Decline in effectiveness of antenatal corticosteroids with time to birth : real or artefact?

The effectiveness of antenatal corticosteroids to prevent neonatal lung disease in women at risk of preterm birth was established by systematic reviews. In addition, subgroup analyses suggested that treatment was most effective in babies born one to seven days after administration. This belief led to widespread use of repeated courses of corticosteroids in women who did not deliver within a week or two of initial treatment. However, the notion that effectiveness declines after seven days may be incorrect, as the analyses that it is based on are unreliable. Here, we discuss the methodological problems of these analyses and their relevance to current randomised controlled trials of repeated versus single courses

Adopting national vegetation guidelines and the National Vegetation Information System (NVIS) framework in the Northern Territory

Guidelines and core attributes for site-based vegetation surveying and mapping developed for the Northern Territory, are relevant to botanical research, forestry typing, rangeland monitoring and reporting on the extent and condition of native and non-native vegetated landscapes. These initiatives are consistent with national vegetation guidelines and the National Vegetation Information System (NVIS) framework. This paper provides a synopsis of vegetation site data collection, classification and mapping in the Northern Territory, and discusses the benefits of consistency between the guidelines, core attributes and the NVIS framework; both of which has an emphasis on the NVIS hierarchical classification system for describing structural and floristic attributes of vegetation. The long-term aim of the NVIS framework is that national attributes are adopted at regional levels to enable comparability of vegetation information within survey and jurisdictional boundaries in the Northern Territory and across Australia. The guidelines and core attributes are incorporated in current and future vegetation survey and mapping programs in the Northern Territory

When to keep it simple - adaptive designs are not always useful.

BACKGROUND: Adaptive designs are a wide class of methods focused on improving the power, efficiency and participant benefit of clinical trials. They do this through allowing information gathered during the trial to be used to make changes in a statistically robust manner - the changes could include which treatment arms patients are enrolled to (e.g. dropping non-promising treatment arms), the allocation ratios, the target sample size or the enrolment criteria of the trial. Generally, we are enthusiastic about adaptive designs and advocate their use in many clinical situations. However, they are not always advantageous. In some situations, they provide little efficiency advantage or are even detrimental to the quality of information provided by the trial. In our experience, factors that reduce the efficiency of adaptive designs are routinely downplayed or ignored in methodological papers, which may lead researchers into believing they are more beneficial than they actually are. MAIN TEXT: In this paper, we discuss situations where adaptive designs may not be as useful, including situations when the outcomes take a long time to observe, when dropping arms early may cause issues and when increased practical complexity eliminates theoretical efficiency gains. CONCLUSION: Adaptive designs often provide notable efficiency benefits. However, it is important for investigators to be aware that they do not always provide an advantage. There should always be careful consideration of the potential benefits and disadvantages of an adaptive design

Evaluation of the effects of an offer of a monetary incentive on the rate of questionnaire return during follow-up of a clinical trial: a randomised study within a trial

BACKGROUND: A systematic review on the use of incentives to promote questionnaire return in clinical trials suggest they are effective, but not all studies have sufficient funds to use them. Promising an incentive once data are returned can reduce the cost-burden of this approach, with possible further cost-savings if the offer were restricted to reminder letters only. This study aimed to evaluate the effect of promising a monetary incentive at first mailout versus a promise on reminder letters only. METHODS: This was a randomised Study Within A Trial (SWAT) nested within BUMPES, a multicentre randomised controlled trial of maternal position in the late stage of labour in women with an epidural. The follow-up questionnaire asked for information on the women's health, wellbeing and health service use one year following the birth of their baby. Women who consented to be contacted were randomised to a promise of a monetary incentive at first mailout or a promise on reminder letters only. Women were given an option of completing the questionnaire on paper or on online. The incentive was posted out on receipt of a completed questionnaire. The primary outcome was the overall return rate, and secondary outcomes were the return rate without any chasing from the study office, and the total cost of the vouchers. RESULTS: A total of 1,029 women were randomised, 508 to the first mailout group and 518 to the reminder group. There was no evidence to suggest a difference between groups in the overall return rate (adjusted RR 1.03 (95 % CI 0.96 to 1.11), however the proportion returned without chasing was higher in the first mailout group (adjusted RR 1.22, 95 % CI 1.07 to 1.39). The total cost of the vouchers per participant was higher in the first mailout group (mean difference £4.56, 95 % CI £4.02 to £5.11). CONCLUSIONS: Offering a monetary incentive when a reminder is required could be cost-effective depending on the sample size of the study and the resources available to administer the reminder letters. TRIAL REGISTRATION: The BUMPES Trial is registered with Current Controlled Trials: ISRCTN35706297 , 26(th) August 2009

Optimal fetal growth – a misconception?

