Clinical trial split into four categories

The adverse reactions experienced by six healthy volunteers during a new drug trial at the clinical pharmacology research unit at Northwick Park Hospital in London last month highlighted the process under which drugs are tested in humans.

The phase I trial of TGN1412, a new monoclonal antibody designed to treat autoimmune disease (in which the immune system attacks the body), resulted in the volunteers developing catastrophic multiple organ failure; two men remain in intensive care.

While the exact cause of the severe reaction has yet to be established, the Medicines and Healthcare Products Regulatory Agency (MHRA) - the UK equivalent of the Irish Medicines Board - has begun a formal inquiry.

Clinical trials are divided into four different categories or phases. In phase I, the new drug is tested in humans for the first time, using a small number of healthy volunteers. Phase II involves recruiting patients with the disease that the new drug is intended to treat to see if it has beneficial effects; this phase typically involves hundreds of patients.

In phase III, the aim is to confirm the efficacy and safety of the drug by testing it on thousands of people in a randomised and controlled way. Half the subjects are given the trial drug while the other half are given a placebo or dummy pill.

Phase IV involves assessing the drug after it has been licensed to check for medium or long-term issues that may not arise in earlier, short-term clinical trials.

In the Republic, just one company is involved in phase I trials; according to the IMB the company is mainly active in modified phase I research which does not involve exposing humans to a new drug for the first time. Most of the clinical trials approved by the IMB each year involve phase III research.

Such research is governed by the 1997 Clinical Trials Act and the 2001 European Directive on Clinical Trials implemented here in 2004. Following the receipt of a trial application by the IMB, its assessors look at the application before sending it forward to the next meeting of the IMB clinical trials subcommittee.

It has nine medically qualified members from across a range of specialities. If the committee deems the research proposal unacceptable, then it asks for further information from the applicant before forwarding the application to the IMB's overall management committee.

An acceptable application is also sent to the management committee which has the final decision on whether to issue a trial authorisation.

IMB involvement does not end there. Visits to the research sites are carried out by inspectors from its compliance department.

"Sites involved in the conduct of clinical trials may be inspected at any stage of the trial, whether pre initiation, ongoing or completed," says Dr Joan Gilvarry, the IMB's human medicines director.