Cervical Intraepithelial NeoplasiaEarly Phase 1NCT01029990
Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program
A Early Phase 1 study testing Telephone arm and Self-test arm in people with Cervical Intraepithelial Neoplasia, run by Göteborg University.
Trial summary
Women who don't participate in Swedish cytology screening program are a minority of about 10%, but constitute the majority of those who acquire cervical cancer. Over 50 000 women in the Västra Götalandregion have abstained from participation in the program for at least 2 screening rounds (6 - 10 years, depending om… Read more about this study
- Who is it for?
- Ages 29 to 63 years, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia
- What is being tested?
- Telephone arm and Self-test arm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8,800 participants
- Where
- No sites listed yet
- Study dates
- Sep 2009to Jan 2011
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 29 to 63 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- No record of PAP smear in the regional screening register for more than two screening rounds (6 - 10 years depending on age).
- Evidence in the regional population register that women have been living in the west region of Sweden during this time.
Who cannot join
- Total hysterectomy
About this study
Women who don't participate in Swedish cytology screening program are a minority of about 10%, but constitute the majority of those who acquire cervical cancer. Over 50 000 women in the Västra Götalandregion have abstained from participation in the program for at least 2 screening rounds (6 - 10 years, depending om age). We plan to test two promising strategies to increase participation. In a study of two different health policies women who have defaulted are randomised to receiving a telephone call from a midwife, receive an offer of a self-test for HPV or being included in a control group. This is an effectiveness study that should give an answer how participation could be increased and give the basis for a calculation of the costs involved, before decisions can be made about implementing either intervention.
Read the detailed description
Background
Cervical cancer today is considered as a disease that to a very large extent is preventable. In Sweden cytological screening has been ongoing since the 60:s and this has made cervical cancer a rare disease. Several new, but costly, methods like HPV-testing and vaccination has been claimed to further reduce cancer incidence, but this has not been scientifically proven so far. A recent audit of the Swedish screening program (Andrae 2008) found that the foremost risk factor for cervical cancer in the context of the program was non participation. Women who do participate are well protected from cervical cancer.
A Swedish study evaluating different strategies to increase participation found telephone contact with defaulters to be the superior intervention (Eaker 2004). This study was done in a region of Sweden with lower coverage (Sparén 2007) and less emphasis on efforts to increase participation. A study from Kalmar, Sweden, with high coverage did not find an extended yield to requests from non-participating women to be cost effective (Oscarsson 2007). Self testing for HPV has been advocated as an effective method and there is a kit commercially available (Stenvall 2007). The procedure is used as a routine in Uppsala county and marketed to other counties.
Aim To study two possible interventions to increase participation
Design Randomised controlled trials of two interventions and a control arm
Hypothesis
Intervention with a) supportive telephone contact, by a midwife, with women who do not have a smear registered for two screening rounds will increase participation, increase uptake of precancerous lesions (CIN2+) and is cost effective. b) selftesting for oncogenic papillomavirus (HPV) will increase participation and is cost effective.
Method: selection of study base
Selection was done by random among women aged 29 - 63 who did not have a pap-smear registered within the two recent screening rounds. Women who were excluded from invitation due to total hysterectomy and women who could be identified as have immigrated into the region under the period were excluded before randomisation. July 1 2008 there was 52362 women who fulfilled the first criteria (before exclusions) identified through the Register for Prevention of Cervical Cancer in West Sweden. 8800 selected women will be included and randomised to one of three arms with the distribution 5:1:5
Methods: Intervention Arm A: 4000 randomised women fulfilling inclusion criteria receive a letter informing them they will be contacted by a midwife by phone, to be offered an appointment to take a smear. They can at that stage decline such contact or if they wish return contact information (telephone number). A week later the women who have not declined will be called by a midwife and offered an appointment for taking a smear. Abnormal smear will be followed up with referral to a gynecologist in concordance with normal screening routine.
Arm B: 800 women will be sent an offer of HPV-self sampling (Aprovix, Uppsala, Sweden). By regular mail the woman can order a test kit, and return this to the laboratory after sampling. The samples will be tested with Hybrid Capture II for high risk HPV. A negative result will be communicated to the women. A positive result will be sent to the gynecological clinic responsible for the work up of abnormal cytological screening smears in the area were the woman lives. The afflicted woman will get information from the clinic and an appointment for colposcopy and cytology. Further investigation will be conducted as clinical routine. Reminders will be sent to women who have ordered the kit and not returned any sample. In order to evaluate the effect of a primary reminder women who have not responded to the primary offer within 60 days will receive a reminder.
