Improving sexual health through partner notification : the LUSTRUM mixed-methods research Programme including RCT of accelerated partner therapy

Background Sexually transmitted infections disproportionately affect young people and men who have sex with men. Chlamydia is Britain’s most common sexually transmitted infection. Partner notification is a key intervention to reduce transmission of sexually transmitted infections and human immunodeficiency virus but is hard to implement. Accelerated partner therapy is a promising new approach. Objectives determine the effectiveness, costs and acceptability of accelerated partner therapy for chlamydia in heterosexual people model the cost effectiveness of accelerated partner therapy and impact on chlamydia transmission develop and cost partner notification interventions for men who have sex with men. Design Mixed-methods study to develop a new sex partner classification and optimise accelerated partner therapy; cluster crossover randomised controlled trial of accelerated partner therapy, with process and cost-consequence evaluation; dynamic modelling and health economic evaluation; systematic review of economic studies of partner notification for sexually transmitted infections in men who have sex with men; qualitative research to co-design a novel partner notification intervention for men who have sex with men with bacterial sexually transmitted infections. Settings Sexual health clinics and community services in England and Scotland. Participants Women and men, including men who have sex with men and people with mild learning disabilities. Interventions Accelerated partner therapy offered as an additional partner notification method. Main outcome measures Proportion of index patients with positive repeat chlamydia test (primary outcome); proportion of sex partners treated; costs per major outcome averted and quality-adjusted life-year; predicted chlamydia prevalence; experiences of accelerated partner therapy. Data sources Randomised controlled trial: partnership type, resource use, outcomes, qualitative data: economic analysis, modelling and systematic review: resource use and unit costs from the randomised controlled trial, secondary sources. Results The sex partner classification defined five types. Accelerated partner therapy modifications included simplified self-sampling packs and creation of training films. We created a clinical management and partner notification data collection system. In the randomised controlled trial, all 17 enrolled clinics completed both periods; 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. Six hundred and sixty-six (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for Chlamydia trachomatis at 12–24 weeks after contact tracing consultation; 31 (4.7%) in the intervention phase and 53 (6.6%) in the control phase had a positive Chlamydia trachomatis test result [adjusted odds ratio 0.66 (95% confidence interval 0.41 to 1.04); p = 0.071]. The proportion of index patients with ≥ 1 sex partner treated was 88.0% (775/881) in intervention and 84.6% (760/898) in control phase, adjusted odds ratio 1.27 (95% confidence interval 0.96 to 1.68; p = 0.10). Overall, 293/1536 (19.1%) index patients chose accelerated partner therapy for 305 partners, of which partner types were: committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Two hundred and forty-eight accepted accelerated partner therapy and 241 partners were sent accelerated partner therapy packs, 120/241 (49.8%) returned chlamydia/gonorrhoea samples (78/119, 65.5%, positive for chlamydia, no result in one), but only 60/241 (24.9%) human immunodeficiency virus and syphilis samples (all negative). The primary outcomes of the randomised trial were not statistically significantly different at the 5% level. However, the economic evaluation found that accelerated partner therapy could be less costly compared with routine care, and mathematical modelling of effects and costs extrapolated beyond the trial end points suggested that accelerated partner therapy could be more effective and less costly than routine care in terms of major outcome averted and quality-adjusted life-years’. Healthcare professionals did not always offer accelerated partner therapy but felt that a clinical management and partner notification data collection system enhanced data recording. Key elements of a multilevel intervention supporting men who have sex with men in partner notification included: modifying the cultural and social context of men who have sex with men communities; improving skills and changing services to facilitate partner notification for one-off partners; and working with dating app providers to explore digital partner notification options. The systematic review found no evaluations of partner notification for men who have sex with men. Modelling of gonorrhoea and human immunodeficiency virus co-infection in men who have sex with men was technically challenging. Limitations In the randomised controlled trial, enrolment, follow-up and repeat infections were lower than expected, so statistical power was lower than anticipated. We were unable to determine whether accelerated partner therapy sped up partner treatment. Mathematical modelling of gonorrhoea/human immunodeficiency virus co-infection in men who have sex with men remained at an experimental stage. It was not feasible to include healthcare professionals in the men who have sex with men intervention development due to the COVID-19 pandemic. Conclusions Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving, but is best suited to sex partners with emotional connection to the index patient. The Programme’s findings about classification of sexual partner types can be implemented in sexual health care with auditable outcomes. Future work Further research is needed on how to increase uptake of accelerated partner therapy and increase sexually transmitted infections self-sampling by partners; understand how services can use partnership-type information to improve partner notification, especially for those currently underserved; overcome challenges in modelling sexually transmitted infections and human immunodeficiency virus co-infection in men who have sex with men; develop and evaluate an intervention to optimise partner notification among men who have sex with men, focusing on one-off partnerships. Trial registration This trial is registered as ISRCTN15996256. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0614-20009) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information

