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Chlamyweb Study II: a randomised controlled trial (RCT) of an online offer of home-based Chlamydia trachomatis sampling in France
  1. Delphine Kersaudy-Rahib1,
  2. Nathalie Lydié1,
  3. Chloé Leroy2,
  4. Laura March1,
  5. Cécile Bébéar2,
  6. Pierre Arwidson1,
  7. Bertille de Barbeyrac2
    1. 1Sexual Health Unit, Santé publique France, Saint-Maurice, France
    2. 2Univ. Bordeaux and INRA, USC EA 3671 Mycoplasmal and Chlamydial Infections in Humans, French National Reference Centre (NRC) for Chlamydial Infections, Bordeaux, France
    1. Correspondence to Delphine Kersaudy-Rahib, 12 rue du Val d'Osne, 94415 Saint-Maurice Cedex, France; delphine.rahib{at}santepubliquefrance.fr

    Abstract

    Background The number of cases of Chlamydia trachomatis (Ct) diagnosed has increased in the past 15 years in France as well as in other European countries. This paper reports a randomised controlled trial (RCT) to evaluate whether the offer of home-based testing over the internet increased the number of young people tested for chlamydia compared with the current testing strategy and to estimate the number and risks factors of the infected population. This RCT took place as an element of the Chlamyweb Study—a study aiming to evaluate an intervention (the Chlamyweb Intervention) involving the offer of a free self-sampling kit online to sexually active men and women aged 18–24 years in France.

    Methods Participants in the Chlamyweb RCT (n=11 075) received either an offer of a free self-sampling kit (intervention group) or were invited to be screened in primary care settings (control group). Risks ratios were used to compare screening rates between the intervention and control groups. Risk factors were analysed for infected people in the intervention group.

    Results The screening frequency was about three times higher among young people who received a self-sampling kit than those who only received a tailored recommendation to be screened (29.2% vs 8.7%). Although rates of screening among men were lower than among women (23.9% vs 33.9%), the intervention effect was greater among men (adjusted risk ratios (aRR)=4.55 vs aRR=2.94). Ct positivity (6.8%) was similar to that observed in STI clinics. It was higher in women (8.3%) than in men (4.4%).

    Conclusions These results invite us to consider the establishment of a large home-based screening programme, although additional studies including economic assessments are needed to evaluate the most appropriate combination of strategies in the French context.

    Trial registraion number AFFSAPS n° IDRCB 0211-A01000-41; Results.

    • CHLAMYDIA TRACHOMATIS
    • HEALTH SERV RESEARCH
    • SCREENING
    • SEXUAL HEALTH
    • INTERVENTION STUDIES
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    Introduction

    The number of Chlamydia trachomatis (Ct) cases diagnosed has increased in the past 15 years in France as well as in other European countries.1 ,2 The proportion of positive tests reported by the French laboratory network increased from 3% in 2004 to 7% in 2013 and Ct incidence was estimated to be 257 per 100 000 in people aged 15–49 years in 2012.3 Ct especially affects youths: the estimated prevalence was up to 3.6% among women aged 18–24 years old and up to 2.7% among men aged 25–29 years old in 2006 in the French population.4

    Early diagnosis and treatment have been considered to be essential strategies to prevent complications and further transmission of the bacteria.5 In the 2000s, many countries in Europe have proposed opportunistic testing for people with multiple sex partners attending selected health facilities. More recently, several countries have implemented systematic screening and treatment of young women (18–25 years old) as a strategy to prevent pelvic inflammatory disease.6 Several population-based programmes used postal test kits and some involved the use of the internet for requesting test kits.7–9

    As the efficiency and effectiveness of the promotion of Ct screening were debated, France has remained undecided whether such screening should be implemented.10 The French national chlamydia control action plan includes sexual health education,11 awareness campaigns, condom promotion and at-risk population screening. Considering the advice of the French National Agency for Accreditation and Evaluation in Healthcare (see online supplementary file 1), systematic screening should be offered only to women aged 15–25 years and men aged 15–30 years who visit centres where testing is offered anonymously and free of charge (STI clinics and family planning centres). General practitioners are not actively involved in Ct screening. They diagnosed <20% of the Ct cases in 2014.12

    In 2012, the French National Institute for Health Prevention and Health Education decided to test free home-based self-sampling kits online to screen this infection among young people aged 18–24 years. The objective of the Chlamyweb randomised controlled trial (RCT) was to evaluate whether the offer of home-based testing via the internet increased the number of young people tested for chlamydia compared with the current testing strategy.

