Assessing the Effect of Offering a Blood-based Colorectal Cancer Screening Test on Screening Adherence and Colonoscopy Completion in Patients Who Have Refused Colonoscopy and FIT
Phase: NA
Conditions: Colorectal Cancer
Sponsor: Peter S. Liang, MD MPH

 
ASSESSING THE EFFECT OF OFFERING A BLOOD-BASED 
COLORECTAL CANCER SCREENING TEST ON SCREENING 
ADHERENCE AND COLONOSCOPY COMPLETION IN 
PATIENTS WHO HAVE REFUSED COLONOSCOPY AND FIT 
 
NCT03598166  
 
 
 
APRIL 19, 2019 
 

PROTOCOL TITLE: Assessing the effect of offering a blood-based colorectal cancer screening 
test 
 
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1) 
Protocol Title 
Assessing the effect of offering a blood-based colorectal cancer screening test on screening 
adherence and colonoscopy completion in patients who have refused colonoscopy and FIT  
 
2) 
Objectives 
Despite multiple options for colorectal cancer (CRC) screening, including several proven to 
reduce CRC mortality, population-level participation rates are suboptimal. In 2015, it was 
estimated that only 62% of Americans aged 50-75 were up to date with screening, which is 
substantially lower than the 80% by 2018 screening goal set by the National Colorectal Cancer 
Roundtable and endorsed by the American Society of Gastrointestinal Endoscopy.1 The US 
Multi-Society Task Force (USMSTF) recommends colonoscopy and fecal immunochemical 
testing (FIT) as Tier 1 screening tests,2 but barriers to completing these tests have been well-
characterized.3 For colonoscopy, patient barriers include an aversion to the bowel preparation 
process, loss of a workday, and the invasive nature of the procedure. For FIT, the main patient 
barrier is a reluctance to handle stool samples. Although blood-based tests are not currently 
recommended in the screening guidelines, they overcome all of these known barriers and may 
substantially improve adherence to screening. Epi proColon is an FDA-approved blood test that 
detects methylated Septin9 DNA, which is increased in individuals with CRC. The test is 
indicated for average-risk individuals who have declined guideline-recommended screening 
options, such as colonoscopy and FIT. Guidelines suggest that patients who decline these Tier 
1 options should be offered Tier 2 or 3 options such as sigmoidoscopy, stool-DNA, CT 
colonography, and capsule colonoscopy. However, since these lower-tier tests face the same 
patient barriers as the Tier 1 tests and are less widely available, individuals who have declined 
both colonoscopy and FIT constitute the de facto target population for the blood test. Studies 
have shown that patients who are offered a choice between the blood test and FIT prefer and 
have higher compliance to the blood test,4,5 but it is unknown what proportion of “screen-
resistant” patients who have declined both colonoscopy and FIT will accept the blood test. This 
is the crucial question that will determine the potential role of the blood test in the CRC 
screening landscape. 
 
The VA New York Harbor Health Care System (VA NYHHCS) offers both colonoscopy and FIT 
for CRC screening and has achieved a screening rate of 80%, but efforts to further improve the 
screening rate by promoting these two tests have resulted in limited success. Since the stability 
of the screening rate likely indicates a saturation of individuals who are willing to undergo either 
colonoscopy or FIT, this is an ideal clinical environment to test the ability of a blood test to 
further improve the screening rate. The convenience of the blood test may expand the number 
of patients who are willing to undergo screening, and patients with positive test results will likely 
be more motivated to undergo potentially cancer-detecting diagnostic colonoscopy. Therefore, 
the introduction of the blood test may effectively convert a proportion of individuals who have 
previously declined colonoscopy to undergo this important procedure. In this study, we will 
assess the effect of the Septin9 blood test on screening rates among screen-resistant veterans 
who have declined both colonoscopy and FIT at the VA NY Harbor Health Care System, as well 
as their follow-through with diagnostic colonoscopy. Our Specific Aims are as follows: 
 
