[How does a new medicine reach the patient?] / Hoe bereikt een nieuw geneesmiddel de patiënt?

The Medicines Evaluation Board (MEB) grants market authorisation for medicinal products in the Netherlands. The European Medicines Agency (EMA) coordinates the evaluation and safeguarding of medicinal products in the European Union. The core task of the MEB is to evaluate the quality of every medicinal product for which marketing authorisation is applied for by the manufacturer, and to assess the risk - efficacy balance of the product concerned. There are three different procedures that a manufacturer can follow: (a) the national procedure; (b) the decentralised procedure or mutual recognition procedure; (c) the centralised procedure. After marketing authorisation has been granted, the MEB ensures pharmacovigilance in cooperation with partners such as the Netherlands Pharmacovigilance Centre (Lareb). The MEB determines the text of the package leaflet, the packaging and the Summary of Product Characteristics (SmPC). The MEB checks the warnings that are sent out by manufacturers if important new information about a medicinal product becomes available.

Reporting bias in imaging: higher accuracy is linked to faster publication.

OBJECTIVES: The objective of this study was to evaluate whether higher reported accuracy estimates are associated with shorter time to publication among imaging diagnostic accuracy studies. METHODS: We included primary imaging diagnostic accuracy studies, included in meta-analyses from systematic reviews published in 2015. For each primary study, we extracted accuracy estimates, participant recruitment periods and publication dates. Our primary outcome was the association between Youden's index (sensitivity + specificity - 1, a single measure of diagnostic accuracy) and time to publication. RESULTS: We included 55 systematic reviews and 781 primary studies. Study completion dates were missing for 238 (30%) studies. The median time from completion to publication in the remaining 543 studies was 20 months (IQR 14-29). Youden's index was negatively correlated with time from completion to publication (rho = -0.11, p = 0.009). This association remained significant in multivariable Cox regression analyses after adjusting for seven study characteristics: hazard ratio of publication was 1.09 (95% CI 1.03-1.16, p = 0.004) per unit increase for logit-transformed estimates of Youden's index. When dichotomizing Youden's index by a median split, time from completion to publication was 20 months (IQR 13-33) for studies with a Youden's index below the median, and 19 months (14-27) for studies with a Youden's index above the median (p = 0.104). CONCLUSION: Imaging diagnostic accuracy studies with higher accuracy estimates were weakly associated with a shorter time to publication. KEY POINTS: • Higher accuracy estimates are weakly associated with shorter time to publication. • Lag in time to publication remained significant in multivariate Cox regression analyses. • No correlation between accuracy and time from submission to publication was identified.

Endorsement of ICMJE's Clinical Trial Registration Policy: a survey among journal editors.

BACKGROUND: Since 2005, the International Committee of Medical Journal Editors (ICMJE) requires researchers to prospectively register their clinical trials in a publicly accessible trial registry. The Consolidated Standards of Reporting Trials (CONSORT) statement has supported this policy since 2010. We aimed to evaluate to what extent biomedical journals have incorporated ICMJE's clinical trial registration policy into their editorial and peer review process. METHODS: We searched journals' instructions to authors and performed an internet survey among all journals publishing reports of randomised controlled trials that follow ICMJE's Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals (n = 695), and/or that endorse the CONSORT statement (n = 404) accessed in January 2011. Survey invitations were sent to the email addresses of the editorial offices and/or editors-in-chief of included journals in June 2011. RESULTS: For 757 ICMJE and/or CONSORT journals, we identified that they published RCT reports. We could assess the instructions to authors of 747 of these; 384 (51%) included a statement of requiring trial registration, and 33 (4%) recommended this. We invited 692 editorial offices for our survey; 253 (37%) responded, of which 50% indicated that trial registration was required; 18% cross-checked submitted papers against registered records to identify discrepancies; 67% would consider retrospectively registered studies for publication. Survey responses and specifications in instructions to authors were often discordant. CONCLUSION: At least half of the responding journals did not adhere to ICMJE's trial registration policy. Registration should be further promoted among authors, editors and peer reviewers.

Podoconiosis, a neglected tropical disease.

Podoconiosis or 'endemic non-filarial elephantiasis' is a tropical disease caused by exposure of bare feet to irritant alkaline clay soils. This causes an asymmetrical swelling of the feet and lower limbs due to lymphoedema. Podoconiosis has a curable pre-elephantiasic phase. However, once elephantiasis is established, podoconiosis persists and may cause lifelong disability. The disease is associated with living in low-income countries in the tropics in regions with high altitude and high seasonal rainfall. It is found in areas of tropical Africa, Central and South America and north-west India. In endemic areas, podoconiosis is a considerable public health problem. Social stigmatisation of patients is widespread and economic losses are enormous since it mainly affects the most productive people, sustaining the disease-poverty-disease cycle. Podoconiosis is unique in being an entirely preventable, non-communicable tropical disease with the potential for eradication. Low-cost preventive measures are a simple but effective solution. However, so far it has received little attention from health care policy makers and, until recently, research into the disease has been scarce and the pathogenesis and genetic basis are partly unclear. A better understanding of these aspects may lead to new prevention and treatment opportunities. In the past few years, several projects fighting podoconiosis have been started by non-governmental organisations. In February 2011, the World Health Organisation designated podoconiosis as one of the 20 neglected tropical diseases, marking an important step in the fight against the disease.

Systematic reviews and meta-analyses of preclinical studies: publication bias in laboratory animal experiments.

In 2006, Peters et al. identified 86 systematic reviews (SRs) of laboratory animal experiments (LAEs). They found 46 LAE meta-analyses (MAs), often of poor quality. Six of these 46 MAs tried to assess publication bias. Publication bias is the phenomenon of an experiment's results determining its likelihood of publication, often over-representing positive findings. As such, publication bias is the Achilles heel of any SR. Since researchers increasingly become aware of the fact that SRs directly support the 'three Rs', we expect the number of SRs of LAEs will sharply increase. Therefore, it is useful to see how publication bias is dealt with. Our objective was to identify all SRs and MAs of LAEs where the purpose was to inform human health published between July 2005 and 2010 with special attention to MAs' quality features and publication bias. We systematically searched Medline, Embase, Toxline and ScienceDirect from July 2005 to 2010, updating Peters' review. LAEs not directly informing human health or concerning fundamental biology were excluded. We found 2780 references of which 163 met the inclusion criteria: 158 SRs, of which 30 performed an MA, and five MAs without an SR. The number of SRs roughly doubled every three years since 1997. The number of MAs roughly doubled every five years since 1999. Compared with before July 2005, more MAs were preceded by SR and reported on (quality) features of included studies and heterogeneity. A statistically significant proportion of MAs considered publication bias (26/35) and tried to formally assess it (21/35).