Dr Muiris Houston, Medical Correspondent, looks at the workings of the Irish Medicines Board and how drugs are approved for use here
Many consultations with a doctor end with a prescription. Whether you have presented with an infection requiring short-term antibiotics or have a chronic condition such as asthma, arthritis or coronary heart disease and need long-term medication, your next stop will be the pharmacy to fill the script.
Or maybe you have cancer and regularly visit hospital to receive the latest chemotherapy drugs.
Whatever the circumstances, did you ever stop and think who has approved this medication? Who says it is safe or that this is the right dose for me? Has anyone checked to ensure the same amount of active ingredient is in each tablet?
Until a commonly used drug such as Vioxx is withdrawn from the market, most of us do not give the subject a second thought. The widely prescribed anti-inflammatory drug was withdrawn in September 2004 after it was discovered that Vioxx was associated with a tripling of the risk of heart attack and stroke in patients (mainly those with arthritis) taking the drug for 18 months or more.
The body responsible for ensuring that the drugs we consume are safe is the Irish Medicines Board (IMB). Some 10 years in existence this year, its chief executive, Pat O'Mahony, describes its mission as one "to protect and enhance public and animal health through the regulation of human and veterinary medicines and medical devices available in Ireland, or manufactured in Ireland for Irish or export markets".
But what actually happens when a pharmaceutical company submits an application to have a new drug approved for human use here?
Dr Joan Gilvarry, director of human medicines at the IMB, and her senior managers explain the process, which is legislatively driven.
The company is obliged to submit data on the drug's quality, safety and efficacy. This information is then analysed using a team approach in which in-house experts in pharmaceuticals, toxicology and medicine combine to asses the data.
Pharmaceutical assessment involves a review of all the elements relating to the quality of the medicine, including how it will be manufactured, and how its quality will be tested. Toxicologists examine animal data to assess the drugs safety record when tested in animals.
And the medical assessment focuses on information from Phase I, II and III clinical trials of the drug (see panel) including information on how the new drug compares with placebo (dummy pill) or with an existing treatment for the disease.
"The assessment process involves critical and peer review and the generation of a list of issues for response by the pharmaceutical company. If necessary, additional advice is sought from scientific experts," Gilvarry says. The Minister for Health appoints a 12-person advisory committee for human medicines to the IMB and it also has access to an expert committee of specialists.
At the end of the assessment, the toxicologists, pharmacists and doctors must all sign off the application. At this point Gilvarry brings a dossier to the IMB's management committee where a final decision on whether to grant a licence is made.
Around 18,000 applications for drug licences were made to the IMB in 2005, so efficient management system is needed to ensure everything works smoothly. The board recently introduced a workflow system, the New Irish Medicines Board Universal System (NIMBUS) under the direction of a workflow manager, which has significantly improved its efficiency.
Although the process involves the exchange of information with the pharmaceutical industry, Gilvarry and her team emphasise that it is carried out on an arm's length basis.
A company cannot request a "favourite" assessor and IMB staff are not permitted to accept gifts or hospitality from the drugs industry.
Ultimately, the assessment is based on a benefit/risk model which takes into account the illness a new drug is designed to treat.
A cancer drug, for example, might be approved despite having significant side effects because it has been shown to prolong life. "If on the basis of the assessment, the medicinal product is considered to be relatively safe and to provide a relative benefit in a specific medical condition, then it can be authorised," Gilvarry says.
How does the IMB monitor drugs that are on the market after they have been licensed? Healthcare professionals and pharmaceutical companies notify the board of suspected adverse reactions (ADRs) in patients. Drug companies must also submit, at regular intervals, periodic safety update reports (PSURs) on each product.
These reports, compiled six monthly in the case of a new drug, include information on global adverse reaction data, information from new and ongoing studies of the drug and updated findings in the medical literature. The process of monitoring drug safety after a drug is placed on the market, called pharmacovigilance, also involves checks for defects in medicines.
Internationally, safety information is compiled by the European Medicines Evaluation Agency (the IMB is represented on 13 of its working parties) and by the World Heath Organisation.
However, the system of regulating drugs does have potential loopholes. Notwithstanding the licensing process, doctors are permitted to use any medicinal product on what is termed an "off-licence" basis.
For example, reports may appear in medical journals that an established blood pressure drug is effective in the treatment of migraine. A doctor here is entitled, based on clinical judgement, to begin to use the drug in migraine patients in advance of a formal licensing of the product for the new disease.
But the doctor using a medicine in this way is responsible for any problems that may arise as a result.
Another situation where unlicensed drugs may be used occurs when a company making the only version of a product licensed for the Irish market either ceases manufacturing or develops temporary production difficulties. This means the drug has to be imported by pharmacists on a "named patient" basis without it having been through the IMB regulatory process.
The IMB agrees tighter regulations are needed for unlicensed medicines. It recently appointed an expert to examine what it calls "the issues surrounding the use of unauthorised medicines".
• Irish Medicines Board staff operate an "on call" rota to answer queries from members of the public. The board recently began publishing a detailed summary of product characteristics (SPC) for all licensed medicines on its website. (www.imb.ie). According to Gilvarry, "this will provide an additional source of accurate, reliable information on medicines for the public".
