On the probability of cost-effectiveness using data from randomized clinical trials

BACKGROUND: Acceptability curves have been proposed for quantifying the probability that a treatment under investigation in a clinical trial is cost-effective. Various definitions and estimation methods have been proposed. Loosely speaking, all the definitions, Bayesian or otherwise, relate to the probability that the treatment under consideration is cost-effective as a function of the value placed on a unit of effectiveness. These definitions are, in fact, expressions of the certainty with which the current evidence would lead us to believe that the treatment under consideration is cost-effective, and are dependent on the amount of evidence (i.e. sample size). METHODS: An alternative for quantifying the probability that the treatment under consideration is cost-effective, which is independent of sample size, is proposed. RESULTS: Non-parametric methods are given for point and interval estimation. In addition, these methods provide a non-parametric estimator and confidence interval for the incremental cost-effectiveness ratio. An example is provided. CONCLUSIONS: The proposed parameter for quantifying the probability that a new therapy is cost-effective is superior to the acceptability curve because it is not sample size dependent and because it can be interpreted as the proportion of patients who would benefit if given the new therapy. Non-parametric methods are used to estimate the parameter and its variance, providing the appropriate confidence intervals and test of hypothesis

Use of progression criteria to support monitoring and commissioning decision making of public health services: : lessons from Better Start Bradford

BACKGROUND:Commissioning and monitoring of community-based interventions is a challenge due to the complex nature of the environment and the lack of any explicit cut-offs to guide decision making. At what point, for example, is participant enrolment to interventions, course completion or satisfaction deemed to be acceptable or sufficient for continued funding? We aimed to identify and quantify key progression criteria for fourteen early years interventions by (1) agreeing the top three criteria for monitoring of successful implementation and progress; and (2) agreeing boundaries to categorise interventions as 'meeting anticipated target' (green); 'falling short of targets' (amber) and 'targets not being met' (red). METHODS:We ran three workshops in partnership with the UK's Big Lottery Fund commissioned programme 'Better Start Bradford' (implementing more than 20 interventions to improve the health, wellbeing and development of children aged 0-3) to support decision making by agreeing progression criteria for the interventions being delivered. Workshops included 72 participants, representing a range of professional groups including intervention delivery teams, commissioners, intervention-monitoring teams, academics and community representatives. After discussion and activities, final decisions were submitted using electronic voting devices. All participants were invited to reconsider their responses via a post-workshop questionnaire. RESULTS:Three key progression criteria were assigned to each of the 14 interventions. Overall, criteria that participants most commonly voted for were recruitment, implementation and reach, but these differed according to each intervention. Cut-off values used to indicate when an intervention moved to 'red' varied by criteria; the lowest being for recruitment, where participants agreed that meeting less than 65% of the targeted recruitment would be deemed as 'red' (falling short of target). CONCLUSIONS:Our methodology for monitoring the progression of interventions has resulted in a clear pathway which will support commissioners and intervention teams in local decision making within the Better Start Bradford programme and beyond. This work can support others wishing to implement a formal system for monitoring the progression of public health interventions

Maternal outcomes at 3 months after planned caesarean section versus planned vaginal birth for twin pregnancies in the Twin Birth Study: a randomised controlled trial

