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Trial registered on ANZCTR


Registration number
ACTRN12618000367246
Ethics application status
Approved
Date submitted
29/01/2018
Date registered
12/03/2018
Date last updated
31/03/2021
Date data sharing statement initially provided
13/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Human Papillomavirus (HPV) self-sampling among un- and under-screened Maori, Pacific and Asian women: a randomised controlled community trial to examine the effect of self-sampling on participation in cervical-cancer screening
Scientific title
Comparison of two invitation-based methods for Human Papillomavirus (HPV) self-sampling with standard recall for usual care among un- and under-screened Maori, Pacific and Asian women: a randomised controlled community trial to examine the effect of self-sampling on participation in cervical-cancer screening
Secondary ID [1] 290421 0
HRC 16/405
Universal Trial Number (UTN)
U1111-1189-0531
Trial acronym
Linked study record
Trial ID ACTRN12616001401448 (HPV-SS) is a feasibility study which we are using to inform the development of this trial (it includes some of the same investigators but was funded and initiated separately).

Health condition
Health condition(s) or problem(s) studied:
Cervical-cancer screening 300762 0
Human papilloma virus 306177 0
Self-sampling 306178 0
Condition category
Condition code
Public Health 300599 300599 0 0
Epidemiology
Cancer 300600 300600 0 0
Cervical (cervix)
Public Health 300601 300601 0 0
Health service research
Infection 306106 306106 0 0
Sexually transmitted infections
Infection 306107 306107 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Assessing uptake and acceptability of a new human papilloma virus (HPV) detection method (low vaginal self-sampling with cotton swab and HPV molecular testing with the Roche cobas 4800 platform) in comparison to (minimally altered) usual care, for primary cervical-cancer screening. Invitation through the primary care clinic (monthly matched lists between primary care enrolled patient and cervical screening register is routine practice, these lists will be used for identifying eligible women). Women will be randomised to one of three arms: clinic-based self-sampling (clinic-based SS), mail-out self-sampling (mail-out SS) or usual care. Clinic-based SS women will be invited to attend the clinic, discuss the study, consent, and complete a questionnaire. Clinic-based SS women able to complete the self-sampling at the clinic (in the bathroom) during this visit or, to ensure clinical safety, they will be able to take the kit home and return it to the clinic, but this will be recorded and analysed separately. Mail-out SS women will be posted a kit (to their home) and asked to complete the consent & laboratory forms, take the sample, complete the questionnaire, and arrange (free) courier pick-up of the completed kit, or to take the completed kit to a community laboratory.
Uptake of the invitation to participate will be monitored via receipt of test results into the study IT system and, for the clinic-based SS group, via clinic attendance record. Four weeks after the invitation letters have been sent, all non-responding women will be sent a reminder text message. The reminder text message for the mail-out SS group will include a telephone number that the woman can use to request that a second sampling kit be sent. Contact details for research nurses are included in the invitation letters. The research nurses will answer any questions that the women have over the telephone.
All results will be provided to women, even if it is usual practice for the clinic not to return negative results. Positive results women will be phoned and asked to attend the clinic to discuss with the GP, practice nurse or research nurse. All screening (including usual care) will be provided free of charge (most women have to pay for cervical screening; secondary care is free of charge in NZ).
The study is assessing the impact of this intervention, and the two different invitation methods, on participation rates for cervical screening among un- and under-screened women.
Intervention code [1] 300036 0
Early detection / Screening
Intervention code [2] 300468 0
Prevention
Comparator / control treatment
Control group is usual care (pap smear [cytology]). The control group will receive very slightly different treatment to standard usual care in that they will have agreed to take part in a study and will therefore receive more information about cervical screening than would usually be provided, and they will be asked to sign a consent form which includes consent for the results of their test being seen by the research team. Also, usual care as part of the study will be more standardised (in terms of invitation, information and results provision) than it is outside of the study, and it will be provided free of charge (most women have to pay for cervical screening in NZ).
Control group
Active

Outcomes
Primary outcome [1] 304477 0
Participation rate (uptake) of HPV self-sampling in both study intervention arms, in comparison with control arm (usual care; cytology). Uptake will be assessed as the proportion of eligible women who were able to be contacted, who perform/have the test and for whom a laboratory test result is received. This will be assessed by ethnicity, age, sampling group and screening history.
Timepoint [1] 304477 0
3 months post offer of test.
Primary outcome [2] 304478 0
Prevalence of high risk HPV genotypes from self-sampled low vaginal swab, as detected by the Roche cobas 4800 platform (negative, positive for HPV16/18, or positive for HPV 'other' risk risk type), and the prevalence of cervical abnormalities in the usual care group.
Timepoint [2] 304478 0
12 months post offer of self-sampling or cytology.
Secondary outcome [1] 342073 0
Follow-up proportion of high risk HPV positive women for cytology with primary care provider or colposcopy at hospital clinic, as assessed by National Cervical Screening Programme Register (records all cytology and histology events), primary care electronic health records, and colposcopy clinical electronic records.
Timepoint [1] 342073 0
6 months post high risk HPV positive test result.
Secondary outcome [2] 342136 0
To determine the level of support needed to achieve the aim of at least 90% follow-up of high risk HPV positive women to attend for cytology or colposcopy.