    Methods

    The Chlamyweb RCT formed part of the Chlamyweb Study, which sought to evaluate the effectiveness of the Chlamyweb Intervention. Participation in the study involved completing an online questionnaire, supplying a valid e-mail, and being a sexually active man or woman aged 18–24 years in France. The intervention, which is described in detail elsewhere,13 took place over the entire 6 weeks of the Study period from 3 September 2012 to 14 October 2012, and consisted in the offer online of a self-testing kit to sexually active men and women aged 18–24 years. The RCT took place over the first 4 weeks of the Intervention, from 3 September 2012 to 4 October 2012, and involved randomising all participants in the Study over that period (n=11 075) either to the Intervention (n=5531) or to a control group (n=5544). The RCT element of the Chlamydia Study ended on 4 October 2012. From then on, Chlamyweb Study participants (n=1684) were all assigned to the Intervention. Thus, the total number of Intervention participants (n=7215) exceeded the total number of participants in the intervention arm of the RCT (n=5531), and the total number of participants in the Chlamyweb Study as a whole (n=12 759) included those in the control group of the RCT as well as those in the Intervention. The relationship between the Chlamyweb Intervention and the Chlamyweb RCT is shown in figure 1.

    Figure 1

    Flow chart of the Chlamyweb intervention and its nested randomised controlled trial, France, 2012.

    RCT participants were randomised at the individual level with no restriction directly after the questionnaire validation. It was a 1:1 computer-controlled randomisation completely automated with no experimenter involvement by the use of the Rand function of Microsoft SQL Server 2005 embedded in the website code.

    The intervention arm of the RCT coincided with the first 4 weeks of the Chlamyweb Intervention and its conduct is described in detail elsewhere.13 The control group received tailored information to be screened in primary care (general practitioners, gynaecologist or free screening centres). Reminders were also sent 2 and 4 weeks after randomisation.

    Those not eligible for the Chlamyweb Study also received tailored information, based on age, sex and sexual activity. A toll-free telephone number was provided to all Study participants for more information about STIs or the testing. The RCT was approved by the Commission on Information Technology and Liberties and Comity for People Protection. It is registered by the French medical authority under number 2011-A01000-41.

    The primary outcome was measured by the percentage of participants in each group (intervention and control) that took a chlamydia test. For control groups, this outcome was the proportion of people reporting having had a Ct screening in the follow-up questionnaire. For the intervention group, it was the proportion of participants who had sent their kit to the National Reference Center for Ct infection (CNR) at the end of the trial. The secondary outcome was the percentage of Ct-positive participants among those tested, obtained via the self-administered follow-up form questionnaire for the control group and via the CNR for the intervention group.

    Cost per screening test

    The costs per screening test and for each group were estimated. These costs were defined as the total of the unit of cost of all consumables (from the self-sampling kit), postage and testing divided by the number of samples returned in the intervention group, and as the total of the unit cost of primary care visits and testing divided by the number of self-reported tested participants in the control group. Costs per positive test were also estimated. Treatment and consultation for treatment prescription were not considered in the estimation. Unit costs were obtained from trial accounting and standard data sources.14 All costs were converted to US dollars with the Word Bank official rate for 2012 (US$1=€0.78).

    Sample size, analysis and statistical methods

    Based on previous research, we expected that half of the participants in the intervention group would order the kit and at least 30% would send it back,15 and a 25% attrition rate and a 2% testing rate in the control group.16 ,17 To detect at least a 1% difference in the testing rate in the intervention versus control group with a power of 90% and p<0.05, we needed 5118 participants in each group.18 We provided 5000 kits.

