Background Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany. Methods This retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ≥18 years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values. Results The analysis included 377 adult PKU patients (< 5 of which were receiving sapropterin dihydrochloride) and 3,770 matched controls. Of the 50 most common comorbidities in the PKU population, those with a statistically significant PR > 1.5 vs controls included major depressive disorders (PR = 2.3), chronic ischemic heart disease (PR = 1.7), asthma (PR = 1.7), dizziness and giddiness (PR = 1.8), unspecified diabetes mellitus (PR = 1.7), infectious gastroenteritis and colitis (PR = 1.7), and reaction to severe stress and adjustment disorders (PR = 1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%). Conclusion The overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease). Electronic supplementary material The online version of this article (10.1186/s13023-019-1153-y) contains supplementary material, which is available to authorized users.

most frequently reported TEAE (vomiting, upper respiratory tract infection, cough, and constipation) none were considered AVXS-101 related, with most events related to patients' underlying illness, not to study drug. CONCLUSIONS: Magnitude of the observed relative treatment effects indicates that AVXS-101 offers promising efficacy compared to nusinersen regarding EFS, reduced requirement for ventilation, and increased achievement of motor milestones.OBJECTIVES: Both natalizumab and glatiramer acetate have been approved for use in disease-modifying treatment for relapsing-remitting multiple sclerosis in Kazakhstan. In this paper we attempt to conduct a review of natalizumab's effectiveness using a network meta-analysis approach for comparing natalizumab and glatiramer acetate, with placebo as a common comparator. METHODS: In accordance with the defined search strategy and inclusion criteria, 2 identified trials on natalizumab and 3 identified trials on glatiramer acetate were included in the present analysis. Studies conducting sub-group analyses of data from previous trials were excluded in favour of inclusion of original studies. The common clinical end point was identified as the proportion of participants who experienced at least 1 relapse. Data were extracted from published articles and meta-analysis was performed using Stata software with "metan" package. RESULTS: The lower pooled estimate for the natalizumab studies (0.464, 95% CI: 0.323-0.666) compared to the pooled estimate for the glatiramer acetate studies (0.858, 95% CI: 0.766-0.961) may suggest greater efficacy for natalizumab compared to glatiramer acetate in regards to reducing relapses. CONCLUSIONS: While the results point to greater efficacy of natalizumab compared to glatiramer acetate, the limited number of studies and other limitations of the study design suggest that further research is needed to ascertain its preferability, in particular clinical trials with direct comparisons of various first-line treatments for relapsing-remitting multiple sclerosis.

A771 was conducted to assess the application of matching and weighting techniques in studies based on German administrative healthcare data published until May 2017. Relevant studies were identified via keywords linking the terms "matching" or "weighting" with various synonyms for claims data and Germany. Titles and abstract were screened by two independent researchers. The studies were stratified by type of used data, category of study objective (e.g. burden of disease) and applied methodology (e.g. propensity score matching or weighting). Results: In total, n= 363 studies were identified of which n= 114 met the inclusion criteria. The most frequent study objectives included cost analyses followed by burden of disease assessments and studies on healthcare resource utilization. Direct matching approaches based on variables such as age and gender were used in almost two thirds of the studies, followed by matching on the propensity score, which was applied in roughly one third of the analyses. Weighting techniques such as inverse probability of treatment weighting or newer approaches such as entropy weighting were rarely incorporated. Claims data from health insurances were the most prominent data source followed by administrative outpatient data. ConClusions: To balance treatment and control groups in German claims data, most researchers rely on matching methods, especially direct matching and propensity score matching. The use of weighting techniques and relatively new approaches is rare in the German context but should be considered in the future.

A697implemented in 2014 in Romania. In this study we are analyzing and comparing the characteristics of HTA process in Romania implemented since 2014 and since 2016 (Bulgaria). Methods: A critical appraisal of HTA Score Card was done based on the legislation, published articles and reports in Romania. HTA legislation and guidelines in Bulgaria have been reviewed and analysed while considering the reasons behind its introduction and analysing the HTA process as a whole. Results: By December 2015, more than 200 HTA dossiers were evaluated and the scorecard HTA results were reflected in three processes of the drug reimbursement list update. The HTA scorecard in Romania is based on six criteria: France and Germany HTA decision, the number of EC reimbursement countries, the local real-world data and a budget impact. For medicinal product inclusion in the PDL in Bulgaria the HTA assessment should be more than 75% of all indicators (965 point) of the Score Cards and also the negative HTA assessments from HAS, NICE and GBA are directly transferred. The submitted 34 INN (71% ) out of 48 INNs were HTA assessed in 2016. ConClusions: A step-by-step process for applying of HTA in decision making reimbursement process of medicines is set up in both surveyed countries. Although the HTA system in Romania makes no direct evaluation of the value of drugs, authorities consider it to be effective, being designed only to favor cost-saving drugs and to promote high discounts. Where in Bulgaria the HTA process is also still controversial because the UK, France and Germany HTA evaluations are directly transferred and not locally assessed.