Application of causal inference methods in individual-participant data meta-analyses in medicine: addressing data handling and reporting gaps with new proposed reporting guidelines.

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) conducted with non-randomized exposures, published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy.

Supporting Local Public Health and Planning Professionals to Implement Built Environment Changes: A Technical Assistance Program to Promote Physical Activity in Texas.

Built environment approaches that improve active transportation infrastructure and environmental design can increase physical activity. Funded by the Centers for Disease Control and Prevention, the Texas Department of State Health Services rejuvenated the Texas Plan4Health program from 2018 to 2023 to expand such approaches in Texas by providing technical assistance to teams of local public health professionals and planners to identify and implement projects connecting people to everyday destinations via active transport in their communities. However, the COVID-19 pandemic prompted Texas Plan4Health to modify the delivery of technical assistance to accommodate restrictions on travel and in-person gatherings. We used qualitative methods to conduct a postintervention process evaluation to describe the modified technical assistance process, understand the experiences of the 4 participating communities, and identify short-term outcomes and lessons learned. Texas Plan4Health helped communities overcome common barriers to built environment change, facilitated collaboration across community public health and planning professionals, and educated professionals about active transportation infrastructure and the relationship between their disciplines, thereby increasing community capacity to implement built environment improvements. This outcome, however, was mediated by the pre-existing resources and previous experiences with active transportation planning among the participating communities. Public health practitioners seeking to improve active transportation infrastructure and environmental design for physical activity should consider community-engaged approaches that advance partnership-building and collaborative experiential education among public health, planning, and other local government representatives, directing particular attention and additional training toward communities with fewer resources.

Overlapping research efforts in a global pandemic: a rapid systematic review of COVID-19-related individual participant data meta-analyses.

BACKGROUND: Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over aggregate data meta-analyses, which pool study-level findings. IPD-MAs are especially important for building and evaluating diagnostic and prognostic models, making them an important tool for informing the research and public health responses to COVID-19. METHODS: We conducted a rapid systematic review of protocols and publications from planned, ongoing, or completed COVID-19-related IPD-MAs to identify areas of overlap and maximise data request and harmonisation efforts. We searched four databases using a combination of text and MeSH terms. Two independent reviewers determined eligibility at the title-abstract and full-text stages. Data were extracted by one reviewer into a pretested data extraction form and subsequently reviewed by a second reviewer. Data were analysed using a narrative synthesis approach. A formal risk of bias assessment was not conducted. RESULTS: We identified 31 COVID-19-related IPD-MAs, including five living IPD-MAs and ten IPD-MAs that limited their inference to published data (e.g., case reports). We found overlap in study designs, populations, exposures, and outcomes of interest. For example, 26 IPD-MAs included RCTs; 17 IPD-MAs were limited to hospitalised patients. Sixteen IPD-MAs focused on evaluating medical treatments, including six IPD-MAs for antivirals, four on antibodies, and two that evaluated convalescent plasma. CONCLUSIONS: Collaboration across related IPD-MAs can leverage limited resources and expertise by expediting the creation of cross-study participant-level data datasets, which can, in turn, fast-track evidence synthesis for the improved diagnosis and treatment of COVID-19. TRIAL REGISTRATION: 10.17605/OSF.IO/93GF2.

Development and validation of the LoVI: the Laws on Violence against women and girls Index.

BACKGROUND: Violence against women and girls (VAWG) is a human-rights violation with adverse long-term and inter-generational consequences. Redefining VAWG as legally unacceptable is one strategy for social change. The co-occurrence of national laws against VAWG is understudied, and tools to monitor the national legal environment are lacking. We developed the Laws on Violence against Women and Girls Index (LoVI) to measure global progress to develop comprehensive national legislation against child marriage, sexual harassment, domestic violence, and marital rape. METHODS: Using data from 2016 and 2018 for 189 countries from the World Bank Women, Business, and the Law database, we used factor analysis to assess the dimensionality of the LoVI. We examined the distribution of the LoVI across countries and regions, and the relationship of national rankings on the LoVI with those for other indicators from the United Nations, Demographic and Health Surveys, and World Factbook. RESULTS: A single LoVI factor showed good model fit in the factor analysis. National LoVI rankings were positively associated with gender equality in human development and economic rights-related rankings and negatively associated with rates of justifying wife beating and of lifetime and prior-year physical and/or sexual IPV. The LoVI was not associated with national indicators for human development and income inequality. CONCLUSION: The LoVI is a concise, coherent, validated index to monitor the progress of nations on adopting comprehensive legislation to advance 2030 Sustainable Development Goal 5, to eliminate VAWG.

