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Purpose: Over the last few years, the share of public spending for orphan drugs (ODs) has increased in several western countries, raising concern on the exemptions granted to this sector with respect to the implementation of health technology assessment (HTA) principles. The aim of this paper is to shed light on both the HTA criteria adopted and the international agreements implemented in the OD regulation, given the new challenges imposed on western countries by a growing number of therapies for rare diseases. Methods: We carried out a literature review to analyse the development of the international debate on the adaptability of HTA criteria for the OD assessment and regulation. The time span lies between January 1990 and May 2018, and the policies considered relate to both market authorization and reimbursement decisions within western countries. We focus specifically on HTA criteria in some of the dimensions included in the Core Model of the European net for HTA (EUnetHTA). Results: OD high prices, the absence of clarity on the possible high revenues realized by the distribution of a new OD outside the national borders, the risk that – once marketed – a new OD can be used to treat common diseases, are all issues that raise concern on OD regulation and have to be carefully monitored by policymakers in the next future. Conclusions: Across western countries, the preferential track granted to ODs in the implementation of HTA principles is not homogeneous, but fragmented and differentiated. The need for common rules at an international level is underlined, with a view to assessing the sustainability of a sector which, due to this regulatory void, can lend itself to producers' strategic and opportunistic behaviours. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the relationship between proton pump inhibitors use and the risk of dementia. Methods: A comprehensive literature search was conducted in English and Chinese databases from origination to December 2018. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. Cochran's Q test and the I2 statistic were used to evaluate the heterogeneity. Publication bias was assessed by Begg's test and Egger's test. Results: Six studies were included, which contained a total of 166,146 participants. The overall result demonstrated a significant increase in dementia risk with proton pump inhibitors use (HR = 1.29, 95% CI = 1.12–1.49). In subgroup analyses, a significant association was detected between proton pump inhibitors use and the risk of dementia in Europe (HR = 1.46, 95% CI = 1.23–1.73) and among participants aged ≥ 65 years (HR = 1.39, 95% CI = 1.17–1.65). For the factor follow-up time ≥ 5 years, the pooled HR was 1.28 (95% CI = 1.12–1.46), demonstrating a 1.28-fold increase in the risk of dementia among proton pump inhibitors users. In the case of regional impact, participants from Europe showed an overall pooled HR estimate of 1.46 (95% CI = 1.23–1.73). There was no evidence of publication bias. Conclusions: The overall result of this meta-analysis supports the hypothesis that proton pump inhibitors increase the risk of dementia. Furthermore, high-quality cohort studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The use of unlicensed and off-label medicines in children is common because trials in children have not usually been performed during the drug development process. Consequently, the information available to paediatricians may not always be as detailed or as robust as that available when prescribing a medicine that is licensed for an approved indication. This has led to concerns that children may be receiving drugs at dosages that either lack efficacy or present safety problems. The latter in particular has received a great deal of attention. In this narrative review, we have evaluated the use of off-label and unlicensed medicines in children and whether and how frequently this predisposes to adverse drug reactions. [ABSTRACT FROM AUTHOR]