European Association of Hospital Pharmacists
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Aspects of quality and safety introduced by new therapies, including genome technology, were discussed at the 12th EAHP congress.
Hannah Pike reports |
This article as a PDF (40K) |
The impact of new technologies on hospital pharmacy
Pharmacists can play a role in
moving the application of pharmacogenetics from the laboratory to the patient’s
bedside, said William Evans, St Jude Children’s Research Hospital, Memphis,
Tennessee, during his keynote presentation.
Dr Evans explained that the technology behind pharmacogenetics is currently
much further ahead than the science (such as the pharmacology and the genetics),
and there is still a lot of work to be done to establish robust diagnostic
models. However, progress is being made, for example in the use of pharmacogenetics
in the research and treatment of diseases such leukaemia.
Genetics can have an overwhelming
influence on the action of drugs, said Dr Evans. He described the work of his
team in using the technology to elucidate the genetic determinants of drug
response to treatment for acute lymphoblastic leukaemia.
Pharmacogenetics will enable us to divide patients into sub-populations based
on their ability or inability to respond to a drug, or their predisposition
to drug toxicity, he explained, rather than grouping patients into “textbook” categories.
“If you genotype a patient correctly you only have to do it once, unlike
blood sugar or serum creatinine,” he said. If that information is put
into a secure database, the patient could authorise their pharmacist or doctor
to
access that information, which could aid clinical decisions about drugs known
to be affected by genetic make-up.
Dr Evans added that there has been some scepticism from the medical profession
about the use of this technology. For example, doctors who have been prescribing
a drug for years may find it hard to understand why a genetic test is suddenly
needed.
“Regardless of whether you are working in cancer, cardiology or other
areas of health care, genetics and genomics are ultimately going to impact
the way
you treat patients and make decisions about drug treatment and drug doses,” he
said.
More guidelines needed for safer clinical trials
Nirmala Bhogal: access to prior information is important |
Using flexible testing strategies and
applying a precautionary principle to clinical trials might have avoided last
year’s incident in the testing
of the monoclonal antibody TGN1412 at
Northwick Park Hospital, said Nirmala Bhogal, from the Fund for the Replacement
of Animals in Medical Experiments, Nottingham.
She said that additional guidelines specifically covering the clinical testing
of biotechnology products are needed (there are currently four or five documents
available worldwide).
“We have novel biotherapeutic [agents] being developed at a dramatic
rate. Some of them have modes of action that resemble products that are already
marketed,
but many do not,” Dr Bhogal said. She explained that where a mechanism
of action is very different from a known mechanism or a drug is likely to cause
multiple effects then caution is needed in clinical studies. Such drugs should
be tested on a single volunteer and administration should be staggered.
During animal trials of TGN1412, macaques developed some (mild) adverse effects
two hours after being given the drug. The volunteers should have been given
the drug no sooner than two hours after each other, she said, but it was administered
to them within minutes of each other.
Turning to the need for information, Dr Bhogal said it is important to have
access to as much information as possible that has previously been collected
about the drug. There is evidence that TGN1412 was not the first antibody to
cause cytokine release. “Why isn’t this information in the public
domain?” she asked.
It can be difficult searching the literature for information about drug pathways
or processes because the information is often presented in different formats
and not presented statistically. “Comparison meta- analysis data is absolutely
dreadful at the moment,” she added. Another obstacle is obtaining the
required data from pharmaceutical companies.
Various testing schemes have been proposed for clinical trials but we need
better schemes for pre-clinical trials, she said. In the case of TGN1412, none
of the preclinical studies was able to predict the effects seen in the human
volunteers.
These studies will potentially take years to conduct which will be unpopular
with the regulators and pharmaceutical companies, Dr Bhogal said, but we do
not currently have simple, fast screens for bioaccumulation and immunogenicity.
Dr Bhogal said that clinical trials need to be designed on a case-by-case basis. “Guidelines
are guidelines. It is down to individual pharmaceutical companies and clinicians
to ensure that how they test the product is the best for that particular
product,” she said.
Challenges of unlicensed drugs in Europe
Irene Krämer: the pharmacist is personally responsible for the
quality of imported drugs |
Purchase of unlicensed oncology medicines is now routine in the pharmacy departments
of tertiary care hospitals across Germany, said Irene Krämer, director
of the pharmacy department, Johannes Gutenberg University Hospital, Mainz.
Speaking at a satellite
symposium sponsored by IDIS,
professor Krämer said that oncology drugs are the most common and the
most expensive imported drugs in Germany.