Arm C (controls) 4000 women will be controls. No specific action will be taken within the study outside routine in the screening program (yearly written reminder when smears are not found in the database)
Methods: Data collection All data about cytology, colposcopy with biopsies and treatment for CIN are registered as a routine in the West Sweden Registry for Cervical Cancer Prevention and data will be extracted from that registry. Data about HPV-testing will be transferred to this registry from the Aprovix laboratory in Uppsala. Man-time needed and costs for material and analyses for the different interventions will be registered as base for health economic assessments.
Primary outcomes: Frequency of testing (cytology in arm A and C and HPV-test in arm B). Frequency of further assessment of abnormal tests (all arms).
Secondary outcomes: (Arm A vs arm C) Frequency of abnormal smears. Frequency of treated CIN, (CIN1, CIN2 and CIN3, grouped as low grade (CIN1) and high grade (CIN2, CIN3, AIS and invasive cancer). Number of invasive cancers and FIGO stadium. Cost of interventions. Cost per CIN2+ found. The study is powered to find a 30% difference in primary outcome based on an expected 20% participation rate in the control group with 80% power at a significance level of 5% for both interventions (A and B compared with C). An expected rate of abnormal smears of 7% among these women with no smear recorded 6 or more years will give a 80% power to find a 60% relative difference in number of abnormal smears (RR=1,6) when intervention arm A is compared with the controls in arm C.
The results from work up of abnormal tests in arm A will be considered representative for arm B as well, given the same level of abnormality.
The cost per participant and per biopsy with CIN found will be calculated. The cost per found and treated high grade CIN will be compared with a reference of estimated €3500 (preliminary figure) per CIN2+ that is eradicated.
Methods:Statistical analysis All analysis will be based on intention to treat. Pearson's Chi2 and Fischers exact test will be used to compare distribution of categorical variables between the groups. One way variances will be used to test differences of means between groups for continuous variables. The cumulated probability for outcome vs. follow up time will be calculated with Kaplan-Meier analysis. Multiple Cox regression will be used to determine relative risks. 95 % confidence intervals will be used throughout and level of significance will be calculated two sided as 5%
- Conditions
- Cervical Intraepithelial Neoplasia
- Being tested
- Telephone arm, Self-test arm
- Keywords
- participation, mass screening, cervical neoplasia, health economics, cost-benefit
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telephone armOther
Midwifes at 72 antenatal care units in West region of Sweden receive lists with names and telephone numbers on women who have no record of screening during two screening rounds (6 - 10 years depending on age). The midwife will make up to ten attempts to reach each woman and is instructed to use no more than 30 minutes on this. If the midwife get in touch with the woman she will encourage participation in regular screening (run by midwives in Sweden) and help the woman to get an appointment.
Self-test armOther
Women receive an offer to order a vaginal self test for HPV. The woman can return a coupon in a postage free envelope and she will receive a self testing kit (dry method) within a couple of days. She will return the test in another postage free envelope. A reminder will be sent to women who order a test but do not return it.
| Study group | Role | What they receive |
|---|---|---|
| Telephone arm | Experimental | A midwife tries to contact the woman by telephone and offer her an appointment for a PAP-smear Receives: Other: Telephone arm |
| Self-test arm | Experimental | Not described Receives: Other: Self-test arm |
| Control arm | No intervention | No intervention other than what is routine in the screening program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of testing (cytology in arm A and C and HPV-test in arm B). F
Measured: 7 months after invitation
Frequency of further assessment of abnormal tests
Measured: 7 months
Secondary outcomes (5)
Frequency of abnormal smears. (Arm A vs arm C)
Measured: 7 months
Frequency of treated CIN (Arm A vs. arm C)
Measured: 7 months
Number of invasive cancers detected classified by FIGO stadium.
