PTQA: A New Paradigm of Transfusion Decision Support for Patients With MDS
Phase: NA
Conditions: Myelodysplastic Syndromes
Sponsor: Dana-Farber Cancer Institute

Title: New Paradigm of Transfusion Decision Support for Patients with 
MDS: Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
NCT Number: NCT03660228 
Document Date: October 17, 2019 

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 1 of 42
DF/HCC NON-CLINICAL PROTOCOL TEMPLATE
Version Date: October 17, 2019
PROTOCOL TITLE:
A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs)
PRINCIPAL INVESTIGATOR:
Gregory Abel, MD, MPH
Division of Population Sciences
617-632-2304
Gregory_Abel@dfci.harvard.edu
VERSION NUMBER:
Version 4
DATE:
October 17, 2019
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 2 of 42
Table of Contents
1.0
Objectives .................................................................................................................3
2.0
Background...............................................................................................................4
3.0
Inclusion and Exclusion Criteria ..............................................................................8
4.0
Study-Wide Number of Subjects..............................................................................9
5.0
Study-Wide Recruitment Methods ...........................................................................9
6.0
Multi-Site Research ................................................................................................10
7.0
Study Timelines......................................................................................................10
8.0
Study Endpoints......................................................................................................11
9.0
Procedures Involved ...............................................................................................11
10.0
Data and Specimen Banking...................................................................................13
11.0
Data Management and Confidentiality...................................................................13
12.0
Provisions to Monitor the Data to Ensure the Safety of Subjects...........................16
13.0
Withdrawal of Subjects...........................................................................................16
14.0
Risks to Subjects.....................................................................................................16
15.0
Potential Benefits to Subjects .................................................................................17
16.0
Vulnerable Populations...........................................................................................17
17.0
Community-Based Participatory Research.............................................................17
18.0
Sharing of Results with Subjects ............................................................................17
19.0
Setting.....................................................................................................................17
20.0
Resources Available ...............................................................................................18
21.0
Prior Approvals.......................................................................................................18
22.0
Recruitment Methods..............................................................................................18
23.0
Local Number of Subjects ......................................................................................19
24.0
Provisions to Protect the Privacy Interests of Subjects ..........................................19
25.0
Compensation for Research-Related Injury............................................................19
26.0
Economic Burden to Subjects.................................................................................19
27.0
Consent Process......................................................................................................20
28.0
Process to Document Consent in Writing...............................................................20
29.0
Drugs or Devices ....................................................................................................20
REFERENCES ..................................................................................................................20
APPENDIX A: THE QUALMS........................................................................................23
APPENDIX B: FOLLOW UP SURVEY..........................................................................26
APPENDIX C: STUDY SCHEMA...................................................................................29
APPENDIX D: QUESTIONNAIRE REMINDER CALL................................................30
APPENDIX E: DSMP .......................................................................................................31
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 3 of 42
1.0
Objectives
1.1
Study Aims
The goal of this multi-center study is to determine how to tailor blood transfusion decisions to 
the quality of life (QOL) changes experienced by individual patients with myelodysplastic 
syndromes (MDS). We will assess this by piloting a peri-transfusion QOL assessment (PTQA) 
approach. The PTQA involves administering a QOL questionnaire (see Appendix A) to study 
participants before and after an upcoming transfusion appointment and comparing QOL scores. 
Specific Aim 1
Assess the feasibility of PTQA. We will assess the feasibility of this new paradigm of 
decision support by determining the enrollment yield as a percentage of all patients 
approached.  We will also assess feasibility by calculating the proportion of enrolled 
participants who complete both the pre- and post-transfusion the Quality of Life in 
Myelodysplasia Scale (QUALMS). 
Specific Aim 2
Assess the potential usefulness of PTQA in improving clinical and utilization 
outcomes. We will use medical record review and match our participants to historical 
controls (matched for transfusion group; IPSS-R; pre-transfusion Hb; and institution) to 
assess our primary outcomes, which are: 
1. The presence of second transfusion after PTQA (for transfusion-naive)
2. The number of red cell units used after PTQA (for transfusion-dependent)
3. The number of hospitalizations after PTQA (for both transfusion groups)
4. The number of clinic visits after PTQA (for both transfusion groups)
Specific Aim 3
Explore the potential impact of PTQA on patient-reported outcomes. At 8 weeks 
post-transfusion, we will send participants a follow-up questionnaire (see Appendix B) to 
assess the following secondary outcomes: 
1. PTQA utilization
2. Decisional regret
3. Perception of care
4. Perceived stress 
1.2
Study Hypothesis
We hypothesize that PTQA may help patients with MDS, primarily by decreasing 
transfusion use and its attendant iron overload. This includes patients who are starting 
transfusions (may hold off on additional transfusions if QOL does not improve) and the 
transfusion-dependent (may extend transfusion interval if QOL does not improve).
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 4 of 42
2.0
Background
2.1
Overview
The myelodysplastic syndromes (MDS) are bone marrow failure disorders that primarily 
affect the elderly. Up to 50,000 people are diagnosed with MDS each year in the United 
States 1,2, making them one of the most common hematologic malignancies. The disease 
can be clinically devastating, as patients who do not succumb to infections or bleeding 
often develop acute leukemia. Many also experience a severe decline in their QOL.3,4 The 
likelihood of increasing MDS incidence as the population ages has prompted the 
American Society of Hematology to include “finding an effective and personalized 
treatment” for MDS as one of its top research priority areas.5
While several potentially disease-modifying medications were approved in the mid-
2000s, progress has been slower since,6 and red cell transfusions remain a mainstay of 
care. Unfortunately, chronic red cell transfusions have many disadvantages, including 
iron overload,7 decreased overall QOL among the transfusion-dependent,8 and increased 
stress on the national blood supply.9 Moreover, some patients experience improved QOL 
after transfusions, others do not. 
While compromised QOL is often invoked to justify transfusions for patients with MDS, 
the question of whether or not QOL improves after transfusion remains unanswered due 
to several barriers.10,11 First, until recently, a rigorous tool to assess MDS-specific QOL 
did not exist. Second, research assessing when QOL concerns might outweigh 
physiologic ones has been limited by a lack of consensus regarding a minimum 
hemoglobin (Hb) that is safe for outpatients with MDS. Third, it has been difficult for 
researchers to systematically identify patients who would benefit from formal QOL 
assessment, such as those starting transfusions and the transfusion-dependent. Finally, 
while some patients likely experience improved QOL after transfusion, others do not, 
even at the same level of Hb. We thus propose that the key question is not whether 
transfusions improve QOL, but how to tailor transfusion decisions to the QOL 
changes experienced by individual patients living with MDS.
2.2
Relevant Preliminary Data
The QUALMS 
From 2011 to 2015, we developed12 and validated13 the Quality of Life in Myelodysplasia 
Scale (QUALMS), a rigorous QOL assessment tool for patients with MDS (see Appendix 
A and Protocols 10-461 and 13-346). With excellent internal consistency, known groups 
validity and responsiveness, the QUALMS has rapidly been incorporated into several 
MDS registries in the U.S., Canada, and Europe. In this current protocol, we will use the 
QUALMS to implement a new paradigm of transfusion support for patients with MDS 
that integrates peri-transfusion QOL assessment (PTQA). The PTQA will involve 
administering the QUALMS before and after red cell transfusions to determine whether 
the patient experiences any changes in QOL. Pre- and post-transfusion surveys will be 
scored, compared, and compiled in a report for patients and providers. These PTQA 
results will help guide future therapy decisions: if QOL post-transfusion is worse for a 
particular patient, a decrease in transfusions will be encouraged.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 5 of 42
Minimum Safe Hb Level
At present, the optimal transfusion strategy for outpatients with MDS remains unknown. 
While high-quality studies of liberal versus restrictive transfusion practices have been 
conducted for other patient populations, there are sparse data on the minimum Hb level at 
