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Rationale, aims and objectives Open-label extension (OLE) studies following blinded randomized controlled trials (RCTs) of pharmaceuticals are increasingly being carried out but do not conform to regulatory standards and questions surround the validity of their evidence. OLE studies are usually discussed as a homogenous group, yet substantial differences in study design still meet the definition of an OLE. We describe published papers reporting OLE studies focussing on stated objectives, design, conduct and reporting. Method A search of Embase and Medline databases for 1996 to July 2008 revealed 268 papers reporting OLE studies that met our eligibility criteria. A random sample of 50 was selected for detailed review. Results Over 80% of the studies had efficacy stated as an objective. The most common methods of allocation at the start of the OLE were for all RCT participants to switch to one active treatment or for only participants on the new drug to continue, but in three studies all participants were re-randomized at the start of the OLE. Eligibility criteria and other selection factors resulted in on average of 74% of participants in the preceding RCT(s) enrolling in the OLE and only 57% completed it. Conclusions Published OLE studies do not form a homogenous group with respect to design or retention of participants, and thus the validity of evidence from an OLE should be judged on an individual basis. The term 'open label' suggests bias through lack of blinding, but slippage in relation to the sample randomized in the preceding RCT may be the more important threat to validity. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) is one of the most common types of cancer in European countries and associated with a high mortality rate. A 16% relative risk reduction (RRR) of mortality was found in a meta-analysis based on four randomized controlled trials (RCT) on CRC screening. The aim of this paper was to scrutinize these trials for potential biases and assess their influence on the screening trials. Methods The four RCTs were reviewed based on the principles of 'Critical Appraisal of the Medical Literature'. Principal investigators of the four RCTs were contacted to clarify uncertainties in their study. Data were collected from The Danish Data Archives. Authors of the Cochrane review were contacted. Results Six biases were identified, of which five favour screening. Three of the biases identified were specific to CRC screening: type of diagnostic method, place of surgery and diagnostic delay. Conclusion The 16% RRR in CRC mortality found in the updated Cochrane review's meta-analysis is overestimated. [ABSTRACT FROM AUTHOR]