Randomized Trial of In-Home Cervical Cancer Screening in Underscreened Women
Phase: NA
Conditions: Cervical Cancer
Sponsor: University of Washington

Revision: March 17, 2015 
 
Page 1 of 18 
ClinicalTrials.gov Identifier:  NCT02005510 
 
OFFICIAL TITLE:  Randomized Trial of In-Home Cervical Cancer Screening in 
Underscreened Women 
 
SHORT TITLE: HOME Study 
 
Coordinating Center: 
University of Washington 
 
Principal Investigator: 
Rachel L. Winer 
Department of Epidemiology 
School of Public Health 
University of Washington 
Seattle, Washington, U.S.A. 
 
Co-Investigator: 
Diana S.M. Buist 
Kaiser Permanente Washington Health Research Institute 
Seattle, Washington, U.S.A. 
 
Study Coordinator: 
 
Tara Beatty 
Kaiser Permanente Washington Health Research Institute 
Seattle, Washington, U.S.A. 
 
Study Exempt from IDE requirements 
On September 12, 2013 (Q130922 Study Determination request) FDA determined 
intervention is a nonsignificant risk (NSR) device as does not meet definition of a significant 
risk (SR) device under §812.3(m) of the investigational device exemptions (IDE) regulation 
(21 CFR 812). 
 
Final Protocol Date: 
March 17, 2015 
 
Protocol Revision Dates: 
March 17, 2015 
 
Initial Protocol Date: 
January 7, 2014 

Revision: March 17, 2015 
 
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SCHEMA, FIGURE 1 
Assessed for eligibility via electronic medical record
Inclusion criteria:
 Received a Pap reminder 5 months prior
 Women aged 30-64 with an intact uterus
 Have a Kaiser Permanente Washington primary care
   provider (PCP)
 Continuously enrolled at Kaiser Permanente
   Washington for ≥41 months
 No Pap within prior 3.4 years
All eligible women randomized 1:1 (round 1) 
In-home HPV screening arm
 Usual care outreach for Pap screening
 Study team mails HPV self-screening kit and study 
information sheet 
 If no kit returned within 3 weeks, study team makes up 
to 3 kit reminder calls*
Usual care arm
 Usual care outreach for Pap screening
 No contact with study team
Exclusion criteria:
 On “do not contact list” for research studies
 Pregnant
 Language interpreter needed
Kit returned
 Patient mails kit 
directly to central 
clinical lab for HPV 
testing
 Electronic results and 
recommended follow-
up released to patient 
and patient’s own 
PCP* 
 Patient’s own PCP 
manages follow-up of 
HPV results*
Re-assessed for eligibility and re-
randomization (1 year post-randomization)
 Re-randomized 1:1 (round 2)
 Re-randomized 1:1 (round 3)
Cervical cancer screening follow-up tracking
(Screening, diagnosis, and treatment**)
No kit returned
Cervical cancer screening follow-up tracking
(Screening, diagnosis, and treatment**)
Survey
Subset of in-home HPV 
screening arm subjects:
 No interview
 By 6-months post-
randomization: 
Completed all 
recommended follow-
up* OR study follow-up 
visit window complete
 Group 1: Returned kit
 Group 2: Did not return
Interview
Subset  in-home HPV 
screening arm subjects:
 Self-screening kit HPV+
 Group 1: Completed all 
recommended follow-
up*
 Group 2: Did NOT 
complete all 
recommended follow-
up*
Safety monitoring
 HPV positive: Study 
team sends secure 
message to provider if 
HPV results are 
undermanaged
* Mirrors clinical system outreach or follow-up procedures
** See Figure 2 for diagram of cervical cancer screening, diagnosis, and treatment outcome definitions and time windows
 

Revision: March 17, 2015 
 
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SCHEMA, FIGURE 2 
Other 
hrHPV+ 
only 
HPV16+ or 
HPV18+
Randomized women
Randomized to in-home HPV screening arm
Randomized to usual care arm
Do not return HPV kit
Return HPV kit
hrHPV-
Pap or co-test
Abnormal
Colposcopy 
referral*
Abnormal
Surveillance
screen follow-up*
Normal
Pap or co-test
 Unsat
Abnormal
Colposcopy 
referral*
Abnormal
Surveillance
screen follow-up*
Normal
Colposcopy
CIN 2+
Treatment
Black boxes represent screening uptake outcomes
 
