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Payers in European countries request studies with high levels of evidence for decision making also for rare diseases like haemophilia B ( HB). The objective of the study was to determine the status quo of current studies in HB regarding the overall level of evidence generated. The methods used for performing the study were systematic literature research in EMBASE and MEDLINE, search terms ' HB' and 'factor IX' ( FIX). The inclusion criteria were journal articles ( JA), conference abstracts ( CA), English language, published between January 2009 and March 2013, studies only; screening of titles, abstracts, full texts subsequently. ClinicalTrials.gov search: unpublished registered trials ( RT) concerning HB or FIX. The analysis was performed on research topic, sponsor, recruitment status and study design. Screening of 1639 hits yielded 31 JA describing 35 studies, and 62 CA. FIX was subject of 21 studies (60.0%) and 29 CA (46.8%). Seven studies focused on various aspects of HB, six on haemophilia studies with separate HB data. Screening of 173 hits from ClinicalTrials.gov yielded 42 RT. Overall, 32 RT (76.2%) related to FIX. Measurement of health-related quality of life ( HRQoL) was identified in none of these studies, four CA (6.5%), four RT (9.5%). Randomized study design was found in one study (2.9%), four RT (9.5%). Three studies (8.6%) and seven RT (16.7%) were prospective, observational and comparative. The majority of published clinical studies do not meet payers' expectations for evidence. Therefore, clinical investigation concepts addressing randomization, outcomes research including HRQoL and comparison of therapy options should be discussed. Refined statistical methods and exploitation of complementary real-life data sources may fill current evidence gaps concerning rare diseases. [ABSTRACT FROM AUTHOR]

A candidate preparation of the fully human anti-tumour necrosis factor (TNF) monoclonal antibody golimumab was formulated and lyophilised at the Medicines and Healthcare products Regulatory Agency (MHRA) prior to evaluation in a collaborative study for its suitability to serve as a World Health Organization (WHO) International Standard (IS)/European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for the potency assay of golimumab. Fifteen laboratories tested the preparations using different cell-based TNF-α neutralisation assays. Among them, seven laboratories also performed binding assays and one additional laboratory assessed antibody-dependent cellular cytotoxicity. The results of this study and the stability data generated by the MHRA indicated that the candidate preparation, coded 22/116, was suitable to serve as an IS for golimumab based on the data obtained for biological activity. This candidate standard was established in 2024 as the first IS for golimumab with an assigned potency of 500 IU per ampoule for TNF neutralising activity. In the same study, the suitability of this preparation of golimumab to serve as the Ph. Eur. BRP for the golimumab potency assay, as described in the Ph. Eur. monographs on Golimumab injection (3187) and Golimumab concentrated solution (3103) , was also evaluated. The corresponding analysis, based on the measurement of the inhibitory action of golimumab on the cytotoxic activity of TNF-α, was performed using data from a subset of six laboratories - whose experts were members of the P4 Biologicals Working Party (responsible for the elaboration of the golimumab monographs) - using the TNF-α-sensitive mouse fibrosarcoma cell lines WEHI-164 or WEHI-164 clone 13 variant (WEHI-13VAR, ATCC CRL-2148) in example bioassay procedure(s) described in Ph. Eur. monographs 3103 and 3187 , or running the same cell-based assays using in-house procedures. The results obtained were compared with those obtained from different cell-based neutralisation assays that were used by other laboratories in the context of establishing the 1st WHO IS for golimumab. Based on the analyses, preparation 22/116 was adopted by the Ph. Eur. Commission in June 2024 as Golimumab BRP batch 1 with an assigned potency of 500 IU of TNF neutralising activity per ampoule., (© Council of Europe 2024.)

Humans spend a considerable portion of their lives engaged in 'stimulus-independent thoughts' (SIT), or mental activity that occurs independently of input from the immediate external environment. Although such SITs are, by definition, different from thoughts that are driven by stimuli in one's external environment (i.e. stimulus-dependent thoughts; SDTs), at times, the phenomenology of these two types of thought appears to be deceptively similar. But how similar are they? We address this question by comparing the content of two types of SIT (dreaming and waking SITs) with the content of SDTs. In this 7 day, smartphone-based experience-sampling procedure, participants were intermittently probed during the day and night to indicate whether their current thoughts were stimulus dependent or stimulus independent. They then responded to content-based items indexing the qualitative aspects of their experience (e.g. My thoughts were jumping from topic to topic). Results indicate substantial distinctiveness between these three types of thought: significant differences between at least two of the three mental states were found across every measured variable. Implications are discussed. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.