Saturday, January 23, 2010

Ancient Cures - Modern Science

The natural world has been medicine's most effective arsenal, providing life-saving antibiotics and our most potent anti-cancer drugs. Although historically most drugs have had their roots in natural products, some scientists worry that the approach is in decline. Eimear Vize examines some of the latest medical research utilising natural ingredients and finds that the apothecary Earth is still dispensing.

When it comes to stocking pharmacy shelves with drugs to treat our ailments and illnesses, Mother Nature still is the ultimate medicinal chemist. An estimated 70 percent of drugs approved to treat infectious disease and cancer over the past 25 years are of natural origin - medicines obtained from sources such as plants and animals, derived from natural products or chemically designed to mimic natural products.

These natural medicines range from aspirin - originally obtained from the willow tree - to taxol, the anti-cancer drug discovered in the Pacific yew tree, and the anti-malaria drug artemisinin from the Chinese wormwood tree.
In recent times, a remarkable number of clinical trials have rediscovered the therapeutic significance of some ancient remedies and uncovered a few new ones from Nature’s extensive medicine cabinet.

Medicines from the Sea

The sea represents an oasis of potential medicines and healing substances. Earlier this year, Norwegian scientists managed to produce completely new antibiotics from marine bacteria. These ‘bioprospectors’ discovered eleven species of bacteria found in the sea, which create substances that kill cancerous cells, and three other bacteria that produce new antibiotics.

Behind the successful collaboration between Professor Sergey Zotchev of NTNU (Norwegian University of Science and Technology) and senior scientist Håvard Sletta of SINTEF (the largest independent research organisation in Scandinavia), lies a long and painstaking process of screening, cultivation, isolation and testing. However, it will still take some time before they can be sure that the process will continue to the phases of commercialisation and medicine production.
“Substances with a new chemical structure and, we hope, with a different mechanism of action than we already know of, could be extremely valuable, for example in fighting cancer. This is why we need more candidate structures. Not all of them can be developed into new medicines, but if we are successful with one or two of them, we will be quite happy,” says NTNU professor Sergey Zotchev.
Recent focus on a few selected bacteria has led to these exciting findings. In Bergen and Moscow, the 11 anti-cancer substances have been tested against leukaemia and stomach, colon and prostate cancers.
“We have found that cancerous cells have been killed, while normal cells survive, and that individual extracts act on different types of cancer cells,” says Håvard Sletta. “However, we still have not identified the active substances in the compounds produced by the bacteria”.

A wise man’s remedy for bladder cancer

Frankincense oil has been highly prized by traditional healers throughout the ages for its wealth of health supporting properties. Now, an enriched extract of the Somalian Frankincense herb Boswellia carteri has been shown to kill off bladder cancer cells, according to research presented recently in the open access journal, BMC Complementary and Alternative Medicine.

The investigators from the University of Oklahoma Health Sciences Center and Oklahoma City VA Medical Center examined the effects of the oil in two different types of cells in culture: human bladder cancer cells and normal bladder cells.  Remarkably, they discovered for the first time that frankincense oil is able to discriminate between normal and cancerous bladder cells in culture, and specifically kill cancer cells.
Gene expression analyses were performed to determine how frankincense oil affects bladder cancer cell survival. It appears the oil suppresses cancer cell growth by arresting cell cycle progression and induces bladder cancer cell death by activating multiple cell death pathways.
Lead researcher, Dr Hsueh-Kung Lin remarked: “Frankincense oil may represent an inexpensive alternative therapy for patients currently suffering from bladder cancer.”