OBJECTIVE: To compare outcomes at 3 months post partum for women randomised to give birth by planned caesarean section (CS) or by planned vaginal birth (VB) in the Twin Birth Study (TBS). DESIGN: We invited women in the TBS to complete a 3-month follow-up questionnaire. SETTING: Two thousand and eight hundred and four women from 25 countries. POPULATION: Two thousand and five hundred and seventy women (92% response rate). METHODS: Women randomised between 13 December 2003 and 4 April 2011 in the TBS completed a questionnaire and outcomes were compared using an intention-to-treat approach. MAIN OUTCOME AND MEASURES: Breastfeeding, quality of life, depression, fatigue and urinary incontinence. RESULTS: We found no clinically important differences between groups in any outcome. In the planned CS versus planned VB groups, breastfeeding at any time after birth was reported by 84.4% versus 86.4% (P = 0.13); the mean physical and mental Short Form (36) Health Survey (SF-36) quality of life scores were 51.8 versus 51.6 (P = 0.65) and 46.7 versus 46.0 (P = 0.09), respectively; the mean Multidimensional Assessment of Fatigue score was 20.3 versus 20.8 (P = 0.14); the frequency of probable depression on the Edinburgh Postnatal Depression Scale was 14.0% versus 14.8% (P = 0.57); the rate of problematic urinary incontinence was 5.5% versus 6.4% (P = 0.31); and the mean Incontinence Impact Questionnaire-7 score was 20.5 versus 20.4 (P = 0.99). Partner relationships, including painful intercourse, were similar between the groups. CONCLUSION: For women with twin pregnancies randomised to planned CS compared with planned VB, outcomes at 3 months post partum did not differ. The mode of birth was not associated with problematic urinary incontinence or urinary incontinence that affected the quality of life. Contrary to previous studies, breastfeeding at 3 months was not increased with planned VB. TWEETABLE ABSTRACT: Planned mode of birth for twins doesn't affect maternal depression, wellbeing, incontinence or breastfeeding

Assessing risk factors and health impacts across different forms of exchange sex among young women in informal settlements in South Africa: A cross-sectional study.

This is the final version. Available from Elsevier via the DOI in this record. Data availability: Data are available at: https://medat.samrc.ac.za/index.php/catalog/WWFor women in South Africa, engaging in exchange sex, including transactional sex (TS), or sex work (SW), is associated with several shared poor health outcomes; yet the practices themselves differ in meaningful ways. SW is a form of commodity exchange, while TS is grounded in gendered relationship expectations of male provision and aspects of emotional intimacy. Additionally, exchange sex types could be imagined on a "continuum of instrumentality" from relationships that do not include material support; to those characterized, but not driven by support; to those primarily motivated by material support. We use cross-sectional data from 644 women ages 18-30 enrolled in a trial addressing intimate partner violence in urban KwaZulu-Natal, South Africa to assess whether these conceptualizations may also map onto different types or levels of risk. Using self-reports, we developed four exchange sex relationship categories corresponding to a continuum of instrumentality: no exchange-based relationship; TS with a main partner only; TS with a casual partner; and SW. Using tests of association and adjusted logistic regression models, we compared socio-economic and behavioural risk factors, and health outcomes across reported forms of exchange sex. We find little difference between women who report no exchange sex and those who report TS only with a main partner. By contrast, as compared to women not in exchange sex, women in casual TS and SW were poorer, and significantly more likely to report problematic alcohol use, past drug use, prior non-partner sexual violence, and PTSD; with aOR higher for women in SW for many outcomes. When comparing casual TS to SW, we find women in SW held more gender equitable attitudes and were more likely to report modern contraceptive use. We discuss the implications for distinguishing between TS and SW, and use of the continuum of instrumentality conceptualization for research and programming.UKRISouth African Medical Research CouncilUK Department for International DevelopmentGCR

Using the Incremental Net Benefit Framework for Quantitative Benefit–Risk Analysis in Regulatory Decision-Making—A Case Study of Alosetron in Irritable Bowel Syndrome

AbstractObjectiveThere is consensus that a more transparent, explicit, and rigorous approach to benefit–risk evaluation is required. The objective of this study is to evaluate the incremental net benefit (INB) framework for undertaking quantitative benefit–risk assessment by performing a quantitative benefit–risk analysis of alosetron for the treatment of irritable bowel syndrome from the patients’ perspective.MethodsA discrete event simulation model was developed to determine the INB of alosetron relative to placebo, calculated as “relative value-adjusted life-years (RVALYs).”ResultsIn the base case analysis, alosetron resulted in a mean INB of 34.1 RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Incorporating parameter uncertainty into the model, probabilistic sensitivity analysis revealed a mean INB of 30.4 (95% confidence interval 15.9–45.4) RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Overall, there was >99% chance that both the incremental benefit and incremental risk associated with alosetron are greater than placebo. As hypothesized, the INB of alosetron was greatest in patients with the worst quality of life experienced at baseline. The mean INB associated with alosetron in patients with mild, moderate, and severe symptoms at baseline was 17.97 (−0.55 to 36.23), 29.98 (17.05–43.37), and 35.98 (23.49–48.77) RVALYs per 1000 patients treated, respectively.ConclusionsThis study demonstrates the potential utility of applying the INB framework to real-life decision-making, and the ability to use simulation modeling incorporating outcomes data from different sources as a benefit–risk decision aid