    Intention-to-treat (ITT) analyses were performed. For this purpose, all participants remained in the group to which they were allocated. Participants who refused the kit in the intervention group and those who did not return the follow-up form in the control group were considered as not having been screened.

    Statistical analyses were performed with Stata V.10. A Wilcoxon test was used to compare distribution between groups. A χ2 test was used for univariate analysis, and a Fisher's exact test was performed when observed value was <5. Proportions and relative risks are presented with a 95% CI. Risks ratios were used to compare screening rate in the intervention and control groups. Crude risk ratios were compared using a Mantel-Haenszel test. Multiple Poisson regression analysis was further performed to determine main characteristics impacting intervention effects for each sex.19 The criterion for entrance into the model was a univariate probability value of p≤0.05. The size of the city where a participant lived was included in the model as confounding factor. Adjustments are specified in each table.

    Logistic regressions were used to identify risk factors for Ct infection, separately for men and women. Only the positive cases tested by the CNR were considered for this analysis (ie, those from the intervention group). The criterion for entrance into the model was a univariate probability value of p≤0.05. Age was included in the model as a confounding factor.

    Results

    In the 6 weeks of the Chlamyweb Study, traffic on the website ranged between 10 000 and 15 000 unique visitors per day. This led to 66 393 accesses to the questionnaire (see online supplementary file 3). In 9874 cases (17.8%), data were insufficient to assess eligibility. Among the 45 444 non-eligible respondents, most were under 18 or over 24 years (60.2%) or refused to provide an e-mail address (30.5%). Others were not sexually active (6.5%) and lived outside mainland France (2.8%). At the end, 12 799 participants completed baseline information, and of these 11 075 did so in the course of the first 4 weeks of the Study and were randomised in the framework of the RCT: 5531 to the intervention group and 5544 to the control group.

    In the intervention group, 47.3% of participants gave their postal address to receive the self-sampling kit and among them, 61.8% returned it. In the control group, the return rate of the follow-up questionnaire was 29.9%.

    Participants' description

    No difference was observed between the intervention and control groups according to participants' characteristics (table 1). The mean age of the participants was 20.7 years. A majority of participants (57.1%) lived in a city of more than 100 000 inhabitants or in the Paris region, while 6.3% lived in a rural area. More than 50% of participants (53.6%) were students, 19.1% were employed, 13.7% were unemployed and 12.3% were in high school or in professional training. The median number of partners in the past year was 2 and 40.8% of participants had at least one new partner in the past 3 months, more in men than in women (50.7% vs 42.6%. p<10−3). About a third (32.5%) had used condoms during the last sexual intercourse. At baseline, only 7.7% of participants reported having already been tested for Ct, with a difference between men and women (4.4% vs 10.6%. p<10−3).

    Table 1

    Baseline characteristics of participants in intervention and control groups, Chlamyweb randomised controlled trial, France 2012

    Primary outcome: rates of screening

    Rates of screening were 29.2% (1616/5531) in the intervention group and 8.7% (480/5544) in the control group. The offer of a self-sampling kit increased the testing rates by more than three times among young people compared with the tailored recommendation to be screened in primary care (RR 3.37 (95% CI 3.05 to 3.74)). Rates of screening were significantly lower among men than among women: 23.9% vs 33.9% in the intervention group (p<0.001) and 5.3% vs 11.6% in the control group (p<0.001). However, the intervention effect was higher in men (RR 4.55 (95% CI 3.77 to 5.49)), (table 2) than in women (RR 2.94 (95% CI 2.60 to 3.33)) (table 3).

    Table 2

    Risk ratios (RR) and adjusted risk ratios (aRR) of being tested for Chlamydia trachomatis with the Chlamyweb randomised controlled trial compared with classic information (control) in men. France, 2012

    Table 3

    Risk ratios (RR) and adjusted risk ratios (aRR) of being tested for Chlamydia trachomatis with the Chlamyweb randomised controlled trial compared with classic information in women. France, 2012

    For both sexes, the intervention effect was higher among participants who were unaware if they had already been tested for Ct, and among participants who declared themselves as never having been tested. In the intervention group, participants used the self-sampling kit equally, regardless of the size of the city they lived in. In the control group, participants living in urban areas were more likely to be screened than those living in small cities or rural areas.