Alterations in fetal growth trajectory, either in terms of individual organs or the fetal body, constitute part of a suite of adaptive responses that the fetus can make to a developmental challenge such as inadequate nutrition. Nonetheless, despite substantial changes in nutrition in many countries over recent centuries, mean birthweight has changed relatively little. Low birthweight is recognised as a risk factor for later noncommunicable disease, although the developmental origins of such risk are graded across the full range of fetal growth and birthweight. Many parental and environmental factors, some biological, some cultural, can influence fetal growth, and these should not be viewed as abnormal. We argue that the suggestion of establishing a universal standard for optimal fetal growth ignores the breadth of these normal fetal responses. It may influence practice adversely, through incorrect estimation of gestational age and unnecessary elective deliveries. It raises ethical as well as practical issues

Doing trials within trials: a qualitative study of stakeholder views on barriers and facilitators to the routine adoption of methodology research in clinical trials

Abstract Background Randomised controlled trials are the cornerstone of evidence-based health care, yet many trials struggle with recruitment and retention. All too often the methodologies employed to address these problems are not evidence-based, as rigorous methodological research on these issues is rare. The current research sought to identify barriers to the routine implementation of methodology research around recruitment and retention. Methods All registered UK clinical trials unit directors were sent a short questionnaire and invited to interview. Representatives of funding bodies and other stakeholders were also approached. Interviews were recorded and the content analysed. Results Data were grouped into four themes: acceptance of the need for methodological research; trial funding and development; trial processes; and organisational factors. The need to improve the evidence base for trials methodology is well established, but numerous barriers to implementation were perceived. Conclusions The knowledge and expertise required to routinely implement methodology research exists within the current research structures, and there are clear opportunities to develop the evidence base. However, for this to be achieved there is also a need for clear strategic coordination within the sector and promotion of the necessary resources

Vaginal microbicides for preventing mother-to-child transmission of HIV infection - no evidence of an effect or evidence of no effect?

Background. Vaginal disinfection is a simple, potentially effective strategy for reducing mother-to-child transmission (MTCT) of HIV that can be implemented in combination with antiretroviraltherapy or even in the absence of prenatal HfV testing. We systematically reviewed currently available randomised controlled trials to estimate the benefits and risks of this intervention.Methods. We conducted an exhaustive search for published and. unpublished trials assessing the effect of vaginal microbicides on MTCT of HIV, extracted data in triplicate, assesed statistical heterogeneity between trial results, and conducted meta-analysis using Mantel-Haenszel's method.Findings. Five potentially eligible studies were iclentified, two of which met eligibility criteria. Pooling the data shows that the effect of vaginal disinfection on the risk of MTCT of HIV relative risk (RR) 0.94, 95% confidence interval (CI) 0.71 1.25) and neonatal death (RR 1.36, 95% CI 0.32- 5.79) is uncertain. The combined data (two trials with 708 participants) had less than 80% power to detect a 30% reduction in the risk of MTCT of HIV from a baseline risk of 30%, and are compatible with a widerange of effects; from a 29% reduction to a 25% increase in risk. One trial with 108 participants, showed no evidence that adverse effects increased inmothers (RR L02, 95% CI 0.87- 1.20) and found that adverse effects decreased in neonates (RR 0.45, 95% CI 0.32 - 0.64).Interpretation. At present there is insufficient and inconclusive evidence on the effect of vaginal microbicides on the risk of MTCT of HIV. This review identifies the need and provides the impetus for an adequately powered randomised controlled trial to assess the effect(s) of this inexpensive intervention