The healing cuppa

The traditional Chinese cure-all Green Tea has just added another notch to its therapeutic belt as a new study of patients with prostate cancer, who consumed the active compounds in green tea, demonstrated a significant reduction in serum markers predictive of prostate cancer progression.
"The investigational agent used in the trial, Polyphenon E, may have the potential to lower the incidence and slow the progression of prostate cancer," confirms lead researcher James A Cardelli, Professor and Director of Basic and Translational Research in the Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center-Shreveport.
This open-label, single-arm, phase II clinical trial included 26 men, aged 41 to 72 years, diagnosed with prostate cancer and scheduled for radical prostatectomy. Patients consumed four capsules containing Polyphenon E until the day before surgery - four capsules are equivalent to about 12 cups of normally brewed concentrated green tea, says to Prof Cardelli.
Findings revealed a significant reduction in serum levels of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostate specific antigen (PSA) after treatment, with some patients demonstrating reductions in levels of greater than 30 percent. Other biomarkers were also positively affected, according to the study published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

In addition, researchers in Hong Kong are reporting new evidence that green tea may also help improve bone health. They found that the tea contains a group of chemicals that can help in the prevention and treatment of osteoporosis and other bone diseases that affect million worldwide. Their findings are in ACS' Journal of Agricultural and Food Chemistry.
And staying with the humble, yet apparently potent cuppa, two scientists at the University of Copenhagen are attempting to develop a new treatment for type-2 diabetic, with the help of a special African tea.
The tea is used as a treatment in traditional Nigerian medicine and is produced from the extract of Rauvolfia Vomitoria leaves and the fruit of Citrus aurantium. The scientists have recently tested the tea on 23 patients with type-2 diabetes over a four-month period and the results are very promising.
“The research subjects drank 750ml of tea each day. The cure appears to differentiate itself from other current type-2 diabetes treatments because the tea does not initially affect the sugar content of the blood. But after four months of treatment with tea we can, however, see a significant increase in glucose tolerance,' explains postdoc Joan Campbell-Tofte from the Department of Medicinal Chemistry.
She and her research partner Prof Per Mølgaard hope that new clinical tests and scientific experiments in the future will result in a new treatment for type-2 diabetics.

The sweet root to preventing colorectal cancer

Doctors at the Vanderbilt University Medical Center in Nashville, Tennessee, are also taking a new look at another ancient remedy – Liquorice - and coming up with some surprising results. Liquorice has been used therapeutically for centuries in both Eastern and Western medicine to treat various conditions. New research published in the Journal of Clinical Investigation has identified a chemical component of liquorice that may offer a new approach to preventing colorectal cancer without the adverse side effects of other preventive therapies.
Drs Raymond Harris and Ming-Zhi Zhang, and colleagues found that inhibiting the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) - either by treatment with glycyrrhizic acid, the main sweet-tasting component of liquorice, or by silencing the 11betaHSD2 gene - prevents colorectal cancer progression in mice predisposed to the disease.
Liquorice, Dr Harris notes, has been used as a nutraceutical for thousands of years for ailments ranging from coughs to constipation. But even liquorice is not without side effects; long-term consumption can lead to low blood potassium and increases in blood pressure - side effects linked to the inhibition of 11betaHSD2.
"These are relatively minor compared to the cardiovascular side effects of COX-2 inhibitors," Dr Harris says. "We didn't see [these side effects] in the mice we treated, but it would be something to be aware of, and something that could easily be treated with a diuretic."
Dr Zhang, an assistant professor of Medicine and of Cancer Biology, plans to look at the enzyme's role in lung cancer and other tumours.

Cherry picking for osteoarthritis

The one in four people in Ireland who suffer from osteoarthritis may find that pain relief can come with a cherry on top. According to researchers with the Dallas-based Baylor Research Institute, tart cherries, in pill form, are a promising pain-reliever for this common and debilitating form of arthritis.
Patients with osteoarthritis of the knees were enrolled in a pilot study to assess potential efficacy of the tart cherry pills. More than half of the patients experienced a significant improvement in pain and function after taking the cherry pills for eight weeks.
Made from Montmorency tart cherries, this preparation is made up of ground whole cherries and given as a soft gelatine capsule (marketed under the brand name CherryFlex).
"This specific type of tart cherry is one of the best studied natural products and anecdotally has been claimed to have a salutary effect on osteoarthritis and other types of arthritis as well," explains Dr John Cush, rheumatologist and principal investigator of the study.
Baylor Research Institute together with the Arthritis Care & Research Institute is currently enrolling patients in a second study, which will test cherry pills versus placebo in an eight-week double blind study.

