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Introduction Immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy, have significantly improved the clinical outcomes of various malignancies. However, they also cause immune-related adverse events (irAEs) that can be challenging to predict, prevent and treat. Although they likely interact with health-related quality of life (HRQoL), most existing evidence on this topic has come from clinical trials with eligibility criteria that may not accurately reflect real-world settings. The QUALITOP project will study HRQoL in relation to irAEs and its determinants in a real-world study of patients treated with immunotherapy.Methods and analysis This international, observational, multicentre study takes place in France, the Netherlands, Portugal and Spain. We aim to include about 1800 adult patients with cancer treated with immunotherapy in a specifically recruited prospective cohort, and to additionally obtain data from historical real-world databases (ie, databiobanks) and medical administrative registries (ie, national cancer registries) in which relevant data regarding other adult patients with cancer treated with immunotherapy has already been stored. In the prospective cohort, clinical health status, HRQoL and psychosocial well-being will be monitored until 18 months after treatment initiation through questionnaires (at baseline and 3, 6, 12 and 18 months thereafter), and by data extraction from electronic patient files. Using advanced statistical methods, including causal inference methods, artificial intelligence algorithms and simulation modelling, we will use data from the QUALITOP cohort to improve the understanding of the complex relationships among treatment regimens, patient characteristics, irAEs and HRQoL.Ethics and dissemination All aspects of the QUALITOP project will be conducted in accordance with the Declaration of Helsinki and with ethical approval from a suitable local ethics committee, and all patients will provide signed informed consent. In addition to standard dissemination efforts in the scientific literature, the data and outcomes will contribute to a smart digital platform and medical data lake. These will (1) help increase knowledge about the impact of immunotherapy, (2) facilitate improved interactions between patients, clinicians and the general population and (3) contribute to personalised medicine.Trial registration number NCT05626764.

Introduction Cardiovascular disease is a leading cause of death globally, responsible for nearly 18 million deaths worldwide in 2017. Medications to reduce the risk of cardiovascular events are prescribed based on evidence from clinical trials which explore treatment effects in an indicated sample of the general population. However, these results may not be fully generalisable because of trial eligibility criteria that generally restrict to younger patients with fewer comorbidities. Therefore, evidence of effectiveness of medications for groups underrepresented in clinical trials such as those aged ≥75 years, from ethnic minority backgrounds or with low kidney function may be limited.Using individual anonymised data from the Ongoing Telmisartan Alone and the Ramipril Global Endpoint Trial (ONTARGET) trial, in collaboration with the original trial investigators, we aim to investigate clinical trial replicability within a real-world setting in the area of cardiovascular disease. If the original trial results are replicable, we will estimate treatment effects and risk in groups underrepresented and excluded from the original clinical trial.Methods and analysis We will develop a cohort analogous to the ONTARGET trial within the Clinical Practice Research Datalink between 1 January 2001 and 31 July 2019 using the trial eligibility criteria and propensity score matching. The primary outcome is a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for congestive heart failure. If results from the cohort study fall within pre-specified limits, we will expand the cohort to include under represented and excluded groups.Ethics and dissemination Ethical approval has been granted by the London School of Hygiene & Tropical Medicine Ethics Committee (Ref: 22658). The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol no. 20_012). Access to the individual patient data from the ONTARGET trial was obtained by the trial investigators. Findings will be submitted to peer-reviewed journals and presented at conferences.

Introduction Identifying design features and implementation strategies to optimise community health worker (CHW) programmes is important in the context of mixed results at scale. We systematically reviewed evidence of the effects of proactive case detection by CHWs in low-income and middle-income countries (LMICs) on mortality, morbidity and access to care for common childhood illnesses.Methods Published studies were identified via electronic databases from 1978 to 2017. We included randomised and non-randomised controlled trials, controlled before–after studies and interrupted time series studies, and assessed their quality for risk of bias. We reported measures of effect as study investigators reported them, and synthesised by outcomes of mortality, disease prevalence, hospitalisation and access to treatment. We calculated risk ratios (RRs) as a principal summary measure, with CIs adjusted for cluster design effect.Results We identified 14 studies of 11 interventions from nine LMICs that met inclusion criteria. They showed considerable diversity in intervention design and implementation, comparison, outcomes and study quality, which precluded meta-analysis. Proactive case detection may reduce infant mortality (RR: 0.52–0.94) and increase access to effective treatment (RR: 1.59–4.64) compared with conventional community-based healthcare delivery (low certainty evidence). It is uncertain whether proactive case detection reduces mortality among children under 5 years (RR: 0.04–0.80), prevalence of infectious diseases (RR: 0.06–1.02), hospitalisation (RR: 0.38–1.26) or increases access to prompt treatment (RR: 1.00–2.39) because the certainty of this evidence is very low.Conclusion Proactive case detection may provide promising benefits for child health, but evidence is insufficient to draw conclusions. More research is needed on proactive case detection with rigorous study designs that use standardised outcomes and measurement methods, and report more detail on complex intervention design and implementation.PROSPERO registration number CRD42017074621.