Aim 1: To measure screening uptake with a blood test in screen-resistant patients who have 
declined both colonoscopy and FIT at the VA New York Harbor Health Care System (VA 
NYHHCS) 
    
 

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Sub-Aim 1a: To assess the proportion of those with a positive blood-based screening 
test who undergo diagnostic colonoscopy 
 
Sub-Aim 1b: To describe the endoscopic findings on diagnostic colonoscopy 
Aim 2: To survey screen-resistant patients to understand their beliefs and attitudes about 
CRC screening and testing options 
 
3) 
Background 
In 2017, over 135,000 people in the US will be diagnosed with CRC and more than 50,000 will 
die from this disease—making it the third most common cancer in both men and women and the 
second leading cause of cancer death.6 A preponderance of data show that both colonoscopy 
and fecal occult blood testing substantially reduce CRC incidence and mortality.7–10 Despite 
these compelling statistics, only 62% of Americans were up to date with CRC screening in 2015, 
which is substantially below our national goal of 80% by 2018 and also falls short of screening 
rates achieved for breast (72%) and cervical (83%) cancer.1 Of the two Tier 1 screening options 
recommended by the USMSTF, colonoscopy is by far the predominant screening modality; 96% 
of individuals who were up to date with screening reporting that they received lower endoscopy, 
compared to 11% for a stool-based test.11 Yet from a patient perspective, neither of these two 
options is ideal. Colonoscopy requires dietary modification, bowel preparation, an invasive 
procedure, time off from work, and an escort for the majority of individuals who receive sedation. 
Despite the gastroenterology community’s continuous efforts to improve the patient experience 
through innovations such as low residue diet, split dose and smaller volume bowel preparation, 
and carbon dioxide, the suboptimal screening rate is proof that a substantial proportion of the 
population still refuses colonoscopy. Similarly, a segment of the population refuses FIT because 
they find the idea of providing a stool sample unhygienic and unappealing. Therefore, despite 
the existence of many CRC screening options, there is still an unmet need for a test that is non-
invasive, does not require a bowel preparation, and does not involve handling stool. The 
Septin9 DNA blood test is the only FDA-approved test that fits this description. Septin9 is 
currently not recommended by the USMSTF as a screening option, but it is not intended to be 
offered to patients in place of the recommended options. Rather, the blood test is intended for 
patients who have declined the available options—usually for the reasons cited above—for 
whom a blood test would be an acceptable alternative. Thus, it is not a competitor to 
colonoscopy but may motivate more patients to participate in screening and ultimately undergo 
diagnostic colonoscopy after a positive test. Both national and VA screening rates have 
plateaued over the last few years, which suggests that a new strategy may be needed to further 
improve screening uptake. The Septin9 blood test may address an unmet need for patients and 
provide a much-needed boost to screening efforts. In this study, we will offer Septin9 to 
individuals who have previously declined both colonoscopy and FIT, which will allow us to 
measure the effect of the test in the real-world clinical situation in which it is indicated. 
 
Our prior work has shown that adherence to fecal testing declines rapidly with successive 
rounds of screening,12 which highlights the potential of a blood-based test with high-compliance 
for capturing non-adherent individuals. The performance of the Septin9 blood test was first 
studied in 7941 asymptomatic individuals, which found an age-standardized 48% sensitivity and 
92% specificity for CRC.13 These results were based on an assay that defined test positivity as 
one of two samples with a positive result. A subsequent study has shown that redefining test 
positivity as one of three samples with a positive result yielded 68% sensitivity and 79% 
specificity for CRC.14 The current FDA-approved Epi proColon assay uses three samples. In a 
trial that compared the blood test to FIT in individuals who were either recently diagnosed with 

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CRC or were undergoing screening colonoscopy, the blood test was found to be non-inferior to 
FIT with respect to sensitivity (73% vs. 68%) for CRC but had lower specificity (82% vs. 97%).15 
Two studies have evaluated uptake of the blood test compared to FIT. In a German study of 109 
individuals who refused screening colonoscopy, 83% chose the blood test and 15% chose FIT. 
In a multi-center randomized controlled trial conducted in the US, patients who were overdue for 
screening were assigned to either the blood test or FIT. Test completion rate was 99.5% for the 
blood test and 88% for FIT. Of the 30 individuals who had a positive blood test, 20 (67%) 
scheduled or completed a diagnostic colonoscopy within 3 months.  
 