which it is safe to forgo transfusions for non-hospitalized patients with MDS.
TRICC, the first of several inpatient studies, demonstrated that a restrictive transfusion 
strategy (Hb threshold of 7.0 g/dL) was effective and possibly superior to a liberal 
transfusion strategy (Hb threshold of 10.0 g/dL) in decreasing the 30-day mortality of 
critically ill patients in the intensive care unit, with the possible exception of patients 
experiencing acute coronary syndromes.14 A second inpatient study, FOCUS, examined 
the effects of a restrictive transfusion strategy (triggered by symptoms of anemia or at 
physician discretion for a Hb of <8 g/dL) versus a liberal strategy (triggered by Hb 
threshold of 10 g/dL) on hip surgery patients with high cardiac risk. This study found 
that a liberal transfusion strategy did not reduce rates of death or disability with respect to 
60-day follow-up.15 TRACS, an additional inpatient study, found that a restrictive 
perioperative transfusion strategy (hematocrit less than 24%) was as safe as a liberal 
strategy (hematocrit less than 30%) in patients undergoing elective cardiac surgery.16 
The above studies focused almost exclusively on inpatients without bone marrow failure 
or MDS. In contrast, few studies have assessed transfusion strategies in patients with 
MDS. A 2015 Cochrane review regarding the impact of transfusion practices on patients 
with bone marrow failure syndromes such as MDS found only one completed 
randomized trial (13 subjects in the Netherlands, published as abstract only).11 The 
quality of the evidence was “very low” across different outcomes according to GRADE 
methodology, and the study mentioned did not report effects of transfusion on QOL. The 
reviewers did also identify two ongoing trials specific to MDS (one in Canada 
[NCT02099669] and the other in the UK [ISRCTN26088319]), each with an accrual goal 
of less than 40 patients, and both testing different Hb thresholds. The authors firmly 
concluded that “further randomized trials with robust methodology are required to 
develop the optimal transfusion strategy for MDS patients.”
For patients without MDS, the literature suggests a consensus on hemoglobin thresholds 
for restrictive versus liberal transfusion strategies. A 2016 Cochrane review of thresholds 
to guide transfusions found that among 31 trials—mostly of inpatients—about half used a 
restrictive transfusion threshold of 7 g/dL and the other half used a threshold between 8-9 
g/dL. The studies found no evidence that a restrictive transfusion strategy impacted 30-
day mortality or morbidity compared with a liberal transfusion strategy, although there 
was more uncertainty concerning patients with hematologic malignancies and bone 
marrow failure.17,18
In view of the sparsity of data, in March 2018 we conducted a qualitative study with 
MDS experts (see Protocol 18-064) to determine the lowest Hb level at which, given no 
end-organ effects of anemia, outpatients with MDS can safely forgo transfusions. We 
utilized the modified Delphi technique, incorporating elements from the Rand/UCLA 
Appropriateness method (RAM).19,20 This is a formal method of working with experts to 
achieve consensus, involving three rounds of assessments and anonymous feedback from 
experts to each other between rounds. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 6 of 42
Per Protocol 18-604, we convened an expert panel of 13 MDS physicians (12 MDS 
experts; 1 blood bank physician) at the national AAMDSIF Symposium to determine the 
minimum safe Hb level. All panel participants received a literature review and 
questionnaire via email prior to the in-person panel. This questionnaire comprised round 
one of the modified Delphi. Among several critical questions (see Protocol 18-604), we 
asked: “Please mark the lowest hemoglobin at which you think it would be safe to forgo 
transfusions for patients with MDS given no evidence of end-organ damage.”  Once we 
received participants’ responses, we tabulated them and provided a summary of the 
results to the experts at our in-person panel. We allowed time for open discussion of each 
question. Following this discussion, we asked participants to fill out a round two 
questionnaire, the results of which were compiled and disseminated via email. We then 
asked the expert panel to fill out a third round of questions via email. While we were 
unable to reach a consensus threshold of 75% after three rounds, we did have 100% 
consensus that the minimum safe Hb level should be no less than 7.5 g/dL. 
Accordingly, we will use this threshold to identify eligible patients for our study, 
meaning patients with an Hb level less than 7.5 g/dL will be ineligible for participation. 
Epic Workbench Report
To systematically identify patients who would benefit from PTQA, a member of our 
study team, Dr. Michael Hassett (Medical Director for Clinical Information Systems at 
DFCI), is currently working with DFCI’s Epic team to create a Workbench report. This 
report will identify patients with MDS that are facing transfusion decisions. Epic is an 
EHR that covers 190 million patients in the U.S., including at the three centers 
participating in this project. Since May 2015, Epic has been the enterprise EHR for 
DFCI/BWH. It was previously adopted by Yale Cancer Center (YCC; 2013) and Wake 
Forest Baptist (WFB; 2012), the other two pilot sites. 
Recent work has harnessed Epic data capture for cancer staging21 and surgical metrics;22 
Dr. Hassett is similarly working with the Partners Epic reporting group to create 
Workbench Reports to use in this current protocol. To ensure high quality care for 
patients who receive blood products, the Epic team at DFCI/BWH created sophisticated 
order sets to facilitate transfusion ordering. Using our Workbench Report, data elements 
from these sets will be mined to identify patients with MDS who might benefit from 
PTQA. 
Our Workbench Reports will identify (1) patients with MDS who have not yet been 
transfused, but have Hb levels approaching 8.5 g/dL during our study’s enrollment period 
(to identify those heading toward first transfusion); and (2) patients with more than one 
transfusion during an 8 week period (to identify the transfusion-dependent; we will use 
the IWG criteria,23 but not restrict to Hb ≤ 9.0]). We are working with the Epic teams at 
YCC and WFB to ensure that they are able to use an identical report at their institutions 
to systematically identify patients for PTQA at these sites.
2.3
The Basis for PTQA
Up to 90% of patients with MDS will receive red cell transfusions during the course of 
their disease, and many will become chronically dependent on them.8 Chronic 
transfusions also lead to an accumulation of iron that, in turn, can lead to cirrhosis, 
cardiomyopathy, and progressive endocrine dysfunction.24 Thus, potential overuse of red 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 7 of 42
cell transfusions by patients with MDS not only contributes to critical national blood 
shortages, such as the one experienced in July 2016,9 but also can be physiologically 
damaging. Moreover, transfusion dependency itself can lead to diminished QOL,25,26 and 
recent work has shown that MDS patients who are at the end of life often avoid hospice 
because of the potential difficulty receiving red cell transfusions there.27,28 One strategy 
to address these issues is to tailor transfusion only to those patients with MDS who 
benefit.
During our QUALMS validation study (see Protocol 13-346), we found that while some 
patients had improved QOL after transfusion, others did not, even at the same level of 
resulting Hb. We thus propose that a better question than “do MDS patients experience 
better QOL after transfusions” is “which MDS patients experience better QOL after 
transfusions.” The best way to determine if a specific patient with MDS benefits from 
transfusions is to measure the patient’s QOL, transfuse, and assess whether or not QOL 
improves. Such “peri-transfusion QOL assessment” (PTQA) is a paradigm shift because 
physicians would not be basing transfusion decisions on Hb level or prior transfusion 
history but on whether transfusion has an effect on the QOL of an individual patient at 
that time in their disease course. 
Recent studies have shown it is possible to collect patient-reported outcomes (PROs) 
such as QOL and use the results to drive clinical care.29,30 One 
analysis specifically demonstrated PTQA is possible, 
measuring the effect of red cell transfusions on PROs in an 
ambulatory oncology population, including 115 transfusion 
episodes.31 Patients were telephoned after 7 days to discuss 
fatigue, shortness of breath, and overall QOL. Of the total 
episodes, 71% resulted in at least one improvement, but for 
29%, there was none. If there is a similarly sized population of 
patients with MDS who do not experience improved QOL after 
transfusions, limiting their transfusion may be of great benefit 
in terms of reducing ferritin, burden of infusion visits, and 
overall red cell use.
3.0
Inclusion and Exclusion Criteria
3.1
Research Subject Eligibility Screening
Potential participants will be screened for eligibility using 
clinic schedule reports or the study-specific Epic Workbench report developed by Dr. 
Hassett (see above). Members of the study team at all three sites will be trained on the 
use of the study-specific Epic report. The report will generate a list of potentially eligible 
participants that will be further screened for eligibility by a designated member of the 
study team at each site (RA or RPM). 
At DFCI, we will ensure eligibility by following the appropriate SOPs (REGIST-100: 
Internal Eligibility Checklist & REGIST-104: Using the Eligibility Checklist). 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 8 of 42
3.2
Inclusion/Exclusion Criteria 
Inclusion criteria: 
1. Age > 18 years of age
2. Patients with MDS, including t-MDS and MDS/MPN
3. Transfusion-naive group: approaching Hb of 8.5 g/dL during enrollment period
a.
Ideally never-transfused (have never received red cell transfusion)
b. If not never-transfused, participants are also eligible for inclusion in this group if 
they have not been transfused with red cells within last 8 weeks
4. Transfusion-dependent group: Patients with >1 transfusion scheduled during 8-week 
period prior to enrollment
5. Ability to read and understand English
Exclusion criteria:
1. Age <18 years
2. Cr > 2
3. Known CHF
4. Unstable Angina
5. Hb level below 7.5 g/dL
6. No plans for potential future outpatient transfusion. 
3.3   Special Populations
Our study will exclude members of the following special populations:

Adults unable to consent

Individuals who are not yet adults (infants, children, teenagers)

Pregnant women

Prisoners
4.0
Study-Wide Number of Subjects
4.1
Accrual Goal
Our study-wide accrual goal is 60 evaluable participants. To reach this accrual goal, we 
will consent and enroll 90 participants as some participants are not able to complete the 
protocol due to a variety of reasons (e.g., participant does not end up requiring future 
transfusions). The 60 evaluable participants will be matched 1:1 to historical controls 
seen between 2015 and 2017, for a total sample size of 120. 
5.0
Study-Wide Recruitment Methods
5.1
NA – Our multicenter study will not be employing recruitment methods that are 
outside the control of the local sites (e.g., call centers, national advertisements).
5.2
NA
5.3
NA
6.0
Multi-Site Research
6.1
Communication Plan
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 9 of 42
As the lead site, DFCI will communicate study updates to participating sites (YCC and 
WFB) via phone call or email. For the duration of the study, the Research Project 
Manager (RPM) will ensure that all sites are using the most current version of the 
protocol and consent documents. YCC and WFB will be asked to send the DFCI study 
team all notifications of approval (including IRB approval of initial protocol, continuing 
reviews, and any study modifications). The DFCI study team will monitor the compliance 
of participating sites during monthly check-in phone calls. In the event of a study 
modification, potential modifications to the protocol will be discussed during monthly 
calls prior to implementation. 
The DFCI study team will be responsible for all monitoring activities related to the study 
across all sites. We will implement a risk-based monitoring approach where monitoring 
activities will be at the discretion of the sponsor/PI (Dr. Gregory Abel). 
We will monitor accrual during our monthly check-in calls. During these calls, we will 
ensure that all sites are enrolling between 1-2 patients per month. With regards to data 
monitoring, the DFCI RPM will review the RedCap database for missing/discrepant data 
every three months. The consent/eligibility for 10% of participants (2 at each site) will be 
verified with source documentation by the RPM. This will be done remotely and the 
participating sites will send the RPM the necessary source documentation.  
6.2
As this study is minimal risk, we do not anticipate any problems or reportable 
events. All other problems, interim results, and study updates will be communicated via 
our monthly study phone call.
6.3
NA
7.0
Study Timelines
7.1
Study Duration

Individual subjects will participate in the study for approximately 10 weeks from the 
time of consent. This includes the completion of the pre-transfusion questionnaire, the 
post-transfusion questionnaire, and the follow-up survey at 8 weeks after transfusion. 
We will assess the number of hospitalizations and clinic visits for each participant 8 
weeks after the index transfusion. 

We anticipate that it will take approximately 18 months to enroll 90 subjects across 
all three sites.

The estimated date for the investigators to complete this study is April 30, 2020. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 10 of 42
8.0
Study Endpoints
8.1
Study Outcomes
Primary Endpoints
Subjects will be compared with historical controls (matched for transfusion group; IPSS-
R; pre-transfusion Hb; and institution) seen 
between 2015 and 2017. For the transfusion-naive, the primary outcome will be receipt of 
second transfusion (yes/no) within 8 weeks following the index transfusion. For the 
transfusion-dependent, the primary 
outcome will be defined as number 
of units pRBCs received within 8 
weeks following the index 
transfusion. For both groups, we 
will also compare the number of 
hospitalizations and clinic visits 
during the 8 weeks after index 
transfusion (Table).
Secondary Endpoints
Secondary endpoints include 
decisional regret, perceptions of care, and perceived stress by the associated scales at two 
months post-transfusion (Table 1).
8.2
Safety Endpoints 
NA. There are no primary or secondary safety endpoints in our study. 
9.0
Procedures Involved
9.1
Study Design
We propose a prospective cohort pilot study where patients will complete the QUALMS 
survey before and after their first/next transfusion. We will aim to have two groups of 
study participants: (1) those that are approaching first transfusion and (2) those that are 
transfusion dependent (n=30 for each group).  
9.2
Study Procedures
Please see study schema (Appendix C) for study flow. 
Pre-Transfusion 
1. Once identified by Epic scheduling report, provider suggestion, or study-specific Epic 
Workbench report, eligible patients will be approached for consent discussion at an 
appointment with their provider. 

Patients with Hb approaching 8.5 g/dLwill be approached at an appointment prior 
to an upcoming transfusion. 

Patients that are transfusion-dependent will be approached at an upcoming 
appointment with their provider or during a transfusion appointment. 
2. During this initial encounter, consenting participants will be given a study packet 
containing a paper copy of the QUALMS. Study participants will be instructed to fill out 
the survey on the day before their upcoming pRBC transfusion. 
Table. Primary and Secondary Outcomes, Measured at Two Months after PTQA
Primary
Presence of second transfusion after PTQA (for those undergoing first transfusion)
Number of red cell units used since PTQA (for transfusion-dependent)
Number of hospitalizations since PTQA
Number of clinic visits since PTQA
Secondary
Decisional Regret
Decision Regret Scale.32 5-item scale provides indicator of health care decision regret; 
will be tailored to measure regret about transfusion decisions.
Perceptions of Care
“About Your Care” Domain of Prior DFCI Survey. We previously developed33 a 6-item 
domain based on the Consumer Assessment of Healthcare Providers and Systems 
Survey “health status” “access,” and “communication” domains.34 
Perceived Stress 
PSS-4.35-37 The PSS-4 was designed for use with patients with at least a junior high school 
education, and takes 3 minutes to complete. It contains four questions about feelings of 
control and overall stress, with simple response alternatives.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 11 of 42
3. Study participants will indicate whether they would like to receive PTQA reports in 
person, via mail, or via email. 
4. Site RAs will call study participants using script (see Appendix D) on the day prior to an 
upcoming transfusion to remind them to complete the QUALMS and bring it with them 
to their transfusion. 
5.  Note: Index transfusion is defined as any upcoming transfusion appointment for which 
the participant has completed both the pre- and post-transfusion QUALMS 
questionnaires.

If a participant does not complete the pre-transfusion questionnaire for any 
reason (i.e., participant forgot to complete at home or forgot to bring in), then 
the RA may ask the participant to complete the questionnaire at home prior to a 
subsequent transfusion appointment. This subsequent transfusion will become 
the index transfusion. 

If a participant does not complete the pre-transfusion QUALMS at home prior 
to the appointment and there are extenuating circumstances (i.e., participant 
does not regularly receive transfusions at the site), then the RA may ask the 
participant to complete the questionnaire in clinic before his/her planned index 
transfusion. 
Post-Transfusion
6. On the day of transfusion, the site RA will collect the completed pre-transfusion 
QUALMS survey. Study participants will then receive a second paper copy of the 
QUALMS, along with a stamped envelope addressed to the appropriate site. 
7. Participants will be instructed to complete this survey exactly one week after transfusion 
and return it using the pre-addressed, pre-stamped envelope. 
8. Site RAs will call participants using script (see Appendix D) to remind them to complete 
the QUALMS survey exactly one week after transfusion. 

The window may increase up to one extra week to accommodate for 
circumstances where the patient is un unable to complete the post-transfusion 
QUALMS (i.e., participant does not feel well or participant forgot). 
PTQA Report
9. Once received, the second assessment will be scored and compared with the first, and 
both the patient and provider will be sent a report with the results. The QUALMS 
validation study suggested that a clinically meaningful difference on the instrument is 
between 5 and 10 points;12 For this study: 

A post-transfusion score that is within 5 points of the pre-transfusion score will 
indicate a stable QOL

A post-transfusion score that increases by 5 or more points will indicate a 
clinically significant improvement in QOL

A post-transfusion score that decreases by 5 or more points will indicate a 
clinically significant decline in QOL 
10. In our report, we will include language that encourages patient and providers to use these 
results to inform their next transfusion decision, specifically suggesting that transfusion 
be halted or decreased in frequency if QOL has worsened. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 12 of 42
Secondary Outcomes Assessment
11. At 8 weeks post-transfusion, all participants will be sent a survey (Appendix B) to assess 
the utilization of the PTQA and patients’ decisional regret, perceptions of care, and 
perceived stress.
9.3
Study Risks
As this is a survey study, we do not anticipate any risks due to study participation. The 
QUALMS survey (see Appendix A) has been extensively vetted to be acceptable to 
patients during its development and validation phases.13 Nevertheless, the PIs will be 
available for consultation if the survey questions make any participant upset and referral to 
appropriate resources (e.g., social work, counseling) will be made available. In the unlikely 
event that a patient is made upset or uncomfortable by the QUALMS survey, the study 
investigators will contact the treating physician to inform him or her of the patient’s 
concerns.
9.4
Data Collection
Data will be collected via medical record reviews, the QUALMS, and several other survey 
instruments. 
Primary medical record review will include:

Sociodemographic information

Information regarding patients’ MDS diagnosis, including IPSS-R score

The number/frequency of transfusions prior to index transfusion (for transfusion-dependent 
patients)

Hemoglobin level prior to index transfusion
Secondary medical record review will include:

The presence of a second transfusion since index transfusion (for those who are starting 
transfusion)

The number of red cell units used since index transfusion (for those who are transfusion-
dependent)

The number of hospitalizations since index transfusion

The number of clinic visits since index transfusion
Survey instruments will include:

The QUALMS to assess pre- and post-transfusion MDS-related QOL (see Appendix A)