Baking soda: For cooking, cleaning and ... kidney disease patients?

Baking soda – that common household essential used for cooking and cleaning – may now have an important role to play in kidney health. A study in the September edition of the Journal of the American Society of Nephrology (JASN) demonstrates that sodium bicarbonate can slow the decline of kidney function in some patients with advanced chronic kidney disease (CKD).

The study included 134 patients with advanced CKD and low bicarbonate levels, also called metabolic acidosis. One group received a small daily dose of sodium bicarbonate in tablet form, in addition to their usual care. For this group, the rate of decline in kidney function was greatly reduced—about two-thirds slower than in the other patients.
"In fact, in patients taking sodium bicarbonate, the rate of decline in kidney function was similar to the normal age-related decline," says principle researcher Dr Magdi Yaqoob, MD, from the Royal London Hospital.
Low bicarbonate levels are common in patients with CKD and can lead to a wide range of other problems. "This is the first randomised controlled study of its kind," adds Dr Yaqoob. "A simple remedy like sodium bicarbonate, when used appropriately, can be very effective."

The hepatitis healing power of blueberry leaves

A chemical found in blueberry leaves has shown a strong effect in blocking the replication of the Hepatitis C virus, opening up a new avenue for treating chronic HCV infections, which affect 200 million people worldwide and can eventually lead to cirrhosis and liver cancer.
Among the areas of especially high Hepatitis C incidence is the Miyazaki prefecture of southern Japan, a trend that led Dr Hiroaki Kataoka and colleagues at the University of Miyazaki and elsewhere in Japan on a search for better treatment options.
They screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry. They purified the compound and identified it as proanthocyandin - a polyphenol similar to the beneficial chemicals found in grapes and wine.
While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold, and similar chemicals are found in many edible plants, suggesting it should be safe as a dietary supplement. In the meantime, the researchers now hope to explore the detailed mechanisms of how this chemical stops HCV replication.

Hookworms in MS trial

Scientists from The University of Nottingham have begun studying the potential health benefits of parasitic worms in treatments for people with the autoimmune condition multiple sclerosis (MS).
Backed by funds of stg£400,000 from the MS Society, their three-year project aims to determine whether infection with a small and harmless number of the worms can lead to an improvement on the severity of MS over a 12-month period.

If the trial is successful, the worms have the potential to provide a simple, cheap, natural and controllable treatment for MS.

The WIRMS (Worms for Immune Regulation in MS) study is led by Professor Cris Constantinescu and Professor David Pritchard and is a randomised, placebo controlled, phase 2 study in people with relapsing remitting MS and will be carried out at multiple centres up and down the country.

The 25 worms are microscopic and are introduced painlessly through a patch in the arm. They are then flushed out after nine months.

“People are really interested in this form of potential therapy because it’s a natural treatment,” says Prof Constantinescu, Professor of Clinical Neurology. “It’s been tested for safety and we now need to study the potential benefits and any side effects.”