4) 
Inclusion and Exclusion Criteria 
Inclusion criteria (based on review of the electronic health record): 
-Age 50-75  
-Declined CRC screening (both colonoscopy and FIT) in the previous 6 months, which must be 
documented in the electronic health record  
 
Exclusion criteria (based on review of the electronic health record data and self-reported 
questionnaire data): 
-Personal history of colonic adenomas (including sessile serrated adenomas), proximal 
hyperplastic polyps, CRC, inflammatory bowel disease, or hereditary gastrointestinal cancer 
syndrome 
-First degree relative with CRC diagnosed at <60 years of age; family history of hereditary 
gastrointestinal cancer syndromes. 
-Patients with severe comorbidities who may not benefit from CRC screening due to limited life 
expectancy (e.g. poorly controlled or end-stage neurologic, cardiac, pulmonary, renal, or 
oncologic disease). 
-Vulnerable populations 
 
-Adult unable to consent 
-Individuals who are not yet adults (infants, children, teenagers) 
-Pregnant women 
-Prisoners 
 
5) 
Study-Wide Number of Subjects 
This is a single site study with a total enrollment of 360 patients. 180 patients each will be in the 
intervention and control groups, respectively. 
 
6) 
Study-Wide Recruitment Methods 
All participants will be primary care patients within the VA NY Harbor Health Care System. We 
will perform an updated CRC screening audit at the beginning of the study to obtain the entire 
pool of eligible patients who are not up to date with screening. Eligible patients will then be 
randomized 1:1 to either an intervention group or a control group. All patients will receive a letter 
noting that they are not up to date on screening and encouraging them to contact a study 
number if they choose to screen with colonoscopy or FIT. Patients who call will speak to a 
research assistant who is trained in patient navigation and can facilitate referrals for 
colonoscopy or FIT. Following the sequential testing approach, letters addressed to the 
intervention group will also include an option to participate in the blood test, with instructions to 
call the study number to schedule the blood draw. In addition to the letter, both groups will also 
receive a follow-up telephone call that reiterates information in the letter. The research assistant 
will make and receive all calls using a standard script. 
 

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7) 
Study Timelines 
Each individual who is enrolled in this study will participate for a maximum of 6 months. 
We anticipate enrollment will take approximately 9 months. From the time that the study 
is approved, we estimate that it will take 18 months to complete the primary analysis. 
8) 
Study Endpoints 
Aim #1: To measure screening uptake with a blood test in screen-resistant patients who have 
declined both colonoscopy and FIT at VA NY Harbor Health Care System. Using the approach 
outlined above, we will identify and randomize 360 eligible patients, with 180 patients each in 
the intervention and control groups (see Sample Size Calculations).  
Primary outcome: Screening rate in the intervention group vs. control group after 6 months. 
Secondary outcomes:  
A) Complete screening rate in both groups, which is defined as completion of the entire 
screening strategy. For colonoscopy, this requires cecal intubation and an adequate bowel 
preparation. For individuals who took Septin9 and FIT, positive results must be followed by a 
colonoscopy with cecal intubation and adequate bowel preparation.  
B) Among individuals in the intervention group who had a positive blood test, proportion who 
completed a follow-up colonoscopy within 6 months.  
C) Endoscopic and pathologic findings among individuals in the intervention group who had a 
diagnostic colonoscopy.  
 
