The aim of this study was to report serum immunoglobulin (Ig) and IgG subclass levels in a large pediatric population with cystic fibrosis, and relate these to measures of disease severity. Total immunoglobulin levels were measured in 154 patients, and IgG subclass levels were measured in 136 patients and compared to age-related normal population data and to levels reported in previously published studies of children with cystic fibrosis. Clinical data were also collected: genotype; height, weight, and BMI standard deviation scores; FEV(1) (as percent predicted); Shwachmann-Kulczycki (S-K) and Northern chest X-ray scores; and Pseudomonas aeruginosa infection status. The clinical well-being of patients with hypo- or hyper-gammaglobulinemia was compared with age- and sex-matched control patients who had normal levels of gammaglobulin. IgG subclass levels were measured, and the results were compared with previous studies. Eleven patients had hypergammaglobulinemia (7.8% compared with 0-69% in the published literature). Patients with hypergammaglobulinemia had lower FEV(1) percent-predicted values, and worse S-K and Northern chest X-ray scores than controls. Three patients had hypogammaglobulinemia (1.9% compared with 0-10.8% in the published literature). There was no difference in any clinical parameter between controls and those with hypogammaglobulinemia. Nineteen patients (14%) had low levels of IgG1, and 40 patients (29%) had low levels of IgG2. The low percentage of patients with abnormally high immunoglobulin levels probably reflects the improved respiratory status of today's children with CF. The low percentage of those with low IgG probably reflects better nutritional status. The finding of worse lung function and clinical scores in patients with hypergammaglobulinemia agrees with the published literature. The high percentage of patients with low IgG2 was unexpected and was not previously reported. The clinical significance of this in patients with CF is unknown.

Not all possible presentations of aBCC were included; the disease is a challenging condition to characterise given its rarity, the nature of the patients affected, and its variable progression. Findings suggest that aBCC is associated with significant burden for individuals, even when their disease is stable or where surgical treatment has been successful.

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Background: The FACT-8D is a new cancer-specific, preference-based measure (PBM) of health, derived from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The FACT-8D's measurement properties have not been tested to date. We assessed it's validity and responsiveness in relapsed/refractory mantle cell lymphoma (RR MCL) and compared the results to the EQ-5D-5L. Methods: Blinded analysis of pooled data from a phase 3 clinical trial. FACT-8D baseline and follow-up data (weeks 4, 7, 16, 31) were scored using Australian preference weights, the first available value-set. Convergent validity was assessed by estimating baseline correlations with the FACT-Lym total score, Trial Outcome Index (TOI), FACT-Lym lymphoma-specific sub-scale (LymS), EQ-5D Visual Analog Scale (VAS), and haemoglobin (HgB). Relevant clinical variables were used to categorise patients to test known groups' validity and responsiveness was investigated using data from baseline (n = 250) and week 31 (n = 130). Results were compared with EQ-5D-5L, scored using the UK 3L crosswalk and the 5L England value-sets. Results: The FACT-8D showed good convergent validity and responsiveness; baseline Pearson correlation coefficients between FACT-8D Index scores and other PRO measures were moderate to very strong (range: 0.49 for the EQ-VAS to 0.79 for FACT TOI) and the size of the change in FACT-8D Index scores at week 31 differed significantly (p < 0.005) between patients categorised as improved, worsened or stable using the FACT-Lym total score, LymS, and HgB. However, when assessing known groups' validity, FACT-8D failed to discriminate between patients categorised by health status on four of the seven variables analysed. Overall, FACT-8D and EQ-5D-5L performed similarly, although EQ-5D-5L showed better known groups' validity.

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Aim: PHEDRA (Platform for Haematology in EMEA: Data for Real World Analysis) is a unique, noninterventional project based on secondary data collection from real-world (RW) patient-level (health record) databases to understand treatment patterns in hematological malignancies. It compares ibrutinib's effectiveness with alternative treatments using RW data (RWD) and randomized clinical trials data. Randomized clinical trials (RCTs) enable medicines to be rigorously evaluated in a controlled environment, through the application of inclusion/exclusion criteria for patient entry into the trial and randomization of treatments administered [1]. However, they do not establish the comparative effectiveness of drugs in real-world (RW) populations, which are often more heterogeneous than trial populations and where treatment is often subject to less close monitoring and frequency of data collection [1][2][3]. There remains insufficient knowledge and limited published literature on routine clinical practice, treatment pathways and outcomes in the management of patients with hematological malignancies. This is needed to guide optimal therapeutic decisions in patients with cancer at different stages of disease, particularly as the number of available treatments and possible drug combinations multiply [4].There is increasing recognition of the value of using real-world data (RWD) alongside RCT data (i.e., historical controls) to generate comparative effectiveness research on new therapies [2,5]. Indeed, with advances in cancer therapy and a multiplicity of comparators/standards of care depending on local routine practice (making it impractical or impossible to obtain data on all potentially relevant comparisons in an RCT setting), the need for RWD to educate regulators, payers, healthcare providers, healthcare decision makers and patients about treatment patterns and outcomes has never been greater [2]. RWD can further demonstrate the comparative effectiveness of a treatment once available on the market as well as inform clinical drug development, for example, by providing information on existing therapies and the profile of patients with poor outcomes who may have specific unmet needs. Although RWD cannot replace RCT data with regard to efficacy and safety, it can challenge and improve understanding of the 'standard of care' [1]. RWD can provide useful outcomes information across multiple relevant

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Purpose To extend existing analyses of whether and how the age of respondents is related to their time trade-off (TTO) valuations of hypothetical EQ-5D-3L health states, and to contribute to the existing debate about the rationale and implications for using age-specific utilities in health technology assessment (HTA). Methods We use data from the MVH UK valuation study. For each profile, the mean TTO value—adjusted by sex, education, self-reported health and personal experience of serious illness—is pairwise compared across the different age groups. A Bonferroni correction is applied to the multiple testing of significant differences between means. Smile plots illustrate the results. A debate regarding whether there is a case for using age-specific utilities in HTAs complements the analysis. Results Results show that the oldest respondents value health profiles lower than younger age groups, particularly for profiles describing problems in the mobility dimension. Conclusion The findings raise the possibility of using age-specific value sets in HTAs, since a technology may not be cost-effective on average but cost-effective for a sub-group whose preferences are more closely aligned to the benefits offered by the technology. Electronic supplementary material The online version of this article (10.1007/s11136-018-2071-5) contains supplementary material, which is available to authorized users.