EACPT Lifetime Achievement Award for Professor Michel Eichelbaum

The 2015 Lifetime Achievement Award of the European Association of Clinical Pharmacology and

Therapeutics will go to German researcher Professor Michel Eichelbaum for his outstanding contribution to the national and international benefits of clinical pharmacology for medicine, health care and patient safety. The Award, which includes the EACPT silver medal, will be presented to Professor Eichelbaum during the 12th EACPT Congress in Madrid on Saturday 27th June 2015.

Michel Eichelbaum's primary research interest is pharmacogenetics of drug metabolizing enzymes and transporter proteins. He was a pioneer in the study of the stereochemistry of drugs,  use of stable isotopes in clinical pharmacology, and intestinal metabolism and transport of drugs. 

In 1975, he discovered a genetic polymorphism in the oxidation of the antiarrhythmic and oxytocic drug, sparteine, which later became known as CYP2D6 polymorphism. This is considered his single most important scientific discovery. Later, he became involved in research on factors involved in the regulation of drug-metabolizing enzymes and transporters with special emphasis on nuclear receptors.

See more about Professor Eichelbaum in my blog on the EACPT site.

The EACPT was founded 22 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.

Moving the new Personalized Medicine to the Clinic

I am on the Advisory Board for a conference to be held 13-14 May in San Francisco on Personalized Medicine from the perspectives of regulators, biotech and pharma interest, health service funders and patient users of new and emerging technologies in this area.

Trusted doctor-patient relationships form a long recognized key underpinning basis for ensuring as effective as possible disease prevention and treatment. That relationship needs to be supported by a strong evidence base on clinical and cost-effectiveness and safety in use of medicines and supporting diagnostics and devices.

Thanks to economies arising from progress in gene technology (Moore's Law applied to medicine) and advances for exponential increase in active partners in this field (Metcalfe's Law applied to medicine), costs of genetic, genomic and other technologies to stratify diagnosis and treatment choice are becoming increasingly affordable in clinical practice.

The Summit is a one-day conference that will gather biotechnology and pharmaceutical experts and healthcare stakeholders as keynote speakers and panel discussants on legal, regulatory, funding and other key issues that will promote research and development, growth and effectiveness  in the short to medium term horizon for emergence of personalized medicine for clinical care.

The summit is co-hosted by the Personalized Medicine Coalition and Foley & Lardner LLP and is supported by major academic, clinical and industry patrons Life Technologies, Cancer Treatment Centers of America and the California Institute of Regenerative Medicine.

See the Personalized Medicine Summit website for more on the conference and how to register.

Selected papers from the conference will be published in the international journal Health Policy and Technology.

New genetic test to decide treatment for difficult childhood asthma

Researchers in Dundee and Brighton have reported in the journal Clinical Science a randomised study using gene testing aimed at improving treatment selection in children with asthma.
The gene variant (Arg16 genotype) they tested has previously been reported to be associated with failure to respond to commonly used beta-2 agonist bronchodilator inhaler treatment.
My comments below on the potential and limitations of the study were included in a briefing by the Science Media Centre.

Prof Donald Singer, Member of the British Pharmacological Society and Professor of Clinical Pharmacology and Therapeutics at the University of Warwick, said:
“This study is important in providing evidence that simple genetic testing can be used to personalize selection of medicine in clinical practice – in this case applied to treatment choice in children with poorly controlled asthma.
“Their main outcome – less time off school because of asthma – is important both for children and their families. The authors were careful to consider poor compliance with asthma treatment as an important alternative explanation for their findings. However this is a small study and needs to be confirmed in larger well-controlled clinical trials.”

Research paper:
Tailored second-line therapy in asthmatic children with the Arg16 genotype.  Lipworth BJ et al., published in Clinical Science on Tuesday 8^th January 2013.

Progress on Personalized Medicine? Updates from Harvard.

