A routine test to screen for patients genetically disposed to serious
side effects from treatment with thiopurine drugs has been widely adopted
following research by the Academic Unit of Clinical Pharmacology at the
University of Sheffield. The test has spared patients painful and
potentially life-threatening sepsis, and saved the considerable associated
treatment costs which have been estimated to be over £9,000 per patient
for a 17 day hospital stay. It has also led directly to a change in
clinical guidelines and recommendations in both the USA and UK.
Warfarin is an anti-coagulant drug prescribed to tens of millions of
people in the UK and US who are at high risk of developing blood clots.
Because individual sensitivity to warfarin varies in the population there
is a risk of overdosing the drug and causing serious bleeding and even
stroke in many people when starting treatment. In 1999 researchers at
Newcastle University were the first to demonstrate a statistically
significant link between a person's genotype and the appropriate dose of
warfarin. In 2010 the US Food and Drug Administration (FDA) mandated
inclusion of a table of dose recommendations based on genotype in the
warfarin prescribing information leaflet accompanying the drug. Newcastle
research forms the basis of the 2009 international standard algorithm for
gene-guided dosing of warfarin. This approach has been adopted by large US
medical centres and the FDA states that it will prevent 17,000 strokes a
year in the US.
Research at the University of Sheffield developed pharmacokinetic tools
that enable prediction of drug absorption, distribution, metabolism and
excretion, and potential drug-drug interactions. In 2001 the University
created a spinout company, Simcyp Ltd, to commercialise the technology.
The impacts are:
Innovative formulation science to create and develop the commercially
successful PowderHale® technology was undertaken within the
Department of Pharmacy & Pharmacology at the University of Bath, and
subsequently by Vectura. This has directly provided the basis for novel,
potentially life-saving treatments for chronic obstructive pulmonary
disease (COPD). Seebri® Breezhaler® and Ultibro®
Breezhaler® are once-daily, maintenance bronchodilators for the
relief of various symptoms due to airways obstruction caused by COPD.
Seebri® Breezhaler® was approved in the EU and Japan
at the end of 2012 and has now been launched by Novartis. Ultibro®
Breezhaler® a first-in-class combination bronchodilator was
approved in Japan and the EU in September 2013. Under the terms of the
licence agreement with Novartis concerning these products, Vectura has
already received $52.5M with an additional >$100M anticipated upon
achievement of regulatory and commercialisation targets. These medicines
are major advances to treat and manage a disease that, according to the
WHO, affects an estimated 210 million people worldwide and was the third
leading cause of death in the developed world in 2012.
Researchers at Newcastle University discovered interactions in vitro
between the widely prescribed
cholesterol-lowering drug rosuvastatin and cyclosporine, and between
gemfibrozil, at the liver transporter protein OATP1B1. Subsequent clinical
trials showed that the
interactions occurred in patients and slowed clearance of rosuvastatin
from the body. The research
findings not only had direct implications for the safe prescribing of
rosuvastatin when it came to be
marketed but also more far-reaching impact. US Food and Drug
Administration and European
Medicines Agency guidelines published in 2012 stipulate that
pharmaceutical companies must
investigate potential drug-drug interactions in the pre-clinical
development phase of all candidates
that bind that transporter.
University of Dundee-led research has changed the international approach
to illicit drug deaths. Though reducing deaths was a national priority, no
systematic research into Scottish deaths had previously occurred.
Highlighting the heterogeneity of the deceased, Dundee researchers
identified deficits in care processes and multi-agency data sharing,
making recommendations regarding monitoring. This directly influenced
government response, introducing a standardised mandatory annual review
process, enhancing understanding of drug death in Scotland and
facilitating targeted prevention approaches. This, and subsequent
Dundee-led research, now informs strategy development in the UK via the
national programme on Substance Abuse Deaths (np-SAD) and the European
Union (European Monitoring Centre for Drugs and Drug Addiction; EMCDDA).
Malignant pleural mesothelioma (MPM) is a treatable but incurable cancer
that originates in the
cells lining the lungs. Over 14,000 people worldwide are diagnosed
annually with MPM. Antifolates
are often used in cancer therapy, but side effects are a major issue. A
retrospective analysis of
cancer trials and phase 1 trial of MPM patients, carried out by Newcastle
in collaboration with Eli
Lilly Pharmaceuticals, determined that plasma homocysteine levels were a
good predictor of drug
toxicity in cancer patients treated with the antifolate pemetrexed, and
that this drug was well
tolerated by patients with low homocysteine levels. It was also determined
treatment should be supplemented with vitamin B12 as well as folic acid,
to reduce drug toxicity.
Ultimately, this permitted the continued development of pemetrexed, which
otherwise would have
been too toxic for clinical use. It is now the only licensed drug for MPM
treatment in combination
with platinum-based chemotherapy.
Bladder cancer is the fifth most common form of cancer, with over 70% of
cases presenting as non-muscle invasive bladder carcinomas (NMIBC).
Research in the Institute of Cancer Therapeutics at the University of
Bradford led to the evaluation of Apaziquone (EO9) in phase II clinical
trials against high risk NMIBC in The Netherlands, and two multi-centre
phase III clinical trials involving 106 centres across the USA, Canada and
Europe. A total of 1,746 patients with low or high risk NMIBC received EO9
and significant reductions in the rates of recurrence at two years have
been reported. Our research has impacted upon the health and welfare of
patients with NMIBC.
A new, more structured way of assessing the various harms done to
individuals, families, communities and wider society by a range of legal
and illegal drugs was first articulated by Professor David Nutt and
colleagues at the University of Bristol. The "rational scale" they
developed in the light of their research has stimulated extensive policy
debate and informed drug classification in the UK and overseas. The
research underpinning the scale has been disseminated through numerous
public lectures and discussions and has stimulated worldwide media
coverage. As a consequence, public awareness of drug harms has increased
and public engagement in important debates about drugs has intensified.
Neuroblastoma is a paediatric cancer that arises from the sympathetic nervous system. The
average age at diagnosis is 18 months and the disease accounts for approximately 15% of all
childhood cancer-related deaths. Determining optimal treatment for individual patients is crucial for
increasing chances of survival and for reducing side effects of chemotherapy and radiotherapy.
Newcastle-led research identified unbalanced 17q gain as the most common segmental
chromosomal abnormality (SCA) in patients with neuroblastoma; this was present in more than
50% of patients. Gain of 17q is now one of the key SCAs used to determine treatment for patients
in a European neuroblastoma trial and in UK treatment centres. Newcastle research also led to the
development of a simple diagnostic test for the detection of the main SCAs in neuroblastoma.