Developing and piloting approaches for the valuation of outcomes associated with sexually transmitted infections

Background Eliciting health-state utility values (HSUVs) for use in cost-utility analysis (CUA) for some diseases is limited by the variation in the duration of the health-states such as it includes both temporary and chronic health-states. There is no 'gold standard' approach for valuing temporary health states (THS). Conventional time trade-off (TTO) is deemed inappropriate because it presents an unrealistic scenario to respondents and the chained TTO has been proposed to solve this problem. This thesis uses a case study, Chlamydia trachomatis (a sexually transmitted infection) to explore this challenge. The main burden of chlamydia is typically believed to be borne by women, with a paucity of studies describing the psychosocial outcomes for men, hence making it difficult to value outcomes associated with men. Objectives This thesis aimed to: develop approaches for valuing the health-states associated with chlamydia and derive utility values for the chronic and temporary health-states associated with chlamydia. An additional objective was to define the psychosocial impact of chlamydia in men via an exploration of the asymmetric nature of the disease burden. Methods The thesis elicited utilities for seven health-states (five THS and two chronic health-state) depicting the symptoms of chlamydia. The health-states were developed using evidence from the literature and interviews with clinical experts. Chained time trade-off (TTO) was applied to THSs and conventional TTO to CHSs. Ectopic pregnancy was used as a lower anchor for chained TTO. The VAS technique was also employed. The study sampled from three different population groups and the survey was administered face-to-face. A qualitative synthesis was conducted using meta-ethnography, to identify the psychosocial impact of chlamydia in men. Discussion The thesis identified appropriate approaches for valuing chlamydia health-states and showed that chained TTO is feasible. Methodological challenges arising from this study include the development of health-state description, the selection of appropriate anchor states and the duration of the anchor state. The HSUV s could potentially be used in cost-utility analyses examining the cost-effectiveness of screening. The meta-ethnography highlighted the need to broaden the focus of future evaluations

Improving sexual health through partner notification: the LUSTRUM mixed-methods research Programme including RCT of accelerated partner therapy

Background: Sexually transmitted infections disproportionately affect young people and men who have sex with men. Chlamydia is Britain’s most common sexually transmitted infection. Partner notification is a key intervention to reduce transmission of sexually transmitted infections and human immunodeficiency virus but is hard to implement. Accelerated partner therapy is a promising new approach. Objectives:1. determine the effectiveness, costs and acceptability of accelerated partner therapy for chlamydia in heterosexual people2. model the cost effectiveness of accelerated partner therapy and impact on chlamydia transmission3. develop and cost partner notification interventions for men who have sex with men.Design: Mixed-methods study to develop a new sex partner classification and optimise accelerated partner therapy; cluster crossover randomised controlled trial of accelerated partner therapy, with process and cost-consequence evaluation; dynamic modelling and health economic evaluation; systematic review of economic studies of partner notification for sexually transmitted infections in men who have sex with men; qualitative research to co-design a novel partner notification intervention for men who have sex with men with bacterial sexually transmitted infections. Settings: Sexual health clinics and community services in England and Scotland. Participants: Women and men, including men who have sex with men and people with mild learning disabilities. Interventions: Accelerated partner therapy offered as an additional partner notification method. Main outcome measures: Proportion of index patients with positive repeat chlamydia test (primary outcome); proportion of sex partners treated; costs per major outcome averted and quality-adjusted life-year; predicted chlamydia prevalence; experiences of accelerated partner therapy. Data sources: Randomised controlled trial: partnership type, resource use, outcomes, qualitative data: economic analysis, modelling and systematic review: resource use and unit costs from the randomised controlled trial, secondary sources. Results: The sex partner classification defined five types. Accelerated partner therapy modifications included simplified self-sampling packs and creation of training films. We created a clinical management and partner notification data collection system.In the randomised controlled trial, all 17 enrolled clinics completed both periods; 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. Six hundred and sixtysix (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for Chlamydia trachomatis at 12–24 weeks after contact tracing consultation; 31 (4.7%) in the intervention phase and 53 (6.6%) in the control phase had a positive Chlamydia trachomatis test result [adjusted odds ratio 0.66 (95% confidence interval 0.41 to 1.04); p = 0.071]. The proportion of index patients with ≥ 1 sex partner treated was 88.0% (775/881) in intervention and 84.6% (760/898) in control phase, adjusted odds ratio 1.27 (95% confidence interval 0.96 to 1.68; p = 0.10). Overall, 293/1536 (19.1%) index patients chose accelerated partner therapy for 305 partners, of which partner types were: committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Two hundred and forty-eight accepted accelerated partner therapy and 241 partners were sent accelerated partner therapy packs, 120/241 (49.8%) returned chlamydia/ gonorrhoea samples (78/119, 65.5%, positive for chlamydia, no result in one), but only 60/241 (24.9%) human immunodeficiency virus and syphilis samples (all negative). The primary outcomes of the randomised trial were not statistically significantly different at the 5% level. However, the economic evaluation found that accelerated partner therapy could be less costly compared with routine care, and mathematical modelling of effects and costs extrapolated beyond the trial end points suggested that accelerated partner therapy could be more effective and less costly than routine care in terms of major outcome averted and quality-adjusted life-years’. Healthcare professionals did not always offer accelerated partner therapy but felt that a clinical management and partner notification data collection system enhanced data recording. Key elements of a multilevel intervention supporting men who have sex with men in partner notification included: modifying the cultural and social context of men who have sex with men communities; improving skills and changing services to facilitate partner notification for one-off partners; and working with dating app providers to explore digital partner notification options. The systematic review found no evaluations of partner notification for men who have sex with men. Modelling of go..