@HealthMed The 8th annual Personalized Medicine Conference took place at Harvard this week - a joint venture of Harvard Medical School, Harvard Business School and Partners Healthcare, lead by Professor Raju Kucherlapati, from the HMS Department of Genetics. Worth checking the excellent archive of past programmes, presentations and podcasts.
Meantime, some of the highlights?
- An excellent narrative on the partnership between Plexxikon (Peter Hirth) and Roche Diagnostics (Suzanne Cheng) to create a companion diagnostic/therapeutic pairing for vemurafenib (Zelboraf), the first FDA approved pairing for BRAF V600E positive metastatic melanoma
- Further case studies illustrating successful drug development using genetic approaches
- Personal case studies on the impact, clinical value and ethical and clinical challenges of genomic screening: from Joe Beery, Life Technologies, on detecting unrecognised treatable serious early childhood disorders, to John Lauerman, Bloomberg News, on consequences of sequencing for asymptomatic adults - questions on penetrance and future screening for onset e.g.  of metabolic disease and cancers

Harvard Medical School: New Research Building - Avenue Pasteur.

- Clinical potential, and regulatory and reimbursement challenges to introducing molecular diagnostics into clinical care pathways
- Leadership award to Randy Scott, In Vitae, whose discussion points included the relevance of Moore's Law (technology advancing) and Metcalfe's Law (people factors: exponential increase in interaction as network expands) to developments in personalized medicine
- Business models and their governance for use of genetic information
- A North Virginia (John Vockley, Inova) pioneering series of projects aiming to assess outcomes of neonatal genomic sequencing: from insight into preterm labour to prospective longitudinal follow-up to adulthood, supported by multi-generation family member sequencing combined with clinical histories
- The US Air Force Programme on Patient-Centered Precision Care (Dr Cecili Sessions), in partnership with the Coriell Institute and Johns Hopkins University,  aims of which include understanding the impact on health-related behaviour of providing personal genetic information on remediable medical disorders and on drug responses.
- A business school case study led by Professor Richard Hamermesh, Director of the HBS HealthCare Initiative, on reactive and proactive responses for development of companion diagnostics (1).
- Pros and cons of liberal vs. restrictive approaches to IP for genetic and other molecular diagnostics
- Engaging the policy community and the public in ethical, clinical, reimbursement and adoption issues for new diagnostics and treatments aimed at personalizing medicine, including case studies from the American Medical Association and the American Assocation for Cancer Research.

Personalized Medicine Conference website 
Companion and coupled diagnostics

More news on the Geneva EACPT 2013 Congress

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Around 10 months to go until the European Association for Clinical Pharmacology & Therapeutics 11th International Congress to be held in beautiful Geneva 28-31 August 2013. The image is one of a series on the congress website showing the best of the city.

Abstract submission is now open for the next EACPT Congress,

Over 900 participants are expected to attend including health professionals, scientists, policy makers, biotechnology and pharmaceutical professionals and others with an interest in basic and clinical pharmacology, pharmacotherapy, drug discovery and development, regulatory affairs and related areas.

Key themes at the congress will range from bedside pharmacology for special patient groups to pharmacology & toxicology, and pharmacology and society. 

Specific topics will include advances in personalised diagnostics to improve the safety and effectiveness of medicines, updates on new biological approaches to ocular disease, therapeutics of cardiovascular, cancer and inflammatory disease, clinical trial design and regulation, and drug safety and toxicology.

See here for more on key themes of the Congress. 

EACPT Geneva 2013 Congress website  

The European Association for Clinical Pharmacology and Therapeutics (EACPT) has its origins in a working party in the early 1980s under the auspices of the World Health Organisation (WHO-Europe). 

The EACPT's next biennial congresses after Geneva 2013 are in Madrid 2015 and in Prague 2017. The EACPT also arranges summer schools, and other scientific and professional activities.

News of the 2013 EACPT Congress in Geneva

@HealthMed The EACPT's next biennial congress will be held in beautiful Geneva, 28th - 31st August in 2013 at the International Congress Centre of Geneva (CICG).

Registration will open 10^th November 2012.
Abstract submissions will also open 10^th November 2012 and will close 8^th February 2013.

To receive updates on the congress before registering, you can submit your email address to the congress organisers.
Over 900 participants are expected to attend including health professionals, scientists, policy makers, biotechnology and pharmaceutical professionals and others interested in basic and clinical pharmacology, pharmacotherapy, drug discovery and development, regulatory affairs and related areas.

Geneva by the lake

Key themes at the congress will range from bedside pharmacology for special patient groups to pharmacology & toxicology, and pharmacology and society. Specific topics will include sessions on communicating with the public, ethics, safe prescribing, clinical trial design and governance, and health policy; new biologicals, translational medicine and pharmacogenetics; advances in personalised diagnostics to improve the safety and effectiveness of medicines, updates on new biological approaches to ocular disease, therapeutics of cardiovascular, cancer and inflammatory disease, clinical trial design and regulation, and drug safety and toxicology. 