Measured: 7 months
Cost of interventions
Measured: 7 months
Cost per CIN2+ found and treated
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2009 (estimated)
- Study startSep 2009
- Primary completionFeb 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 8,800 participants (actual)
Sponsor and investigators
- Lead sponsor
- Göteborg University
- Sponsor type
- University, hospital or other
- Collaborators
- Vastra Gotaland Region, Assar Gabrielsson Cancer Foundation, Sweden
- Responsible party
- Sponsor
- Investigators
- Björn Strander, MD, PhD, Principal investigator, Göteborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01029990
- Sponsor's protocol ID
- OCGbgSw0101
- Status last verified
- Aug 2012
- First submitted
- 9 Dec 2009
- Last updated
- 30 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program
- ClinicalTrials.gov ID
- NCT01029990
- Acronym / sponsor ID
- OCGbgSw0101
- Conditions
- Cervical Intraepithelial Neoplasia
- Keywords
- participation, mass screening, cervical neoplasia, health economics, cost-benefit
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8,800 participants (actual)
- Lead sponsor
- Göteborg UniversityUniversity, hospital or other
- Collaborators
- Vastra Gotaland Region, Assar Gabrielsson Cancer Foundation, Sweden
- Study start
- Sep 2009
- Primary completion
- Feb 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 10 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Women who don't participate in Swedish cytology screening program are a minority of about 10%, but constitute the majority of those who acquire cervical cancer. Over 50 000 women in the Västra Götalandregion have abstained from participation in the program for at least 2 screening rounds (6 - 10 years, depending om age). We plan to test two promising strategies to increase participation. In a study of two different health policies women who have defaulted are randomised to receiving a telephone call from a midwife, receive an offer of a self-test for HPV or being included in a control group. This is an effectiveness study that should give an answer how participation could be increased and give the basis for a calculation of the costs involved, before decisions can be made about implementing either intervention.
Detailed description
Background
Cervical cancer today is considered as a disease that to a very large extent is preventable. In Sweden cytological screening has been ongoing since the 60:s and this has made cervical cancer a rare disease. Several new, but costly, methods like HPV-testing and vaccination has been claimed to further reduce cancer incidence, but this has not been scientifically proven so far. A recent audit of the Swedish screening program (Andrae 2008) found that the foremost risk factor for cervical cancer in the context of the program was non participation. Women who do participate are well protected from cervical cancer.
A Swedish study evaluating different strategies to increase participation found telephone contact with defaulters to be the superior intervention (Eaker 2004). This study was done in a region of Sweden with lower coverage (Sparén 2007) and less emphasis on efforts to increase participation. A study from Kalmar, Sweden, with high coverage did not find an extended yield to requests from non-participating women to be cost effective (Oscarsson 2007). Self testing for HPV has been advocated as an effective method and there is a kit commercially available (Stenvall 2007). The procedure is used as a routine in Uppsala county and marketed to other counties.
Aim To study two possible interventions to increase participation
Design Randomised controlled trials of two interventions and a control arm
Hypothesis
Intervention with a) supportive telephone contact, by a midwife, with women who do not have a smear registered for two screening rounds will increase participation, increase uptake of precancerous lesions (CIN2+) and is cost effective. b) selftesting for oncogenic papillomavirus (HPV) will increase participation and is cost effective.
Method: selection of study base
Selection was done by random among women aged 29 - 63 who did not have a pap-smear registered within the two recent screening rounds. Women who were excluded from invitation due to total hysterectomy and women who could be identified as have immigrated into the region under the period were excluded before randomisation. July 1 2008 there was 52362 women who fulfilled the first criteria (before exclusions) identified through the Register for Prevention of Cervical Cancer in West Sweden. 8800 selected women will be included and randomised to one of three arms with the distribution 5:1:5
Methods: Intervention Arm A: 4000 randomised women fulfilling inclusion criteria receive a letter informing them they will be contacted by a midwife by phone, to be offered an appointment to take a smear. They can at that stage decline such contact or if they wish return contact information (telephone number). A week later the women who have not declined will be called by a midwife and offered an appointment for taking a smear. Abnormal smear will be followed up with referral to a gynecologist in concordance with normal screening routine.
Arm B: 800 women will be sent an offer of HPV-self sampling (Aprovix, Uppsala, Sweden). By regular mail the woman can order a test kit, and return this to the laboratory after sampling. The samples will be tested with Hybrid Capture II for high risk HPV. A negative result will be communicated to the women. A positive result will be sent to the gynecological clinic responsible for the work up of abnormal cytological screening smears in the area were the woman lives. The afflicted woman will get information from the clinic and an appointment for colposcopy and cytology. Further investigation will be conducted as clinical routine. Reminders will be sent to women who have ordered the kit and not returned any sample. In order to evaluate the effect of a primary reminder women who have not responded to the primary offer within 60 days will receive a reminder.
