BackgroundThe increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention.Methodology/Principal FindingsWe review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40–62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies.ConclusionsRecent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research. Health Technol Assess 2000;4(3). Health Technology Assessment is indexed in Index Medicus/MEDLINE and Excerpta Medica/ EMBASE. Copies of the Executive Summaries are available from the NCCHTA web site (see overleaf). NHS R&D HTA Programme T he overall aim of the NHS R&D Health Technology Assessment (HTA) programme is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and work in the NHS. Research is undertaken in those areas where the evidence will lead to the greatest benefits to patients, either through improved patient outcomes or the most efficient use of NHS resources. The Standing Group on Health Technology advises on national priorities for health technology assessment. Six advisory panels assist the Standing Group in identifying and prioritising projects. These priorities are then considered by the HTA Commissioning Board supported by the National Coordinating Centre for HTA (NCCHTA). This report is one of a series covering acute care, diagnostics and imaging, methodology, pharmaceuticals, population screening, and primary and community care. It was identified as a priority by the Population Screening Panel and funded as project number 93/33/03. The views expressed in this publication are those of the authors and not necessarily those of the Standing Group, the Commissioning Board, the Panel members or the Department of Health. The editors wish to emphasise that funding and publication of this research by the NHS should not be taken as implicit support for the recommendations for policy contained herein. In particular, policy options in the area of screening will be considered by the National Screening Committee. This Committee, chaired by the Chief Medical Officer, will take into account the views expressed here, further available evidence and other relevant considerations. Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. Criteria for inclusion in the HTA monograph series Reports are published in the HTA monograph series if (1) they have resulted from work either prioritised by the Standing Group on Health Technology, or otherwise commissioned for the HTA Programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Objectives: Assess the degree to which research project findings were published and explore factors that influenced publication. Methods: Questionnaire to project leaders. Classification of publications and findings. Chi-squared; univariate and multivariate Cox regression analyses. Results: Forty percent of projects published in peer-reviewed journal; highly statistically significant relationships between publication in peer-reviewed journals and (1) projects in Responsive/Fellowships streams (p = .045); and (2) projects awarded >£22,713 (p = .02); influence of study findings not statistically significant. Conclusions: Funders should consider the significant number of studies that did not result in publication and the higher rate of publication in peer-reviewed journals from some programs.

Aim-To compare the costs and cost eVectiveness of universal and targeted screening for the haemoglobinopathies; to compare the cost of two laboratory methods; and to estimate the cost eVectiveness of programmes at diVerent levels of prevalence and mix of haemoglobinopathy traits. Methods-A retrospective review of laboratory and follow up records to establish workload and costs, and estimation of costs in a range of circumstances was made in a haematology department and sickle cell and thalassaemia centre, providing antenatal and neonatal screening programmes in Inner London. The costs for 47 948 babies, screened during 1994, of whom 25 had clinically significant haemoglobinopathies and 704 had haemoglobinopathy traits, were retrospectively assessed. Results-The average cost per baby tested (isoelectric focusing and high power liquid chromatography) was £3.51/£3.83 respectively; the cost per case of sickle cell disease identified (IEF/HPLC) was £6738/ £7355; the cost per trait identified (IEF/ HPLC) was £234/£255; the cost per extra case of SCD and trait identified by universal programme varied. Conclusions-IEF and HPLC are very similar in terms of average cost per test. At 16 traits/1000 and 0.5 SCD/1000 there was no significant identification cost difference between universal and targeted programmes. Below this prevalence, a targeted programme is cheaper but likely to miss cases of SCD. If targeted programmes were 90-99% eVective, universal programmes would cease to be good value except at very high prevalence. Greater use of prenatal diagnosis, resulting in termination, and therefore fewer aVected births, reduces the cost eVectiveness of universal screening. Screening services should aim to cover a screened population which will generate a workload over 25 000 births a year, and preferably over 40 000. (Arch Dis Child Fetal Neonatal Ed 1998;79:F161-F167) Keywords: screening; haemoglobinopathies; cost eVectiveness; workloadThe costs of screening and diagnosis of haemoglobinopathies in newborns reported here are for a region where the prevalence is relatively high, but the model presented allows costs to be quantified for both targeted and universal screening in areas of diVering prevalence. It is intended that this analysis will inform commissioning decisions on appropriate levels of screening for diVerent health districts and supplement existing guidance. 1These decisions should depend on the proportions of the population who carry haemoglobinopathy traits, which are related to the concentration of specific ethnic populations (African, Caribbean, Mediterranean, Asian, and those from the Far East and Middle East) and costs of selection, screening, and follow up.