Grey boxes represent diagnosis and treatment outcomes 
Dashed lines represent non guideline-recommended management
                   *
Asterisk notes follow-up per current national guidelines (2012 cervical cancer screening [1] and 2013 abnormal result management guidelines [2]), i.e.,
    - Colposcopy referral: Pap and/or HPV result of ≥LSIL or ASC-US & HPV+, or HPV 16/18+
    - Surveillance screen follow-up: Pap and/or HPV result of ASC-US or LSIL & HPV–, or Pap– & HPV+
Abbreviations:
CIN, cervical intraepithelial neoplasia; LSIL, low-grade squamous intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; HPV, human papillomavirus; hrHPV, high risk human papillomavirus
Diagnosis
CIN 2+ captured up
to 6 months after 
screening
results 
Treatment
Treatment captured 
up to 6 months
after CIN 2+
results
Up to 18m 
0m
Unsatisfactory
Unsatisfactory
Colposcopy
CIN 2+
Treatment
≤CIN 1
≤CIN 1
Screening
Screening uptake captured up to 6 months after 
randomization
 
1,2 

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SUMMARY OF CHANGES – PROTOCOL 
 
# 
Date 
Change 
1. 
March 17, 2015 
One-year post-randomization, control group participants re-
assessed for eligibility and re-randomized. 
2. 
 
 
3. 
 
 
4. 
 
 
5. 
 
 
 
 

Revision: March 17, 2015 
 
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TABLE OF CONTENTS 
SCHEMA, Figure 1 .........................................................................................................................2 
SCHEMA, Figure 2 .........................................................................................................................3 
SUMMARY OF CHANGES – Protocol .........................................................................................4 
1. 
OBJECTIVES ......................................................................................................................6 
1.1 
Primary Objectives...................................................................................................6 
1.2 
Secondary Objectives...............................................................................................6 
2. 
BACKGROUND .................................................................................................................6 
2.1 
Study Disease(s).......................................................................................................6 
2.2 
Rationale ..................................................................................................................7 
3. 
PATIENT SELECTION ......................................................................................................7 
3.1 
Eligibility Criteria ....................................................................................................7 
3.2 
Exclusion Criteria ....................................................................................................8 
3.3 
Inclusion of Women and Minorities ........................................................................8 
3.4 
Inclusion of Children ...............................................................................................8 
4. 
STUDY PROCEDURES .....................................................................................................8 
4.1 
Subject Recruitment and Screening .........................................................................8 
4.2 
Procedures ................................................................................................................9 
4.3 
Early Termination ..................................................................................................10 
5. 
STATISTICAL CONSIDERATIONS...............................................................................10 
5.1 
Sample Size ............................................................................................................11 
5.2 
Analysis Plans ........................................................................................................11 
6. 
ADVERSE EVENTS:  REPORTING REQUIREMENTS ...............................................12 
6.1 
Determination of Study Risk .................................................................................12 
6.2 
Reporting Adverse Events .....................................................................................13 
6.3 
Reporting the Intensity of an Adverse Event .........................................................13 
6.4 
Reporting the Relationship of an Adverse Event to intervention ..........................13 
7. 
STUDY OVERSIGHT AND DATA REPORTING / REGULATORY 
REQUIREMENTS .............................................................................................................14 
7.1 
Protocol Review .....................................................................................................14 
7.2 
Informed Consent...................................................................................................14 
7.3 
Changes to Protocol ...............................................................................................14 
7.4 
Data and Safety Monitoring Plan ...........................................................................14 
8. 
REFERENCES ..................................................................................................................16 
APPENDIX A 
NCI Common Terminology Criteria for Adverse Events 
CTC AE v3.0 18 

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1. 
OBJECTIVES 
 
1.1 
Primary Objectives 
 
1.1.1 Histologically-diagnosed CIN 2+ within 6 months after an abnormal screening result (up 
to 12 months post-randomization) 
 
