Feasibility of Comparative Health Research Outcome of Novel Surgery in prostate cancer (IP4-CHRONOS): statistical analysis plan for the randomised feasibility phase of the CHRONOS study

Background Randomised controlled trials (RCTs) for surgical interventions have often proven difficult with calls for innovative approaches. The Imperial Prostate (IP4) Comparative Health Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS) study aims to deliver level 1 evidence on outcomes following focal therapy which involves treating just the tumour rather than whole-gland surgery or radiotherapy. Our aim is to test the feasibility of two parallel RCTs within an overarching strategy that fits with existing patient and physician equipoise and maximises the chances of success and potential benefit to patients and healthcare services. Methods and design IP4-CHRONOS is a randomised, unblinded multi-centre study, including two parallel randomised controlled trials targeting the same patient population: IP4-CHRONOS-A and IP4-CHRONOS-B. IP4-CHRONOS-A is a 1:1 RCT and the other is a multi-arm, multi-stage (MAMS) RCT starting with three arms and a 1:1:1 randomisation. The two linked RCTs are discussed with patients at the time of consent and the choice of A or B is dependent on physician and patient equipoise. The primary outcome is the feasibility of recruitment, acceptance of randomisation and compliance to allocated arm. Results This paper describes the statistical analysis plan (SAP) for the feasibility study within IP4-CHRONOS given its innovative approach. Version 1.0 of the SAP has been reviewed by the Trial Steering Committee (TSC), Chief Investigator (CI), Senior Statistician and Trial Statistician and signed off. The study is ongoing and recruiting. Recruitment is scheduled to finish later in 2021. The SAP documents approved methods and analyses that will be conducted. Since this is written in advance of the analysis, we avoid bias arising from prior knowledge of the study data and findings. Discussion Our feasibility analysis will demonstrate if IP4-CHRONOS is feasible in terms of recruitment, randomisation and compliance, and whether to continue both A and B or just one to the main stage. Trial registration ISRCTN ISRCTN17796995. Registered on 08 October 2019

The European Social Survey (ESS) and comparative health research

The present article represents the first attempt to collect all health-related ESS articles for a systematic review. Although the European Social Survey (ESS) is not primarily a health survey, we have seen an increasing use of data from the ESS in comparative health research in the last few years, and the number is increasing year by year. The present article mainly aims at describing the findings from these studies and to highlight the main methodological differences between these studies. Although a synchronisation of methodological approaches would increase the comparability between ESS studies, the varying approaches are one of the main features that increase the interest in the ESS: both because it improves the robustness of the results, but also because it reflects the flexibility that the ESS offers as a data source. Twenty-one studies using the ESS for health-comparative analyses could be found and the number of studies is increasing year by year. A key result from these studies is that fundamental inequalities continue to exist according to many socio-economic indicators in the Nordic countries despite high living standards and egalitarian policies.