Aim #2: To survey screen-resistant patients to understand their beliefs and attitudes about CRC 
screening and testing options. Both intervention and controls groups will be invited to complete 
a brief questionnaire. Questionnaire questions are shown in the Table and are adapted from a 
previous study that offered both the blood test and FIT to patients who had refused screening 
colonoscopy.4 All response options will be presented in a multiple-choice format. The full 
questionnaire is shown in the Appendix.  
Primary outcome: Demographic and health-related predictors of accepting the blood test in the 
intervention group. 
Secondary outcomes:  
A) Proportion of both groups who answered that they would be willing to take a blood test for 
colorectal cancer screening 
B) The most commonly cited advantages of a blood test compared to colonoscopy and stool 
test in both groups 
C) The most commonly cited reasons for not taking the blood test in the intervention group. In 
an exploratory analysis, we will stratify results by race/ethnicity, self-reported health, frequency 
of healthcare access, and self-perceived risk of CRC. 
 
Table. Select Questionnaire Questions 
Demographics 
What is your age? 
What is your race? 
What is your ethnicity? 
Health status and medical history 
How would you rate your overall health? 
How many visits have you had with your primary care doctor in the past year? 
What do you think is your own risk of getting colorectal cancer? 
Colorectal cancer testing 
Have you ever had a colonoscopy? If so, when? 
Have you ever had a stool-based test? If so, when? 

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Why did you decide not to do a colonoscopy when offered in the past 6 months? 
What would make you change your mind and get a colonoscopy? 
Why did you decide not to do a stool test (fecal immunochemical test/FIT) when offered in the 
past 6 months? 
What would make you change your mind and take a stool test? 
Why did you decide to take a blood test? 
What are the advantages of a blood test compared to colonoscopy and stool test? 
Why did you decide not to take a blood test? 
What would make you change your mind and take a blood test? 
 
 
9) 
Procedures Involved 
The proposed study is a randomized controlled trial that will 1) assess the uptake of a CRC 
screening blood test among patients who have declined both colonoscopy and FIT in the 
previous 6 months, including diagnostic evaluation of positive results and 2) survey patients 
about their beliefs and attitudes regarding CRC screening and testing options. All participants 
will be primary care patients at the VA NY Harbor Health Care System. Based on a recent 
internal audit, there were 1502 patients who had at least one primary care visit from August 
2016 through August 2017 and were not up to date with CRC screening. Up to date CRC 
screening is defined as either 1) a colonoscopy within the past 10 years or 2) FIT within the past 
year. We will perform an updated CRC screening audit at the beginning of the study to obtain 
the entire pool of eligible patients who are not up to date with screening. Eligible patients will 
then be randomized 1:1 to either an intervention group or a control group. All patients will 
receive a letter noting that they are not up to date on screening and encouraging them to 
contact a study number if they choose to screen with colonoscopy or FIT. Patients who call will 
speak to a research assistant who is trained in patient navigation and can facilitate referrals for 
colonoscopy or FIT. Following the sequential testing approach, letters addressed to the 
intervention group will also include an option to participate in the blood test, with instructions to 
call the study number to schedule the blood draw. In addition to the letter, both groups will also 
receive a follow-up telephone call that reiterates information in the letter. The research assistant 
will make and receive all calls using a standard script. All patients will also be asked to complete 
a questionnaire about their beliefs and attitudes regarding CRC screening (see Appendix). The 
questionnaire will be mailed with the invitation letter and will also be administered over the 
telephone by the research assistant. The study team will notify patients and their primary care 
physicians of blood test results and will facilitate a colonoscopy referral for those with positive 
tests. Primary care physicians will not be asked to notify the patients or make the colonoscopy 
referral because most will not have adequate knowledge of the Septin9 test to provide 
appropriate patient education.  
 
Participants who are randomized to the blood test arm will undergo phlebotomy, which will be 
performed by the study research assistant. The blood sample will be temporarily stored on-site 
and then transported to an off-site commercial laboratory to run the assay. 
 
Clinical outcomes for both the intervention and control group participants will be measured as a 
secondary outcome. This includes timing and result of a screening colonoscopy or FIT for 
individuals in the controls group as well as diagnostic colonoscopy for participants who had a 
positive blood test. 