    For the men, the intervention effect was higher among those who did not report a new partner in the previous 3 months (adjusted risk ratios (aRR) 5.97 (95% CI 4.46 to 7.99)) than those who did (aRR 3.60 (95% CI 2.81 to 4.62)). In the intervention group, the screening rate increased with age, unlike in the control group.

    For the women, the intervention effect was higher among those who declared only one partner in the previous year (aRR 3.51 (2.89 to 4.27)) than among those who declared more than one (aRR 2.60 (2.21 to 3.06)). Screening rates were positively correlated with age. In the intervention group, screening rates differed according to the place of birth: half of women born in the French Caribbean (47.6%) were screened compared with 33.6% of women who were born elsewhere (p=0.02). The same trend was observed for men but without significance.

    Secondary outcome: Ct positivity

    Global positivity rate was 6.8% (110/1616) in the intervention group and 6.3% (30/480) in the control group with no significant difference. Among sampling analysed by the CNR (N=1616), the Ct positivity rate was higher in females than in males (8.3% vs 4.4%; p<0.001) (table 4). Those rates remain high in a low-risk population, such as those who had not had a partner in the previous 3 months (2.8% of men and 5.2% of women). In multivariate analysis, the risk factors associated with Ct infection in women screened with a home-based self-sampling kit were then in professional training or employment, had several sexual partners in the past year and had not used a condom during the last sexual intercourse. In men, having had several partners in the previous year was the only risk factor associated with Ct infection.

    Table 4

    Proportions and factors associated with Chlamydia trachomatis infections in men and woman in randomised controlled trial intervention group

    Of the 1616 people who used the self-sampling kit, 1201 (74.3%) answered the follow-up questionnaire. Among them, 67 (5.58%) reported having received a positive result. Of these 67 individuals, 61 reported having seen a doctor after being made aware of their positive result; 58 received treatment and 52 informed their partner(s).

    Cost per screening

    We estimated costs to be €73 ($93) per test for clinic testing and €32 ($41) per test for home-based self-sampling kit testing (see online supplementary file 4). If we consider costs per positive test, the cost for STI clinics was three times higher than for home-based self-sampling kit testing (€1123/$1443 vs €375/$482). In men, this ratio was 1.7 (€1272/$1634 vs €738/$949).

    Discussion

    Statement of principle findings

    The offer of home-based testing over the internet increased by about three times the rate of chlamydia testing in the 18–24 years old compared with tailored recommendation to be screened in primary care or in a free and anonymous STI centre (29.2% vs 8.7%). A higher number of women underwent the screening than men, but there was a greater increase of screening with the self-sampling kits in men, as previously demonstrated by a Danish study.20

    Overall, Ct positivity rate was high (more than 6%), even among youth with a single partner or those without a recent partner. This rate is higher than that measured nationally in the general population in 20064 and similar to those measured in the STI clinics (around 7%).12 As expected, sexual behaviour was strongly associated with the risk of Ct infection in both genders. Finally, this strategy appears to be cost saving in a single round as the test is positive or negative.

    Strengths and weakness of the study (RCT)

    Home sampling kits have been used in many countries using a variety of request and delivery strategies. However, to our knowledge, this is the first large RCT including self-sampling kit intervention to increase Ct testing that was entirely implemented online.

    Our study has some limitations. In the control group, the main outcome measure was based on self-reports that could not be verified and the return rate of follow-up questionnaires was around 30%. Follow-up rates vary from one study to another and depend on the duration, intensity and quality of follow-up.21 ,22 Attrition rates are generally high in internet-based trials.16 ,23 Thus, analyses in ITT yield a conservative estimate of efficacy.

