Randomized Controlled Trials Versus Real World Evidence: Neither Magic Nor Myth.

Compared with drugs from the blockbuster era, recently authorized drugs and those expected in the future present a heterogenous mix of chemicals, biologicals, and cell and gene therapies, a sizable fraction being for rare diseases, and even individualized treatments or individualized combinations. The shift in the nature of products entails secular trends for the definitions of "drugs" and "target population" and for clinical use and evidence generation. We discuss that the lessons learned from evidence generation for 20th century medicines may have limited relevance for 21st century medicines.

Guidance on development and operation of Young Persons' Advisory Groups.

Background: Engaging patients and the public as collaborators in research is increasingly recognised as important as such partnerships can help improve research relevance and acceptability. Young Persons' Advisory Groups (YPAGs) provide a forum for clinical researchers and triallists to engage with children and young people on issues relevant to the design, conduct and translation of paediatric clinical trials. Until fairly recently, there was very little information available to guide the successful development and operation of YPAGs.

The future of cystic fibrosis care: a global perspective.

The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young children. However, although life expectancy for people with cystic fibrosis has increased substantially, the disease continues to limit survival and quality of life, and results in a large burden of care for people with cystic fibrosis and their families. Furthermore, epidemiological studies in the past two decades have shown that cystic fibrosis occurs and is more frequent than was previously thought in populations of non-European descent, and the disease is now recognised in many regions of the world.

Industry and Patient Perspectives on Child Participation in Clinical Trials: The Pediatric Assent Initiative Survey Report.

Background: Obtaining assent from children participating in clinical trials acknowledges autonomy and developmental ability to contribute to the consent process. This critical step in pediatric drug development remains poorly understood, with significant room for improving the clarity, efficiency, and implementation of the assent process. Beyond ethical necessity of informing children about their treatment, the assent process provides the advantages of including children in discussions about their diagnosis and treatment-allowing greater understanding of interventions included in the study.

A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved.

Pediatric Medicine Development: An Overview and Comparison of Regulatory Processes in the European Union and United States.

Pediatric legislation in the US and the EU is driving pediatric product development on an international scale. To facilitate harmonization and global development of pediatric medicines, it is important to understand the legislative requirements that must be met along with incentives that exist in the US and the EU to include pediatric patients in therapeutic clinical trials. Although there are many similarities, differences exist.

The future of the development of medicines in idiopathic pulmonary fibrosis.

The development of treatments for idiopathic pulmonary fibrosis (IPF) has been often disappointing. Building on authorized treatments that can benchmark the validity of treatment effect measures, the time has come to standardize endpoints and achieve consensus on their use for different clinical questions and specific IPF phenotypes. In order to facilitate the development of new medicines for IPF it is crucial that the knowledge of the disease and lessons learnt from past trials are taken forward to create international trial networks with involvement of patients, including biobanks and clinical data collection through a multinational registry.

Assessing the relative efficacy of new drugs: an emerging opportunity.

The increasing availability of individual-level data from clinical trials could allow the relative efficacy of new drugs to be assessed in a robust, cost-effective and timely way.

Lung transplantation in children and young adults: a 20-year single-centre experience.

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria. Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan-Meier curves.

The K+ channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients.

Background: The identification of strategies to improve mutant CFTR function remains a key priority in the development of new treatments for cystic fibrosis (CF). Previous studies demonstrated that the K⁺ channel opener 1-ethyl-2-benzimidazolone (1-EBIO) potentiates CFTR-mediated Cl⁻ secretion in cultured cells and mouse colon. However, the effects of 1-EBIO on wild-type and mutant CFTR function in native human colonic tissues remain unknown.

Minimal acute rejection in pediatric lung transplantation--does it matter?

In adult lung transplantation, a single minimal AR episode is a significant predictor of BOS independent of other factors. However, the significance of single minimal AR episodes in children is unknown. A retrospective, multi-center analysis was performed to determine whether isolated single AR episodes are associated with an increased BOS risk in children.

Cytomegalovirus immunoglobulin decreases the risk of cytomegalovirus infection but not disease after pediatric lung transplantation.

Background: Cytomegalovirus (CMV) has been associated with morbidity, including chronic allograft rejection, in transplant recipients. Data from adult centers suggests that CMV hyperimmune globulin (CMVIG) and ganciclovir together are superior in preventing CMV viremia than ganciclovir alone.

Methods: A retrospective review of pediatric lung transplant recipients at 14 sites in North America and Europe was conducted to evaluate the effect of adding cytomegalovirus immunoglobulin (CMVIG) prophylaxis to at least 3 weeks of intravenous ganciclovir therapy in pediatric lung transplant recipients.