Violence against children in Latin America and the Caribbean: What do available data reveal about prevalence and perpetrators?

OBJECTIVE: To describe the prevalence of recent physical, sexual, and emotional violence against children 0 - 19 years of age in Latin America and the Caribbean (LAC) by age, sex, and perpetrator. METHODS: A systematic review and analysis of published literature and large international datasets was conducted. Eligible sources from first record to December 2015 contained age-, sex-, and perpetrator-specific data from LAC. Random effects meta-regressions were performed, adjusting for relevant quality covariates and differences in violence definitions. RESULTS: Seventy-two surveys (2 publications and 70 datasets) met inclusion criteria, representing 1 449 estimates from 34 countries. Prevalence of physical and emotional violence by caregivers ranged from 30% - 60%, and decreased with increasing age. Prevalence of physical violence by students (17% - 61%) declined with age, while emotional violence remained constant (60% - 92%). Prevalence of physical intimate partner violence (IPV) ranged from 13% - 18% for girls aged 15 - 19 years. Few or no eligible past-year estimates were available for any violence against children less than 9 years and boys 16 - 19 years of age; sexual violence against boys (any age) and girls (under 15 years); IPV except for girls aged 15 - 19 years; and violence by authority figures (e.g., teachers) or via gangs/organized crime. CONCLUSION: Past-year physical and emotional violence by caregivers and students is widespread in LAC across all ages in childhood, as is IPV against girls aged 15 - 19 years. Data collection must be expanded in LAC to monitor progress towards the sustainable development goals, develop effective prevention and response strategies, and shed light on violence relating to organized crime/gangs.

Measurement properties of the project-level Women's Empowerment in Agriculture Index.

Women's empowerment is a process that includes increases in intrinsic agency (power within); instrumental agency (power to); and collective agency (power with). We used baseline data from two studies-Targeting and Realigning Agriculture for Improved Nutrition (TRAIN) in Bangladesh and Building Resilience in Burkina Faso (BRB)-to assess the measurement properties of survey questions operationalizing selected dimensions of intrinsic, instrumental, and collective agency in the project-level Women's Empowerment in Agricultural Index (pro-WEAI). We applied unidimensional item-response models to question (item) sets to assess their measurement properties, and when possible, their cross-context measurement equivalence-a requirement of measures designed for cross-group comparisons. For intrinsic agency in the right to bodily integrity, measured with five attitudinal questions about intimate partner violence (IPV) against women, model assumptions of unidimensionality and local independence were met. Four items showed good model fit and measurement equivalence across TRAIN and BRB. For item sets designed to capture autonomy in income, intrinsic agency in livelihoods activities, and instrumental agency in: livelihoods activities, the sale or use of outputs, the use of income, and borrowing from financial services, model assumptions were not met, model fit was poor, and items generally were weakly related to the latent (unobserved) agency construct. For intrinsic and instrumental agency in livelihoods activities and for instrumental agency in the sale or use of outputs and in the use of income, items sets had similar precision along the latent-agency continuum, suggesting that similar item sets could be dropped without a loss of precision. IRT models for collective agency were not estimable because of low reported presence and membership in community groups. This analysis demonstrates the use of IRT methods to assess the measurement properties of item sets in pro-WEAI, and empowerment scales generally. Findings suggest that a shorter version of pro-WEAI can be developed that will improve its measurement properties. We recommend revisions to the pro-WEAI questionnaire and call for new measures of women's collective agency.

