Conventional clinical trial design involves considerations of power, and sample size is typically chosen to achieve a desired power conditional on a specified treatment effect. In practice, there is considerable uncertainty about what the true underlying treatment effect may be, and so power does not give a good indication of the probability that the trial will demonstrate a positive outcome.Assurance is the unconditional probability that the trial will yield a 'positive outcome'. A positive outcome usually means a statistically significant result, according to some standard frequentist significance test. The assurance is then the prior expectation of the power, averaged over the prior distribution for the unknown true treatment effect.We argue that assurance is an important measure of the practical utility of a proposed trial, and indeed that it will often be appropriate to choose the size of the sample (and perhaps other aspects of the design) to achieve a desired assurance, rather than to achieve a desired power conditional on an assumed treatment effect. We extend the theory of assurance to two-sided testing and equivalence trials. We also show that assurance is straightforward to compute in some simple problems of normal, binary and gamma distributed data, and that the method is not restricted to simple conjugate prior distributions for parameters. Several illustrations are given.

SUMMARYThe objective of the CERTS Microgrid Test Bed project was to enhance the ease of integrating energy sources into a microgrid. The project accomplished this objective by developing and demonstrating three advanced techniques, collectively referred to as the CERTS Microgrid concept, that significantly reduce the level of custom field engineering needed to operate microgrids consisting of generating sources less than 100kW. The techniques comprising the CERTS Microgrid concept are: 1) a method for effecting automatic and seamless transitions between grid-connected and islanded modes of operation, islanding the microgrid's load from a disturbance, thereby maintaining a higher level of service, without impacting the integrity of the utility's electrical power grid; 2) an approach to electrical protection within a limited source microgrid that does not depend on high fault currents; and 3) a method for microgrid control that achieves voltage and frequency stability under islanded conditions without requiring high-speed communications between sources.These techniques were demonstrated at a full-scale test bed built near Columbus, Ohio and operated by American Electric Power. The testing fully confirmed earlier research that had been conducted initially through analytical simulations, then through laboratory emulations, and finally through factory acceptance testing of individual microgrid components. The islanding and resychronization method met all Institute of Electrical and Electronics Engineers Standard 1547 and power quality requirements. The electrical protection system was able to distinguish between normal and faulted operation. The controls were found to be robust under all conditions, including difficult motor starts and high impedance faults.The results from these tests are expected to lead to additional testing of enhancements to the basic techniques at the test bed to improve the business case for microgrid technologies, as well to field demonstrations involving microgrids that involve one or more of the CERTS Microgrid concepts. Future planned microgrid work involves unattended continuous operation of the microgrid for 30 to 60 days to determine how utility faults impact the operation of the microgrid and to gage the power quality and reliability improvements offered by microgrids.

BackgroundUlcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients’ quality of life. The burden for the NHS is substantial.ObjectivesTo evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities.Data sourcesPeer-reviewed publications, European Public Assessment Reports and manufacturers’ submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals.Review methodsA systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model.ResultsTen randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade®, Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira®, AbbVie) or golimumab (GOL) (Simponi®, MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32–52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8–32 and 32–52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8–32 weeks and GOL 50 mg at 32–52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32–52 weeks was significant. The greatest effects were associated with GOL (at 8–32 weeks) and ADA (at 32–52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained.LimitationsThe health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review.ConclusionsAdult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC.Study registrationThis study is registered as PROSPERO CRD42013006883.FundingThe National Institute for Health Research Health Technology Assessment programme.

STS HH and TM with medical support provided during office hours showed beneficial trends, particularly in reducing all-cause mortality for recently discharged patients with heart failure. Where 'usual' care is less good, the impact of RM is likely to be greater.