Carers' Health-Related Quality of Life in Global Health Technology Assessment: Guidance, Case Studies and Recommendations.

Including health outcomes for carers as well as patients in economic evaluations can change the results and conclusions of the analysis. Whilst in many disease areas there can be clear justification for including carers' health-related quality of life (HRQL) in health technology assessments (HTAs), we believe that, in general, the perspective of carers is under-represented in HTA. We were interested in the extent, and methods by which, HTA bodies include carers' HRQL in economic evaluation. We reviewed guidance from 13 HTA bodies across the world regarding carers' HRQL. We examined five interventions, as case studies, assessed by different HTA bodies, and extracted information on whether carers' HRQL was included by the manufacturers or assessors in their dossiers of evidence, the data and methods used, and the impact on the results. We developed recommendations to guide analysts on including carers' HRQL in economic evaluations. When reviewing the methods guides: two bodies recommend including carers' HRQL in the base case, two referred to outcomes for all individuals, two preferred to exclude carers, three said it depended on other conditions, and it was unclear for four. Across the five case studies: five source studies for carers' HRQL and two different modelling approaches were used. Including carers' HRQL increased incremental quality-adjusted life-years (QALYs) in 19/23 analyses (decreased it in two); there was substantial variation in the magnitude of change. We recommend: (1) the inclusion of carers is clearly justified, (2) the use of HRQL data from the population under comparison where possible, (3) the use of data from another disease area or country is clearly justified (and transferability/applicability issues are discussed), (4) the use of external data to derive comparisons for cross-sectional data is justified, (5) assumptions and implications of the modelling approach are explicit, and (6) disaggregated results for patients and carers are presented.

Competition between antagonistic complement factors for a single protein on N. meningitidis rules disease susceptibility.

Genome-wide association studies have found variation within the complement factor H gene family links to host susceptibility to meningococcal disease caused by infection with Neisseria meningitidis (Davila et al., 2010). Mechanistic insights have been challenging since variation within this locus is complex and biological roles of the factor H-related proteins, unlike factor H, are incompletely understood. N. meningitidis subverts immune responses by hijacking a host-immune regulator, complement factor H (CFH), to the bacterial surface (Schneider et al., 2006; Madico et al., 2007; Schneider et al., 2009). We demonstrate that complement factor-H related 3 (CFHR3) promotes immune activation by acting as an antagonist of CFH. Conserved sequences between CFH and CFHR3 mean that the bacterium cannot sufficiently distinguish between these two serum proteins to allow it to hijack the regulator alone. The level of protection from complement attack achieved by circulating N. meningitidis therefore depends on the relative levels of CFH and CFHR3 in serum. These data may explain the association between genetic variation in both CFH and CFHR3 and susceptibility to meningococcal disease.