Facilitating Activity and Self-management for people with Arthritic knee, hip or lower back pain (FASA): A cluster randomised controlled trial.

Background: Chronic musculoskeletal pain including osteoarthritis (OA) can significantly limit the functional independence of individuals. The spine and hip and knee are predominantly affected; management guidelines for each recommend exercise and education to support self-management.

Objectives: This study investigated the effectiveness of a generic exercise and self-management intervention for people over-50 with hip/knee OA and/or lower back pain compared to continued GP management.

How to design a dose-finding study using the continual reassessment method.

Introduction: The continual reassessment method (CRM) is a model-based design for phase I trials, which aims to find the maximum tolerated dose (MTD) of a new therapy. The CRM has been shown to be more accurate in targeting the MTD than traditional rule-based approaches such as the 3 + 3 design, which is used in most phase I trials. Furthermore, the CRM has been shown to assign more trial participants at or close to the MTD than the 3 + 3 design.

Adaptive designs in clinical trials: why use them, and how to run and report them.

Adaptive designs can make clinical trials more flexible by utilising results accumulating in the trial to modify the trial's course in accordance with pre-specified rules. Trials with an adaptive design are often more efficient, informative and ethical than trials with a traditional fixed design since they often make better use of resources such as time and money, and might require fewer participants. Adaptive designs can be applied across all phases of clinical research, from early-phase dose escalation to confirmatory trials.

A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol.

Background: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control.

The Prognostic Value of Patient-Reported Outcome Data in Patients With Colorectal Hepatic Metastases Who Underwent Surgery.

Introduction: Patient-reported outcomes (PROs) are critical to evaluate clinically effective treatments and evidence suggests that PROs might predict survival. The prognostic value of PROs in patients with isolated liver metastases from colorectal cancer (CRC) who undergo surgery is unclear. In this study we investigated whether baseline PROs are prognostic in this patient group.

Applying optimal model selection in principal stratification for causal inference.

Noncompliance to treatment allocation is a key source of complication for causal inference. Efficacy estimation is likely to be compounded by the presence of noncompliance in both treatment arms of clinical trials where the intention-to-treat estimate provides a biased estimator for the true causal estimate even under homogeneous treatment effects assumption. Principal stratification method has been developed to address such posttreatment complications.

Performance of statistical methods for analysing survival data in the presence of non-random compliance.

Noncompliance often complicates estimation of treatment efficacy from randomized trials. Under random noncompliance, per protocol analyses or even simple regression adjustments for noncompliance, could be adequate for causal inference, but special methods are needed when noncompliance is related to risk. For survival data, Robins and Tsiatis introduced the semi-parametric structural Causal Accelerated Life Model (CALM) which allows time-dependent departures from randomized treatment in either arm and relates each observed event time to a potential event time that would have been observed if the control treatment had been given throughout the trial.

The use of fixed appliances in the UK: a survey of specialist orthodontists.

Objective: To investigate the use of fixed appliances in the UK.

Design: Prospective postal questionnaire.

Setting: UK.