The stepped wedge trial design: a systematic review

BACKGROUND: Stepped wedge randomised trial designs involve sequential roll-out of an intervention to participants (individuals or clusters) over a number of time periods. By the end of the study, all participants will have received the intervention, although the order in which participants receive the intervention is determined at random. The design is particularly relevant where it is predicted that the intervention will do more good than harm (making a parallel design, in which certain participants do not receive the intervention unethical) and/or where, for logistical, practical or financial reasons, it is impossible to deliver the intervention simultaneously to all participants. Stepped wedge designs offer a number of opportunities for data analysis, particularly for modelling the effect of time on the effectiveness of an intervention. This paper presents a review of 12 studies (or protocols) that use (or plan to use) a stepped wedge design. One aim of the review is to highlight the potential for the stepped wedge design, given its infrequent use to date. METHODS: Comprehensive literature review of studies or protocols using a stepped wedge design. Data were extracted from the studies in three categories for subsequent consideration: study information (epidemiology, intervention, number of participants), reasons for using a stepped wedge design and methods of data analysis. RESULTS: The 12 studies included in this review describe evaluations of a wide range of interventions, across different diseases in different settings. However the stepped wedge design appears to have found a niche for evaluating interventions in developing countries, specifically those concerned with HIV. There were few consistent motivations for employing a stepped wedge design or methods of data analysis across studies. The methodological descriptions of stepped wedge studies, including methods of randomisation, sample size calculations and methods of analysis, are not always complete. CONCLUSION: While the stepped wedge design offers a number of opportunities for use in future evaluations, a more consistent approach to reporting and data analysis is required

The spectrum of hypoxaemia in children admitted to hospital in The Gambia, West Africa.

OBJECTIVE: Hypoxia predicts mortality in children with acute lower respiratory infections (ALRIs). We investigated the prevalence and predictive value of hypoxia in ALRI and other acute infectious diseases. METHODS: We studied the spectrum of hypoxaemia in 4,047 children admitted to a tertiary hospital in The Gambia. Oxygen saturation was measured shortly after admission. Severe hypoxaemia was defined as an oxygen saturation below 90%. RESULTS: 5.8% of all admissions had severe hypoxaemia. Prevalence of hypoxaemia varied between disease groups: it was 11.7% in ALRI cases, 16.5% in neonates; 2.9% in malaria cases overall but 6.5% in cerebral malaria patients; and 2.7% in children with meningitis. Hypoxaemia predicted a poor outcome; the odds ratio for death among paediatric admissions overall was 7.45 [95% confidence intervals (CI) 5.40-10.29]. Surprisingly, it was lowest for children with ALRI [OR 3.53 (95% CI 1.13-10.59)], and higher for those with malaria 9.90 [95% CI 4.39-22.35]. CONCLUSION: Hypoxaemia is common among Gambian children admitted to hospital and it is often associated with a poor outcome. A similar situation is likely in many other developing countries. Thus, equipment for measuring oxygen saturation, and facilities and equipment for effective oxygen delivery need to be made available in developing countries

Clinical trials of TB vaccines: Harmonization and cooperation

A new efficacious tuberculosis (TB) vaccine has the potential to dramatically assist control efforts for the global TB epidemic. Good progress has been made with the clinical development of new TB vaccine candidates with twelve being actively tested in clinical trials. However, there are challenges that would need to be addressed before a new vaccine is licensed for public use. The diversity of risk in populations would need to be factored into clinical development plans. Specific but feasible clinical endpoints need to be agreed upon. TB vaccines would need to be efficacious in both uninfected and infected populations. An achievable efficacy target needs to be set. Standardisation of trial outcomes and the development pipeline would need to be brought about. Alternative routes of administration should be thoroughly explored. There should be sufficient adequately prepared trial sites for doing TB vaccine assessments. Creative use of study designs should be used to expedite progress towards licensure but at the same time containing costs. There should be sufficient funding to support the TB vaccine development. These challenges can be met through commitment by role-players within the TB vaccine arena and with support by external stakeholders.http://www.journals.elsevier.com/tuberculosis/am2013ay201