1.1.2 Treated CIN 2+ within 6 months after diagnosed CIN 2+ (up to 18 months post-
randomization) 
 
1.2 
Secondary Objectives 
 
1.2.1 Screening uptake within 6 months after randomization 
 
1.2.2 Abnormal screening result within 6 months after randomization 
 
1.2.3 Predictors of screening uptake and intervention effectiveness through administrative data 
 
1.2.4 Experiences and attitudes associated with in-home HPV testing uptake (through surveys) 
 
1.2.5 Experiences and attitudes associated with follow-up of positive in-home HPV testing 
results (through semi-structured interviews) 
 
 
2. 
BACKGROUND 
 
2.1 
Study Disease(s) 
 
Despite large-scale efforts to encourage routine Papanicolaou (Pap) screening for cervical cancer 
prevention, 20%-30% of U.S. women ≥30 years of age have not been screened in the past 3 
years.3,4 More than half of all cervical cancers in the U.S. are diagnosed in these unscreened or 
underscreened women.5–7 2012 national guidelines identify increasing screening coverage as the 
#1 research priority for reducing cervical cancer-related morbidity and mortality.1 Innovative 
strategies that eliminate the need for clinic-based primary screening could effectively improve 
screening compliance while maintaining high-quality care. 
 
Studies have demonstrated improved sensitivity and cost effectiveness for detecting pre-
cancerous cervical neoplasia grade 2 to 3, carcinoma in situ, and invasive cervical cancer 
(hereafter referred to as CIN 2,3+) from Pap co-testing with FDA-approved tests for high-risk 
(hr) HPV infection compared to Pap screening alone for women ≥30 years of age.8,9 While this 
approach is endorsed by all major U.S. guidelines as a preferred or acceptable screening 
strategy1,10 and has advantages over traditional Pap screening, co-testing is no more likely to 
attract women who delay attending clinic-based screening. There is growing interest in an 
alternative primary screening strategy – hrHPV screening followed by triage of women with 
hrHPV+ test results to cytology, with studies suggesting that such a strategy could be cost-

Revision: March 17, 2015 
 
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effective and sensitive for detecting CIN 2,3+.11,12 If samples for hrHPV screening could be self-
collected at home (with in-clinic follow-up of hrHPV-positive women), the need for in-clinic 
screening could be eliminated for a majority of women.  
 
2.2 
Rationale 
 
Despite the availability of highly effective prophylactic hrHPV vaccines, screening remains a 
necessary priority for cervical cancer prevention.1,10 Current vaccines do not protect against all 
hrHPV types, nor do they protect women already infected with vaccine-types from developing 
cervical neoplasia.13 Furthermore, because these vaccines have only been available since 2006, 
are only recommended for women ≤26 years of age,14 and have not been widely used even 
among the recommended target population,15 the majority of women ≥30 years of age (the age 
group at highest risk for cervical cancer) are unvaccinated. Although Pap screening programs 
have been highly effective in reducing cervical cancer rates over the past 50 years, a significant 
portion of U.S. women do not participate in regular Pap screening; 20%-30% of U.S. women 
≥30 years of age have not been screened in the past three years.3,4 These are the women at 
highest risk for cervical cancer, as over half of the 12,000 cervical cancers diagnosed in the U.S. 
each year16 are in women who have not been screened in the past three years.5–7 Reaching 
underscreened women is a top national priority for reducing disparities in cervical cancer 
prevention; in fact, the 2012 joint cervical cancer screening guidelines state that the #1 research 
priority is to increase screening coverage.1 There is a significant need for targeted, innovative 
interventions that increase screening participation and adherence to recommended screening 
intervals, while maintaining high quality care. The joint guidelines advocate for novel programs 
incorporating self-sampling for hrHPV testing, and evaluation of the “scale-up, implementation, 
and acceptability of such programs17” targeting underscreened women.1 Our proposed RCT is 
directly responsive to this national recommendation, and will provide definitive evidence-based 
data on the ability of an in-home programmatic HPV screening outreach strategy to enhance 
early detection of cervical neoplasia and improve screening compliance. It is likely that this 
innovative study could change the ways in which women participate in cervical cancer screening 
programs. Furthermore, we will investigate patient experiences and attitudes that are associated 
with in-home HPV screening uptake and complete follow up of hrHPV+ test results. The latter is 
particularly important for understanding adherence to the continuum of cervical cancer 
prevention, from screening through treatment. While the majority of cervical cancers are 
attributable to lack of screening, up to 13% of cervical cancers diagnosed in fully-insured women 
are attributable to delayed follow up of abnormal Pap results.7,18,19 
 
