Methodological bias in cluster randomised trials

Background: Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods: We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster trials with a sample of potentially biased trials. We also compared the effect sizes, in a funnel plot, between hip protector trials that used individual randomisation compared with those that used cluster randomisation. Results: There is a tendency for cluster trials, with evidence methodological biases, to also show an age imbalance between treatment groups. In a funnel plot we show that all cluster trials show a large positive effect of hip protectors whilst individually randomised trials show a range of positive and negative effects, suggesting that cluster trials may be producing a biased estimate of effect. Conclusion: Methodological biases in the design and execution of cluster randomised trials is frequent. Some of these biases associated with the use of cluster designs can be avoided through careful attention to the design of cluster trials. Firstly, if possible, individual allocation should be used. Secondly, if cluster allocation is required, then ideally participants should be identified before random allocation of the clusters. Third, if prior identification is not possible, then an independent recruiter should be used to recruit participants

Health care costs of women with symptomatic vertebral fractures

Background: An important aspect of the economics of fracture prevention is averted fracture costs. However, while vertebral fractures represent a significant burden to society, quantifying their cost is difficult for several reasons. In this paper, we examine the health care costs of symptomatic vertebral fractures occurring in women aged 50 years and above in the UK. Methods: We used a variety of data sources. The prevalence of pharmaceutical treatment for fracture prevention and number of general practitioner consultations, referrals, and hospital admissions associated with a diagnosis of vertebral fracture were identified from a case control study. For the unit cost of a general practitioner consultation, referral, and cost per inpatient day, we used 2002 data produced by the Personal Social Services Research Unit. Hospital Episode Statistics (HES) for 2001–2002 were used to estimate the median length of stay in hospital for women aged 50 years and above, and the Monthly Index of Medical Specialities (MIMS) was used to identify the costs of pharmaceutical treatments. Costs were discounted at 6%. Results: From these data, we estimated that for the year prior and post diagnosis the average additional health care costs for those diagnosed with vertebral fracture were £165, £134, and £2314 for general practitioner consultations, referrals, and hospital admissions, respectively (i.e., £2613). The cost of pharmaceutical treatments prescribed for fracture prevention in the year following diagnosis was £97. Discussion: Vertebral fractures are associated with significantly increased health care costs. These costs need to be set against the costs of fracture prevention

Boundary stabilization of extensible and unshearable marine risers with large in-plane deflection

© 2016 Elsevier LtdThis paper proposes a constructive design of boundary controllers for globally (practically) K8-exponential stabilization of extensible and unshearable marine risers with large in-plane deflection under sea loads. Linearization or Maclaurin expansion of the strain and cross section rotation are not required. The control design is based on the Lyapunov direct method. Well-posedness and stability of the closed-loop system are analyzed by two Lyapunov-type theorems developed for study of existence and uniqueness, and stability of nonlinear evolution systems in Hilbert space