Challenges and opportunities in coproduction: reflections on working with young people to develop an intervention to prevent violence in informal settlements in South Africa

Coproduction is widely recognised as essential to the development of effective and sustainable complex health interventions. Through involving potential end users in the design of interventions, coproduction provides a means of challenging power relations and ensuring the intervention being implemented accurately reflects lived experiences. Yet, how do we ensure that coproduction delivers on this promise? What methods or techniques can we use to challenge power relations and ensure interventions are both more effective and sustainable in the longer term? To answer these questions, we openly reflect on the coproduction process used as part of Siyaphambili Youth (‘Youth Moving Forward’), a 3-year project to create an intervention to address the social contextual factors that create syndemics of health risks for young people living in informal settlements in KwaZulu-Natal province in South Africa. We identify four methods or techniques that may help improve the methodological practice of coproduction: (1) building trust through small group work with similar individuals, opportunities for distance from the research topic and mutual exchanges about lived experiences; (2) strengthening research capacity by involving end users in the interpretation of data and explaining research concepts in a way that is meaningful to them; (3) embracing conflicts that arise between researchers’ perspectives and those of people with lived experiences; and (4) challenging research epistemologies through creating spaces for constant reflection by the research team. These methods are not a magic chalice of codeveloping complex health interventions, but rather an invitation for a wider conversation that moves beyond a set of principles to interrogate what works in coproduction practice. In order to move the conversation forward, we suggest that coproduction needs to be seen as its own complex intervention, with research teams as potential beneficiaries

Why interventions to prevent intimate partner violence and HIV have failed young women in southern Africa

INTRODUCTION: Adolescent girls and young women aged 15 to 24 years have some of the highest HIV incidence rates globally, with girls two to four times more likely to be living with HIV than their male peers. High levels of intimate partner violence (IPV) experienced by this age group is a significant risk factor for HIV acquisition. While behavioural interventions to prevent IPV and HIV in southern Africa have seen some success in reducing self-reported experiences of IPV, these interventions have largely failed to achieve similar outcomes for young women. DISCUSSION: We identify three main reasons for the failure of IPV/HIV interventions for many young women in southern Africa. First, interventions are usually developed without the meaningful involvement of both young women and young men. Youth input into research design is largely focused on user testing or consultation of targeted groups, involving relatively low levels of participation. Second, interventions are focused on addressing individual risk factors rather than broader social and structural contexts of being a young woman. "Risk factor" interventions, rather than supporting women's agency, can pose a major barrier for supporting changes in behaviour among young women because they often fail to dislodge well-entrenched gender and age-related inequalities. Third, current intervention models have not adequately accounted for changes in gender norms and relationships across southern Africa. Individuals are getting married later in life (or not at all), new technologies are transforming romantic interactions and opening new opportunities for violence, and discussions about women's rights are both challenging gender inequalities and reinforcing them. CONCLUSIONS: In order to move beyond the status quo of current approaches, and to support real innovation, IPV/HIV prevention interventions need to be co-developed with youth as part of a meaningful participatory process of research, intervention design, youth involvement in development and implementation. This process of co-development needs to be radical and break with the current focus on adapting existing interventions to meet the needs of young people, which are not well understood and often do not directly reflect their priorities. Broader social contexts and compound lenses are needed to avoid narrow approaches and to accommodate evolving norms