 
3. 
PATIENT SELECTION 
 
3.1 
Eligibility Criteria  
 
3.1.1 Female sex 
 
3.1.2 30 years to 64 years of age 
 

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3.1.3 Have a primary care provider at Kaiser Permanente Washington 
 
3.1.4 Received annual "birthday letter" with Pap screening reminder 5 months earlier 
 
3.1.5 No Pap test in the past 3.4 years 
 
3.1.6 Continuously enrolled at Kaiser Permanente Washington for at least 3.4 years 
 
3.1.7 No hysterectomy 
 
3.2 
Exclusion Criteria 
 
3.2.1 Currently pregnant 
 
3.2.2 Language interpreter needed 
 
3.2.3 On "do not contact list" for research studies 
 
3.3 
Inclusion of Women and Minorities 
 
The scientific objective of the proposed research is to study the ability of an in-home 
programmatic HPV screening outreach strategy to enhance early detection of cervical neoplasia 
and improve screening compliance. Because cervical cancer only affects women, our entire study 
population will be composed of women. 
 
Race and ethnicity are not eligibility requirements for participation in our study. We will include 
all minorities that are Kaiser Permanente Washington members and meet our study eligibility 
requirements. The ethnic/racial composition of our study population will therefore largely reflect 
the ethnic/racial composition of Kaiser Permanente Washington women members. The projected 
proportions of participants from different ethnic/racial backgrounds are based on the composition 
of Kaiser Permanente Washington members (See Planned Enrollment Report table in Section 
5.1). 
 
3.4 
Inclusion of Children 
 
We are not enrolling women younger than age 21 in the current study.  All current guideline 
recommendations (2012) are that cervical cancer screening should begin at age 21 years 
(regardless of sexual history).  Screening before age 21 should be avoided because women less 
than 21 years old are at very low risk of cancer.  Screening these women may lead to 
unnecessary and harmful evaluation and treatment. 
 
 
4. 
STUDY PROCEDURES 
 
4.1 
Subject Recruitment and Screening 
 

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4.1.1 Primary objectives, and secondary objectives one (1.2.1), two (1.2.2), and three (1.2.3) 
 
Eligible women will be identified using electronic medical record (EMR) data; all eligible 
women will be enrolled under a waiver of consent. The study programmer will use SAS software 
built in simple random sample procedure to randomly allocate participants 1:1 to the intervention 
arm or the control arm over a 2.5 year recruitment period. One-year post-randomization, control 
arm participants will be re-assessed for eligibility and re-randomized.  
 
Women in the control arm will receive usual care reminders to attend Pap screening. Women 
randomized to the usual care arm will not receive any study-related interventions or contact from 
the study team. 
 
Women in the intervention group will receive usual care plus a mailed HPV self-sampling kit 
with a pre-paid envelope addressed to Kaiser Permanente Washington to return the kit to the 
central clinical laboratory. The mailing will include an invitation letter, research information 
sheet, and materials for self-collecting and returning a sample. Because home HPV self-
screening is not standard of care in the US, the invitation letter will advise women to receive 
routine Pap tests, regardless of whether they select to complete HPV self-sampling. Women will 
be informed participation is voluntary and provided with a telephone number to call with 
questions or to “opt-out” of having their individual-level medical record data used for research. 
To mirror Kaiser Permanente Washington prevention outreach protocols, if the kit is not returned 
within three weeks, study staff will make up to three reminder calls. 
 
4.1.2 Secondary objective four (1.2.4), survey 
 
We will mail survey invitation letters to intervention arm participants six months after trial 
randomization. We will sample two groups based on kit return status, using EMR data to identify 
and recruit “kit returners” and “non-returners”. Invitation letters will ask women to complete a 5-
10 minute web survey about their experience with a “health screening kit” mailed 6 months 
prior. 
 