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10) Data and Specimen Banking 
Blood specimens for individuals in the intervention group will be assayed but not stored. No data 
other than what is described the sections above will be stored. 
 
11) Data Management 
Blood specimens will be transported and assayed by an outside commercial laboratory. Result 
will then be uploaded to the electronic medical record.  
 
All personnel who will be working on this project will have completed the necessary CITI and 
TMS training for research involving patient data. Data will be collected from the electronic 
medical record, which only individuals credentialed by the VA can access using password-
protected accounts. All data collected will be compiled in a password-protected spreadsheet, 
and sharing of data will be restricted to the study personnel listed on the proposal using VA 
email. After data has been collected from the electronic health record, the data will be de-
identified prior to analysis.  
 
Data Analysis 
Aim 1: Screening rates in the intervention vs. control groups will be compared using the chi-
squared or Fisher’s exact test. Clinical outcomes of individuals who took the blood test will be 
reported as descriptive statistics.  
Aim 2: We will use a multivariable logistic regression model to assess demographic and health-
related predictors of accepting the blood test. We will perform descriptive statistics to assess the 
secondary outcomes. Results for secondary outcomes will also be reported stratified by 
race/ethnicity, self-reported health, frequency of healthcare access, and self-perceived risk of 
CRC. 
 
Sample Size Calculations 
Aim 1: Two prior studies that have measured uptake of the Septin9 blood test have found very 
high rates of 84% and 99%, respectively.4,5 The study that found 84% uptake involved patients 
who had previously declined colonoscopy and were subsequently given a choice between the 
blood test and FIT. Since our study population has previously declined both colonoscopy and 
FIT, their uptake of the blood test will likely be lower. We estimate that uptake in our population 
will be 50% and will power our study to detect a 15% absolute difference in screening rate. With 
alpha = 0.05 and 80% power, the required sample size in each group is 170. To account for 
drop-out, we will include 180 patients in each group. 
Aim 2: Assuming a 50% uptake in the intervention group of 170 individuals, there will be an 
estimated 85 individuals who take the blood test. We will select variables with the strongest 
association with blood test completion on bivariate analysis, which will be entered into the final 
multivariable logistic regression model. The number of variables in the final model will be limited 
to ensure that there are at least 10 events per variable, which is the conventional minimum 
standard to preserve model validity.16 
 
 
12) Provisions to Monitor the Data to Ensure the Safety of Subjects 
We believe this study poses no more than Minimal Risk to study participants, and 
therefore there are no plans to establish a data monitoring committee. However, any 
unexpected adverse events will be reported immediately to the PI, who will report to the 
IRB on an ad-hoc basis. 

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13) Withdrawal of Subjects 
There are no anticipated circumstances under which subjects will be withdrawn from the 
research without their consent. Participants may choose to withdraw from the study at any point 
by giving notification to the study team. Patients who withdraw from the study will no longer be 
tracked in the electronic medical record after the time of withdrawal.  
 
14) Risks to Subjects 
The proposed study contains minimal risk. All participants in the study are due for colorectal 
cancer screening and will receive a letter stating this and encouraging them to screen with 
either colonoscopy or FIT. These are considered standard of care clinical tests. For the 
intervention group, the blood-based screening test is also presented as an alternate option. This 
is a FDA-approved test, although it is currently not available in the VA. Individuals in the 
intervention group who choose to undergo the blood test would undergo a single blood draw. A 
final risk is that of breach in patient confidentiality. 
 
15) Potential Benefits to Subjects 
Nearly 20% of age-eligible veterans cared for at the VA NY Harbor Health Care System 
are not up-to-date on colorectal cancer screening. The introduction of a non-invasive test 
that also does not involve handling stool may increase participation in screening in this 
refractory population. 
 
16) Vulnerable Populations 
Vulnerable populations will not be enrolled. 
 
17) Sharing of Results with Subjects 
The study team will share the results of the blood test with patients by telephone or mail 
and notify their primary care physicians using a CPRS note. 
 
