The effects of biliverdin on pressure-induced unfolding of apomyoglobin: The specific role of Zn ions.

Apomyoglobin (apoMb), a model protein in biochemistry, exhibits a strong propensity to bind various ligands, which makes it a good candidate as a carrier of bioactive hydrophobic drugs. The stability of its hydrophobic pocket determines its potential as a carrier of bioactive compounds. High pressure (HP) is a potent tool for studying protein stability, revealing the specific role of hydrophobic cavities in unfolding.

Additional consensus recommendations for conducting complex innovative trials of oncology agents: a post-pandemic perspective.

In our 2020 consensus paper, we devised ten recommendations for conducting Complex Innovative Design (CID) trials to evaluate cancer drugs. Within weeks of its publication, the UK was hit by the first wave of the SARS-CoV-2 pandemic. Large CID trials were prioritised to compare the efficacy of new and repurposed COVID-19 treatments and inform regulatory decisions.

Effective delivery of Complex Innovative Design (CID) cancer trials-A consensus statement.

The traditional cancer drug development pathway is increasingly being superseded by trials that address multiple clinical questions. These are collectively termed Complex Innovative Design (CID) trials. CID trials not only assess the safety and toxicity of novel anticancer medicines but also their efficacy in biomarker-selected patients, specific cancer cohorts or in combination with other agents.

Comparing access to orphan medicinal products in Europe.

Objectives: The primary objective of this study was to compare the availability and access of orphan medicinal products (OMPs) in the devolved nations in the United Kingdom (UK), France, Germany, Italy and Spain. Availability is defined as the possibility to prescribe OMPs. Access refers to their full or partial reimbursement by the public health service.

Late translational research: putting forward a new model for developing new anti-cancer treatments that addresses the needs of patients and society.

Bringing therapeutic innovation and the latest science to routine patient care, while safeguarding principles of affordability and equality, is a challenging mission in the current complex multi-stakeholder environment. Precision oncology and new approaches to clinical trials (methods and clinical setting) have dramatically changed clinical research and the clinical development of new treatments. Improved understanding of molecular biology and immunology paves the way for innovative pharmacological approaches.

A mathematical framework to quantify the masking effect associated with the confidence intervals of measures of disproportionality.

Background: The lower bound of the 95% confidence interval of measures of disproportionality (Lower95CI) is widely used in signal detection. Masking is a statistical issue by which true signals of disproportionate reporting are hidden by the presence of other medicines. The primary objective of our study is to develop and validate a mathematical framework for assessing the masking effect of Lower95CI.

Integrating health technology assessment requirements in the clinical development of medicines: the experience from NICE scientific advice.

Purpose: The primary objective of the study was to analyse the proposed clinical development and economic evaluation plans for investigational medicinal products for which pharmaceutical companies have sought health technology assessment (HTA) scientific advice (SA).

Methods: We have selected and analysed all the scientific advice procedures undertaken by National Institute for Health and Care Excellence (NICE) SA between 1 January 2009 and 3 December 2015 for investigational medicinal products. We have mapped the questions asked by the companies and the areas of advice highlighted in the advice reports to the sections of the NICE methods guide to the technology appraisals (2013).

A conceptual approach to the masking effect of measures of disproportionality.

Background: Masking is a statistical issue by which true signals of disproportionate reporting are hidden by the presence of other products in the database. Masking is currently not perfectly understood. There is no algorithm to identify the potential masking drugs to remove them for subsequent analyses of disproportionality.

Assessing the extent and impact of the masking effect of disproportionality analyses on two spontaneous reporting systems databases.

Background: Masking is a statistical issue by which signals are hidden by the presence of other medicines in the database. In the absence algorithm, the impact of the masking effect has not been fully investigated.

Objective: Our study is aimed at assessing the extent and the impact of the masking effect on two large spontaneous reporting databases.

A case of therapy-related myeloid neoplasm in a patient with Crohn's disease treated with azathioprine.

Acute leukaemia (AL) has been observed in association with Crohn's disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia.

Validation of statistical signal detection procedures in eudravigilance post-authorization data: a retrospective evaluation of the potential for earlier signalling.

Background: Screening large databases of spontaneous case reports of possible adverse drug reactions (ADRs) is an established method of identifying hitherto unknown adverse effects of medicinal products; however, there is a lack of consensus concerning the value of formal statistical screening procedures in guiding such a process. This study was performed to clarify the nature of any added benefits and additional effort required when established pharmacovigilance techniques are supplemented with statistical screening.

Objective: To evaluate whether statistical signal detection in spontaneous reporting data can lead to earlier detection of drug safety problems and to assess the additional regulatory work entailed.

Modelling the time to onset of adverse reactions with parametric survival distributions: a potential approach to signal detection and evaluation.

Background: It has been postulated that the time to onset of adverse drug reactions is connected to the underlying pharmacological (or toxic) mechanism of adverse drug reactions whether the reaction is time dependent or not.

Objective: We have conducted a preliminary study using the parametric modelling of the time to onset of adverse reactions as an approach to signal detection on spontaneous reporting system databases.

Methods: We performed a parametric modelling of the reported time to onset of adverse drug reactions for which the underlying toxic mechanism is characterized.