The Wisdom of the Ancients

Some scientists around the world are getting historical in their hunt for superior medicine. Researchers at the University of Pennsylvania are hoping to rediscover ancient healing wisdom using chemical tests to identify the herbs used medicinally in ancient Egypt.
By studying the residue of ingredients added to wine in ancient clay jars, these researchers hope to unlock some of the medical understanding held by physicians thousands of years ago.
Ancient Egypt was renowned for its prowess in the field of medicine, so much so that sick people travelled there from abroad in search of herbal remedies. Archaeologists know that the herbs were administered in a potent blend with wine. But the identity of many of those medicinal additives is a mystery - their names recorded in hieroglyphics that have resisted modern efforts at translation.
Now, two University of Pennsylvania scientists have begun to crack the puzzle with chemistry. In research published recently in the online edition of Proceedings of the National Academy of Sciences, the pair reported some of the earliest evidence of just what those long-ago physicians were prescribing.
One Egyptian clay jar, estimated to be more than 5,000 years old, yielded flaky residue that suggests a veritable apothecary of possible ingredients: coriander, senna, germander, balm, and savoury, among others. Samples scraped from the inside of a newer jar, just 1,500 years old, yielded compounds that likely came from rosemary.
These studies stem from more than just historical curiosity. Senior author Patrick McGovern, an "archaeochemist" at Penn's Museum of Archaeology and Anthropology, wants to know if the ancient herbalists came up with anything that really works.
And researchers at Penn's Abramson Cancer Center are similarly intrigued. They are already studying herbs identified in some of Mr McGovern's previous experiments. A derivative of the wormwood plant, found in a 3,200-year-old fermented beverage from China, has shown some promise against tumour cells in preliminary lab studies.
"I think people should be open-minded [about ancient remedies],” says Prof Wafik S El-Deiry, a Penn Professor of Medicine, Genetics, and Pharmacology, "because there may be hidden treasures."

Clinical Research in Ireland

The test results are back. Dr Brian Moulton, CEO of ICORG – the national cancer clinical trials organisation, spreads the word and the research team is delighted. The news is good; a groundbreaking genetic test confirms that the patient’s cancer will in all probability never recur. ICORG investigator Dr John Kennedy can give that life-affirming guarantee to his patient at their next consultation, such assurances he thought would never be possible in 2010.

It’s the science of Tomorrow’s World: a test called the Oncotype DX Breast Cancer Assay, which measures the activity of a set of genes in breast tumour tissue, can accurately forecast the risk of a patient’s cancer recurring, thus allowing clinicians to tailor treatment accordingly. And depending on the test result, high-scoring patients can steel themselves against the months of necessary chemotherapy ahead, or it can take the terrible uncertainty of recurrence out of the equation for others with low scores, who will receive a more palatable hormone treatment.
This opportunity is being made available to Irish breast cancer patients under the US coordinated TAILORx Trial. Ireland is the only country participating outside of North America.
Before the trial ends in mid 2010, the genetic test will be offered to well over 500 Irish women with early-stage breast cancer (a third of all eligible patients) by their oncologists in 14 hospitals around the country through ICORG - the All-Ireland Co-operative Oncology Research Group.
This cutting edge cancer test is one of dozens of equally exciting clinical research trials ongoing in this country in various therapeutic areas. Ireland may be a small country, but the patient ‘take up’ of these trials is higher per capita here than even the USA. In fact, it’s more than twice as high. In oncology, where the greatest cohesive research efforts are taking place across a specialty, a record 5 percent of patients with cancer in Ireland had access to a clinical trial in 2009, compared to just 2 per cent in the US.
The consultant oncologists who spoke to Scope agree that this impressive result is driven primarily by the Irish patient; his or her willingness to participate in a clinical trial, without guarantee that they will receive the new agent, appears equally rooted in the desire to serve the greater good through the development of new treatments as any personal health gain that may be achieved.
This heroic commitment, however, was not always matched by the powers that be. Less than ten years ago, the role of clinical research in the health system in Ireland had hardly registered on the Government’s radar. There was scarcely mention of fostering clinical research to be found in ministerial speeches or policy documents. When ICORG set up on a shoestring budget 13 years ago, it was because of the vision and hard work of a handful of oncologists. However, it appears that the Government – in its clamber to build Ireland’s smart economy – is throwing its hat into the ring and plans to develop health research through the island on an unprecedented level.
Late last year, the Department of Health (DoH) published its ‘Action Plan For Health Research 2009 – 2013’ together with the Health Research Board's (HRB) “Strategic Business Plan 2010 – 2014”, both championing the goal of positioning Ireland as a leading international location for health focused clinical research.
Speaking about the new HRB strategic business plan, Enda Connolly, Chief Executive, says, “Our ambition is to put health research at the heart of the health system. This will improve people's health, change how we deliver patient care, ensure evidence is applied in policy and medical practice and create opportunities for new enterprise to support our economy."
Indeed, the HRB lists the “development of excellent clinical research” as its primary strategic goal for the next five years, which represents a major departure from its previous focus on early stage biomedical research and population health studies.
A key ambition, as set out in both of these new documents, is to bring together for the first time fragmented health research activity in Ireland into an integrated and focused health research system. This would involve providing strategic leadership, setting priorities, and addressing the bottlenecks hampering clinical research, taking into account the widely unpopular changes to national regulations.
The DoH’s Action Plan has pledged to establish clinical trials networks in targeted disease areas, which it maintains would increase the volume of trials conducted in Ireland along with investment. The HRB echoes this ambition, adding that it would like to see “more clinicians and health professionals conducting top quality research”.
Scope magazine understands from well-placed sources that, as part of its five-year strategy, the HRB may soon issue calls to interested consultants to set up clinical research groups in selected therapeutic specialties.
This organised mobilisation of experts in a disease area has never proved to be a straightforward endeavour. Lack of resources and leadership, even professional jealousies, has heretofore hampered most efforts in that direction. As it stands, only ICORG has managed in a little over a decade to secure membership of more than 97 percent of oncologists working in Ireland and has trials available to patients in every hospital where cancer services are provided.

