Evaluating Drugs for Rare Diseases (DRDs) for the purpose of reimbursement and beyond represents a tremendous challenge for most health care priorities. A consensus is set about the irrelevance of cost e ectiveness analysis to evaluate such drugs. The appeal for multi criteria decision aid models seems reasonable as the evaluation of DRDs is indeed multifaceted. However, the application of MCDA for the purpose of evaluating DRDs is yet primitive and simplistic. The present work tries to tackle the issue of evaluating DRDs from a decision maker angle by adopting an innovative robust ordinal regression MCDA method, UTADIS-GMS, that helps the decision maker discern between the DRDs based on their multi criteria value.

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This work examines the isotopic composition and abundance of helium in a number of different crustal environments with a view to understanding its production and transport in the crust. The work was largely carried out using existing instrumentation, but a dedicated interface was also built to allow computer control of a quadrupole mass spectrometer for rare gas abundance pattern determination. Conventional calculations of the radiogenic <SUP>3</SUP>He/<SUP>4</SUP>He production ratio based on the assumption of a chemically homogeneous composition cannot adequately account for the <SUP>3</SUP>He/<SUP>4</SUP>He ratio in waters from the Carnmenellis Granite of SW England. Alpha tracking and back-scattered electron microscopy show that the majority of the U and Th are concentrated in volumetrically insignificant accessory minerals. A new model has been devised, taking this heterogeneity into account, to explain the Carnmenellis data. Helium isotopic analysis of the granite itself revealed isotopic disequilibrium with the circulating waters. This may be related to differential release of <SUP>3</SUP>He and <SUP>4</SUP>He associated with different formation sites. A survey was made of the helium abundance and isotopic composition of groundwaters from the Pannonian Basin of Hungary in order to study the behaviour of mantle-derived fluids in an area of major recent crustal extension and volcanism. More than 80 samples were analysed covering most of the basin, and almost all contained a component of mantle-derived helium. Although <SUP>3</SUP>He/<SUP>4</SUP>He ratio is not clearly correlated with the surface expression of volcanism, it may act as an indicator of intrusion at depth. The <SUP>3</SUP>He flux through the Hungarian crust is ≈4 atoms.cm<SUP>-2</SUP>.s<SUP>-2</SUP>. If the mechanism of extraction is partial melting, then by analogy with melt production at mid-ocean ridges, addition of a 20-40 metre layer of basalt (for 5-10% partial melting) must be added to the Hungarian crust in a million years to support the present day <SUP>3</SUP>He flux.

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