FIP Congress 2006
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Public demand for innovation places a considerable
burden on health care providers. The four symposia of the congress's
pharmacy practice programme examined innovations in patient treatment,
innovative health care delivery, using innovations to improve patient
safety (reported by Pamela Mason) and innovations in learning and
education (reported by Steven Kayne) and described possible solutions
that are being developed
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 The World Congress of Pharmacy and Pharmaceutical Sciences,
the 66th International FIP Congress, was organised by the International
Pharmaceutical Federation in association with the Federal
Council of Pharmacy of Brazil.
It took place in Salvador da Bahia from August 26 to 31, 2006
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Innovations that will bring huge advantages are just
around the corner
Introducing a session on innovations in patient treatment, chairman
Philip Schneider, of the Ohio State University, US, explained that there
are
huge advances in medical treatment for patients just around the corner. “Pharmacists
need to be up to speed with these innovations or we will be left out
in the cold,” he said.
Joseph Saseen, of the University of Colorado Health Sciences Centre,
US, gave his perspective on the future of drug therapy and the implications
for patient care. A big target for future drug therapies is metabolic
syndrome, he said. Patients with metabolic syndrome are at high risk
for progressing to type 2 diabetes and cardiovascular disease.
Diabetes
is a major threat to public health with one in 10 deaths in adults aged
35 to 64 years currently attributable to this condition. The prevalence
is set to rise, due mainly to the rapidly rising prevalence of obesity.
Unfortunately, traditional diabetes drugs have negative or neutral effects
on obesity. Sulphonylureas, thiazolidinediones and insulin are associated
with increased body weight, while biguanides, a-glucosidase inhibitors
and meglitinides have no effect on weight. Moreover, although these drugs
improve insulin deficiency or insulin resistance, they have no impact
on other diabetic parameters, including elevated glucagon secretion,
gastric emptying and ß-cell impairment.
However, improvements in treatment are in the pipeline. One new drug
target is glucagon-like peptide (GLP)-1, an incretin-like hormone released
by the gut in response to food which stimulates insulin secretion. Another
new target is the hormone amylin. The effects of both these hormones
are blunted in patients with diabetes. Incretin mimetics (eg, exenatide)
and amylomimetics (eg, pramlintide), both intravenous preparations, have
been developed. These drugs target biological factors, including body
weight, elevated glucagon, gastric emptying and ß-cell impairment,
which are not targeted by older drugs.
Future innovations in diabetes
pharmacotherapy include dipeptidyl peptidase-4 (DP-4) inhibitors (sitagliptin,
vildagliptin), which inhibit breakdown of endogenous GLP-1, other incretin
mimetics (eg, liraglutide), GLP-1 receptor antagonists and dual-acting
peptide for diabetes (DAPD), which has GLP-1 receptor agonist activities
and glucagon receptor antagonist activities. Another new drug which may
be beneficial in patients with metabolic syndrome is rimonabant, an oral
therapy that selectively inhibits the cannabinoid-1 (CB-1) receptor,
producing weight loss, reduced insulin resistance and triglycerides and
raised high-density lipoprotein cholesterol and glucose tolerance.
Turning his attention to the evolution of pharmacotherapy for rheumatoid
arthritis, Professor Saseen described the “old treatment paradigm” in
which patients had to progress to severe disease (ie erosion and distortion
of bone with symptoms of severe joint pain and swelling) before they
received aggressive disease modifying therapy because of the high toxicity
of these drugs.
Evidence, however, has led to the development of a “new
paradigm” in which rheumatoid arthritis is managed earlier with
disease modifying therapy given “up front” as part of initial
management. Increased understanding of the role of cytokines in rheumatoid
arthritis, particularly their up-regulation as a cause of inflammation
has led, since 1998, to the development of a range of new medicines,
which produce significant clinical benefits.
These include TNF-a blockers
(eg, etanercept, infliximab, adalibumab), the interleukin 1 antagonist
(anakinra) and the T-cell inhibitor (abatacept). Capitalising on the
science of rheumatoid arthritis and targeting biomarkers of the disease,
these medicines reduce joint damage, preserve joint integrity and improve
the quality of life, especially in severe disease.