Does the type of abortion provider influence contraceptive uptake after abortion? An analysis of longitudinal data from 64 health facilities in Ghana.

BACKGROUND: Understanding what factors influence the receipt of postabortion contraception can help improve comprehensive abortion care services. The abortion visit is an ideal time to reach women at the highest risk of unintended pregnancy with the most effective contraceptive methods. The objectives of this study were to estimate the relationship between the type of abortion provider (consultant physician, house officer, or midwife) and two separate outcomes: (1) the likelihood of adopting postabortion contraception; (2) postabortion contraceptors' likelihood of receiving a long-acting and permanent versus a short-acting contraceptive method. METHODS: We used retrospective cohort data collected from 64 health facilities in three regions of Ghana. The dataset includes information on all abortion procedures conducted between 1 January 2008 and 31 December 2010 at each health facility. We used fixed effect Poisson regression to model the associations of interest. RESULTS: More than half (65 %) of the 29,056 abortion clients received some form of contraception. When midwives performed the abortion, women were more likely to receive postabortion contraception compared to house officers (RR: 1.18; 95 % CI: 1.13, 1.24) or physicians (RR: 1.21; 95 % CI: 1.18, 1.25), after controlling for facility-level variation and client-level factors. Compared to women seen by house officers, abortion clients seen by midwives and physicians were more likely to receive a long-acting and permanent rather than a short-acting contraceptive method (RR: 1.46; 95 % CI: 1.23, 1.73; RR: 1.58; 95 % CI: 1.37, 1.83, respectively). Younger women were less likely to receive contraception than older women irrespective of provider type and indication for the abortion (induced or PAC). CONCLUSIONS: When comparing consultant physicians, house officers, and midwives, the type of abortion provider is associated with whether women receive postabortion contraception and with whether abortion clients receive a long-acting and permanent or a short-acting method. New strategies are needed to ensure that women seen by physicians and house officers can access postabortion contraception and to ensure that women seen by house officers have access to long-acting and permanent contraceptive methods.

How to plan and manage an individual participant data meta-analysis. An illustrative toolkit.

Individual participant data meta-analyses (IPD-MAs) have several benefits over standard aggregate data meta-analyses, including the consideration of additional participants, follow-up time, and the joint consideration of study- and participant-level heterogeneity for improved diagnostic and prognostic model development and evaluation. However, IPD-MAs are resource-intensive and require careful budgeting of time from data contributing groups, a dedicated management team, diversity of expertise, clearly documented data sharing and authorship agreements, and consistent and clear communication. We present a toolkit to facilitate the implementation and management of IPD-MAs, from study recruitment to retrospective harmonization. The toolkit was developed and refined over our work on multiple multinational IPD-MA projects over the last 13 years. The toolkit's budget and email templates, agreements, project management spreadsheets, and standard operating procedures are meant to facilitate routine IPD-MA tasks to expedite implementing and managing future IPD-MA projects.

Reconciling the biomedical data commons and the GDPR: three lessons from the EUCAN ELSI collaboratory.

The coming-into-force of the EU General Data Protection Regulation (GDPR) is a watershed moment in the legal recognition of enforceable rights to informational self-determination. The rapid evolution of legal requirements applicable to data use, however, has the potential to outstrip the capabilities of networks of biomedical data users to respond to the shifting norms. It can also delegitimate established institutional bodies that are responsible for assessing and authorising the downstream use of data, including research ethics committees and institutional data custodians. These burdens are especially pronounced for clinical and research networks that are of transnational scale, because the legal compliance burden for outbound international data transfers from the EEA is especially high. Legislatures, courts, and regulators in the EU should therefore implement the following three legal changes. First, the responsibilities of particular actors in a data sharing network should be delimited through the contractual allocation of responsibilities between collaborators. Second, the use of data through secure data processing environments should not trigger the international transfer provisions of the GDPR. Third, the use of federated data analysis methodologies that do not provide analysis nodes or downstream users access to identifiable personal data as part of the outputs of those analyses should not be considered circumstances of joint controllership, nor lead to the users of non-identifiable data to be considered controllers or processors. These small clarifications of, or modifications to, the GDPR would facilitate the exchange of biomedical data amongst clinicians and researchers.

