Economic Evaluation of Three Populational Screening Strategies for Cervical Cancer
Economic Evaluation of Three Populational Screening Strategies for Cervical Cancer
The aim of this study was to compare the effectiveness and the costs of three types of
 population interventions to increase the number of female participants in the screening
 programmes for cancer of the cervix carried out by Primary Care in four Basic Health Care
 Areas.
Background A high percentage of cervical cancer cases have not undergone cytological tests
 within 10 years prior to diagnosis. Different population interventions could improve coverage
 in the public system, although costs will also increase. The aim of this study was to compare
 the effectiveness and the costs of three types of population interventions to increase the
 number of female participants in the screening programmes for cancer of the cervix carried
 out by Primary Care in four basic health care areas.

 Methods A cost-effectiveness analysis will be performed from the perspective of public health
 system including women from 30 to 70 years of age (n=20,994) with incorrect screening
 criteria from four basic health care areas in the Valles Occidental, Barcelona, Spain. The
 patients will be randomly distributed into the control group and the three Intervention
 Groups (IG1: invitation letter to participate in the screening; IG2: invitation letter and
 informative leaflet; IG3: invitation letter, informative leaflet and a phone call reminder)
 and followed for three years. Clinical effectiveness will be measured by the number of Human
 Papillomavirus (HPV), epithelial lesions and cancer of cervix cases detected. The number of
 deaths avoided will be secondary measures of effectiveness. The temporal horizon of the
 analysis will be the life expectancy of the female population in the study. Costs and
 effectiveness will be discounted at 3 %. In addition, univariate and multivariate sensitivity
 analysis will be carried out.

 Expected results IG3 is expected to be more cost-effective intervention than IG1 and IG2,
 with greater detection of HPV infections, epithelial lesions and cancer than other
 strategies, albeit at a greater cost.

 METHODS

 An economic evaluation of three populational screening strategies for cervical cancer will be
 performed. Particularly, a cost-effectiveness analysis will be conducted. These interventions
 will be compared to the current opportunistic screening strategy using data of the
 multicentre randomised trial (CRICERVA). The analysis will be conducted from the National
 Health Care System perspective.

 Design: Pragmatic, blinded, multicentre, randomised, controlled clinical trial with four
 branches, and a three years follow-up. The randomisation unit was Basic Health Care Area
 (BHCA).

 Setting: Primary Health Care Services (PCS) of Cerdanyola-Ripollet, province of Barcelona,
 comprising 4 municipalities and 5 BHCA. The population covered by this Primary Care Service
 (PCS) is 120,293 inhabitants over 14 years. As there are four study groups and 5 BHCAs, only
 4 BHCAs with most homogeneous socioeconomic criteria will be considered.

 Population: 20,994 women from 30 to 70 years of age with incorrect screening criteria (data
 obtained from Data Base of Primary Health Care Services) ascribed to the BHCA will be
 included in the study. Incorrect screening will be defined as [9]: 1.- No cytology in the
 last 3 years from women between 30 to 40 years, 2.- No cytology in the previous 5 years from
 women between 40 to 65 years, 3.- No previous cytology history for females older than 65
 years or women who have not had their last cytology before the age of 60. The exclusion
 criteria will be: (a) hysterectomised women, with a current history of pre-malignant lesions
 [Atypical Glandular Cells of Undetermined Significance (AGUS), Atypical Squamous Cells of
 Undetermined Significance (ASCUS), Low-grade Squamous Intraepithelial Lesions (LSIL),
 High-grade Squamous Intraepithelial Lesions (HSIL)], carcinoma in situ and cervical-uterine
 cancer, Human Immunodeficiency Virus (HIV) positive or other causes of immunosuppression
 (since these women follow a specific protocol); (b) those residing outside the study setting
 for more than 6 months; and (c) those ascribed to the study BHCA but with a physician
 assigned in an UBA of another zone different from the one considered in the study.

 Sample size: The sample size has been calculated based on the detection of a difference in
 effectiveness compared with the Non Intervention Group (NIG). It has been calculated by
 multiplying the size of a simple randomised design by the design effect or factor of
 inflation. For the simple randomised design, on accepting an alpha risk of 0.05 and a beta
 risk of 0.20 in a bilateral contrast, 59 subjects will be required in the first group and 59
 in the second group to detect a difference greater than or equal to 28.4 % in the screening
 coverage of the 41.6 % in the Non Intervention Group (NIG). The lost to follow up rate has
 been estimated at 20 %. The calculation of the sample has been performed with the Granmo 5.2
 computer programme for Windows. According to a review of the literature [23-25], considering
 an intraclass correlation coefficient of 0.05 and a mean number of 3,500 women from 30 to 70
 years of age with incorrect screening by BHCA, the design effect will be 176 and thus, 20,768
 women with incorrect screening will be required.