Level of support required to ensure 90% follow-up of high risk HPV positive women will be determined using a tracking tool within the study database. Women who have a high risk HPV positive result will be flagged in the database as requiring action. The research nurses will work with the women, primary care and the support-to-services provider to ensure a high level of follow-up. Follow-up interactions/attempts will be recorded in the study database, including the type of support provided, e.g. phone calls, transport, childcare, visit attendance support, etc. Analysis at the completion of the study will determine numbers of women requiring either cytology or colposcopy and the type of support required.
Timepoint [2] 342136 0
6 months post high risk HPV positive result recorded on the National Cervical Screening Programme Register
Secondary outcome [3] 342137 0
Association between acceptance of self-sampling and demographic and other factors, assessed through the acceptability questionnaire. The acceptability questionnaire has been specifically designed for this study. It is based on the questionnaire used for the comparable iPAP trial (ACTRN12613001104741) in Australia (with permission), however, it has been adapted to the New Zealand context following feedback from women and research nurses involved in a local feasibility study (ACTRN12616001401448 (HPV-SS)).
Timepoint [3] 342137 0
End of study
Secondary outcome [4] 342138 0
Time for return of sample from mail-out group women (number of days from when sample taken to when sample received by laboratory).
Timepoint [4] 342138 0
End of study
Secondary outcome [5] 342334 0
Percentage of unsatisfactory cytology tests, HPV tests and colposcopy examinations.

The proportion of unsatisfactory HPV tests will be measured by the rate of internal control failure on Roche cobas 4800 testing. All invalid samples will be reported and a repeat sample requested. All follow-up of invalid tests will be managed by the research nurses.

The proportion of unsatisfactory cytology tests will be assessed by the proportion recorded as unsatisfactory (in accordance with New Zealand standard practice) on the National Cervical Screening Programme (NCSP) Register .

The proportion of colposcopy tests reported as unsatisfactory will be assessed by the proportion recorded as unsatisfactory (in accordance with New Zealand standard practice) on the colposcopy report.
Timepoint [5] 342334 0
End of study
Secondary outcome [6] 342335 0
Experience of the test, enablers/barriers of screening, and factors associated with screening preferences (from the acceptability questionnaire, described in Secondary Outcome 3).
Timepoint [6] 342335 0
End of study
Secondary outcome [7] 343685 0
Number of women who cannot be contacted, defined as the number of women whose pre-invite letter is returned to the study marked 'gone, no address', 'return to sender' or similar. This will be recorded in the study database.
Timepoint [7] 343685 0
End of study
Secondary outcome [8] 343686 0
Number of women who opt-out of the study prior to randomisation, defined as the number of women who contact the study requesting to opt-out, after receiving their pre-invite letter but before they have been randomised. This will be recorded in the study database.
Timepoint [8] 343686 0
End of study

Eligibility
Key inclusion criteria
Age 30-69
Never-screened or under-screened (at least 5 years from previous test)
Maori, Pacific or Asian ethnicity
Resident in Waitemata District Health Board (DHB), Auckland DHB or Capital & Coast DHB
Enrolled in an Auckland or Wellington general practice
Minimum age
30 Years
Maximum age
69 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusions as per New Zealand National Cervical Screening Programme Guidelines, including women:
1. who have had a benign total hysterectomy
2. who have previously or currently have cervical cancer
3. who are symptomatic (abnormal bleeding, pelvic pain, or symptoms of a sexually transmitted infection).

In addition, women:
1. who have previously had a high-grade lesion and have not attended for colposcopy (remaining at high clinical risk)
2. who are currently pregnant.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is an open label trial, however, at the time of ascertainment of eligibility to participate in the trial, the person determining this eligibility will be unaware, when this decision was made, to which group the subject would be allocated because randomisation will occur after initial invitation to participate.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation will be used for stratified allocation. Stratification will be on ethnicity (Maori, Pacific and Asian) within study site (Auckland and Wellington).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
A nested substudy will be undertaken at selected clinics at the Auckland site whereby any women who have been invited to have cervical screening as part of the study (in any of the three arms) but who have not done so three months after invitation will be opportunistically invited to self-sample at the clinic when they visit over the following six months (modified from the original nine months). For the main analyses these women will be regarded as non-responders to the initial invitation. The same outcomes will be measured for the sub-study as in the main study.