Pregnant women's perceptions on Information Sources on Zika Virus: a qualitative study.

The Zika virus (ZIKV) epidemic had a sanitary, psychosocial, and economic impact on individuals of reproductive age. The primary concern revolved around infection during pregnancy due to possible vertical transmission and its association with adverse fetal and infant outcomes, known as Congenital Zika Syndrome (CZS). This qualitative study employs phenomenology and grounded theory. This study includes interviews with 98 women, some pregnant during the ZIKV epidemic in Brazil, Colombia, and Puerto Rico, who had children with CZS or without diagnosed neurological impairment. Additionally, the study included a group of women who were pregnant during the COVID-19 pandemic in these same countries. In both groups, interviewees had varying levels of knowledge about ZIKV. The study found that messages conveyed through the media tended to be alarmist, in contrast to the information provided by healthcare professionals, which was considered more trustworthy. Pregnant women during the ZIKV epidemic reported receiving their ZIKV and CSZ infection diagnoses late, either during or after childbirth. The study underscores the needs of pregnant women in high-risk scenarios, the importance of health education processes, and the necessity to reinforce communication and continuing education.

A epidemia do vírus Zika (ZIKV) teve impacto sanitário, psicossocial e econômico sobre pessoas em idade reprodutiva. A principal preocupação foi a infecção durante a gravidez devido a possível transmissão vertical e sua associação com resultados fetais e infantis adversos, conhecida como síndrome congênita associada à infecção pelo Vírus Zika (SCZ). Este estudo qualitativo utiliza a fenomenologia e a teoria fundamentada. O estudo inclui entrevistas com 98 mulheres, parte grávida durante a epidemia de ZIKV no Brasil, Colômbia e Porto Rico e que tiveram filhos com SCZ ou sem comprometimento neurológico diagnosticado. Além disso, o estudo inclui um grupo de mulheres grávidas durante a pandemia de COVID-19 nos mesmos países. Em ambos os grupos, as entrevistadas tinham diferentes níveis de conhecimento sobre ZIKV. O estudo constatou que as mensagens veiculadas por meio da mídia eram alarmistas; em contraste com as informações fornecidas por profissionais de saúde, consideradas mais confiáveis. Mulheres gestantes durante a epidemia do ZIKV relataram ter recebido seu diagnóstico de infecção por ZIKV e SCZ tardiamente ou após o parto. O estudo destaca as necessidades das mulheres grávidas em cenários de alto risco, a importância de processos de educação em saúde e a necessidade de reforçar a comunicação e a educação continuada.

"I found out about Zika virus after she was born." Women's experiences of risk communication during the Zika virus epidemic in Brazil, Colombia, and Puerto Rico.

Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women's perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development. We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women's experiences of Zika virus (ZIKV) test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews. Participants in Brazil and Colombia reported that the healthcare system's lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy. Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families' preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication.

"How about me giving blood for the COVID vaccine and not being able to get vaccinated?" A cognitive interview study on understanding of and agreement with broad consent for future use of data and samples in Colombia and Nicaragua.

Broad consent for future use, wherein researchers ask participants for permission to share participant-level data and samples collected within the study for purposes loosely related to the study objectives, is central to enabling ethical data and sample reuse. Ensuring that participants understand broad consent-related language is key to maintaining trust in the study and public health research. We conducted 52 cognitive interviews to explore cohort research participants' and their parents' understanding of the broad consent-related language in the University of California at Berkeley template informed consent (IC) form for biomedical research. Participants and their parents were recruited from long-standing infectious disease cohort studies in Nicaragua and Colombia and interviewed during the COVID-19 pandemic. We conducted semi-structured interviews to assess participants' agreement with the key concepts in the IC after clarifying them through the cognitive interview. Participants did not understand abstract concepts, including collecting and reusing genetic data. Participants wanted to learn about incidental findings, future users and uses. Trust in the research team and the belief that sharing could lead to new vaccines or treatments were critical to participant support for data and sample sharing. Participants highlighted the importance of data and sample sharing for COVID-19 response and equitable access to vaccines and treatments developed through sharing. Our findings on participants' understanding of broad consent and preferences for data and sample sharing can help inform researchers and ethics review committees working to enable ethical and equitable data and sample sharing.