The European Association for Clinical Pharmacology and Therapeutics (EACPT) has its origins in a working party in the early 1980s under the auspices of the World Health Organisation (WHO-Europe). The EACPT's next biennial congresses after Geneva 2013 are in Madrid 2015 and in Prague 2017. The EACPT also arranges summer schools, and other scientific and professional activities.

For more on the Congress, how to contact the organisers, and how to register to receive updates, see:

Congress Website: http://www.eacpt2013.org

Secretariat email: eacptreg@mci-group.com

MHRA alert on mislabelled high strength codeine in UK co-codamol batch

@HealthMed Co-codamol contains two types of painkiller. Paracetamol and the opiate drug codeine. The UK Medicines regulator, the MHRA, has warned that around 39,000 packets of these combination tablets have been issued to wholesalers and pharmacies, with the opiate codeine present in 4 times the strength on the label: 30mg instead of 8mg per tablet. The strength of the paracetamol in the tablets said to be unaffected. Lower dose codeine forms of co-codamol (in the UK 8mg or 12.8mg per tablet) are available over the counter in pharmacies. The higher dose codeine 30mg per tablet form of co-codamol is a prescription only medicine. This dose may be quite appropriately be prescribed by a doctor, after taking into account a patient's medical history and current drug treatment.
However codeine in high dose in at risk groups of patients is more likely to cause serious adverse effects such as drowsiness, confusion, and reduced respiratory drive and blood pressure. People at particular risk include the elderly, those with liver or kidney or lung disease, and people already on medicines known to cause these adverse effects. 
Codeine is a prodrug: it has to be converted in the body to its active forms (mainly to morphine) before it can be effective in relieving pain. Therefore people who are genetically able to activate codeine very rapidly are more likely to experience adverse effects when exposed to higher than expected doses of codeine.
High doses of codeine can also cause constipation as a troublesome adverse effect.
These 30mg strength codeine forms of co-codamol tablets have on them the mark "CCD30" on one side with "CP" on the second side.
As recommended by the MHRA, anyone concerned that they may have been incorrectly given the high strength co-codamol should contact their GP or pharmacist promptly. The reported batch number is LL11701, expiry date September 2014.

See also:
Reuters report
Daily Express report
New England J Med report on codeine intoxication associated with ultrarapid CYP2D6 metabolism

Clinical pharmacology theme for Spring 2012 WMPA conference

@HealthMed Registration is now open for members and guests for the Spring meeting of the West Midlands Physicians Association.
The next meeting of the WMPA has updates on Clinical Pharmacology as its major theme and will be held on Wednesday 16th May 2012 at the Clinical Sciences Building at the University Hospital Campus in Coventry. Key speakers will include Dr Andrew Kicman (King's College London) on drugs in sport, Professor of Psychiatry Femi Oyebode (Birmingham) on medicines in psychiatry, Dr Richard Fitzpatrick (Liverpool) on advances in pharmacogenetics and Dr Paul Newrick (Worcestershire Royal Hospital)on medical advances in managing diabetes mellitus.
In view of the large number of high quality abstracts submitted, an attended poster session will be included in the May 2012 meeting.
Registration is open to members and guests (subject to availability of places).
For further information, contact the WMPA organizers.
See the WMPA blog or the WMPA website for more on the WMPA 2012 Spring conference and on the history of this 62 year old medical society.

Networks and personalized medicine for better drugs?

For more on this theme see 
- article with Andrew Marsh in the inaugural March 2012 issue of Health Policy and Technology
- article in the October 2011 issue of Public Service Review: Science and Technology Review.  

For many individual patients treatments may not exist, may not be very effective, or may result in unpleasant adverse effects. How can prescribers improve drug selection andreduce the harmful effects of medicines? Are there better ways to develop drugs for patients who are difficult to treat?  And what can we do to improve poor adherence to medicines? These elements underpin ‘personalized medicine’, in current use the concept that by considering differences among patients in genetics, disease burden and other factors, more effective and safer drugs can be developed. Personalizing medicine is a path to better disease prevention and control where limited treatment options exist, such as for many cancers, resistant infections and dementia syndromes, and better drug development for new medical challenges. These concepts have in recent years attracted interest from the Royal Society, the Nuffield Council on Bioethics and cognate international institutions.