The Decision Regret Scale, “About Your Care” domain of prior DFCI survey, and the PSS-
4 to assess secondary outcomes related to decisional regret, perception of care, and 
perceived stress (see Appendix B)
10.0
Data and Specimen Banking
10.1
Data Storage
All data will be entered into a password-protected RedCap database, with hard copies 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 13 of 42
stored in locked file cabinets. We will not bank data for future use after study completion. 
This study does not involve specimen banking. 
10.2 NA
10.3 NA
11.0
Data Management and Confidentiality
11.1 Data Analysis Plan
Feasibility
Feasibility will be characterized by calculating (1) the proportion of enrolled patients out 
of all patients approached, and (2) the proportion of patients who completed both the pre-
and post-transfusion QUALMS surveys out of all enrolled patients. A convenience 
sample of 60 evaluable patients will be enrolled to the study. To reach this goal, we will 
enroll 90 participants total, with the expectation that some patients will not be able to 
complete the study protocol, despite being eligible at the time of consent (e.g., do not end 
up requiring future transfusions). If the observed survey completion rate is 50% (i.e. 
30/60), then this observed rate is consistent, with 95% confidence, with the true survey 
completion rate being as low as 38% or as high as 62%.    
Clinical and Utilization Outcomes
To be assessed for clinical and utilization outcomes, participants must have completed a 
pre-transfusion QUALMS, received an index transfusion, and completed a post-
transfusion QUALMS. Each of the 60 enrolled evaluable patients will be matched 1:1 to 
historical controls seen between 2015 and 2017, for a matched sample size of 120 
patients total. Subjects will be matched for transfusion group, IPSS-R, pre-transfusion 
Hb, and institution). Comparative analyses will be conducted separately by transfusion 
group. For the transfusion-naive, the primary outcome will be receipt of second 
transfusion (yes/no) within two months following the first transfusion. For the 
transfusion-dependent, the primary outcome will be defined as number of units pRBCs 
received within two months following the next transfusion. 
For both groups, we will also compare the number of hospitalizations and clinic visits 
two months after index transfusion (Table).
PTQA Utilization and Patient-Reported Outcomes
We may find that patients and hematologists do not use the information in their PTQA 
reports to truly affect decision-making, as both may be anxious to forgo transfusions 
despite the fact that QOL did not improve. We plan to assess this parameter at two 
months post-transfusion by asking participants whether they discussed the PTQA report 
with their physician (see Appendix B). To help prevent the PTQA going unused, we will 
make sure that providers at each site have access to the consensus Hb data from our 
previous qualitative study (Protocol 18-064). These results will be disseminated to 
providers prior to study initiation. In addition, we will work closely with the DFCI Adult 
Patient and Family Advisory Council (PFAC) to vet the routine language in our PTQA 
patient reports so that is optimally educational and anxiety-reducing.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 14 of 42
Exploratory analyses (e.g. descriptive statistics such as means and standard deviations) 
using the results from the follow-up survey (see Appendix B) will characterize decisional 
regret, perceptions of care, and perceived stress by the associated scales at two months 
post-transfusion (Table).
11.2
Power Analysis 
Transfusion-naive patients: With a type I error of 5% and a sample size of 60 transfusion-
naive patients total (30 PTQA versus 30 historical controls), we will have 85% power to 
detect changes in the proportion of transfusion-naive patients receiving second 
transfusion from 100% to 70%. 
Transfusion-dependent patients: With a type I error rate of 5% and a sample size of 60 
transfusion-dependent patients total (30 PTQA versus 30 historical controls), we will 
have 83% power to detect a decrease in mean number of units received from 8.0 to 6.5 if 
the standard deviation is 2.0 units.
11.3 Securing of Data 
As mentioned above, data will be stored in a password-protected RedCap database. 
Participants will be linked to a deidentified study ID to ensure confidentiality. Please see 
the Data Safety Monitoring Plan (Appendix E) for further detail. 
11.4 Quality Control of Data 
We will make every effort to collect all QUALMS data from study participants. RAs will 
call participants to remind them to complete the questionnaire and to either bring it with 
them to clinic (pre-transfusion) or mail it back to the site (post-transfusion). We have 
piloted this technique with 3 patients with MDS at DFCI; all complied. If a QUALMS 
survey is not complete, the site PI will personally contact each participant. Participants 
that do not complete the pre-transfusion QUALMS despite personal contact by the PI will 
be regarded as not having enrolled. We will record all reasons for non-enrollment, and 
account for all approached participants in the reports. 
There may be participants who enroll and complete the pre-transfusion QUALMS, but do 
not complete the post-transfusion QUALMS. In this case, a PTQA report will not be 
generated. We will attempt to replace participants who do not complete the post-
transfusion questionnaire, although this may prove unfeasible during the two-year 
timeframe of the study. Whether these participants are replaced or not, we will evaluate 
the outcomes of these participants, as we may find that there is a change in future 
transfusion decisions simply from drawing attention to QOL through the pre-transfusion 
QUALMS. If appropriate, sensitivity analyses will be performed among the subset of 
patients for whom a PTQA report was generated.  
It is possible, although rare, for a patient to die within the two-month follow up period; 
such patients will be included in analyses based on their clinical and utilization outcomes 
observed before death. 
We will record the number of patients who do not complete the two-month follow up 
surveys (PTQA utilization, decisional regret, perceptions of care, and perceived stress), 
and compare patient characteristics between those who do and do not complete the two-
month follow up surveys.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 15 of 42
11.5 Handling of Data
All study three sites will enter study data into a password protected, secure RedCap 
database that will be managed by the DFCI study team. Data will be stored for the 
duration of the study enrollment and analysis period and will be deleted once study 
analysis/write-up is complete. Hard copies of the questionnaires will be kept in a locked 
filing cabinet and destroyed upon study completion. 
12.0
Provisions to Monitor the Data to Ensure the Safety of Subjects
12.1
NA
13.0
Withdrawal of Subjects
13.1 Subjects may be withdrawn without consent if their treating provider feels they 
should no longer participate in the study. 
13.2 In the event of orderly termination, subjects will be notified that they will no longer 
be enrolled in the study. Study PIs will be made available to discuss any of the 
subjects’ questions or concerns. 
13.3 If a subject wishes to withdraw fully from the study, the study team will cease all 
data collection relating to the withdrawn subject, including review of primary 
outcomes. If a subject wishes to forgo the completion of the post-transfusion 
QUALMS or two=month follow-up questionnaire, the study team will confirm with 
the participant whether it is permissible to continue collecting data regarding the 
patient’s health outcomes/healthcare utilization, as relevant to the study. 
14.0
Risks to Subjects
14.1
As this is a survey study, we do not anticipate any risks due to study participation. 
The only foreseeable risk is potential emotional distress due to the nature of the 
questionnaires. If a participant becomes upset at any point, he/she will be referred to 
appropriate resources (e.g., social work, counseling). In the unlikely event that a patient is 
made upset or uncomfortable by the QUALMS survey, the study investigators will 
contact the treating physician to inform him or her of the patient’s concerns.
14.2 NA
14.3 NA
14.4 NA
15.0
Potential Benefits to Subjects
15.1
Potential Benefits 
It is possible that this research study may benefit participants directly if subjects and/or 
their physician take the results of the PTQA report into consideration when making 
transfusion decisions. It is our goal that providing patients/providers with an accurate 
assessment of pre- and post-transfusion QOL will facilitate a better-informed discussion 
regarding transfusion. 
15.2
Other
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 16 of 42
If participants and/or providers elect not to use the results of the PTQA report to guide 
transfusion decisions, then this study will not benefit participants directly. 
16.0
Vulnerable Populations
16.1 NA
17.0
Community-Based Participatory Research
17.1 NA
18.0
Sharing of Results with Subjects
18.1
Study participants and their providers will receive the results of the PTQA. Once 
the participant has completed the post-transfusion QOL assessment, the RA will generate 
a report that compares the participant’s pre- and post-transfusion QOL scores. This 
information will be compiled in a PTQA report and shared with the provider and patient 
via email. 
19.0
Setting
19.1
Once a potentially eligible subject is identified and upon provider approval, the 
RA will meet the patient in clinic to initiate the consent discussion. After a patient 
consents to the study, he/she will be given a copy of the QUALMS and instructed to 
complete the survey at home on the day before the upcoming transfusion. The RA will 
meet the participant in clinic when he/she comes in for a scheduled transfusion. At this 
appointment, the RA will collect the completed pre-transfusion survey and will give the 
participant a second copy of the QUALMS to take home. The participant will be 
instructed to complete the survey at home one week post transfusion and return it by 
mail. Study participants will also receive the follow-up questionnaire by mail to be 
completed at home.
20.0
Resources Available
20.1  Study Team 
Dr. Gregory Abel (DFCI) will serve as Principal Investigator, and Drs. Amer Zeidan 
(YCC) and Heidi Klepin (WFB) will be Co-Investigators. In addition to all having MDS 
clinical expertise, Dr. Abel has QOL expertise, Dr. Zeidan has MDS clinical trial 
expertise, and Dr. Klepin has geriatrics expertise. The research team also includes Dr. 
Michael Hassett, Medical Director for Clinical Information Systems at DFCI. 
20.2 Other Resources
The three study sites—DFCI, YCC, and WFB—all have large MDS populations and 
demonstrated track records in high-impact research in MDS, QOL, geriatrics and 
hematologic malignancies.
21.0
Prior Approvals
21.1
We have obtained multi-center approval. No other approval is necessary for this 
study. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 17 of 42
22.0
Recruitment Methods
22.1 Recruitment Procedure
Once the RA has identified potential study participants and confirmed eligibility 
with the patients’ provider, potential study participants will be informed of the 
study at the appointment prior to their first/next transfusion.
o
Patients that are nearing first transfusion will be approached at the 
appointment prior to their first transfusion. 
o
Patients that are transfusion-dependent will be approached at an upcoming 
appointment or transfusion. 
Study consent will take place during these visits. Potential participants will be 
given the opportunity to ask questions, opt out of consideration, and take a 
consent form home to discuss further with their family and/or other clinicians. We 
will be clear that enrollment does not mean patients are required to forgo future 
transfusion if the resulting PTQA report indicates an unimproved or worsened 
QOL post-transfusion.  
Once consented, all DF/HCC study participants will be registered in the DFCI OnCore 
Clinical Trial Management System by the RA as required by DF/HCC SOP REGIST-
101. 
22.2 The source population for this study is patients with MDS that are presenting to 
clinic for treatment with blood transfusion. 
22.3 Eligible subjects will be identified using our study-specific Epic Workbench Report 
(as described above). 
22.4 NA
22.5 NA
23.0
Local Number of Subjects
23.1 The target accrual at DFCI will be dependent upon accrual at external sites. 
subjects. 
23.2 We will approach 90 participants across all three sites with a goal of enrolling 60 
total evaluable participants study-wide. In addition to these 60 evaluable 
participants, we will have 60 historical controls that will be matched based on 
transfusion group. 
24.0
Provisions to Protect the Privacy Interests of Subjects
24.1 During the consent process, the consenting member of the study team will 
communicate clearly that participants should feel no obligation to share more 
information than they are comfortable with. It will be made clear that participants 
can opt out of any question(s) on the questionnaire that may cause uneasiness. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 18 of 42
24.2 The study team will be trained to respond to participant questions and inquiries with 
compassion and professionalism. Again, participants will be informed that they can 
skip any questions that cause discomfort.  
24.3 The research team will only have access to information that is relevant to the study, 
including in participants’ medical records. The team will follow HIPAA guidelines 
regarding patient information. 
25.0
Compensation for Research-Related Injury
25.1 NA
25.2 NA
26.0
Economic Burden to Subjects
26.1 NA. There are no costs that subjects may be responsible for because of participation 
in the research.
27.0
Consent Process
27.1 We will be obtaining written consent for this study per SOP: Informed Consent 
Process (CON-100). Once a potentially eligible subject is identified, the RA will 
approach the subject at an upcoming appointment. The RA will book a consult 
room on the clinic floor to discuss the study with the subject either before or after 
an appointment with a provider. If the subject is interested, but not prepared to sign 
consent on the day of discussion, he/she can opt to sign up for the study at a later 
date. 
28.0
Process to Document Consent in Writing
28.1 To obtain written consent, we will follow the DFCI SOP for the Informed Consent 
Process (CON-100). 
28.2 NA. We will not be requesting a waiver of the requirement to obtain written 
documentation of consent.
28.3 We have submitted an Informed Consent Form for review alongside this protocol. 
29.0
Drugs or Devices
29.1 NA
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 19 of 42
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Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