18) Setting 
Study recruitment and phlebotomy will be performed at the VA NY Harbor Health Care 
System. The lab assay will be performed offsite at a commercial laboratory because the 
equipment is not available onsite. 
19) Resources Available 
The Principal Investigator (PI) is a board-certified gastroenterologist and clinical 
researcher with expertise in colorectal cancer screening. He has master’s level training 
in epidemiology and biostatistics and is able to perform all of the planned analysis. 
The research assistant will be credentialed in phlebotomy and trained by the PI in 
principles of patient navigation. 
The PI has the full support of the Epigenomics, which makes the blood-based test. 
Epigenomics has agreed to cover the cost of the study. 

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20) Confidentiality 
 
Patients will be informed of the potential risks as part of the informed consent process. All 
efforts will be made to ensure patient confidentiality and assurance of HIPAA compliance. 
Participant data will be de-identified using a protocol-specific unique code that will 
be used for all further data management. A list matching the patient medical record number to 
the protocol specific unique code will be maintained in a password-protected file in the PI’s 
private drive on the VA network. There will be no data entry or interpretation outside of the VA 
NY Harbor Health Care System. The names of the patients will not be revealed in written 
reports or publications detailing the research findings. 
 
21) Provisions to Protect the Privacy Interests of Subjects 
 
The study team will take every possible precaution to protect the privacy of study participants. 
Only study team members who have been trained by the PI will be allowed to access patient 
data. Participants data will be de-identified for analysis and only aggregate data will be 
presented for publication. In addition, participants will not be required to answer any 
questionnaire question that may make him/her not at ease. 
 
22) Compensation for Research-Related Injury 
N/A  
 
23) Consent Process 
We are requesting waiver of HIPAA and informed consent for the purpose of screening patients 
who are eligible for participating in the study. For the control arm, we are requesting waiver of 
HIPAA and informed consent to access their medical record and determine whether they 
undergo a colonoscopy for FIT within 6 months of the initial invitation letter. For participants in 
the intervention arm who elect to undergo the blood test, written informed consent and HIPAA 
authorization will be obtained onsite prior to phlebotomy. All patients will also be invited to 
participate in a short anonymous questionnaire by mail and if needed, by phone. A one-page 
description of the questionnaire and how to contact the research team will be provided in the 
mailing and reiterated in the phone call. However, we are requesting waiver of documentation of 
consent for the anonymous questionnaire. 
 
24) Drugs or Devices 
N/A 
 
 
 
 