It is clear that there needs to be consistent investment and support from policy makers and regulators to develop and sustain the academic and industry pharmacology expertise and activity needed for the long-term success of a personalized medicine strategy, so that we can continue to be able to improve the health of the public and individual patients.

NICE is an international leader in developing evidence-based treatment guidelines. Its reports increasingly recognize the need to refine drug choice based on patient characteristics. For example, updated national hypertension guidelines released in August 2011 advise drug selection guided by age, gender, ethnicity, and monitoring, with treatment modified depending on clinical response. NICE also recognizes the need for research on ways, tailored to patient preference, to improve long-term adherence to drug treatment.

Pharmacologists are developing two complementary approaches aimed at achieving “precision medicine” in as many patients as possible: better drug discovery combined with high definition biomarkers for drug selection and monitoring. Network pharmacology brings together sophisticated databases of genetic mechanisms for disease, pharmacological pathways, candidate drugs, and population data describing important variants among individuals in drug handling and responsiveness.  These methods also allow ways to find previously unexpected “off-target” actions of existing or new drugs, which may accelerate discovery of new treatments for serious diseases.

Diagnostic methods are increasingly being used to improve drug selection for individual patients. For example growth tyrosine kinase receptors can be blocked using the biological agent imatinib to treat particular patterns of Philadelphia chromosome-positive chronic myeloid leukaemia, and rare gastro-intestinal tumours. Understanding genes and drugs that influence enzymes that modify drugs in the body, improves accuracy in defining patients who will not respond to a given medicine, or may develop adverse effects.  For example, to minimize risk of serious harm, pharmacogenetic testing is recommended for variability in a specific liver enzyme before deciding whether or not to prescribe the anti-HIV drug abacavir. This knowledge also allows better prediction of a patient’s risk of harm from interactions between treatments, based on recognition of medicines and other remedies that interfere with how drugs are cleared by the body. 

See my previous blogs on 
- preventing adverse drug reactions
- new UK guidelines on managing high blood pressure

Improving prevention of serious adverse drug reactions

Around 1 in 20  admissions to hospital are due to adverse drug reactions in the UK and other countries with well-developed health services. There are multiple causes for this surprisingly high rate of adverse reactions to medicines: the patient might not have followed established guidelines, such as avoiding alcohol; the wrong drug or dose might have been prescribed; an interaction between two drugs might have been overlooked; the patient's genetic makeup might cause an anomalous reaction; the patient might be taking contaminated drugs bought from unregulated sources on the internet; an unknown adverse reaction to a new drug might have been missed in the development and safety testing of that drug.
Many of the adverse drug reactions are preventable. We need to make sure medical students and prescribers are aware of how to prescribe safely, know common and high risk drugs well and, importantly, to make sure adverse reactions are recorded on patients' records so that they don't happen again. Now that people are able to obtain  prescription drugs on the internet, systems also need to be improved in order to better regulate drugs that are accessed in this way. 
Today's national and international regulations on medicine safety have evolved over than a century. In 1906 came a major focus on medicine safety in the USA, with the Food and Drugs Act signed by President Theodore Roosevelt. The UK went on in 1941 with the Pharmacy and Medicines Act to force manufacturers to list active ingredients on drug packaging, and restrict manufacturers from general advertising about medical claims of their products. The thalidomide disaster of the late 1950s and early 1960s brought about further major improvements: previously drug testing was very limited. Now great care is taken in assessing possible risks of medicines during pregnancy.
Many serious adverse drug reactions happen in people with genetic reasons for reduced ability to handle drugs in the body. Drug leaflets now specify if there is any known 'pharmacogenetic’ information on a medicine. The potential seriousness of these differences between people is shown by the example that the Japanese regulatory authorities are unwilling to license drugs for use in their country unless they have been tested on Japanese people.
New pharmacogenetic provide the opportunity to reduce exposure of patients to potentially harmful medicines based on recognizing an increased genetic risk. And new chemical genomics methods allow ways to identify safer and more effective use of current and new medicines.
For further details on these themes, see my interview with Amy McLeod from Warwick's Knowledge Centre.