“ICORG is a fairly unique organisation in Ireland, I don’t think there is any similar group in any other disease area. As a result of ICORG’s cohesive and formal structure, patients with cancer in Ireland have benefited greatly from clinical trials over the years,” explains Consultant Medical Oncologist Dr John Kennedy, former ICORG chairman and its principle investigator at St James’s Hospital.
“We have a cohesive group of oncologists working together to make trials available to patients and that’s a real advantage. We’re able to basically provide the trials for patients, who are attracted in such numbers that we can be seen internationally as being major contributors, despite having a relatively small population by European standards.”
He adds: “ICORG has forged links with the large North American academic centres and the leading research groups and has done so very successfully. ICORG is seen by a number of these groups as being a real asset in terms of access to Europe and access to European investigators and institutions.”
It would appear to the observer that ICORG’s success on the international stage must have contributed to at least some of this extraordinary and coordinated shift towards realising Ireland’s bright future in the clinical research arena. As an internationally recognised and respected high quality clinical trials group, ICORG has opened well over 100 trials and made a research option available to more than 4000 Irish cancer patients since its establishment in 1996.
“Investment in oncology research is on the up,” observes Dr Brian Moulton, the founding CEO of ICORG. “The actual statistics are that five years ago one in five research dollars in the world were spent in the area of oncology, which was quite an impressive statistic historically, but now it’s one in three. It’s a huge move, and it’s because of the early successes of a number of exciting new treatments such as the tyrosine kinase inhibitors and monoclonal antibodies that has brought this increasing investment.
“Next year, we will have available through trials between 6 and 10 of the most exciting, lead candidate drugs in cancer from the world’s top pharmaceutical companies - the best cancer drugs that are in development in the world - available in Ireland through clinical trials, and part of the reason that this is happening is the partnership and attitude of Irish patients who in the past participated in ICORG trials.”
At present, ICORG is coordinating 44 cancer trials throughout the country. The Group will this month announce a record-breaking enrollment of more than 1,000 patients participating in its trials in 2009, which is a tremendous achievement when you consider the research group’s modest beginnings.
Dr Moulton has met with many hospital consultants in various specialties over the years, offering advice on how to set up a clinical research group. His dominant message has always been for them to unify as a community; without a majority membership in their specialty, there is little chance of success.
“We’re just too small a country for fragmentation within the specialty. If you want to go out into the world and bring the best research to Ireland you need a critical mass. And the critical mass in most areas, probably in all areas, would require everybody in the country to be on the same team, in the same group,” he maintains.
Dr Kennedy adds that there is “very substantial enthusiasm” among most Irish consultants with regard to participating in clinical trials. “The problem is that some of them work in institutions that are so significantly under resourced they just don’t have the time to do it. We still have a situation in some hospitals where there is only one medical oncologist – the idea that someone in a single-handed practice could conduct clinical trials is just not tenable.”
Dr Moulton concurs that funding is too often an insurmountable barrier for many trying to set up research groups, especially in the current regulatory environment, which is far more onerous than when ICORG set up in the 1990s.
“Back in those days the regulatory pressure wasn’t as high, now if an organisation was to set up in cardiology for example about 50 percent of the first six people they employ to help organise them  - my guess is six is about the minimum – would have to be employed in the regulatory compliance area. In the early days for us, only one of our first 6 employees was in regulatory compliance,” he says.
In 2004, Dr John Crown from ICORG and Dr Martine Piccart from the Brussels based Breast International Group spearheaded a major campaign by thousands of academics and scientists across Europe, seeking to repeal a new European Directive on Clinical trials, due to come into effect on 1 May that year.
They warned that this new legislation would seriously hamper, if not bring to a halt, the performance of academic clinical trials in Europe. It was claimed that the bureaucracy and additional costs associated with the new rules would make it almost impossible to sustain most publicly funded clinical research.
The 2,000-strong lobby proved unsuccessful and the revised EU-wide legislation was introduced as planned. In Ireland, the HRB, which was monitoring the implementation of this new directive, expressed its concern in 2005 to the Department of Health about the difficulties these regulations were causing for clinical trial activity in Ireland.
“Before the Clinical Trials Directive came into place in 2004 there were 300 clinical trials a year being submitted to the IMB. In 2003, about 75 of these were by academic bodies, about 25 of which were ICORG. Two years later there were less than 100 clinical trials in total, including the pharmaceutical sector.  So it has dropped substantially,” reflects Dr Moulton.
A Galway consultant working outside of oncology contacted by Scope, who preferred not to be named, confided that the regulatory obligations were defeating her attempts to get patients onto clinical trials: “It’s extraordinarily difficult to get on clinical trials in Ireland. Our regulation is through the Irish Medicines Board and they are very strict. It’s just very, very hard to get patients in the trials in Ireland.”