4.1.3 Secondary objective five (1.2.5), interview 
 
Potential interview participants will be identified 1 to 2 weeks after completing all recommended 
diagnostic follow-up or treatment, or after they are no longer being assessed for main trial 
outcomes if recommended follow-up was not completed. An invitation letter and information 
sheet will be mailed with a telephone number to opt-out. If the potential participant does not opt-
out, an interviewer will call a few days later to conduct a 15–20 minute interview. 
 
4.2 
Procedures 
 
4.2.1 Medical records history 
 
We will obtain the following from subject medical records: (1) cervical cancer screening, 
diagnosis, and treatment, (2) medical information related to cervical cancer risk factors, and (3) 
demographic information. For example, doctor visits and lab tests, age, ethnic background and 

Revision: March 17, 2015 
 
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other demographics, tobacco use, diagnoses, and disease history. 
 
4.2.2 Clinical outcomes 
 
We will obtain cervical cancer screening, diagnosis, and treatment results from subject medical 
records up to 18 months post-randomization. 
 
4.2.3 Self-collect vaginal specimen for HPV testing 
 
Subjects randomized to the intervention arm (in-home screening) will be asked to wash their 
hands and then push a polyester swab into their vagina as far as they can with no pain.  Rotate 
three times and take the swab out.  Put the swab in a specimen cup.  Repeat the sample collection 
on a second swab. Place the specimen in a return mailer and mail the sample to the Kaiser 
Permanente Washington central laboratory. 
 
4.2.4 Survey 
 
Subjects will be asked questions about their attitudes and knowledge of the self-sampling kit 
previously mailed to them, and preference for at-home screening compared vs. clinic-based 
screening, and their knowledge of cervical cancer and cervical cancer screening. 
 
4.2.5 Interview 
 
Subjects will be asked about their experience and thoughts about the self-sampling kit previously 
mailed to them, Pap testing, their test preferences, their knowledge of cervical cancer and 
cervical cancer screening, and their contacts with their doctor or health care team. 
 
4.3 
Early Termination 
 
Any subjects experiencing a serious adverse event felt to be related to study procedures should 
be withdrawn from the study.  Any subject withdrawing their consent to participate in the study 
or their authorization to use their protected health information will be withdrawn from the study. 
 
All subjects randomized into the study will be included in the final study analyses.  Subjects may 
be withdrawn from the study if: 
 
    1) Voluntary patient withdrawal; 
    
Reasons why subjects are discontinued from the clinical trial will be documented on the study 
termination tracking log. 
 
 
5. 
STATISTICAL CONSIDERATIONS 
 
 

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5.1 
Sample Size 
 
PLANNED ENROLLMENT REPORT 
 
ANTICIPATED/PLANNED ENROLLMENT for ENTIRE STUDY: 
Number of Participants (must provide exact numbers. i.e. no range) 
 
Ethnic Categories 
 
 
 
Sex/Gender 
 
Females 
Males 
Total 
Hispanic or Latino 
880 
0 
880 
Not Hispanic or Latino 
16,711 
0 
16,711 
Ethnic Categories: Total of All 
Participants 
17,591 
0 
17,591 
 
                  Racial Categories 
American Indian/Alaska Native 
705 
0 
705 
Asian 
1,406 
0 
1,406 
Native Hawaiian or Other Pacific Islander 
176 
0 
176 
Black or African American 
880 
0 
880 
White 
14,424 
0 
14,424 
Racial Categories: Total of All 
Participants  
17,591 
0 
17,591 
 
Estimated based on the number and racial and ethnic distribution of underscreened women in 
2011 in Kaiser Permanente Washington 
 
5.2 
Analysis Plans 
 
5.2.1 Analysis plan relevant to primary objectives and secondary objectives one (1.2.1), two 
(1.2.2), and three (1.2.3) 
 
Data will be analyzed based on the intention-to-treat principle. Denominators for each arm will 
generally include all women randomized to that arm, minus the women identified post-
randomization as ineligible. For diagnosed and treated CIN 2+, abnormal screening results, and 
screening uptake, we will compare the proportion of outcomes detected in the intervention arm 
to the proportion detected in the usual care arm and estimate relative risks using log-binomial 
regression. Robust variances estimates will be used to account for within-subject correlation due 
to re-randomized subjects contributing more than one observation period. If differences are 
observed in the distribution of EMR-derived subject characteristics across arms despite 
randomization, we will adjust for the relevant covariates in the regression models. Subject 
characteristics of interest include age, race, ethnicity, length of health plan enrollment before 
randomization, etc. 
 