She explained that legislative changes have meant that a number of drugs formerly
licensed in Germany now need to be re-approved, and many drug companies are
not willing to go through this procedure with drugs that have a small share
of the market. Since most of these drugs have been used for decades as part
of internationally approved protocols, they are not considered to pose a risk,
despite their unlicensed status.
Professor Krämer outlined the restrictions on purchasing unlicensed drugs
and explained that, under German legislation, imported drugs may not be stocked
in the pharmacy. Furthermore, the pharmacist is personally responsible and
liable for the quality and safety of drugs imported.
Professor Krämer said that there is still a problem with reimbursement
for unlicensed drugs in Germany, and obstacles to overcome regarding the compassionate
use of these drugs.
Risk assessment
Allan Karr, pharmacy business services
manager at University College London Hospitals NHS Trust gave the symposium
an overview of the role of hospital pharmacists in dealing with unlicensed
medicines in the UK, including their roles in drug and therapeutics committees,
quality assurance, clinical pharmacy, purchasing and the
dispensing service.
Mr Karr also said that although risk assessments are now commonly carried out,
he does not believe that enough attention is focused on risk reduction. Risk
reduction areas include:
• Assessing the clinical risk. Is it worth using an unlicensed medicine for
a
self-healing skin condition, for example?
• Quality assurance. Is the expense of analysing a product in a full quality
assurance assessment warranted?
• Ensuring that patient information is translated into English.
• Promoting reporting of adverse drug events to the Medicines and Healthcare
products Regulatory Agency.
• Providing GPs with full details of the unlicensed product.
• Keeping full records, including details of any adverse reactions and records
of any risk assessment and risk reduction tools.
Mr Karr said that at UCLH they are currently developing a software application,
together with Guy’s and St Thomas’ NHS Foundation Trust, to standardise
a risk assessment and risk reduction tool.
“We hope that in the next year or two we will have an application that
will help improve the way we manage unlicensed medicines and reduce risks,” he
said.
Shortages of medicines in the European Union
Hospital staff need more and better
information about changes in drug preparations to deal effectively with the
problem of drug shortages, said Walter Deutschmann, from Klinikum Bremen
Mitte in Germany.
He said that his hospital pharmacy supplies drugs to four hospitals, with a
total of about 3,600 beds. They conducted a four-year study into the effect
of drug shortages and bottlenecks (defined as a manufacturer not being able
to deliver a drug within one week) on the hospital.
Results showed that there was an average of 100 bottlenecks per year, with
the incidence of supply problems increasing each year. Dr Deutschmann said
that the staff were rarely informed by the companies about stock problems. “Mostly,
we had to ask for outstanding deliveries or were informed merely with the shipping
papers of other products,” he said.
The shortages were overcome by using existing stock or another pack size (in
56.7 per cent of cases) or procuring an identical preparation from a wholesaler
(in 11.9 per cent of cases). In 28.7 per cent of cases the patient was given
a different drug, either imported (4.2 per cent of cases), an identical preparation
from an alternative manufacturer (21.7 per cent of cases) or a different drug
with a similar mode of action (2.8 per cent). In 2.6 per cent of cases it was
not possible to make a suitable substitute.
Dr Deutschmann explained that, with the exception of some antidotes, German
legislation does not allow unlicensed drugs to be stocked in pharmacies. The
unacceptable delay in getting a drug to a patient that would occur if the drugs
were procured in the usual way means that hospital pharmacies do stock imported
drugs, but are in conflict with the law.
Dr Deutschmann said that about 840 working hours were spent managing the drug
shortages over the four year study period. In addition to being time consuming,
the market price is also affected. “In 2006 supply bottlenecks resulting
from the shutdowns of intravenous immunoglobulin preparations and other blood
derivatives led to subsequent rationing and a considerable increase in prices,” he
added.
Regulatory changes
Rui dos Santos Ivo, from the European Commission, said that there is clearly
a need for regulatory changes to support the availability of medicines across
Europe. He gave an overview of recent reforms to pharmaceutical legislation
covering issues such as the obligation of continuous supply by wholesalers,
the organisation of data protection periods, measures to reinforce pharmacovigilance
and new rules on labelling and patient information leaflets. He acknowledged
the challenges involved in translating these directives into practice.
He summarised ongoing and future
European initiatives to support medicines availability. These include changes
in legislation regarding studying drugs for paediatric use, and the creation
of a European database containing information on all medicinal products for
human or veterinary use that have been authorised in the European Union and
the European Economic Area.
The database, currently under development, can
be viewed at www.eudrapharm.eu |
Hospital
Pharmacist