Improving sexual health through partner notification: the LUSTRUM mixed-methods research Programme including RCT of accelerated partner therapy

Background: Sexually transmitted infections disproportionately affect young people and men who have sex with men. Chlamydia is Britain’s most common sexually transmitted infection. Partner notification is a key intervention to reduce transmission of sexually transmitted infections and human immunodeficiency virus but is hard to implement. Accelerated partner therapy is a promising new approach. Objectives:1. determine the effectiveness, costs and acceptability of accelerated partner therapy for chlamydia in heterosexual people2. model the cost effectiveness of accelerated partner therapy and impact on chlamydia transmission3. develop and cost partner notification interventions for men who have sex with men.Design: Mixed-methods study to develop a new sex partner classification and optimise accelerated partner therapy; cluster crossover randomised controlled trial of accelerated partner therapy, with process and cost-consequence evaluation; dynamic modelling and health economic evaluation; systematic review of economic studies of partner notification for sexually transmitted infections in men who have sex with men; qualitative research to co-design a novel partner notification intervention for men who have sex with men with bacterial sexually transmitted infections. Settings: Sexual health clinics and community services in England and Scotland. Participants: Women and men, including men who have sex with men and people with mild learning disabilities. Interventions: Accelerated partner therapy offered as an additional partner notification method. Main outcome measures: Proportion of index patients with positive repeat chlamydia test (primary outcome); proportion of sex partners treated; costs per major outcome averted and quality-adjusted life-year; predicted chlamydia prevalence; experiences of accelerated partner therapy. Data sources: Randomised controlled trial: partnership type, resource use, outcomes, qualitative data: economic analysis, modelling and systematic review: resource use and unit costs from the randomised controlled trial, secondary sources. Results: The sex partner classification defined five types. Accelerated partner therapy modifications included simplified self-sampling packs and creation of training films. We created a clinical management and partner notification data collection system.In the randomised controlled trial, all 17 enrolled clinics completed both periods; 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. Six hundred and sixtysix (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for Chlamydia trachomatis at 12–24 weeks after contact tracing consultation; 31 (4.7%) in the intervention phase and 53 (6.6%) in the control phase had a positive Chlamydia trachomatis test result [adjusted odds ratio 0.66 (95% confidence interval 0.41 to 1.04); p = 0.071]. The proportion of index patients with ≥ 1 sex partner treated was 88.0% (775/881) in intervention and 84.6% (760/898) in control phase, adjusted odds ratio 1.27 (95% confidence interval 0.96 to 1.68; p = 0.10). Overall, 293/1536 (19.1%) index patients chose accelerated partner therapy for 305 partners, of which partner types were: committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Two hundred and forty-eight accepted accelerated partner therapy and 241 partners were sent accelerated partner therapy packs, 120/241 (49.8%) returned chlamydia/ gonorrhoea samples (78/119, 65.5%, positive for chlamydia, no result in one), but only 60/241 (24.9%) human immunodeficiency virus and syphilis samples (all negative). The primary outcomes of the randomised trial were not statistically significantly different at the 5% level. However, the economic evaluation found that accelerated partner therapy could be less costly compared with routine care, and mathematical modelling of effects and costs extrapolated beyond the trial end points suggested that accelerated partner therapy could be more effective and less costly than routine care in terms of major outcome averted and quality-adjusted life-years’. Healthcare professionals did not always offer accelerated partner therapy but felt that a clinical management and partner notification data collection system enhanced data recording. Key elements of a multilevel intervention supporting men who have sex with men in partner notification included: modifying the cultural and social context of men who have sex with men communities; improving skills and changing services to facilitate partner notification for one-off partners; and working with dating app providers to explore digital partner notification options. The systematic review found no evaluations of partner notification for men who have sex with men. Modelling of go..

Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.

TRIAL DESIGN A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. METHODS Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 μg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. RESULTS A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98;  = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94;  = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. LIMITATIONS The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. FUTURE WORK Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. CONCLUSIONS Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. TRIAL REGISTRATION Current Controlled Trials ISRCTN17405024. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 68. See the NIHR Journals Library website for further project information