To evaluate predictors of screening uptake, we will use log-binomial regression to estimate the 
effects of subject characteristics on the probability of screening uptake. To test for effect 
modification by randomization arm (i.e., to test if home HPV screening is more effective at 
increasing uptake than usual care for subgroups of women), we will test characteristic-by-
randomization arm interaction terms using log-binomial regression comparing the relative risk of 
screening uptake in the intervention arm relative to the usual care arm by characteristics of 

Revision: March 17, 2015 
 
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interest. 
 
In an exploratory analysis, positive predictive value (PPV) of an abnormal screening test for 
detecting CIN 2+ will be estimated within each arm. The denominator will include women who 
receive an abnormal screening result within 6 months of randomization that warrants referral to 
colposcopy, and the numerator will include women with diagnosed CIN 2+. We will also 
calculate PPV restricting the denominator to women who receive colposcopy within 6 months of 
the abnormal screening result. 
 
5.2.2 Analysis plans relevant to secondary objectives four (1.2.4) and five (1.2.5) 
 
Through surveys and in-depth interviews of women in the in-home HPV screening arm, we will 
identify patient experiences and attitudes that are associated with in-home HPV testing uptake 
and complete follow up of hrHPV+ test results. We will describe frequency distributions of 
responses to survey questions about patient experiences and attitudes (aligned with our 
conceptual model–adapted from Andersen-Aday20–22 & Proctor23). We will transcribe, code and 
analyze the semi-structured interviews to examine experiences and attitudes related to timely 
completion of follow up of hrHPV+ results. Together with the system-level impact data, these 
results will provide important information about how multi-level systems can support timely 
follow up for hrHPV+ women, and areas for additional educational intervention. 
 
6. 
ADVERSE EVENTS:  REPORTING REQUIREMENTS  
 
6.1 
Determination of Study Risk 
 
This is a minimal risk study where the medical intervention has similar potential adverse events 
as women undergoing standard clinical procedures such as Pap, human papillomavirus (HPV) or 
other sexually transmitted disease testing.  Based on our own previous and ongoing studies and 
numerous other prior studies involving self-collected vaginal swabs, we expect adverse events 
will be rare and minor in severity.  The study questionnaires and interviews also present minimal 
risk to subjects as they do not address highly sensitive information.  As such, the principal 
investigator will continuously monitor adverse events as they are reported to the study hotline 
and also through women’s primary care teams.  Both reviewing institutional review boards for 
this study (University of Washington and Kaiser Permanente Washington) have ruled in 
agreement with this assessment. 
 
Discomfort and light bleeding are the expected adverse events (AEs). In our previous University 
of Washington studies of in-home HPV testing, light bleeding was reported by a small minority 
of subjects who used in-home HPV test kits (less frequent than bleeding from standard Pap 
testing). We have no plan for stopping rules due to bleeding because we are only capturing AEs 
through self-report to the study hotline or primary care teams, and do not expect that the number 
of reports of bleeding would exceed the frequency of bleeding from standard Pap testing.  All 
adverse events will be continuously monitored by the Principal Investigator. 
 
Toxicities and adverse events will be assessed using the NCI Common Toxicity Criteria for 
Adverse Events v3.0 (CTCAE; see Appendix A). 

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6.2 
Reporting Adverse Events 
 
All adverse events, whether solicited or spontaneous, must be documented in the adverse event 
(AE) case report form (CRF). 
 
Adverse events will be reported by patients via the study telephone hotline, or via report to their 
Kaiser Permanente provider (providers will report AEs to study staff).  All AEs reported to study 
staff, regardless of causality, must be recorded immediately in the AE CRF. 
 
The Principal Investigator will designate a medical monitor that will be responsible for following 
AEs that are serious or that cause the patient to discontinue before completing the study, through 
an appropriate health care option.  The patient should be followed until the event resolves or 
stabilizes.  Frequency of follow-up is at the discretion of the medical monitor.  The medical 
monitor must follow the clinical course of each AE until resolution or stabilization. Serious AEs 
ongoing at the end of the study period must be followed up to final outcome. 
 
