by physicians involved in the study of the beta testing 
study. If interested, research staff will be notified and consent will be obtained if they desire 
participation. Physicians will be asked to identify potential patient and parent/caregiver 
participants. If potential participants agree to talk with research staff, the study will be introduced 
and, if interested, consent will be obtained. 
 
Decision Aid Testing: Sickle cell healthcare providers who see patients at these sites will be 
provided with study information and asked to present the study to patients who are considering 
a therapy new to their care (chronic blood transfusion, hydroxyurea, bone marrow 
transplantation). After the healthcare provider obtains permission from the patient, a research 
team member will approach the patient to introduce the study. 
 

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Consenting 
 
Needs Assessment Interviews: Potential participants may be introduced to the study by a 
member of the sickle cell healthcare team who will obtain permission for the individual to be 
approached by a member of the research team. Patients and/or caregivers may be approached 
directly by research team members for participation in the needs assessment. The potential 
participant may also directly contact the study coordinator via contact information provided on 
the study flyer. Screening for eligibility will be completed. If eligible, and the individual is 
interested, the consent will be verbally reviewed, including expected study activities, and 
potential risks and benefits. The individual will have an opportunity to discuss potential study 
participation with significant others, including caregivers and other family prior to consenting. All 
questions will be answered by a member of the research team and/or the PI. If the individual 
agrees to participate, he/she will be verbally consented in-person or via telephone. 
 
Beta Testing 
Potential participants will be introduced to the study by a member of their healthcare team who 
will obtain permission for the individual to be approached by a member of the research team. If 
permission is obtained for discussion with the research staff, the research staff will introduce the 
study. The consent will be reviewed. All questions will be answered. If the individual is 
interested in participation verbal consent will be obtained. 
 
Decision Aid Testing: Potential participants will be introduced to the study by their primary sickle 
cell healthcare provider who will obtain permission for the patient to be approached by a 
member of the research team. The potential participant will be screened for eligibility. If eligible, 
and the individual is interested, the consent will be reviewed, including expected study activities, 
and potential risks and benefits. The individual will have an opportunity to take the consent 
home to discuss it with significant others, including caregivers and other family. The individual 
will also be given the opportunity to discuss it with his/her hematologist. All questions will be 
answered by a member of the research team and/or the PI. If the individual agrees to 
participate, he/she will be consented. A copy of the signed consent will be given to the 
participant. 
 
 
Analytic Methods 
Qualitative analysis will be performed using qualitative descriptive methods which is influenced 
and a similar to interpretive descriptive analysis. Qualitative descriptive 45,46 analysis requires 
less interpretation than other types of qualitative analysis, such as phenomenological or 
interpretive description. Qualitative description lends itself to a more straightforward analysis 
that, by the nature of its methods, lends itself to this study. Analysis of these data will rely on 
components of the Ottawa Decision Support Framework for development of a codebook. This 
framework provides operational definitions of needs in the decision making process, such as 
decisional conflict (uncertainty), knowledge and expectations, personal values, and 
support/resources available. Additionally, data will be quantitized or translated to numerical data 
for improved understanding of results 47. This method of analysis allows for quantification of 
themes, patterns, and idiosyncrasies unique to qualitative research that may otherwise be 
discarded as outliers in quantitative analysis 47.  
 
 
We propose a randomized controlled trial of decision aid vs. usual care to determine its impact 
on previously defined endpoints measuring decisional process and decisional quality. 
Avoidance of bias 

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Selection biases occur when the groups to be compared are different. We anticipate that 
randomization will avoid selection bias as well as volunteer or referral bias. A drop out analysis 
will be carried out to determine the contribution of attrition bias. Measurement biases involve 
systematic error that can occur in collecting relevant data and include, insensitive measure bias, 
expectation bias , recall or memory bias, attention bias, and verification or work-up bias. 
Systematic validation of the decision aid will avoid insensitive measure bias which occurs when 
instruments used are not sensitive enough to detect what might be important differences in the 
variable of interest. The risk of Expectation bias, when observers may err in measuring data 
toward the expected outcome will be avoided by masking or blinding the reviewer of the survey 
about the arm to which the patient was randomized . Recall or memory bias which can occur if 
outcomes being measured require that subjects recall past events will be avoided by 
administering surveys within days of the interaction with their health care provider. 
 
 
 
 
Human Subjects 
 
Protected Health Information 
Name, address, telephone number, and email address (if appropriate) will be recorded to 
facilitate contact with study subjects and to mail gift cards.  No other PHI will be collected or 
recorded.  
 
Third Party Information 
1. Information will be gathered from participants with sickle cell disease regarding 
individuals/family members (caregivers/parents/legal guardians) who assist with sickle 
cell healthcare decision making, including but not limited to relationship to participant, 
age, gender, marital status, education level of individuals/family members. 
2. Parent/legal guardian of the child with sickle cell disease will be asked information 
including but not limited to their relationship to that child, the child’s role in decision 
making regarding sickle cell healthcare, number of siblings the child has, demographic 
information such as gender, age, and education level of the child. 
 
 
Potential Risks 
There is a risk of breach of confidentiality. The web-based decision aid is maintained on a 
secure server and requires a unique individualized identification and password to log on. Users 
will be instructed to protect their log-on information, to not share it with anyone else, and to be 
aware of the presence of others when logging on to the site. All efforts will be made to avoid 
breach of confidentiality.  
 
There is a risk of discomfort with qualitative interviews. The participant is not required to answer 
and question he/she does not feel comfortable answering. The participant may speak with the 
primary investigator, his/her physician or a member of the healthcare team as needed.  
 
Potential Benefits 
There are no direct benefits for participation in the Needs Assessment interviews though 
information learned may be used to benefit others in the future. There is a potential benefit of 
participating in Testing Decision Aid secondary to increased access to information that may 
increase the ability to make an informed values based decision regarding sickle cell treatment. 

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Data and Safety Monitoring Plan 
Research staff directly involved in the study will have access to data collected during this study. 
Paper documents will be filed in a locked filing cabinet in a secure office setting. Electronic data 
will be maintained on a secure Hematology/Oncology share-drive with limited access behind a 
secure firewall at Emory University. Participant data will be identified with a unique number. The 
key connecting the participant to the ID number will be maintained separately from the study 
data and will be destroyed upon completion of the study, to include dissemination of findings. 
The ID key will be accessible only to members of the research team. All audio recordings will be 
identified on the recording with the unique participant identification number. All transcripts will be 
identified using the participant identification number and names of parents and health care 
providers will be indicated with “XXX” in the transcription. Audio transcriptions will be destroyed 
after transcription is complete and verified, analyzed and findings are disseminated.  
 
The data and safety monitoring team will include the Principal Investigator and the study 
coordinator. Meetings will occur every 3 months from time of enrollment of the first patient. 
DSMP reports will be generated for each meeting. Any information regarding increased risks, 
modifications necessary to ensure patient safety, and adverse events will be discussed and 
submitted to the IRB according to established guidelines. All study data reviewed and discussed 
during these meetings will be kept confidential. Any breach in confidentiality will be reported to 
the IRB and regulatory agencies. The investigator will continue to review all available 
information and study results regarding this patient population. The PI will report to the IRB 
within 24 hours any serious adverse event occurring that is associated with this research study. 
Unexpected adverse events of moderate severity in associate with the research intervention will 
be reported to the IRB within 5 business days. Reporting of adverse events to sponsors and 
federal agencies will be the responsibility of the investigator. 
 
 
Withdrawal from Study 
The participant may withdraw from the study at any time by notifying the PI and/or the research 
team. All data collected up until the point of withdrawal will be included in data analysis. No 
further data will be collected. 
 
The participant may be withdrawn from the study if the participant does not participate in the 
educational process of usual care or if the participant assigned to intervention does not view the 
website prior to the next scheduled clinic appointment or does not show for the next 
appointment and does not reschedule that appointment within 4 weeks of the originally 
scheduled appointment.  
 
 
 
Compensation 
Study participants, (patients, parents/legal guardians) will be provided with a $25 gift card for 
each completed set of survey questions.  
 
Participants (patients, parents/legal guardians and caregivers) will be provided with a $25 gift 
card for completion of each qualitative interview.  
 
Healthcare providers and stakeholders will be given a sickle cell tie, bowtie or scarf for their 
participation in this study. 
 

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There will be no compensation provided for participation in the Hindi beta testing.