    Half of our sample consisted of students, who are easy to reach due to their intensive use of internet.24 Conversely, some young people living at home probably refused postal samples as they did not want their families to know they were sexually active. Although in the first instance the online procedure instilled confidence that anonymity would be preserved, this was breached latterly when receiving the self-sampling kit. Although the average age of first intercourse in France was around 17 years, people under 18 have not been included due to French law. Findings may not apply to these subgroups of the population.

    Strategies combining the internet with home-based chlamydia testing have been evaluated, but we have to be cautious about international comparisons because programme designs are different and participants may not be comparable. In Sweden,7 20.2% of the participants aged 16–29 years requested a kit through the internet after receiving an invitation letter and 78.9% returned samples. In Australia,25 53.9% of women aged 18–35 years reached by telephone agreed to complete telephone interviews and 67.1% provided urine specimens through the mail for chlamydia testing. In France, in the Ct prevalence survey implemented in a national population-based survey carried out by telephone in 2006,4 76.3% of men and women aged 18–44 years agreed to receive the kit and 68.3% returned it. In our RCT, 47.3% of participants agreed to receive the test kit and 61.8% returned it. The acceptance rate was high, considering that there was no interaction. This suggests that young people are ready to engage in this type of intervention.

    Lessons to be learnt: possible mechanisms and implications for clinicians or policymakers

    An internet-based approach, when reliable and user specific, is well adapted for healthy young people, particularly men who consult a doctor less often than women26 and for whom there are many missed opportunities to engage them with chlamydia screening.27 This procedure is nevertheless interesting for women who, as some studies show, prefer home-based self-sampling kits rather than providing a sample in a primary care setting.28 ,29 Moreover, access to screening in primary care presented geographical inequalities that could be solved with a home sample kit, in men as well as in women. However, home-based testing was not suitable to all young people who have to be reached by other ways. That is why it should be considered as an addition to other strategies. If a higher prevalence was recorded for people presenting with known risk factors, the recorded rates among those considered less at risk were far from zero. Hence, the value, at least initially, of offering screening to all people aged 18–24 years, is independent of any risk factors.

    Additional studies, including economic assessments, are needed to evaluate the most appropriate strategies in the French context. While this test appears to be cost-effective in a single round, to be able to accurately estimate cost-effectiveness, other aspects have to be considered for chlamydia control activities as treatment for the index patient, partner notification30 and retesting. Further researches on chlamydia sequelae on quality of life are also needed.

    Key messages

    • In France, a home-sampling kit promoted by the internet significantly increased the rate of chlamydia testing among young people.

    • The internet enabled a large population to be reached and appears as a solution to reducing geographical inequalities in access to screening.

    • Chlamydia trachomatis positivity rate is high even among youth considered less at risk, which invites us to consider the establishment of a large home-based screening programme.

    Acknowledgments

    The authors would like to acknowledge Lucile Bluzat and the McCann France agency, which managed the information website and advertisements; Bérengère Gall and Jean Baptiste Gautherin, who assisted in the data collection and data management. The authors also thank members of the scientific committee who are not authors of this paper for their advice: Josiane Warszawski, Véronique Goulet, Nathalie Spenatto, Carine Favier and all the young people who participated in the study.

    References

    View Abstract

    Supplementary materials

    • Abstract in French

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • Handling editor Jackie A Cassell

    • Collaborators Lucile Bluzat; Bérengère Gall.

    • Contributors DK-R and NL designed the study, analysed and interpreted data, and wrote the article. BdB and CLR collected biological data and performed biological test. LM performed the economic analysis. PA and CB reviewed the manuscript. All authors read and approved the final manuscript.

    • Funding The trial was funded by the French Institute for Health Promotion and Health Education (INPES). INPES was funded by the French Ministry of Health and National Health Insurance. INPES became Santé publique France the 1st may 2016.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval This study was approved by the French National Commission for Information Technology and Liberties (CNIL) and a Regional Ethics Committee (CPP). The trial is registered with a French medical authority under the reference number 2011-A01000-41.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data created during this research are available on demand at Santé Publique France, the French national public health agency. Please contact the corresponding author.

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