Adjusting for misclassification of an exposure in an individual participant data meta-analysis.

A common problem in the analysis of multiple data sources, including individual participant data meta-analysis (IPD-MA), is the misclassification of binary variables. Misclassification may lead to biased estimators of model parameters, even when the misclassification is entirely random. We aimed to develop statistical methods that facilitate unbiased estimation of adjusted and unadjusted exposure-outcome associations and between-study heterogeneity in IPD-MA, where the extent and nature of exposure misclassification may vary across studies. We present Bayesian methods that allow misclassification of binary exposure variables to depend on study- and participant-level characteristics. In an example of the differential diagnosis of dengue using two variables, where the gold standard measurement for the exposure variable was unavailable for some studies which only measured a surrogate prone to misclassification, our methods yielded more accurate estimates than analyses naive with regard to misclassification or based on gold standard measurements alone. In a simulation study, the evaluated misclassification model yielded valid estimates of the exposure-outcome association, and was more accurate than analyses restricted to gold standard measurements. Our proposed framework can appropriately account for the presence of binary exposure misclassification in IPD-MA. It requires that some studies supply IPD for the surrogate and gold standard exposure, and allows misclassification to follow a random effects distribution across studies conditional on observed covariates (and outcome). The proposed methods are most beneficial when few large studies that measured the gold standard are available, and when misclassification is frequent.

FAIR, ethical, and coordinated data sharing for COVID-19 response: a scoping review and cross-sectional survey of COVID-19 data sharing platforms and registries.

Data sharing is central to the rapid translation of research into advances in clinical medicine and public health practice. In the context of COVID-19, there has been a rush to share data marked by an explosion of population-specific and discipline-specific resources for collecting, curating, and disseminating participant-level data. We conducted a scoping review and cross-sectional survey to identify and describe COVID-19-related platforms and registries that harmonise and share participant-level clinical, omics (eg, genomic and metabolomic data), imaging data, and metadata. We assess how these initiatives map to the best practices for the ethical and equitable management of data and the findable, accessible, interoperable, and reusable (FAIR) principles for data resources. We review gaps and redundancies in COVID-19 data-sharing efforts and provide recommendations to build on existing synergies that align with frameworks for effective and equitable data reuse. We identified 44 COVID-19-related registries and 20 platforms from the scoping review. Data-sharing resources were concentrated in high-income countries and siloed by comorbidity, body system, and data type. Resources for harmonising and sharing clinical data were less likely to implement FAIR principles than those sharing omics or imaging data. Our findings are that more data sharing does not equate to better data sharing, and the semantic and technical interoperability of platforms and registries harmonising and sharing COVID-19-related participant-level data needs to improve to facilitate the global collaboration required to address the COVID-19 crisis.

Application of Causal Inference Methods to Pooled Longitudinal Non- Randomized Studies: A Methodological Systematic Review.

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis. Unfortunately, we found that causal methodologies were rarely implemented, and reporting was generally poor across studies. Specifically, only three of the 29 articles used quasi-experimental methods, and no study used G-methods to adjust for time-varying confounding. To address these issues, we propose stronger collaborations between physicians and methodologists to ensure that causal methodologies are properly implemented in IPD-MAs. In addition, we put forward a suggested checklist of reporting guidelines for IPD-MAs that utilize causal methods. This checklist could improve reporting thereby potentially enhancing the quality and trustworthiness of IPD-MAs, which can be considered one of the most valuable sources of evidence for health policy.

Narrative skill and syntactic complexity in school-age children with and without late language emergence.