 ETHICAL ASPECTS The investigators are committed to respect the prevailing norms of Good
 Clinical Practice as well as the requisites of the Declaration of Helsinki and the clauses of
 general and particular ethical conditions related to the right to privacy, anonymity and
 confidentiality. Neither the first name nor surname or any other type of data indicating the
 identification of the women will be registered. Therefore, identification will be made by
 numeric codes. Since this type of study is developed in the usual clinical setting,
 authorisation and support must be and has already been granted by the representatives and
 authorities of the collectives involved and thus, individualised informed consent is not
 necessary. Nonetheless, the research team decided that women attending the consultation for
 the cytology should sign the consent form. The protocol has been evaluated by the Clinical
 Investigation Ethics Committee of the IDIAP Jordi Gol.

 LIMITATIONS Randomisation by groups will avoid the potential introduction of selection bias
 which may be produced among the interventions performed at the same site. Since the
 characteristics of the study do not allow the application of the double-blind masking
 technique, the masked response evaluation will be used to ensure that the measurement and
 interpretation of the dependent variables is carried out the same way in all groups. The
 possible loss of information, which may be produced in women doing screening outside public
 health care if they are not contacted by the research team, will be minimised with a phone
 call reminder. This will be made when the women do not attend the appointment. The language
 difficulties in women from other countries will be solved with cultural mediators at each
 site. Within the setting of the study, the administrative personnel have been updating the
 postal addresses of the users attending the BHCA since 2007 and, therefore the postal
 registry is quite precise, thereby reducing the potential loss of letters.

 List of abbreviations

 AETM Agency for Evaluation of Technology and Medical Investigation BHCA Basic Health Care
 Area AGUS Atypical glandular cells of undetermined significance ASCUS Atypical squamous cells
 of undetermined significance PCC Primary Care Centre ECCI Ethical Committee of Clinical
 Investigation eCCN Electronic Data Collection Notebook PCT Primary Care Team c-CH
 Computerised Clinical History IT Investigative Team IG Intervention Group NIG Non
 intervention Group HC2 Hybrid Capture 2 HSIL High grade Squamous Intraepithelial Lesion CIO
 Catalan Institute of Oncology CIH Catalan Institute of Health IIPC Institute of Investigation
 in Primary Care LSIL Low grade Squamous Intraepithelial Lesion SRHC Sexual and Reproductive
 Health Care PCS Primary Care Service ISU Investigation Support Unit HSV Herpes Simple Virus
 HIV Human Immunodeficiency Virus HPV Human Papilloma Virus UBA Unitat Bàsica Assistencial
 (General Practicioner and Nurse Team)

 Financial support

 This protocol has received financial support from the Fondo de Investigación Sanitaria del
 Instituto Carlos III de Madrid (exp PI10/01275).
Inclusion Criteria:

 20,994 women from 30 to 70 years of age with incorrect screening criteria (data obtained
 from Electronic Medical Records) ascribed to the Basic Health Care Area will be included in
 the study. Incorrect screening will be defined as [9]:

 1. - No cytology in the last 3 years from women between 30 to 40 years,

 2. - No cytology in the previous 5 years from women between 40 to 65 years,

 3. - No previous cytology history for females older than 65 years or women who have not
 had their last cytology before the age of 60

 Exclusion Criteria:

 -  hysterectomised women, with a current history of pre-malignant lesions (Atypical
 glandular cells of undetermined significance, Atypical squamous cells of undetermined
 significance, Low grade Squamous Intraepithelial Lesion, High grade Squamous
 Intraepithelial Lesion), carcinoma in situ and cervical-uterine cancer, HIV positive
 or other causes of immunosuppression (since these women follow a specific protocol);

 -  those residing outside the study setting for more than 6 months;

 -  those ascribed to the study Basic Health Care Area but with a physician assigned in an
 UBA (General Practicioner and Nurse Team) of another zone different from the one
 considered in the study