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REFERENCES 
 
1.  
White A, Thompson TD, White MC, et al. Cancer Screening Test Use — United States, 
2015. MMWR Morb Mortal Wkly Rep. 2017;66(8):201-206. doi:10.15585/mmwr.mm6608a1 
2.  
Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: Recommendations 
for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. 
Gastrointest Endosc. 2017;86(1):18-33. doi:10.1016/j.gie.2017.04.003 
3.  
Honein-AbouHaidar GN, Kastner M, Vuong V, et al. Systematic Review and Meta-study 
Synthesis of Qualitative Studies Evaluating Facilitators and Barriers to Participation in 
Colorectal Cancer Screening. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res 
Cosponsored Am Soc Prev Oncol. 2016;25(6):907-917. doi:10.1158/1055-9965.EPI-15-
0990 
4.  
Adler A, Geiger S, Keil A, et al. Improving compliance to colorectal cancer screening using 
blood and stool based tests in patients refusing screening colonoscopy in Germany. BMC 
Gastroenterol. 2014;14:183. doi:10.1186/1471-230X-14-183 
5.  
Liles EG, Coronado GD, Perrin N, et al. Uptake of a colorectal cancer screening blood test 
is higher than of a fecal test offered in clinic: A randomized trial. Cancer Treat Res 
Commun. 2017;10:27-31. doi:10.1016/j.ctarc.2016.12.004 
6.  
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. 
doi:10.3322/caac.21387 
7.  
Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term 
prevention of colorectal-cancer deaths. N Engl J Med. 2012;366(8):687-696. 
doi:10.1056/NEJMoa1100370 
8.  
Nishihara R, Wu K, Lochhead P, et al. Long-term colorectal-cancer incidence and mortality 
after lower endoscopy. N Engl J Med. 2013;369(12):1095-1105. 
doi:10.1056/NEJMoa1301969 
9.  
Mandel JS, Church TR, Bond JH, et al. The effect of fecal occult-blood screening on the 
incidence of colorectal cancer. N Engl J Med. 2000;343(22):1603–1607. 
10.  Shaukat A, Mongin SJ, Geisser MS, et al. Long-Term Mortality after Screening for 
Colorectal Cancer. N Engl J Med. 2013;369(12):1106-1114. doi:10.1056/NEJMoa1300720 
11.  National Center for Health Statistics. National Health Interview Survey, 2015. Public-use 
data file and documentation. Available from URL: 
http://www.cdc.gov/nchs/nhis/quest_data_related_1997_forward.htm. 
12.  Liang PS, Wheat CL, Abhat A, et al. Adherence to Competing Strategies for Colorectal 
Cancer Screening Over 3 Years. Am J Gastroenterol. 2016;111(1):105-114. 
doi:10.1038/ajg.2015.367 
13.  Church TR, Wandell M, Lofton-Day C, et al. Prospective evaluation of methylated SEPT9 
in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63(2):317-325. 
doi:10.1136/gutjnl-2012-304149 

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14.  Potter NT, Hurban P, White MN, et al. Validation of a real-time PCR-based qualitative 
assay for the detection of methylated SEPT9 DNA in human plasma. Clin Chem. 
2014;60(9):1183-1191. doi:10.1373/clinchem.2013.221044 
15.  Johnson DA, Barclay RL, Mergener K, et al. Plasma Septin9 versus fecal immunochemical 
testing for colorectal cancer screening: a prospective multicenter study. PloS One. 
2014;9(6):e98238. doi:10.1371/journal.pone.0098238 
16.  Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the 
number of events per variable in logistic regression analysis. J Clin Epidemiol. 
1996;49(12):1373-1379. 
 
 
 

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APPENDIX 
 
 
Dear Veteran,  
 
We are conducting a research study to understand people’s thoughts about colorectal cancer 
and colorectal cancer screening. We would greatly appreciate it if you would be willing to 
participate by filling out the enclosed questionnaire. It should take less than 5 minutes.  
 
If you choose to participate by completing the questionnaire and mailing it back to us in the 
addressed stamped envelope, please rest assured that it is anonymous and we will not connect 
your answers to you. We will combine your answers with that of other study participants before 
analyzing the results. Whether or not you choose to participate will not affect your clinical care in 
any way.  
 
If you have any questions about the study, please call 212-686-7500 x5745 and ask to speak 
with a member of the study team. 
 
Sincerely, 
 
 
 
Peter S. Liang, MD MPH 
Division of Gastroenterology  
VA New York Harbor Health Care System Manhattan Medical Center 
 
 
 

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Demographics 
 
1) What is your age? 
☐ 50-60 
☐ 61-75 
 
2) What is your race? 
☐White 
☐Black 
☐Asian 
☐Other 
 
 
3) What is your ethnicity? 
☐Hispanic 
☐non-Hispanic 
 
4) What is your employment status? 
☐Employed 
☐Not employed 
 
5) What is the highest level of education that you’ve completed? 
☐High school/GED 
☐College 
☐Graduate degree 
 
Health status and medical history 
 
6) How would you rate your overall health? 
☐Very poor 
☐Poor  
☐Good 
☐Very Good 
 
7) How many visits have you had with your primary care doctor in the past year? 
☐0-1  
☐2-5  
☐6-10  
☐>10 
 
8) Do you know anyone who has been diagnosed with colorectal cancer? 
☐Yes  
☐No 
 
9) What do you think is your own risk of getting colorectal cancer? 
☐Low 
☐Below Average  
☐Above Average 
 