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Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
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Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 21 of 42
APPENDIX A: Survey Cover Page 
A New Paradigm of Transfusion Decision 
Support for Patients with MDS
Pre-Transfusion Questionnaire
Instructions:
Please complete this survey at home on the day before your next transfusion 
and bring it with you to your appointment. 
Initials:  ______
Study ID:  ______
Date survey complete:  ____________
How would you like to receive your quality of life report?           Mail        Email 
In person
If by email, what is your email address?  _________________
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 22 of 42
APPENDIX B: THE QUALMS 
Initials: ____
Study ID: ____
Date: ____
Pre or Post Transfusion: ____
The QUALMS
Copyright © 2013 Dana-Farber Cancer Institute, Inc. and CHEO Research Institute, Inc. All 
rights reserved.
The Quality of Life in Myelodysplasia Scale
Patients often have different experiences over the course of their illness; however, please limit your 
responses to your experience over the past week only. The information you provide will remain strictly 
confidential.
During the past week, how often…
Never
Rarely
Sometimes
Often
Always
1
…did you feel as though there was a lack of clear 
information about your disease?





2
…have you felt there was limited emotional support 
available for patients with MDS beyond their 
families?





3
…did you feel as though you couldn’t do anything 
about your disease?





4
…did you feel the course of your disease was 
unpredictable?





5
…did you have difficulty explaining MDS to your 
friends or family?





6
…did you have trouble concentrating?





7
…have you considered changing long-term plans     
due to health concerns?





8
…have you experienced shortness of breath?





9
…did low energy levels cause you to change your 
schedule?





10
…did you feel as though your life was organized 
around medical appointments?





11
…have you felt a sense of hopelessness?





12
…have you been worried about getting an infection?





13
…have you had sufficient energy for routine tasks?





14
…were you afraid of dying?





15
…did you feel angry about your diagnosis?





Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 23 of 42
For the following questions, please again mark the answer choice that best represents your experiences 
and feelings over the past week. The information you provide will remain strictly confidential.
16
…were you worried about bleeding?





17
…did you feel a sense of gratitude for a part of life 
that you took for granted before?





18
…did you feel nauseated?





19
…did you worry about your MDS progressing or 
developing into leukemia?





20
…did you take into account that you might be 
fatigued when planning your activities?





During the past week, how often…
Never
Rarely
Sometimes
Often
Always
21
…were you concerned that your MDS caused a 
financial burden for you or your family?





22
…did you feel your family relationships were 
strained by your disease?





23
…have you felt weak?





24
…have you been too tired to take on the 
responsibilities you used to have?





25
…did you worry about becoming a burden to your 
friends or family?





26
…were you unable to participate in activities you are 
used to doing?





27
…have you felt anxious about test or lab results?





28
…did you avoid crowds because of fear of getting an 
infection?





29
…did you find yourself grateful for tomorrow?





30
…did you feel you were able to find quality 
information about MDS treatments?





31
…were you concerned about bruising?





32
…did you feel as though there were a lack of concrete 
answers about what will happen with your MDS?





33
…did you experience a change in bowel habits?





Please continue on
to the next page 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 24 of 42
For the following questions, you may select “not applicable” if the question does not apply to you. 
During the past week, how often…
Never
Rarely
Sometimes
Often
Always
34
…were you afraid of losing your job? (check here 
if not applicable because you are unemployed/retired)





35
…did you feel too tired to drive? (check here  if not 
applicable because you do not drive)





36
…were you afraid to have sex due to your blood 
counts? (check here  if not applicable because you
are not currently sexually active)





37
…were you afraid that your MDS treatment would 
stop working? (check here  if not applicable 
because you are not currently being treated)





38
…have you been too tired to take care of a family 
member or loved one? (check here  if not 
applicable because you are not providing such care)





Thank you for completing 
the QUALMS.
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you fo co pleti g
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the QUALMS
the QUALMS

