Design of the screening programme
STI AIDS Netherlands coordinates the screening programme, and the local Public Health Services carry it out, expanding the screening in a phased implementation (stepped wedge, cluster, randomised design). The Centre for Infectious Disease Control, a section of the National Institute for Public Health and the Environment (RIVM), is responsible for the formal evaluation process. An advisory committee consisting of experts and other relevant parties, including the Ministry of Health, support the executive board of the screening programme. The Ethics Committee of the Free University of Amsterdam (METC number: 2007/239) has approved the study, which conforms to national and international legislation. Participants provide online informed consent. The time frame of the demonstration project is 2008-2010.
Rationale for register-based screening
We chose to organise the screening as register-based (i.e. all individuals registered in the target population are actively approached for participation) as opposed to opportunistic (screening offered during consultations or outreach).
The only two published randomised controlled trials (RCTs) investigating the individual benefits of screening assessed systematic screening [6, 7] and have shown a reduction in pelvic inflammatory disease (PID). A new trial has recently been added to this body of evidence [8]. The programme coverage (or effective test rate) is critical for achieving not only individual benefit (reduction of complications by means of early diagnosis and treatment), but also a reduction of transmission at the population level. The reported population coverage of ongoing opportunistic programmes is limited [9]. In contrast, a Danish study has shown that the eligible population was 11 times as likely to be tested in home-based screening as in the opportunistic testing that doctors offer during routine care [10]. In addition, a recent review shows that the evidence base for opportunistic screening is poor [11, 12]. We have demonstrated the feasibility and acceptability of register-based systematic screening in the Netherlands via the Municipal Health Services in a previous study [3, 13].
Rationale for population selection for screening
The demonstration programme has been implemented in three regions: two large cities (Amsterdam and Rotterdam) and one somewhat more rural area (South Limburg). Each year, all residents aged 16-29 years receive an invitation letter. Our previous research showed that prevalence in the population of highly urbanised areas in the Netherlands is well above 3% [3]. People living in Amsterdam and Rotterdam are advised to participate if they are (or have been) sexually active. In areas of lower population density, the population prevalence is between 0.6% and 2%, so that selective screening based on risk profiles is required to reach a better cost-effectiveness profile [3, 4]. Therefore, eligibility for screening in South Limburg is assessed on the basis of individual risk scores calculated from invitees' information online. The web-based questionnaire asks nine questions about demographics and sexual behaviour, and each item contributes to the risk score (Additional file 1). The invitee can request a test kit only if the risk score reaches a predefined value. The prediction rule for this selective screening is based on previous research [4] and aims at a C. trachomatis positivity yield of 4-5%.
We chose to include both men and women in the screening. Population studies show prevalence rates among men comparable to those among women. Including men in the screening makes them part of the solution rather than the problem [14]. Models show that screening both men and women can have more impact than screening only women [15]. However, the impact of screening both men and women on community prevalence has yet to be demonstrated in real life. In fact, a recent literature review called for more high-quality RCTs to ascertain the impact on individual complications like PID and infertility, as well as the impact on community prevalence [12]. We are expanding our screening area by area, and we are including all eligible residents of a geographically confined area within a limited time. This strategy covers social and sexual networks in order to grasp any community impact of accelerated screening.
Logistics
Figure 1 presents the framework of the logistics. The local Public Health Services send invitations to all 16 to 29-year-olds in Amsterdam, Rotterdam, and South Limburg. Municipal population registers supply the addresses. The order of invitations is cluster-randomised per area or municipality according to postal codes lists within clusters in each of the three participating regions. The invitations contain an information leaflet and a letter, advising those who are (or have been) sexually active to participate. The invitation letters provide a unique ID number (login code) that enables the invitee to request a test kit at http://www.chlamydiatest.nl (Figure 2). The invitation letter and information materials (text and website) have been developed and pretested with the relevant age, sex, and cultural groups. In the lower prevalence area, South Limburg, anyone who visits the website must first do a short online risk assessment, and can only request a test kit if the risk score reaches a predefined level of 6 or more, compatible with an estimated positivity rate of 4-5% (see Additional file 1).
Those who have not reacted to the initial invitation within 4 weeks receive a reminder invitation. A reminder is e-mailed to those who do not send a sample to the laboratory within 2 weeks of their request for a test kit; a second reminder is e-mailed 1 week later. Invitees who send a sample to the laboratory receive an e-mail and/or SMS to inform them when their test result is available online. Chlamydia trachomatis positive participants can print the PDF letter with their test results and information for health care providers. The test results on the website can only be accessed by personal login. If the test results are not accessed within 14 days, a reminder e-mail is sent. Everyone with a positive result who has not checked the test result within 4 weeks is sent a letter with the result at the address provided.
The test kit includes a home sample kit (Figure 3; men: urine sample, women: vaginal swab or urine sample). The participants send the self-collected samples to the regional laboratory in an envelope suitable for mailing biological materials. The three participating laboratories are all certified, take part in quality control programmes and use certified nucleic acid amplification techniques according to the manufacturer's guidelines. The one laboratory that uses pooling retests positive pools individually. The two laboratories that do not pool confirm positive tests with a second test on the same specimen.
The patient's GP provide treatment, but if a participant prefers, the local STI centre provides it. The current sex partners of participants with positive test results are advised to be treated simultaneously or seek prompt testing and treatment. Previous partners are notified predominantly by patient referral. Additionally, participants with positive test results can also use the website, anonymously if they wish, to notify previous sex partners of the last 6 months via e-mail. These partners are offered testing within the existing screening programme. Participants who test positive receive a new test kit automatically after 6 months.
Data collection and evaluation
The programme's central database automatically stores data from all invitees. The database includes data pertaining to progression through the screening process and data from the local population registers, the laboratories, and the company responsible for handling the mailings. The central database enables process monitoring, evaluation, and uploading of regular time-framed overviews of key outcomes and indicators of programme performance. Data obtained from online questionnaires for participants and mailed questionnaires for non-responders, including characteristics such as self-reported sexual history and clinical symptoms, are also linked to the central database to allow for more detailed analyses.
The evaluation of the screening implementation consists of various components. A detailed description of the design of the evaluation is given elsewhere [16]. The first part concerns process evaluation, including non-response and acceptability studies [17]. In the second part, the effects of screening are evaluated. For evaluation purposes, we chose a phased implementation of the screening. This 'stepped-wedge design' enables a sequential roll-out in geographical clusters (neighbourhoods), randomised within a number of periods. The design allows for:
1. Estimation of the effect of one or two screening rounds on the population prevalence of C. trachomatis and self-reported PID.
2. Determination of trends of participation in different screening rounds.
3. Assessment of baseline ecological trends among those who have not received a screening invitation at the end of the second screening round.
Other important components of the evaluation are the modelling of positivity and prevalence, and the cost-effectiveness analyses.