BACKGROUND: Children who do not produce single words by the expected age have been described as 'late talkers' or as demonstrating 'late language emergence' (LLE). Although their short-term growth in vocabulary is often strong, longer-term consequences of LLE remain in dispute. It has been argued that the majority of school-age children who had LLE move into the average range for narrative production, though studies have not examined narrative comprehension. It has also been argued that school-age children with LLE score in the average range on standardized tests of syntax, though studies have not examined performance in conversational contexts. AIMS: This article compared school-age children with and without histories of LLE for performance on standardized narrative comprehension and production tasks, as well as the use of complex sentences and relative clauses in narration and conversation. Both complex syntax and relative clause use are reduced in children with specific language impairment (SLI), so these structures may be useful as indicators of linguistic weakness. METHODS & PROCEDURES: The participants were twenty-two 8-year-old children, divided into two groups. Eleven children who had been diagnosed with LLE at 30 months were compared with a control group of 11 children with typical development (TD). All participants completed a standardized test of narrative comprehension and production and a 10-min conversational sample. Both narrative and conversational samples were analysed for the number of complex sentences and relative clauses. OUTCOMES & RESULTS: Overall results indicated that children with a history of LLE did not have comprehension or production scores that were significantly different from the TD group on the standardized narrative test; nor did groups differ for production of complex sentences or relative clauses in narrative samples. However, a significant difference was found for the production of complex sentences in conversational samples, with the children diagnosed with LLE producing fewer complex sentences than the TD group. There was no difference between groups for relative clause use in conversation or in narratives. CONCLUSIONS & IMPLICATIONS: These data suggest that children with a history of LLE may exhibit age-appropriate performance on a standardized narrative test, but still lack the syntactic complexity of their TD peers in conversation. Assessments for school-age children with a history of language delay should include analysis of syntactic complexity in conversation to identify continuing weakness. Future research should examine use of other specific types of complex structures (e.g. infinitival and clausal complements) in this population, as well the feasibility of increasing complex sentence production through intervention. In addition, future studies should examine whether this decreased production of complex syntax in conversation is noted by naive listeners.

Heterogeneity of Zika virus exposure and outcome ascertainment across cohorts of pregnant women, their infants and their children: a metadata survey.

OBJECTIVES: To support the Zika virus (ZIKV) Individual Participant Data (IPD) Consortium's efforts to harmonise and analyse IPD from ZIKV-related prospective cohort studies and surveillance-based studies of pregnant women and their infants and children; we developed and disseminated a metadata survey among ZIKV-IPD Meta-Analysis (MA) study participants to identify and provide a comprehensive overview of study-level heterogeneity in exposure, outcome and covariate ascertainment and definitions. SETTING: Cohort and surveillance studies that measured ZIKV infection during pregnancy or at birth and measured fetal, infant, or child outcomes were identified through a systematic search and consultations with ZIKV researchers and Ministries of Health from 20 countries or territories. PARTICIPANTS: Fifty-four cohort or active surveillance studies shared deidentified data for the IPD-MA and completed the metadata survey, representing 33 061 women (11 020 with ZIKV) and 18 281 children. PRIMARY AND SECONDARY OUTCOME MEASURES: Study-level heterogeneity in exposure, outcome and covariate ascertainment and definitions. RESULTS: Median study sample size was 268 (IQR=100, 698). Inclusion criteria, follow-up procedures and exposure and outcome ascertainment were highly heterogenous, differing meaningfully across regions and multisite studies. Enrolment duration and follow-up for children after birth varied before and after the declaration of the Public Health Emergency of International Concern (PHEIC) and according to the type of funding received. CONCLUSION: This work highlights the logistic and statistical challenges that must be addressed to account for the multiple sources of within-study and between-study heterogeneity when conducting IPD-MAs of data collected in the research response to emergent pathogens like ZIKV.

Do laws promoting gender equity and freedom from violence benefit the most vulnerable? A multilevel analysis of women's and adolescent girls' experiences in 15 low- and-middle-income countries.