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 25 of 42
APPENDIX C: PTQA Reports
PTQA Score Report (UNCHANGED SCORE)
Thank you for participating in the Peri-Transfusion Quality of Life Assessment (PTQA) study. 
The goal of this study is to determine whether the use of a quality of life questionnaire can help 
patients with MDS and their providers make better informed transfusion decisions. We hope 
that you will use the information in this PTQA score report to discuss future transfusion options 
with [Provider name]. 
Your Score
Before Transfusion
[xx] points
After Transfusion
[xx] points
Your score has [increased/decreased] by [xx] points.
What does your score mean?
Since your first and second scores are within 5 points of each other, your quality of life has 
remained stable after transfusion. 
How should you use the score?
Given that your quality of life did not improve after your transfusion, we recommend that you 
discuss the benefits and risks of transfusion with your doctor. 
Based on a focus group we conducted as part of our research, experts on myelodysplastic 
syndromes (MDS) agree that it is safe for patients with MDS to increase the time between 
transfusions or stop them altogether, as long as they are otherwise healthy, experience no 
significant benefit in their quality of life, and their hemoglobin level stays above 7.5 g/dL. 
Your PTQA score suggests that you might consider limiting the number of transfusions you 
receive. However, there may be other explanations for your quality of life score. We encourage 
you to use this report to discuss future transfusion decisions with your doctor. 
What are the next steps in the study?
The study team will contact you to complete your follow-up survey during the week of [date].
Questions or comments?
Please contact the [study team - provide site-specific study contact]. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 26 of 42
PTQA Score Report (DECREASE)
Thank you for participating in the Peri-Transfusion Quality of Life Assessment (PTQA) study. 
The goal of this study is to determine whether the use of quality of life assessments can help 
patients with MDS and their providers make better informed transfusion decisions. We hope 
that you will use the information in this PTQA score report to discuss future transfusion options 
with [Provider name]. 
Your Score
Before Transfusion
[xx] points
After Transfusion
[xx] points
Your score has [increased/decreased] by [xx] points.
What does your score mean?
Since your second score is more than 5 points lower than your first, you have experienced a 
clinically significant decrease in your quality of life after transfusion. 
How should you use the score?
Given that your quality of life did not improve after your transfusion, we recommend that you 
discuss the benefits and risks of transfusion with your doctor. 
Based on a focus group we conducted as part of our research, experts on myelodysplastic 
syndromes (MDS) agree that it is safe for patients with MDS to increase the time between 
transfusions or stop them altogether, as long as they are otherwise healthy, experience no 
significant benefit in their quality of life, and their hemoglobin level stays above 7.5 g/dL.
Your PTQA score suggests that you should consider limiting the number of transfusions you 
receive. However, there may be other explanations for this change in your quality of life score. 
We encourage you to use this report to discuss future transfusion decisions with your doctor.  
What are the next steps in the study?
The study team will contact you to complete your follow-up survey during the week of [date]. 
Questions or comments?
Please contact the [study team - provide site-specific study contact]. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 27 of 42
PTQA Score Report (INCREASE SCORE)
Thank you for participating in the Peri-Transfusion Quality of Life Assessment (PTQA) study. 
The goal of this study is to determine whether the use of quality of life assessments can help 
patients with MDS and their providers make better informed transfusion decisions. We hope 
that you will use the information in this PTQA score report to discuss future transfusion options 
with [Provider name]. 
Your Score
Before Transfusion
[xx] points
After Transfusion
[xx] points
Your score has [increased/decreased] by [xx] points.
What does your score mean?
Since your second score is more than 5 points higher than your first, you have experienced a 
clinically significant increase in your quality of life after transfusion. 
How should you use the score?
Given that your score indicates a clinically significant increase in your quality of life, we do not 
recommend that you change your transfusion plan at this time. We encourage you and your 
provider to take changes in your quality of life into consideration when making transfusion 
decisions in the future. 
What are the next steps in the study?
The study team will contact you to complete your follow-up survey during the week of [date]. 
Questions or comments?
Please contact the [study team - provide site-specific study contact]. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 28 of 42
APPENDIX D: PTQA Email Example
Dear Dr. [Provider name], 
Please see the attached reports for QOL changes pre/post transfusion for the patients below. I’ll also 
send the patients these reports.  
[Pt Initials] (MRN) – Index transfusion on [Date]
-
This participant’s score increased from 80 to 90 points, indicating a clinically significant increase 
in QOL. 
-
Per the study, we do not recommend any change in transfusion plan at this time. 
[Pt Initials] (MRN) – Index transfusion on [Date]
-
This participant’s score remained stable at 39 points, indicating no clinically significant changes 
in QOL.
-
Per the study, we suggest that she may consider limiting the number of transfusions she receives, 
given no end-organ effects of anemia and if her Hb stays above 7.5 g/dL
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 29 of 42
APPENDIX E: TWO-MONTH FOLLOW UP SURVEY
Initials: ____
Study ID: ____
Date: ____
PTQA UTILIZATION
Please think back to the PTQA results report you received after your post-transfusion 
questionnaire.
1.
Did you and your doctor discuss the results of your PTQA report?
a.
Yes
b.
No
If yes…
2.
Who initiated the PTQA/quality of life discussion?
a.
I did
b.
My doctor did
3.
Did the results of the report affect your or your doctor’s decision to pursue future transfusions?
a.
Yes
b.
No
DECISION REGRET SCALE
Please think about the decision you made about future blood transfusions after talking to your 
doctor. Please show how you feel about these statements by circling a number from 1 (strongly 
agree) to 5 (strongly disagree).  
4. It was the right 
decision
1
Strongly 
Agree
2
Agree
3
Neither Agree Nor 
Disagree
4 
Disagree
5
Strongly 
Disagree
5. I regret the choice that 
was made
1
Strongly 
Agree
2
Agree
3
Neither Agree Nor 
Disagree
4 
Disagree
5
Strongly 
Disagree
6. I would go for the 
same choice if I had to do 
it over again
1
Strongly 
Agree
2
Agree
3
Neither Agree Nor 
Disagree
4 
Disagree
5
Strongly 
Disagree
7. The choice did me a lot 
of harm
1
Strongly 
Agree
2
Agree
3
Neither Agree Nor 
Disagree
4 
Disagree
5
Strongly 
Disagree
8. The decision was a 
wise one
1
Strongly 
Agree
2
Agree
3
Neither Agree Nor 
Disagree
4 
Disagree
5
Strongly 
Disagree
ABOUT YOUR CANCER CARE 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 30 of 42
These questions ask about your outpatient cancer care during the past twelve months; remember 
that you can leave any questions blank if you are not comfortable answering. When answering, 
please do not include care you got when you stayed overnight in a hospital.
9. Using any number from 0 to 10, where 0 is the worst possible and 10 is the best possible, what 
number would you use to rate your cancer care overall?
0
1
2
3
4
5
6
7
8
9
10
Worst
care 
possible
Best
care 
possible
10. In the last 12 months, when you needed care right away from your cancer doctor for a new symptom 
or condition, how often was your concern addressed as soon as you wanted? 
1
Never
2
Sometimes
3
Usually
4       Always
5       Not applicable, never needed care right away
11. Using any number from 0 to 10, where 0 is the worst possible and 10 is the best possible, what 
number would you use to rate the doctor who prescribes your chemotherapy or hormonal therapy? 
0
1
2
3
4
5
6
7
8
9
10
Worst
cancer
doctor 
possible
Best
cancer
doctor 
possible
12. In the last 12 months, how often did your cancer doctors, nurses or other cancer providers spend 
enough time with you? 
1
Never
2
Sometimes
3
Usually
4       Always 
13. In the last 12 months, how often did your cancer doctors, nurses or other cancer providers explain 
things in a way you could understand?  
1
Never
2
Sometimes
3
Usually
4
Always
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	


PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 31 of 42
14.  The role patients would like to play in making treatment decisions about their cancer may 
sometimes differ from how decisions actually get made. Which statement best describes the role you 
would prefer to play when decisions about treatment for your cancer are made?
1
I prefer to make decisions about my treatment with little/no input from my doctors
2
I prefer to make the decisions after considering my doctor’s opinion 
3
I prefer that my doctors and I make the decisions together
4
I prefer that my doctors make the decisions after considering my opinion
5
I prefer my doctors make the decisions with little or no input from me
PERCEIVED STRESS
15. The following questions ask you about your feelings and thoughts during the last month. In the last 
month, how often have you felt …  
Never
Often
...that you were unable to control the important 
things in your life? ...............................................
1
2
3
4
5
...confident about your ability to handle your 
personal problems? 
1
2
3
4
5
...that things were going your way? ......................
1
2
3
4
5
...difficulties were piling up so high that you 
could not overcome them? ....................................
1
2
3
4
5

	


PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 32 of 42
APPENDIX F: STUDY SCHEMA
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 33 of 42
APPENDIX G: QUESTIONNAIRE REMINDER CALL
PRE-TRANSFUSION
Hello - may I please speak to [PATIENT NAME]?
My name is [RESEARCH ASSISTANT], and I am calling from Dr. [NAME OF PROVIDER] office 
regarding the quality of life study you signed up for at your last appointment. This is a reminder to fill 
out your pre-transfusion study survey today. Please bring it with you to your upcoming transfusion 
appointment. I will meet you during your appointment to collect your completed survey and give you a 
second questionnaire for you to fill out one week after your appointment. Do you have any questions for 
me today?
Great! I’m looking forward to seeing you at your appointment. Thank you!
POST-TRANSFUSION
Hello - may I please speak to [PATIENT NAME]?
My name is [RESEARCH ASSISTANT], and I am calling from Dr. [NAME OF PROVIDER] office 
regarding the quality of life study. This is a reminder to fill out your post-transfusion study survey today. 
Once you’ve completed it, please send it back to us using the pre-stamped, pre-addressed envelope I 
gave you at your last appointment. Once we receive the completed survey, we will compare the results 
from your pre- and post-transfusion surveys and send you and your doctor a report with the results. Do 
you have any questions for me today?
30.0
Great! I’m looking forward to seeing you at your appointment. Thank you!
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 34 of 42
APPENDIX H: DSMP
INTRODUCTION
The Dana-Farber/Harvard Cancer Center Multi-Center Data and Safety Monitoring Plan (DF/HCC 
DSMP) outlines the procedures for conducting a DF/HCC Multi-Center research protocol. The 
DF/HCC DSMP serves as a reference for any sites external to DF/HCC that are participating in a 
DF/HCC clinical trial. 
Purpose
To establish standards that will ensure that a Dana-Farber/Harvard Cancer Center Multi-Center 
protocol will comply with Federal Regulations, Health Insurance Portability and Accountability 
Act (HIPAA) requirements and applicable DF/HCC Standard Operating Procedures.
Multi-Center Data and Safety Monitoring Plan Definitions
DF/HCC Multi-Center Protocol:  A research protocol in which one  or more outside institutions 
are collaborating with Dana-Farber/Harvard Cancer Center where  a DF/HCC investigator is the 
sponsor. DF/HCC includes Dana-Farber/Partners Cancer Care (DF/PCC) Network Clinical Trial 
Affiliates. 
Lead Institution:  One of the Dana-Farber/Harvard Cancer Center consortium members (Dana-
Farber Cancer Institute (DFCI), Massachusetts General Hospital (MGH), Beth Israel Deaconess 
Medical Center (BIDMC), Boston Children’s Hospital (BCH), Brigham and Women’s Hospital 
(BWH) responsible for the coordination, development, submission, and approval of a protocol as 
well as its subsequent amendments per the DFCI IRB and applicable regulatory guidelines (CTEP, 
Food and Drug Administration (FDA), Office of Biotechnology Activities (OBA) etc.).  The Lead 
Institution is typically the home of the DF/HCC Sponsor. The Lead Institution also typically serves 
as the Coordinating Center for the DF/HCC Multi-Center Protocol.  
DF/HCC Sponsor:  The person sponsoring the submitted Multi-Center protocol who takes 
responsibility for initiation, management and conduct of the protocol at all research locations. In 
applicable protocols, the DF/HCC Sponsor will serve as the single liaison with any regulatory 
agencies. The DF/HCC Sponsor has ultimate authority over the protocol and is responsible for the 
conduct of the study at DF/HCC and all Participating Institutions. In most cases the DF/HCC 
Sponsor is the same person as the DF/HCC Overall Principal Investigator; however, both roles can 
be filled by two different people.
Participating Institution:  An institution that is outside the DF/HCC and DF/PCC consortium that 
is collaborating with DF/HCC on a protocol where the sponsor is a DF/HCC Investigator.  The 
Participating Institution acknowledges the DF/HCC Sponsor as having the ultimate authority and 
responsibility for the overall conduct of the study.   
Coordinating Center: The entity (i.e. Lead Institution, Medical Monitor, Contract Research 
Organization (CRO), etc) that provides administrative support to the DF/HCC Sponsor in order that 
he/she may fulfill the responsibilities outlined in the protocol document and DSMP, and as specified 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 35 of 42
in applicable regulatory guidelines (i.e. CTEP Multi-Center Guidelines). In general, the Lead 
Institution is the Coordinating Center for the DF/HCC Multi-Center Protocol. 
DF/HCC Office of Data Quality (ODQ): A group within DF/HCC responsible ensuring high-
quality standards are used for data collection and the ongoing management of clinical trials, 
auditing, and data and safety monitoring. ODQ also coordinates quality assurance efforts related to 
multi-center clinical research.
DF/HCC Clinical Trials Research Informatics Office (CTRIO): A group within DF/HCC 
responsible for providing a comprehensive data management platform for managing clinical trial 
data.
GENERAL ROLES AND RESPONSIBILITIES
For DF/HCC Multi-Center Protocols, the DF/HCC Sponsor, the Coordinating Center, and the 
Participating Institutions (Yale Cancer Center and Wake Forest Baptist) are expected to adhere to 
the following general responsibilities: 
DF/HCC Sponsor
The DF/HCC Sponsor, Gregory Abel, MD, MPH, will accept responsibility for all aspects of 
conducting a DF/HCC Multi-Center protocol which includes but is not limited to: 