But Mr Pat O’Mahony, Chief Executive of the IMB, told Scope that the regulatory requirements for the approval of clinical trials in Ireland are in line with other European countries. “These requirements are reviewed on a regular basis and the IMB actively participates in the Clinical Trials Facilitation Group and the EU Commission working groups established to assess the implementation and impact of the legislation,” he comments.
Mr O’Mahony stresses that while fees for clinical trials are on a par with those for other Member States, academic (non-commercial) investigators can apply for a fee waiver and these are generally approved.

“A voluntary harmonisation procedure was recently introduced to facilitate the authorisation of multi-centre trials in the EU. The IMB is highly supportive of this procedure and no additional fee for participation in this procedure is proposed at present,” he adds.
Although it was suggested to Scope that the roll of the IMB should include “a strong collaborative arm” with regard to clinical trials, Mr O’Mahony points out that the IMB is the independent regulator and is not a collaborator in clinical trials but does aim to facilitate a positive research environment in Ireland.
With this fresh, concerted national drive to expand and harmonise clinical research in Ireland kicking off in 2010, perhaps the future is bright for both consultants and patients interested in participating in trials.
“I hope so,” says Dr Moulton. “What I know is that clinical research is now a recognised priority. What I don’t know is that the money will be there to do it.
“I’m nervous about our situation; I’m nervous that some people will take ICORG as big enough and strong enough, that we’re already there. The truth is we’ve reached the end of the beginning of our development, if you know what I mean. We have a fantastic platform now to grow from. But we already know we have less funding for 2010 and that we can therefore open fewer new trials in 2010, but if that trend continues for the next three years, frustratingly, we could even end up back where we started.”
In 2008, the cancer initiative cost the Government about €4.5 million. In the same year ICORG, through its research trials, brought into the country more than € 4 million worth of free drugs as part of these trials.
Dr Moulton suggests: “If you made an investment in 2010 of €6 million in oncology clinical research, for example, not only would you have a high chance of bringing in €6 million worth of extra benefit in the form of free drug and diagnostic tests etc and also add value to the research system and increase options for Irish cancer patients but you also would have an opportunity to expand this area and create more jobs. Let’s hope those with the power and the purse strings embrace this opportunity.”