Going on to discuss the pharmacotherapy of hypertension, he said that
most currently used drugs target the angiotensin-renin pathway, but only
after the pathway is activated. However, future innovations will target
the renin pathway before activation. Agents in development include aliskiren
(a renin inhibitor), darusentan (a selective endothelin receptor antagonist)
and nebivolol (a beta blocker with vasodilator activities).
Concluding, Professor Saseen said that innovations in drug therapy will
impact on patient care, improving quality of life, changing disease distribution
and reducing mortality. Combination therapies will be used increasingly
with, for example, three or more drugs the norm in diabetes. Innovations
will also expand pharmacists’ roles as care providers, care co-ordinators
and cost managers in all settings. Impact of gene therapy Gavin Brooks, head of the school of pharmacy at the University of Reading,
UK, considered gene therapy and its impact on pharmacy and pharmacists.
Professor Brooks began by reminding the audience that gene therapy
is a technique for correcting defective genes responsible for disease
development.
There are two types of gene therapy, he said. First, there is somatic
gene therapy (involving cells other than germline cells); used extensively,
this method only affects the treated patient. Secondly, there is germline
gene therapy (using sperm or egg cells); this method raises ethical problems
around passage of genes from generation to generation.
However, with
this method, permanent genetic cures might be achieved by delivering
a functional copy of a mutated gene to every cell of the resulting progeny.
Successful gene therapy involves isolation of the gene responsible for
the disease by cloning/sequencing. The gene is then inserted into a vector
and the vector introduced into the affected cells. This results in expression
of the healthy gene and disease cure.
Delivery of the therapeutic gene
is achieved by viral (eg, common cold virus, retrovirus) or non-viral
(eg, liposomes, DNA vaccines, antisense oligonucleotides, DNA decoys)
means. Non-viral delivery is associated with poor levels of gene delivery,
but fewer potential side effects than viral
delivery.
Professor Brooks explained that to date there have been almost 1,200
gene therapy clinical trials, of which 67 per cent have been conducted
in the US and 29 per cent in Europe. Within the EU, the UK has conducted
the largest number of trials. Gene therapy has been successfully used
for the treatment of adenosine deaminase (ADA) severe combined immune
deficiency. The first patients, two girls aged 4 and 11 years, were treated
with the ADA gene in 1990. They also received the standard treatment
of PEG-ADA enzyme, but at reduced dosage. Overall the treatment was associated
with improved outcomes and the patients are still doing well.
Gene therapy
is also being used in cancer. Professor Brooks described a phase III
trial published in 2005 where the researchers gave 12 patients with recurrent
glioblastoma multiforme (a type of cancer) intra-tumour injection of
retroviral vector producing cells, followed by intravenous ganciclovir.
The treatment was well tolerated with only minor adverse
events and provided effective delivery of therapeutic genes to target
tumour cells. Tumour responses were seen in 50 per cent of cases. Another
potential clinical use for gene therapy is the treatment of vascular
disease.
Results from phase I and II studies investigating intra-operative
E2F (edifoligide) gene therapy in patients receiving bypass vein grafts
have been promising, with fewer graft occlusions or critical stenoses
than when no treatment is given. However, phase III trial results showed
that edifoligide is no more effective than placebo in preventing vein
graft failure following coronary artery bypass graft surgery and that
ex vivo treatment of lower extremity vein grafts with edifoligide does
not confer protection from the need to reintervene for graft failure.
Turning to the implications of gene therapy for pharmacists, Professor
Brooks said that like any new therapy, it provides pharmacists with the
opportunity and responsibility to develop new skills and expand pharmacy
services. However, pharmacists cannot assume they will automatically
be given responsibility for dispensing gene therapy products. Many DNA
and virus products may not be considered “drugs” in the traditional
sense so other health care specialists may assume responsibility for
their dispensing and clinical use. However, pharmacists should fight
for their role, he added.
For pharmacists who are involved it is important to know that gene therapy
clinical trials are different from those for standard small molecule
drugs. Every trial is different in terms of standard
operating procedures (SOPs), but SOPS specific to gene therapy include
handling, storage, cleaning, dispensing, transport and waste disposal.
All
gene therapy products must be handled in validated biological safety
cabinets (Class
II) or negative pressure isolators, and most require ultra-low temperature
(–70C) freezers, which are not available in most hospital pharmacies.