Oversee the coordination, development, submission, and approval of the protocol as well as 
subsequent amendments. 

Ensure that the investigators, study team members, and Participating Institutions are 
qualified and appropriately resourced to conduct the protocol.  

Include the Multi-Center Data and Safety Monitoring Plan as an appendix to the protocol.

Ensure all Participating Institutions are using the correct version of the protocol.

Ensure that each participating investigator and study team member receives adequate 
protocol training (and/or a Site Initiation Visit prior to enrolling participants) and throughout 
trial’s conduct as needed.

Ensure the protocol will be provided to each participating site. 

Monitor progress and overall conduct of the study at all Participating Institutions. 

Ensure all DFCI Institutional Review Board (IRB), DF/HCC, and other applicable reporting 
requirements are met. 

Review data and maintain timely submission of data for study analysis. 

Ensure compliance with all requirements as set forth in the Code of Federal Regulations, 
applicable DF/HCC requirements, HIPAA requirements, and the approved protocol.

Commit to the provision that the protocol will not be rewritten or modified by anyone other 
than the DF/HCC Sponsor.

Identify and qualify Participating Institutions and obtain accrual commitments prior to 
extending the protocol to that site.

Monitor accrual and address Participating Institutions that are not meeting their accrual 
requirements. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 36 of 42
Coordinating Center 
The general responsibilities of the Coordinating Center may include but are not limited to:

Assist in protocol development. 

Review registration materials for eligibility and register participants from Participating 
Institutions in the DF/HCC clinical trial management system (CTMS).

Distribute protocol and informed consent document updates to Participating Institutions as 
needed.

Oversee the data collection process from Participating Institutions.

Maintain documentation of Serious Adverse Event (SAE) reports and deviations/violation 
submitted by Participating Institutions and provide to the DF/HCC Sponsor for timely 
review and submission to the DFCI IRB, as necessary. 

Distribute serious adverse events reported to the DF/HCC Sponsor that fall under the DFCI 
IRB Adverse Event Reporting pPolicy to all Participating Institutions.

Provide Participating Institutions with information regarding DF/HCC requirements that 
they will be expected to comply with.

Carry out plan to monitor Participating Institutions either by on-site or remote monitoring. 

Maintain Regulatory documents of all Participating Institutions which includes but is not 
limited to the following: local IRB approvals/notifications from all Participating 
Institutions, confirmation of Federalwide Assurances (FWAs) for all sites,  all SAE 
submissions, Screening Logs for all sites, IRB approved consents for all sites

Conduct regular communications with all Participating Institutions (conference calls, 
emails, etc) and maintain documentation all relevant communications.
Participating Institution
Each Participating Institution is expected to comply with all applicable federal regulations and 
DF/HCC requirements, the protocol and HIPAA requirements. 
The general responsibilities for each Participating Institution may include but are not limited to:

Document the delegation of research specific activities to study personnel.

Commit to the accrual of participants to the protocol.

Submit protocol and/or amendments to their local IRB of record.

Maintain regulatory files as per sponsor requirements.

Provide the Coordinating Center with regulatory documents or source documents as 
requested.

Participate in protocol training prior to enrolling participants and throughout the trial as 
required (i.e. teleconferences).

Update Coordinating Center with research staff changes on a timely basis.

Submit Serious Adverse Event (SAE) reports to local IRB per institutional requirements 
and to the Coordinating Center, in accordance with DF/HCC requirements. 

Submit protocol deviations and violations to local IRB per institutional requirements and to 
the DF/HCC Sponsor in accordance with DF/HCC requirements.

Have office space, office equipment, and internet access that meet HIPAA standards.

Participate in any quality assurance activities and meet with monitors or auditors at the 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 37 of 42
conclusion of a visit to review findings.

Promptly provide follow-up and/or corrective action plans for any monitoring queries or 
audit findings.
DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS
The following section will clarify DF/HCC Requirements and further detail the expectations for 
participating in a DF/HCC Multi-Center protocol. 
Protocol Distribution
The Coordinating Center will distribute the final DFCI IRB approved protocol and any subsequent 
amended protocols to all Participating Institutions. 
Protocol Revisions and Closures
The Participating Institutions will receive notification of protocol revisions and closures from the 
Coordinating Center.  It is the individual Participating Institution’s responsibility to notify its IRB 
of these revisions.

Non life-threatening revisions: Participating Institutions will receive written notification 
of protocol revisions regarding non life-threatening events from the Coordinating Center. 
Non-life-threatening protocol revisions must be IRB approved and implemented within 90 
days from receipt of the notification.

Revisions for life-threatening causes: Participating Institutions will receive immediate 
notification from the Coordinating Center concerning protocol revisions required to protect 
lives with follow-up by fax, mail, e-mail, etc.  Life-threatening protocol revisions will be 
implemented immediately followed by IRB request for approval.

Protocol closures and temporary holds: Participating Institutions will receive notification 
of protocol closures and temporary holds from the Coordinating Center. Closures and holds 
will be effective immediately.  In addition, the Coordinating Center, will update the 
Participating Institutions on an ongoing basis about protocol accrual data so that they will 
be aware of imminent protocol closures.
Informed Consent Requirements
The DF/HCC approved informed consent document will serve as a template for the informed 
consent for Participating Institutions. The Participating Institution consent form must follow the 
consent template as closely as possible and should adhere to specifications outlined in the DF/HCC 
Guidance Document on Model Consent Language for Investigator-Sponsored Multi-Center Trials.  
This document will be provided separately to each Participating Institution upon request.
Participating Institutions are to send their version of the informed consent document and HIPAA 
authorization, if a separate document, to the Coordinating Center for review and approval prior to 
submission to their local IRB. The approved consent form must also be submitted to the 
Coordinating Center after approval by the local IRB for all consent versions.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 38 of 42
The Principal Investigator (PI) at each Participating Institution will identify the members of the 
study team (Research Assistant and Project Manager) who will be obtaining consent and signing 
the consent form. Participating institutions must follow the DF/HCC requirements for consent. As 
this study does not involve an investigational drug, biologic, or device, non-physicians (Research 
Assistants and Project Managers) are able to obtain consent and sign the consent forms.  
IRB Documentation
The following must be on file with the Coordinating Center:

Initial approval letter of the Participating Institution's IRB. 

Copy of the Informed Consent Form(s) approved by the Participating Institution’s IRB. 

Participating Institution’s IRB approval for all amendments.