It is anticipated that a separate, short questionnaire will be developed and administered with verbal consent by telephone to a random sample of 50-100 non-responding women to examine their reasons for non-participation. It is anticipated that this will be a sub-project undertaken by a Masters student, and separate approvals and funding will be sought before it is started.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size (1,866 Maori, 1,866 Pacific, and 1,866 Asian women (5,598 in total)) gives 99.95% power to detect a 15% difference between the usual care and the self-sampling clinic-based group within each ethnic group, assuming a 25% response proportion in the self-sampling clinic-based group and a 10% response proportion in the usual care (cytology) group, with an alpha of 0.05. We have greater power for all ethnic groups combined.

The main analyses will focus on the primary outcome of the study: participation, i.e. the proportion of women who provide a self-sample compared with the proportion who attend for cytology, by ethnicity. These will initially be assessed simply by comparing the proportions who ‘participated’ in each group; this will be followed by a multiple logistic regression analysis to adjust for potential confounders (e.g. age, ethnicity, screening history, socio-economic position, study site) and to assess which factors (in addition to the intervention) affect participation. The same analyses will be repeated for un- and under-screened women separately, providing important information on whether screening history affects participation.

We will also analyse the prevalence of oncogenic HPV in the self-sampling groups, and the prevalence of cervical abnormalities in the cytology group. Prevalence odds ratios will be calculated using logistic regression and compared across ethnicities, adjusting for age.
Secondary analyses will assess the association between acceptance of self-sampling and demographic and other factors. For comparisons across ethnicity and screening-history (un- and under-screened) groups, multiple linear or logistic regression (as appropriate) will be used, adjusting for age and other potential confounding variables. Time for return of sample will be calculated for self-sampling groups as policy-relevant information; laboratory turnaround time and proportion of unsatisfactory samples will be monitored.

Experience of the test, enablers/barriers of screening (including preference, measured through uptake, for returning samples by courier or through clinics/laboratories), and factors associated with screening preferences will be described for each group (self-sampling or cytology), by ethnicity and demographic factors. Standard descriptive statistical methods will be used. t-tests and Chi-square tests will be used to assess statistical significance. Multiple linear or logistic regression (as appropriate) will be used to compare these responses between the two groups (self-sampling or cytology), adjusting for potential confounders.

We will document whether we achieve our aim of following-up 90% of oncogenic HPV positive women and what is required to follow-up these women. In addition, the data will deliver information on: 1) the level of comprehension of instructions for self-sampling to ensure future clarity and acceptability; and 2) a cost-benefit analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/03/2018
Actual
8/06/2018
Date of last participant enrolment
Anticipated
Actual
13/05/2020
Date of last data collection
Anticipated
Actual
4/01/2021
Sample size
Target
5598
Accrual to date
Final
5546
Recruitment outside Australia
Country [1] 9498 0
New Zealand
State/province [1] 9498 0
Auckland

Funding & Sponsors
Funding source category [1] 298435 0
Government body
Name [1] 298435 0
Health Research Council of New Zealand
Country [1] 298435 0
New Zealand
Primary sponsor type
University
Name
Centre for Public Health Research, Massey University
Address
Wellington Campus
PO Box 756
Wellington 6140
New Zealand
Country
New Zealand
Secondary sponsor category [1] 298004 0
None
Name [1] 298004 0
Address [1] 298004 0
Country [1] 298004 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299431 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 299431 0
Ethics committee country [1] 299431 0
New Zealand
Date submitted for ethics approval [1] 299431 0
15/06/2017
Approval date [1] 299431 0
26/10/2017
Ethics approval number [1] 299431 0
17/NTB/120

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70022 0
Prof John Potter
Address 70022 0
Centre for Public Health Research
Massey University
PO Box 756
Wellington 6140
New Zealand
Country 70022 0
New Zealand
Phone 70022 0
+64 4 979 3106
Fax 70022 0
Email 70022 0
[email protected]
Contact person for public queries
Name 70023 0
Naomi Brewer
Address 70023 0
Centre for Public Health Research
Massey University
PO Box 756
Wellington 6140
New Zealand
Country 70023 0
New Zealand
Phone 70023 0
+64 4 979 3106
Fax 70023 0
Email 70023 0
[email protected]
Contact person for scientific queries
Name 70024 0
Naomi Brewer
Address 70024 0
Centre for Public Health Research
Massey University
PO Box 756
Wellington 6140
New Zealand
Country 70024 0
New Zealand
Phone 70024 0
+64 4 979 3106
Fax 70024 0
Email 70024 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified participant data, after final publication of the results.
When will data be available (start and end dates)?
Immediately following final publication, no end date determined.
Available to whom?
Case-by-case basis at the discretion of Principal Investigator.
Available for what types of analyses?
Only for research for the public good.
How or where can data be obtained?
Access subject to approvals by Principal Investigator.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAcceptability of human papillomavirus (HPV) self-sampling among never- and under-screened Indigenous and other minority women: a randomised three-arm community trial in Aotearoa New Zealand.2021https://dx.doi.org/10.1016/j.lanwpc.2021.100265
N.B. These documents automatically identified may not have been verified by the study sponsor.