The risk, prevention, and outcome of cytomegalovirus after pediatric lung transplantation.

Background: A retrospective review of pediatric lung transplant recipients at 14 centers in North America and Europe was conducted to characterize the epidemiology and the risk factors for cytomegalovirus (CMV) and to explore the impact of preventative antiviral therapy.

Methods: Data were recorded for 1 year posttransplant. Associations between CMV and continuous and categorical risk factors were assessed using Wilcoxon rank sum and chi-square tests, respectively.

Increased mortality after pulmonary fungal infection within the first year after pediatric lung transplantation.

Background: Risk factors, morbidity and mortality from pulmonary fungal infections (PFIs) within the first year after pediatric lung transplant have not previously been characterized.

Methods: A retrospective, multicenter study from 1988 to 2005 was conducted with institutional approval from the 12 participating centers in North America and Europe. Data were recorded for the first post-transplant year.

Variability in immunization guidelines in children before and after lung transplantation.

Lung transplant candidates and recipients are at high risk of infections from vaccine-preventable diseases. However, well-established guidelines neither exist for pre- and post-transplant vaccination nor do monitoring guidelines for pediatric lung transplant recipients. To ascertain the current vaccination and monitoring practices of pediatric lung transplant centers, a self-administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative in April 2006.

Clinical pharmacology study of Bramitob, a tobramycin solution for nebulization, in comparison with Tobi.

Background And Objectives: To compare in vitro characteristics and pharmacokinetics of Bramitob, a preservative-free tobramycin solution for nebulization, and Tobi in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa infection.

Methods: In vitro characteristics of Bramitob and Tobi were evaluated using Pari TurboBoy/LC Plus and the Systam 290 LS nebulizers. In the randomized, double-blind, two-way crossover pharmacokinetic study, 11 patients with CF received a single nebulized dose (300mg) of Bramitob or Tobi, separated by a 7-day washout period.

Laser acupuncture and probiotics in school age children with asthma: a randomized, placebo-controlled pilot study of therapy guided by principles of Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) postulates an interaction between the lung as a Yin-organ and the large intestine as a Yang-organ. The aim of this pilot study was to investigate in asthmatic school age children whether treatment with laser acupuncture and probiotics according to TCM portends a clinical benefit to standard medical treatment performed according to pediatric guidelines. Seventeen children aged 6-12 yr with intermittent or mild persistent asthma were enrolled in this randomized, placebo-controlled, double-blind pilot study.

Possible dysregulation of chaperon and metabolic proteins in cystic fibrosis bronchial tissue.

Cystic fibrosis (CF) is an autosomal recessive disease due to mutations of the CF transmembrane conductance regulator gene. A systematic approach to generate a protein expressional pattern in CF bronchial tissue has not been performed so far. It was the aim of this hypothesis-generating study to construct differential proteomes of bronchial biopsies in controls (n = 8) and CF patients (n = 9).

CFTR Cl- channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis.

Background & Aims: Cystic fibrosis (CF) is caused by over 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and presents with a widely variable phenotype. Genotype-phenotype studies identified CFTR mutations that were associated with pancreatic sufficiency (PS). Residual Cl- channel function was shown for selected PS mutations in heterologous cells.

Negative expiratory pressure: a new tool for evaluating lung function in children?

The negative expiratory pressure technique (NEP) has been applied in adults with chronic obstructive pulmonary disease (COPD), demonstrating flow limitation in many of these patients. Because this technique does not require patient cooperation, it is of potential interest for application in the pediatric population. This study was performed to test the feasibility of NEP in children, and to further investigate it in children with asthma and cystic fibrosis (CF).

Acrodermatitis enteropathica-like eruption as the presenting sign of cystic fibrosis--case report and review of the literature.

Unlabelled: In most patients with cystic fibrosis (CF), pulmonary symptoms are the first sign of presentation. Another predominant feature is maldigestion, frequently starting in early childhood. Pancreatic exocrine dysfunction causes maldigestion, characterised by failure to thrive, diarrhoea, hypoproteinaemia, oedema and anaemia.

Improvements of lung function in cystic fibrosis.

Improved care for patients with cystic fibrosis (CF) has led to their improved survival. We analyzed retrospectively whether improvements in lung function (LF) could be detected in our CF patients over the decade 1980-1990. In 72 patients, 153 LF measurements were performed in their first year of life (1980-1991), and then 189 LF measurements were performed again in 60 of those patients during their sixth year of life (1987-1997).