Annual approval letters by the Participating Institution's IRB.
IRB Re-Approval
Verification of IRB re-approval from the Participating Institutions is required in order to continue 
research activities.  There is no grace period for continuing approvals.
The Coordinating Center will not register participants if a re-approval letter is not received from 
the Participating Institution on or before the anniversary of the previous approval date.  
Participant Confidentiality and Authorization Statement
In 1996, congress passed the first federal law covering the privacy of health information known as 
the Health Insurance Portability and Accountability Act (HIPPA). Any information, related to the 
physical or mental health of an individual is called Protected Health Information (PHI). HIPAA 
outlines how and under what circumstances PHI can be used or disclosed. 
In order for covered entities to use or disclose protected health information during the course of a 
study, the study participant must sign an authorization statement.  This authorization statement may 
or may not be separate from the informed consent document.  The Coordinating Center, with the 
approval from the DFCI IRB, will provide a consent template, with information regarding 
authorization for the disclosure of protected health information. 
The DF/HCC Sponsor will use all efforts to limit its use of protected health information in its trials. 
However, because of the nature of these trials, certain protected health information must be 
collected. DF/HCC has chosen to use authorizations, signed by the participant in the trial, rather 
than limited data sets with data use agreements.
 DF/HCC Multi-Center Protocol Confidentiality
All documents, investigative reports, or information relating to the participant are strictly 
confidential. Whenever reasonably feasible, any participant specific reports (i.e. Pathology Reports, 
MRI Reports, Operative Reports, etc.) submitted to the Coordinating Center should be de-
identified. It is recommended that the assigned protocol case number (as described below) be used 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 39 of 42
for all participant specific documents. Participant initials may be included or retained for cross 
verification of identification.
DF/HCC Multi-Center Protocol Registration Policy
Participant Registration and Randomization 
Each site will be responsible for registering study participants according to their own 
institutional policies and procedures. The Coordinating Center will only register patients that 
are consented and enrolled at DFCI in the DF/HCC CTMS.
Although we will not register participants from Participating Institutions in the DF/HCC OnCore 
system, Participating Institutions will still be required to complete:

Signed informed consent document

Completed Eligibility Checklist 
Participating Institutions will notify the Coordinating Center about registrations via monthly 
phone call. 
Protocol-specific interventions may begin once the Participating Institution has 
registered the participant at their specific site.
 Eligibility Exceptions
No exceptions to the eligibility requirements for a protocol without DFCI IRB approval will be 
permitted. All Participating Institutions are required to fully comply with this requirement. 
DF/HCC Protocol Case Number
At the time of registration, the following identifiers are required for all subjects: initials, date of 
birth, gender, race and ethnicity. Once eligibility has been established and the participant 
successfully registered, the participant is assigned a unique protocol case number. 
Case numbers will be assigned consecutively by DFCI as participants are enrolled. Participating 
Institutions will be responsible for tracking the appropriate case number as participants are enrolled. 
Protocol Deviations, Exceptions and Violations
Federal Regulations require an IRB to review proposed changes in a research activity to ensure 
that researchers do not initiate changes in approved research without IRB review and approval, 
except when necessary to eliminate apparent immediate hazards to the participant. DF/HCC 
requires all departures from the defined procedures set forth in the IRB approved protocol to be 
reported to the DF/HCC Sponsor, who in turn is responsible for reporting to the DFCI IRB.
For reporting purposes, DF/HCC uses the terms “violation”, “deviation” and “exception” to 
describe departures from a protocol. All Participating Institutions must adhere to these 
requirements for reporting to the DF/HCC Sponsor and will follow their institutional policy for 
reporting to their local IRB.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 40 of 42
 Definitions
Protocol Deviation: Any departure from the defined procedures set forth in the IRB-approved 
protocol which is prospectively approved prior to its implementation.
Protocol Exception:  Any protocol deviation that relates to the eligibility criteria, e.g.
enrollment of a participant who does not meet all inclusion/exclusion criteria.
Protocol Violation: Any protocol departure that was not prospectively approved by the IRB prior 
to its initiation or implementation. 
 Reporting Procedures
DF/HCC Sponsor: is responsible for ensuring that clear documentation is available in the medical 
record and/or regulatory documents to describe all protocol exceptions, deviations and violations. 
The DF/HCC Sponsor will also be responsible for ensuring that all protocol violations/deviations 
are promptly reported per DFCI IRB guidelines. 
Participating Institutions: Protocol deviations require prospective approval from the DFCI IRB. The 
Participating Institution must submit the deviation request to the Coordinating Center who will then 
submit the deviation request to the DFCI IRB. Upon DFCI IRB approval the deviation is submitted 
to the Participating Institution IRB, per institutional policy. A copy of the Participating Institution’s 
IRB report and determination will be forwarded to the Coordinating Center within 10 business days 
after the original submission.  The deviation may not be implemented without all required 
approvals.
All protocol violations must be sent to the Coordinating Center in a timely manner. The 
Coordinating Center will provide training for the requirements for the reporting of violations. 
Coordinating Center:  Upon receipt of the violation/deviation report from the Participating 
Institution, the Coordinating Center will submit the report to the DF/HCC Sponsor for review. 
Subsequently, the Participating Institution’s IRB violation/deviation report will be submitted to the 
DFCI IRB for review per DFCI IRB reporting guidelines. DF/HCC will forward all violation reports 
to CTEP via an internal DF/HCC process, as applicable.
Safety Assessments and Monitoring
The study teams at all participating institutions are responsible for protecting the safety, rights and 
well-being of study participants. Recording and reporting of adverse events that occur during the 
course of a study help ensure the continuing safety of study participants. As this is a survey study, 
we do not anticipate any issues with regards to patient safety.
Data Management
All sites, including the Coordinating Center and Participating Sites, will enter data into a RedCap 
database that will be managed by the study team. We will not use case report forms developed by 
DF/HCC CTRIO for this study. 
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 41 of 42
MONITORING: QUALITY CONTROL
The quality control process for a clinical trial requires verification of protocol compliance and data 
accuracy. The study team at the Coordinating Center will provide quality control oversight for the 
protocol.
Ongoing Monitoring of Protocol Compliance
The Coordinating Center will implement ongoing monitoring activities to ensure that Participating 
Institutions are complying with regulatory and protocol requirements, data quality, and participant 
safety. Monitoring practices may include but are not limited to source data verification, and review 
and analysis of eligibility requirements, informed consent procedures, adverse events and all 
associated documentation, review of study drug administration/treatment, regulatory files, protocol 
departures reporting, response assessments, and data management. 
The Coordinating Center will monitor the progress of the study during monthly calls with 
Participating Institutions. During these call, the Coordinating Center will assess whether 
Participating Institutions are enrolling patients in a timely manner. In preparation for these calls, 
the Coordinating Center will prepare a data report to ensure timely completion of data entry tasks 
in RedCap. 
Monitoring Reports
The DF/HCC Sponsor will review all monitoring reports to ensure protocol compliance. The 
DF/HCC Sponsor may increase the monitoring activities at Participating Institutions that are unable 
to comply with the protocol, DF/HCC Sponsor requirements or federal and local regulations. 
Accrual Monitoring
Prior to extending a protocol to an external site, the DF/HCC Sponsor will establish accrual 
requirements for each participating institution. Accrual will be monitored for each participating 
institution by the DF/HCC Sponsor or designee. Sites that are not meeting their accrual 
expectations may be subject to termination. Each site will be expected to accrue 20 patients over 
the course of 18-months, with a minimum accrual requirement of 1-2 patients per month at each 
site. 
AUDITING: QUALITY ASSURANCE
Auditing is a method of Quality Assurance and involves the systematic and independent 
examination of all trial related activities and documents.  Audits determine if evaluated activities 
were appropriately conducted and whether data was generated, recorded and analyzed, and 
accurately reported per the protocol, applicable Policies, and the Code of Federal Regulations 
(CFR).
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019

PROTOCOL TITLE: A New Paradigm of Transfusion Decision Support for Patients with MDS: 
Using Peri-Transfusion Quality of Life Assessments (PTQAs) 
Page 42 of 42
DF/HCC Internal Audits
 
All Participating Institutions are subject to audit by the DF/HCC Office of Data Quality (ODQ). 
Typically, approximately 3-4 participants would be audited at the site over a 2-day period. If 
violations which impact participant safety or the integrity of the study are found, more participant 
records may be audited. 
Audit Notifications
It is the Participating Institution’s responsibility to notify the Coordinating Center of all external 
audits or inspections that involve this protocol. All institutions will forward a copy of final audit 
and/or re-audit reports and corrective action plans (if applicable) to the Coordinating Center, within 
12 weeks after the audit date. 
Audit Reports 
The DF/HCC Sponsor will review all final audit reports and corrective action plans, if applicable. 
The Coordinating Center, must forward any reports to the DF/HCC ODQ per DF/HCC policy for 
review by the DF/HCC Audit Committee. For unacceptable audits, the DF/HCC Audit Committee 
would forward the final audit report and corrective action plan to the DFCI IRB as applicable.
Participating Institution Performance
The DF/HCC Sponsor and the IRB of record are charged with considering the totality of an 
institution’s performance in considering institutional participation in the protocol.
Participating Institutions that fail to meet the performance goals of accrual, submission of timely 
and accurate data, adherence to protocol requirements, and compliance with state and federal 
regulations, may be recommended for a six-month probation period. Such institutions must respond 
with a corrective action plan and must demonstrate during the probation period that deficiencies 
have been corrected, as evidenced by the improved performance measures. Participating 
Institutions that fail to demonstrate significant improvement will be considered by the DF/HCC 
Sponsor for revocation of participation. A DF/HCC Sponsor and/or the DFCI IRB may terminate a 
site’s participation if it is determined that a site is not fulfilling its responsibilities as described 
above.
Dana Farber
IRB NUMBER: 18-307
IRB APPROVAL DATE: 12/23/2019