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As part of a currently intense research effort into the development of novel potent macromolecular pharmaceuticals, diagnostic tools and carriers for targeted drug delivery, this project involved the synthesis of glycopolymers. Polymethacrylate derivatives carrying carbohydrate residues were efficiently prepared in a stereo-controlled manner, following two different routes. As revealed by a thorough characterisation of the materials obtained, the synthetic procedure strongly affected the polymers' composition and, in turn, their properties, such as their self-association in aqueous media and the interaction of the compounds bearing D-galactose units with a specific lectin. Polymers containing peracetylated saccharide residues were shown to be surface-active, forming stable spread Langmuir films. These monolayers acted as effective dl-aspartic acid nucleation promoters, whilst the soluble analogues (for which the sugars are deacetylated) seemed to possess a certain activity as dl-aspartic acid growth inhibitors. The behaviour of the deprotected polymers in aqueous solution was thoroughly investigated, prior to testing whether the materials carrying galactosyl units on the side chains could be recognised by a galactose-specific protein. For the first time for polymeric glycoconjugates, thermodynamic binding parameters relative to this protein-carbohydrate interaction were directly evaluated using isothermal titration microcalorimetry.

Thesis advisor: Michael D. Grubb / The aim of this paper is two-fold: 1) to explore the ex-ante relatedness of merging pharmaceutical companies and 2) to study the ex-post effects of mergers on R&D innovation and drug prices, where innovation is quantified by the number of patents granted. Annual firm-specific financial and patent data in this study were obtained for years between 1987 and 2014, while quarterly drug price data spanned from 2006 Q1 to 2015 Q1. The empirical results suggest that on average, heightened M&A activity leads to diminished R&D output and higher drug prices. These results are confirmed using time series models and by comparing post-merger performance of merged firms to that of their respective control groups through a propensity score matching method. / Thesis (BS) — Boston College, 2015. / Submitted to: Boston College. Carroll School of Management. / Discipline: Departmental Honors. / Discipline: Economics.

This thesis was motivated by the collaborative research undertaken by QMUL and Pfizer UK into improving experiments at pre-clinical drug development. In theory, the most efficient designs for these particular experiments, as well as for many other studies, are optimal designs. Since, however, their implementation poses challenges — and several emerged during the project — optimal designs are uncommon in practice. To address these challenges the thesis introduces a comprehensive design framework, which both generalizes and simplifies optimal design. At the core of this framework are optimal relaxed designs, seldom considered before. Like a standard design measure a relaxed design has non-integer replications and is mathematically tractable; unlike the former, whose replications must sum to one, it allows the replications total to be unconstrained. The methodology discussed in this thesis assumes design of experiments for parameter estimation, given a response model, but also applies to broader problems. Although the motivation and applications come from the pharmaceutical project, the ultimate goal is to develop an intuitive and versatile design toolkit for experimenters in various practical fields.

The U.S. pharmaceutical industry has been remarkably successful in developing new treatments for many of the leading causes of morbidity and mortality. These new treatments and their high prices lead government and private parties to increase spending and raise the issue of access. Price and cost increases have stimulated insurance costs, raising questions about the value of new technologies. A key way to address the increase in pharmaceutical prices is to investigate the impact of newer therapies on overall health expenditure. There is a conflict among researchers about the benefits and costs of newer and better drugs. Some researchers argue that newer and better drugs keep people out of hospitals and provide significant cost savings. Another group of researchers argue in their work that newer drugs do not really provide significant cost savings. This dissertation investigates the impacts of break-through drug classes on overall health care expenditures. Empirical evidence presented in this dissertation shows that drugs belonging to new drug classes provide significant advances in treatment of conditions compared to other drugs. The results indicate that all new drug classes except Fluoroquinolones provide substantial cost savings on overall health care expenditures. This dissertation also explores the relations between FDA Therapeutic Drug Classification and total health care expenditures. It offers a better methodology by incorporating both the quality and the age of the drugs to capture their effects on total health care expenditures. It studies the impacts of the quality and the age of the drugs on the diseases of following therapeutic classes: musculoskeletal system and connective tissue, skin and subcutaneous tissue, neoplasm, mental disorders, nervous system and sense organs, circulatory system, respiratory system, digestive system, genitourinary system. The nature of therapeutic conditions coupled with their duration lead us to conclude that for some therapeutic categories newer priority drugs are preferable, for others newer standard drugs are better. The results suggest that there is no general rule to state that newer priority drugs decrease health care expenditures.

The U.S. pharmaceutical industry has been remarkably successful in developing new treatments for many of the leading causes of morbidity and mortality. These new treatments and their high prices lead government and private parties to increase spending and raise the issue of access. Price and cost increases have stimulated insurance costs, raising questions about the value of new technologies. A key way to address the increase in pharmaceutical prices is to investigate the impact of newer therapies on overall health expenditure. There is a conflict among researchers about the benefits and costs of newer and better drugs. Some researchers argue that newer and better drugs keep people out of hospitals and provide significant cost savings. Another group of researchers argue in their work that newer drugs do not really provide significant cost savings. This dissertation investigates the impacts of break-through drug classes on overall health care expenditures. Empirical evidence presented in this dissertation shows that drugs belonging to new drug classes provide significant advances in treatment of conditions compared to other drugs. The results indicate that all new drug classes except Fluoroquinolones provide substantial cost savings on overall health care expenditures. This dissertation also explores the relations between FDA Therapeutic Drug Classification and total health care expenditures. It offers a better methodology by incorporating both the quality and the age of the drugs to capture their effects on total health care expenditures. It studies the impacts of the quality and the age of the drugs on the diseases of following therapeutic classes: musculoskeletal system and connective tissue, skin and subcutaneous tissue, neoplasm, mental disorders, nervous system and sense organs, circulatory system, respiratory system, digestive system, genitourinary system. The nature of therapeutic conditions coupled with their duration lead us to conclude that for some therapeutic categories newer priority drugs are preferable, for others newer standard drugs are better. The results suggest that there is no general rule to state that newer priority drugs decrease health care expenditures.

Wastewaters from rural sewage lagoons in Manitoba contain pharmaceuticals that are potentially harmful to non-target organisms and reduce overall water quality when released. An option for reducing exposure to wastewater contaminants and potential toxicity is surface flow treatment wetlands. However, little is known of the fate of pharmaceuticals in these types of systems. The fate and effects of six pharmaceuticals (carbamazepine, clofibric acid, fluoxetine, naproxen, sulfamethoxazole, sulfapyridine) were assessed in mesocosms simulating treatment wetlands in two separate 28-day experiments in the summer and fall of 2011, respectively: with and without significant aquatic plant communities, and with additional nutrients and harvesting of biomass. The removal of pharmaceuticals had half-lives that ranged from 0.23 to 9.4 days and 1.4 to 18 days during the summer and fall, respectively, and were predicted to occur primarily through photolysis and sorption. No overt toxicity from pharmaceuticals was observed for the common wetland macrophytes Myriophyllum sibiricum and Typha spp., but there was partitioning and bioaccumulation into macrophyte biomass. Treatment wetlands appeared to reduce pharmaceuticals and nutrients adequately, and may be a cost-effective means of treating rural wastewater.