6.3 
Reporting the Intensity of an Adverse Event 
 
The intensity of an AE will be described and graded per NCI Common Terminology Criteria for 
Adverse Events CTC AE v3.0  
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf) . 
 
6.4 
Reporting the Relationship of an Adverse Event to intervention 
 
The medical monitor will determine the assessment of the causal relationship of the event to 
study intervention using the following guidelines: 
 
 Attribution of the AE: 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
All adverse events, regardless of severity, will be classified as expected or unexpected and 
reported to the Kaiser Permanente Washington Human Subjects Review Committee, per current 
Kaiser Permanente Washington Human Subjects Review Committee Incident Guidelines. 
 
 

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7. 
STUDY OVERSIGHT AND DATA REPORTING / REGULATORY 
REQUIREMENTS 
 
7.1 
Protocol Review 
 
The protocol and informed consent forms for this study must be reviewed and approved in 
writing by a properly constituted independent Ethics Committee (EC) or Institutional Review 
Board (IRB) prior to any patient being registered on this study. 
 
7.2 
Informed Consent 
 
7.2.1 Primary objective and secondary objectives one (1.2.1), two (1.2.2), and three (1.2.3) 
 
All consent conduct in compliance with Code of Federal Regulations, Title 45, Part 46 (45 CFR 
part 46). To reduce participation bias, all eligible women will be enrolled into the trial under a 
waiver of consent. Informed consent of intervention arm kit recipients will be per a waiver of 
documentation of consent. Intervention arm women will have the ability to opt-out of having 
their individual-level medical record data used in the research, but passive consent will be 
utilized which will significantly enhance the generalizability of the findings. 
 
7.2.2 Secondary objectives four (1.2.4) and five (1.2.5) (surveys and in-depth interviews of 
women in the in-home HPV screening arm) 
 
In compliance with 45 CFR part 46, informed consent will be obtained from all women via a 
waiver of documentation of consent.  
 
7.3 
Changes to Protocol 
 
Any modification of this protocol must be approved by the Principal Investigator and approved 
by the IRB(s), before the revision or amendment may be implemented.  The only circumstance in 
which the amendment may be initiated without regulatory approval is for a change necessary to 
eliminate an apparent and immediate hazard to the patient.  In that event, the investigator must 
notify the IRB in writing per current IRB rules. 
 
7.4 
Data and Safety Monitoring Plan 
 
An interim data look at the kit return rate in the intervention arm will be reviewed by limited 
study staff 6 weeks after reaching 50% of the expected target accrual; a kit return rate of >10% is 
set as the threshold for continuing the trial because a lower return rate will make the intervention 
not clinically viable. 
 
Study staff involved in interim data activities will not be involved in any scientific decisions 
about modifications to the study protocol, but may consult with an external scientific advisory 
committee if review of study data raises any potential ethical concerns. Membership on the 

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external scientific committee will include a Kaiser Permanente Washington Health Research 
Institute biostatistician and a University of Washington clinician. The scientific leadership 
committee, comprised of the Principal Investigator, project PhD biostatistician, and one 
additional co-investigator, will be blinded to all primary and secondary outcomes analyses until 6 
months after the last subject is enrolled. 
 
 
 
 

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8. 
REFERENCES 
 
1.  
Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for 
Colposcopy and Cervical Pathology, and American Society for Clinical Pathology 
screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J 
Clin. 2012;62(3):147-172. doi:10.3322/caac.21139 
2.  
Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the 
management of abnormal cervical cancer screening tests and cancer precursors. Obstet 
Gynecol. 2013;121(4):829-846. doi:10.1097/AOG.0b013e3182883a34 
3.  
Health US, 2009: With Special Feature on Medical Technology. Hyattsville, MD: National 
Center for Health Statistics; 2010. 
4.  
The State of Healthcare Quality 2010. The National Committee for Quality Assurance; 
2010. 
5.  
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APPENDIX A 
NCI COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS CTC AE V3.0 
 
Adverse events will be assessed using the NCI Common Toxicity Criteria for Adverse Events 
v3.0 (CTCAE).  A copy can be downloaded from the CTEP home page. 
 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm