How do pilot and feasibility studies inform randomised placebo-controlled trials in surgery? A systematic review.

INTRODUCTION: Randomised controlled trials (RCTs) with a placebo comparator are considered the gold standard study design when evaluating healthcare interventions. These are challenging to design and deliver in surgery. Guidance recommends pilot and feasibility work to optimise main trial design and conduct; however, the extent to which this occurs in surgery is unknown. METHOD: A systematic review identified randomised placebo-controlled surgical trials. Articles published from database inception to 31 December 2020 were retrieved from Ovid-MEDLINE, Ovid-EMBASE and CENTRAL electronic databases, hand-searching and expert knowledge. Pilot/feasibility work conducted prior to the RCTs was then identified from examining citations and reference lists. Where studies explicitly stated their intent to inform the design and/or conduct of the future main placebo-controlled surgical trial, they were included. Publication type, clinical area, treatment intervention, number of centres, sample size, comparators, aims and text about the invasive placebo intervention were extracted. RESULTS: From 131 placebo surgical RCTs included in the systematic review, 47 potentially eligible pilot/feasibility studies were identified. Of these, four were included as true pilot/feasibility work. Three were original articles, one a conference abstract; three were conducted in orthopaedic surgery and one in oral and maxillofacial surgery. All four included pilot RCTs, with an invasive surgical placebo intervention, randomising 9-49 participants in 1 or 2 centres. They explored the acceptability of recruitment and the invasive placebo intervention to patients and trial personnel, and whether blinding was possible. One study examined the characteristics of the proposed invasive placebo intervention using in-depth interviews. CONCLUSION: Published studies reporting feasibility/pilot work undertaken to inform main placebo surgical trials are scarce. In view of the difficulties of undertaking placebo surgical trials, it is recommended that pilot/feasibility studies are conducted, and more are reported to share key findings and optimise the design of main RCTs. PROSPERO REGISTRATION NUMBER: CRD42021287371.

Subtypes of early childhood caries predict future caries experience.

OBJECTIVES: To test whether postulated subtypes of early childhood caries (ECC) are predictive of subsequent caries experience in a population-based cohort of Swedish children. METHODS: The study included children aged between 3 and 5 years at study entry with dental records available for at least 5 years of follow-up. Dental record data were retrieved from the Swedish Quality Registry for Caries and Periodontal disease (SKaPa) for the initial and follow-up visits. Participants who had ECC at study entry were assigned to one of five ECC subtypes (termed classes 1-5) using latent class modelling of tooth surface-level caries experience. Subsequent experience of caries was assessed using the decayed, missing and filled surfaces indices (dmfs/DMFS) at follow-up visits, and compared between ECC subtypes using logistic and negative binomial regression modelling. RESULTS: The study included 128 355 children who had 3 or more dental visits spanning at least 5 years post-baseline. Of these children, 31 919 had caries at the initial visit. Baseline ECC subtype was associated with differences in subsequent disease experience. As an example, 83% of children who had a severe form of ECC at age 5 went on to have caries in the permanent dentition by the end of the study, compared to 51% of children who were caries-free at age 5 (adjusted odds ratio of 4.9 for new disease at their third follow-up). CONCLUSIONS: ECC subtypes assigned at a baseline visit are associated with differences in subsequent caries experience in both primary and permanent teeth. This suggests that the development and future validation of an ECC classification can be used in addition to current prediction tools to help identify children at high risk of developing new caries lesions throughout childhood and adolescence.

Metabolic disorders and the risk of head and neck cancer: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer internationally. Established risk factors include smoking, alcohol and presence of human papillomavirus (HPV). The incidence rate of new disease continues to rise, despite falls in alcohol consumption and a reduction in smoking, the rising rates are unlikely to be solely attributed to HPV status alone. Obesity and its associated conditions such as type 2 diabetes (T2D) are implicated in the risk and progression of a variety of cancers, but there is paucity of evidence regarding its role in HNSCC. METHODS AND ANALYSIS: A systematic review of cohort studies, reporting a risk of incident HNSCC, will be included. A systematic search strategy has been developed, multiple databases will be searched from January 1966 to November 2021, including Cochrane Library, OVID SP versions of Medline and EMBASE. The primary outcome will be incident HNSCC based on exposures of T2D, obesity, dyslipidaemia and hypertension as defined by the WHO. A combined risk effect across studies will be calculated using meta-analysis, although depending on the heterogeneity in study design, exposure and outcome reporting this may not be possible. ETHICS AND DISSEMINATION: No ethical approval is required for this systematic review. The review will be published in a relevant peer-review journal and findings will be presented at scientific meetings in both poster and oral presentation form. PROSPERO REGISTRATION NUMBER DETAILS: This study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) with study registration number CRD42021250520. This protocol has been developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance statement.

Protocol for the systematic review of the reporting of transoral robotic surgery.

INTRODUCTION: Transoral robotic surgery (TORS) has been adopted in some parts of the world as an innovative approach to the resection of oropharyngeal tumours. The development, details and outcomes of early-to-later phase evaluation of this technique and the quality of evidence to support its adoption into practice have hitherto not been summarised. The aim of this review is to identify and summarise the early and later phase studies of, and evidence for, TORS and to understand how early phase studies report intervention development, governance procedures and selection and reporting of outcomes to optimise methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice. The protocol has been written in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. METHODS AND ANALYSIS: Electronic searches in OVID SP versions of Medline and EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from the start of indexing to 30 April 2017 will identify studies reporting TORS. At least two independent researchers will identify studies for inclusion. Two researchers will extract data from each paper. Studies will be categorised into IDEAL stages of study design from 'pre-IDEAL' to randomised controlled trials (stage 3). Data will be collected about the (1) novel intervention and criteria for modification, (2) governance arrangements and patient information provision, (3) outcome domains selected and reported and (4) quality of study design, conduct and reporting. Descriptive statistics and a narrative synthesis will be presented. ETHICS AND DISSEMINATION: The results of this systematic review will be presented at relevant conferences. The methods will be used to inform future reviews exploring other novel surgical innovations. The findings will be published in a peer-reviewed journal. This study does not require ethical approval.