☐High 
 
10) Have you ever been diagnosed with any of the following conditions: pre-cancerous colon 
polyp (adenoma), colorectal cancer, ulcerative colitis, Crohn’s disease, hereditary 
gastrointestinal cancer syndrome (e.g. Lynch syndrome or FAP)? 
☐Yes  
☐No 
 
11) Do you have a parent or sibling who was diagnosed with colorectal cancer before age 60? 
☐Yes  
☐No 
 
12) Do you have a family history of a hereditary gastrointestinal cancer syndrome  (e.g. Lynch 
syndrome or FAP)? 
☐Yes  
☐No 
 
Colorectal cancer screening 
 
13) Have you ever had a colonoscopy? 
☐Yes  
☐No (SKIP to 14) 
 
13a) How long ago was your last colonoscopy? 

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☐Less than 10 years  
☐More than 10 years  
 
14) Have you ever had a stool-based test (e.g. fecal occult blood test/FOBT or fecal 
immunochemical test/FIT)?  
☐Yes  
☐No (SKIP to 15) 
 
14a) How long ago was your last stool-based test? 
☐Less than 12 months 
 
☐More than 12 months  
 
15) Why did you decide not to do a colonoscopy when offered in the past 6 months? 
☐I don’t want to take the bowel prep  
 
☐I don’t want to know if I have colorectal cancer 
 
☐Colonoscopy is painful 
 
 
☐I don’t have time 
 
 
☐I don’t have an escort  
 
☐I’m at low risk and don’t need screening  
 
☐Other 
 
☐I wasn’t offered the test in the past 6 months 
 
16) What would make you change your mind and get a colonoscopy? 
☐If the bowel prep were easier 
☐If I knew colonoscopy can prevent cancer by removing pre-cancerous polyps 
☐Overcoming my fears about colonoscopy 
☐If my doctor recommended it 
☐If I knew it wasn’t going to hurt 
☐If I had time/could get time off from work 
☐If I could find an escort 
☐Other 
☐Nothing would change my mind 
 
17) Why did you decide not to do a stool test (fecal immunochemical test/FIT) when offered in 
the past 6 months? 
☐I don’t want to handle stool 
☐I don’t want to know if I have colorectal cancer 
☐The directions for the stool test was too complicated 
☐I don’t think a stool test is accurate  
☐I don’t have access to a toilet that’s suitable for collecting the stool sample 
☐Other 
☐I wasn’t offered the test in the past 6 months 
 
18) What would make you change your mind and take a stool test? 
☐If the directions for the stool test was easier to understand 
☐If I knew the stool test was accurate 
☐If I had access to a toilet that’s suitable for collecting the stool sample 
☐Other 
☐Nothing would change my mind 
 

PROTOCOL TITLE: Assessing the effect of offering a blood-based colorectal cancer screening 
test 
 
Page 14 of 14 
 
19) Would you take a blood test to screen for colorectal cancer? 
☐Yes  
☐No (SKIP to 22) 
 
20) Why would you take the blood test? 
☐A blood test is easy/convenient 
☐A blood test is not painful 
☐A blood test is accurate 
☐Other 
 
21) What do you think are the advantages of a blood test compared to colonoscopy and stool 
test? 
☐It’s more convenient than a colonoscopy or a stool test 
☐I don’t have to do any special preparation to take the test 
☐I’m used to getting blood tests 
☐I think blood tests are more accurate than other tests 
☐The test is done by a medical professional and I don’t have to do anything myself 
☐Other 
 
22) Why would you not take a blood test? 
☐I don’t like getting my blood drawn 
☐I don’t think a blood test is as accurate as a colonoscopy or stool test 
☐I don’t want to know if I have colorectal cancer 
☐Other 
 
23) What would make you change your mind and take a blood test? 
☐If I knew the blood test is better than colonoscopy and the stool test 
☐If my primary care physician recommended the test 
☐Other 
☐Nothing would change my mind