In this analysis, we assess whether laws that promote gender equity and freedom from violence are associated with a lower risk of prior-year physical and sexual intimate partner violence (IPV) among adolescent girls and adult women (AGW) and whether these laws protect more and less vulnerable AGW equally. We included all 15 countries that administered the Domestic Violence Module in a Demographic and Health Survey since 2015. The primary exposure was a validated, country-level index of laws on violence against women and girls (LoVI). A multilevel approach was used to model five forms of violence (prior-year partner physical, sexual, physical or sexual violence and prior-year non-partner physical violence or sexual violence) among ever-partnered, non-widowed adolescent girls 13-19 years (n = 6691) and women 20-49 years (n = 119 343). Across countries, partner physical violence ranged from 0% to 33% and sexual violence from 0% to 23%. Laws on marital rape, child marriage and sexual harassment were negatively associated with prior-year physical and sexual IPV for women and girls. Comprehensive domestic violence legislation was unrelated to girls' experiences of prior-year physical or prior-year sexual IPV. No interaction was observed between LoVI component laws and a score meant to capture adolescent vulnerability. Three of the four LoVI component laws had consistent, negative associations with partner violence for girls and women, but negative associations were stronger for women than girls. Thus, while laws promoting gender equity and freedom from violence are generally protective, they may be more so for women than adolescent girls. Future research should explore the impact of gender equitable laws on women's and adolescent girls' experiences of violence, and countries may consider more comprehensive legal protections against violence for adolescent girls.

A blank check or a global public good? A qualitative study of how ethics review committee members in Colombia weigh the risks and benefits of broad consent for data and sample sharing during a pandemic.

Broad consent for future use facilitates the reuse of participant-level data and samples, which can conserve limited resources by confirming research findings and facilitate the development and evaluation of public health and clinical advances. Ethics review committees (ERCs) have to balance different stakeholder concerns when evaluating the risks and benefits associated with broad consent for future use. In this qualitative study, we evaluated ERC members' concerns about different aspects of broad consent, including appropriate governance, community engagement, evaluation of risks and benefits, and communication of broad consent for future use in Colombia, which does not currently have national guidance related to broad consent for future use. We conducted semi-structured, in-depth interviews with 24 ERC members from nine Colombian ERCs. We used thematic analysis to explore ERC members' concerns related to broad consent for future use. Most ERC members expressed concern about the idea of not specifying the purposes for which data would be used and by whom and suggested that pre-specifying governance procedures and structure would address some of their concerns about broad consent. ERC members emphasized the need for engaging communities and ensuring research participants understood broad consent for future use-related language in informed consent forms. Researchers and research institutions are under increasing pressure to share public health-related data. ERC members play a central role in balancing the priorities of different stakeholders and maintaining their community's trust in public health research. Further work is needed on guidelines for developing language around broad consent, evaluating community preferences related to data sharing, and developing standards for describing governance for data or sample sharing in the research protocol to address ERC members' concerns around broad consent for future use.

Neurodevelopment in Normocephalic Children Exposed to Zika Virus in Utero with No Observable Defects at Birth: A Systematic Review with Meta-Analysis.

Zika virus (ZIKV) infection during pregnancy is a cause of pregnancy loss and multiple clinical and neurological anomalies in children. This systematic review aimed to assess the effect of ZIKV exposure in utero on the long-term neurodevelopment of normocephalic children born to women with ZIKV infection in pregnancy. This review was conducted according to the PRISMA guidelines for systematic reviews and meta-analyses. We performed a random effects meta-analysis to estimate the cross-study prevalence of neurodevelopmental delays in children using the Bayley Scales for Infant and Toddler Development (BSID-III). The risk of bias was assessed using Cochrane's Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Full-text reviews were performed for 566 articles, and data were extracted from 22 articles corresponding to 20 studies. Nine articles including data from 476 children found 6.5% (95% CI: 4.1-9.3) of infants and children to have any type of non-language cognitive delay; 29.7% (95% CI: 21.7-38.2) to have language delay; and 11.5% (95% CI: 4.8-20.1) to have any type of motor delay. The pooled estimates had a high level of heterogeneity; thus, results should be interpreted with caution. Larger prospective studies that include a non-exposed control group are needed to confirm whether ZIKV exposure in utero is associated with adverse child neurodevelopmental outcomes.