Arm C (controls) 4000 women will be controls. No specific action will be taken within the study outside routine in the screening program (yearly written reminder when smears are not found in the database)
Methods: Data collection All data about cytology, colposcopy with biopsies and treatment for CIN are registered as a routine in the West Sweden Registry for Cervical Cancer Prevention and data will be extracted from that registry. Data about HPV-testing will be transferred to this registry from the Aprovix laboratory in Uppsala. Man-time needed and costs for material and analyses for the different interventions will be registered as base for health economic assessments.
Primary outcomes: Frequency of testing (cytology in arm A and C and HPV-test in arm B). Frequency of further assessment of abnormal tests (all arms).
Secondary outcomes: (Arm A vs arm C) Frequency of abnormal smears. Frequency of treated CIN, (CIN1, CIN2 and CIN3, grouped as low grade (CIN1) and high grade (CIN2, CIN3, AIS and invasive cancer). Number of invasive cancers and FIGO stadium. Cost of interventions. Cost per CIN2+ found. The study is powered to find a 30% difference in primary outcome based on an expected 20% participation rate in the control group with 80% power at a significance level of 5% for both interventions (A and B compared with C). An expected rate of abnormal smears of 7% among these women with no smear recorded 6 or more years will give a 80% power to find a 60% relative difference in number of abnormal smears (RR=1,6) when intervention arm A is compared with the controls in arm C.
The results from work up of abnormal tests in arm A will be considered representative for arm B as well, given the same level of abnormality.
The cost per participant and per biopsy with CIN found will be calculated. The cost per found and treated high grade CIN will be compared with a reference of estimated €3500 (preliminary figure) per CIN2+ that is eradicated.
Methods:Statistical analysis All analysis will be based on intention to treat. Pearson's Chi2 and Fischers exact test will be used to compare distribution of categorical variables between the groups. One way variances will be used to test differences of means between groups for continuous variables. The cumulated probability for outcome vs. follow up time will be calculated with Kaplan-Meier analysis. Multiple Cox regression will be used to determine relative risks. 95 % confidence intervals will be used throughout and level of significance will be calculated two sided as 5%
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Telephone arm | Experimental | Other: Telephone armA midwife tries to contact the woman by telephone and offer her an appointment for a PAP-smear |
| Self-test arm | Experimental | Other: Self-test arm |
| Control arm | No intervention | –No intervention other than what is routine in the screening program |
Who may qualify
- Ages
- 29 to 63 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- No record of PAP smear in the regional screening register for more than two screening rounds (6 - 10 years depending on age).
- Evidence in the regional population register that women have been living in the west region of Sweden during this time.
Key exclusion criteria (1 listed)
- Total hysterectomy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telephone armMidwifes at 72 antenatal care units in West region of Sweden receive lists with names and telephone numbers on women who have no record of screening during two screening rounds (6 - 10 years depending on age). The midwife will make up to ten attempts to reach each woman and is instructed to use no more than 30 minutes on this. If the midwife get in touch with the woman she will encourage participation in regular screening (run by midwives in Sweden) and help the woman to get an appointment. | Other | Telephone arm |
| Self-test armWomen receive an offer to order a vaginal self test for HPV. The woman can return a coupon in a postage free envelope and she will receive a self testing kit (dry method) within a couple of days. She will return the test in another postage free envelope. A reminder will be sent to women who order a test but do not return it. | Other | Self-test arm |
Primary outcome
Frequency of testing (cytology in arm A and C and HPV-test in arm B). F
Time frame: 7 months after invitation
Frequency of further assessment of abnormal tests
Time frame: 7 months
5 secondary outcomes
Frequency of abnormal smears. (Arm A vs arm C)
Time frame: 7 months
Frequency of treated CIN (Arm A vs. arm C)
Time frame: 7 months
Number of invasive cancers detected classified by FIGO stadium.
Time frame: 7 months
Cost of interventions
Time frame: 7 months
Cost per CIN2+ found and treated
Time frame: 7 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Björn Strander, MD, PhD principal investigator
Göteborg University
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Telephone arm and Self-test arm in people with Cervical Intraepithelial Neoplasia, run by Göteborg University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of testing (cytology in arm A and C and HPV-test in arm B). F (time frame: 7 months after invitation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2012; AzTrials last refreshed its copy on 27 Oct 2026.