A Win Win Scenario

Saying yes to a clinical trial may be very good for your health. That’s the message from UK researchers who found that patients with chronic heart failure, who agreed to take part in clinical trials, had a better prognosis than those who do not.
Publishing their findings in recently in the European Journal of Heart Failure, the authors remarked that this positive outcome may even call into question the commonplace ethical requirement of most clinical trials that by choosing not to take part in the study a patient will not be disadvantaged.
The study involved 2,332 consecutive patients diagnosed with chronic heart failure at Castle Hill Hospital in Hull, UK. After a median follow-up of 55.7 months, analysis of the full cohort showed that 792 (34 percent) had died. However, survival was significantly associated with a willingness to take part in clinical trials, which more than halved the risk of death.
The authors note that outcomes for patients with chronic heart failure are generally very poor; epidemiological studies show that around 40 percent of patients diagnosed with chronic heart failure die within a year of diagnosis.
"However," says investigator Dr Andrew Clark from Castle Hill Hospital, "two-year mortality rate in recent trials of chronic heart failure trials has been in the order of 20 percent. And even in studies of very sick patients, mortality has only been 30 percent."
Irish hospital consultants agree that the overall patients benefit from enrolling in clinical trials. Volunteering for research studies can give patients access to promising new drugs long before they are available to the general public, but even for those not on the active arm of a research trial, there are well-documented benefits to their health.
“There is some evidence that patients who participate in clinical trials do better in general than people who don’t participate in clinical trials. That’s just a fact,” says Dr John Kennedy, Consultant Medical Oncologist in St James’s Hospital.
“Secondly, the treatment must be delivered in exactly the same way as all over the world for the scientific validity of the trial, so the patients are very closely monitored and scans happen on time, all of the things that you’d wish was the same for every patients happens for research patients.”

Colon Cancer Trial

Ten percent of all cancer diagnosed in Ireland is colon cancer, far too often presenting in a more advanced and harder to treat phase. So when Dr Seamus O’Reilly had the opportunity to enrol some of his patients in a promising international research trial combining Vectibix - a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR) - and chemotherapy, he signed up as one of the lead investigators in Ireland.
“We were approached by Amgen (a leading human therapeutics company in the biotechnology industry) to see if we were interested in getting involved in the study. It seemed interesting, with a newer, second generation of a drug that we have been using, but had the potential for less allergic reactions because it was more humanised,” explains Dr O’Reilly, a consultant medical oncologist in Cork University Hospital.
In fact, the trial demonstrated significantly improved median progression-free survival, and Vectibix was found to be very well tolerated.  
“What was particularly interesting about this study was the opportunity to identify those patients who would benefit most from the drug by testing for the KRAS wild-type tumours. Just over 90 percent of the patients will have this gene, whether it’s wild or mutated.
“We now routinely test for tumour KRAS status; we send the samples to the UK for testing and we’ve been doing that for about 18 months. It means that instead of treating everybody and hoping you’ll get a benefit, you’ll test everyone and approximately 50 percent of the patients will have the wild type and 50 percent will have the mutated form of KRAS. If it’s the latter then you don’t treat them. In this way the patients are spared unnecessary treatment and it also reduces the expense of treatment as well.
“In fact, it has resulted in significant resource savings for our day wards, but also there is nothing worse for a patient than to go through a treatment and find after all that, it hasn’t worked. There’s benefit all-round,” Dr O’Reilly adds.