Disinfection and decontamination procedures need to be specific to each
viral product and aseptic technique must be used throughout the dispensing
process. Often gene therapy products are of small volume and require
multiple, complex dilutions for reconstitution, which is best achieved
with micropipettes rather than needles and syringes.
Professor Brooks concluded by saying that despite almost 1,200 clinical
trials since 1989, results overall have been disappointing. Many questions
remain to be answered, including effective doses and long-term effects
of therapy. There is a need to improve non-viral delivery methods and
the targeting of genetic material to the site of action.
“There
have been some promising clinical data but the jump from bench to bedside
has been rapid and we must proceed with caution. However, improvements
in vector technology and development of RNA interference technology could
provide real opportunities for gene therapy, making it an important alternative
to usual treatments.”
Ethics and cost of gene therapies
 Jerry
Siegel, of the Ohio State University, US discussed how the costs
of innovations create ethical dilemmas
for health care
providers. Innovations are expensive to develop and produce, and
which patients
should receive them is a matter of perspective.
From a doctor’s
perspective the concern is to do no harm, hospitals have to manage
limited resources, the pharmacist is concerned with the appropriate
use of medicines at the lowest cost and the patient wants treatment
at any cost. But perspectives are changing, he added. Doctors
are becoming more cost-conscious, and evidence-based medicine
and drug
budgets are increasingly important issues for pharmacists.
Faced with the use of high-cost drugs, doctors, pharmacists and
patients have several options. Doctors can simply treat the patient
and let
someone else worry about the cost or they can become informed about
cost, evaluate the risks and benefits of therapies and develop
a systematic and realistic approach for determining the clinical
needs
of the patient.
Pharmacists, on the other hand, can focus on obtaining
medicines at the lowest possible cost while assuring the integrity
of the supply chain. They can conduct pharmacoeconomic analyses,
inform health care professionals about reimbursement strategies
and, in some countries, provide patients with information to
obtain medicines
from industry and government programmes. Patients also have several
options. They can pay personally, borrow or raise the money, obtain
industry or government sponsorship, become a volunteer in a clinical
trial or decide on no treatment.
In making a decision it is easy to fall into traps of various types,
he said. Key decision traps include “frame blindness” (ie,
losing sight of the objectives and solving the wrong problem) “group
failure” (a group decision should be better than one made
by an individual) and “fooling yourself about feedback”(eg,
failure to identify appropriate clinical data, believing a treatment
is better than it really is and letting a patient have an expensive
treatment simply because the family can pay).
Professor Siegel concluded
by making several recommendations for avoiding such “decision
traps”: First, establish an ethics committee with “24/7
access”, secondly define roles and responsibilities of decision
makers (eg, medical, pharmacy and hospital directors) and, thirdly,
decide who makes the final decision. Should it be the doctor, the
pharmacist or the patient? Should it be a consensus or a majority
decision? And is it only a matter of money? |
Role of nanotechnology Claus-Michael Lehr, of the department of biopharmaceutics and pharmaceutical
technology, Saarland University, Saarbrucken, Germany, discussed the
role of nanotechnology in overcoming biological barriers and providing
novel routes for drug delivery. The “nano cosmos” is extremely
small (10–9m), but using scanning force microscopy it is possible
to see biological structures (eg, cells, atoms and the DNA double helix)
in this
dimension.
He went on to highlight several pharmaceutical applications of nanotechnology.
The first was colitis where diarrhoea makes it difficult to put a drug
in place. However, small “nano” particles can be selectively
deposited and accumulated in the inflamed intestinal tissue. This technology
has been successfully used to deliver the anti-inflammatory, rolipram,
to colitis tissue with improvement in symptoms and reduction in adverse
effects compared with rolipram alone.
Nanotechnology has also been used
successfully for delivery of drugs through the skin. Nano-encapsulated
flufenamic acid has been shown to penetrate the skin more efficiently
than the free molecule. Another promising new area for nanomedicine is
the delivery of drugs to the lungs.
Professor Lehr concluded by saying that nanotechnology offers great potential
for the targeted delivery of drugs to the site of action and for the
improved delivery of modern biopharmaceuticals (eg, peptides, genes)
across biological barriers such as the skin and lung. “This field
is moving fast and to maintain their position as drug experts, pharmacists
must be educated in nanotechnology,” he said. |
The
Pharmaceutical Journal