Experts call for phase I trial safety rules to be tightened up

Rules governing early-stage clinical trials of higher-risk drugs should be tightened up, according to recommendations by a group of experts set up by the Department of Health after the Northwick Park Hospital disaster earlier this year.

Six healthy male volunteers were hospitalised in March with multiple organ failure after being given the experimental monoclonal antibody, TGN1412 in a trial at the hospital in north-west London conducted by contract research firm, Parexel, on behalf of German biotech firm, TeGenero.

Regulators concluded that the drug appeared to cause an unprecedented biological reaction in humans by stimulating the immune system, a reaction not seen in animal tests.

The interim report into the TGN1412 trial, by the scientific expert group chaired by Gordon Duff, said that the first dose of higher-risk drugs should be given to one person only. It also recommended that drugs affecting the immune system, such as TGN1412, might be more suitable for testing on patients suffering with a disease, rather than on healthy volunteers.

ìClinical trials in general have an excellent safety record, but in the light of the TGN1412 incident there is a need to look at the future safety of clinical trials involving novel and potentially higher risk drugs,î said Duff.

The recommendations mirror those published on Monday (July 24) by a joint taskforce set up by the Association of the British Pharmaceutical Industry (ABPI) and the BioIndustry Association (BIA).

The industry taskforce made the following specific recommendations:

• Use of an alternative initial dose-setting assessment for certain novel agents

• Giving only one subject the active medicine on the first day

• Following this with `staggered dosing' as doses are increased

• Conducting such studies at a hospital with intensive care facilities

• Providing all investigators with appropriate training in such studies

• Giving particular emphasis to manufacturing controls to ensure safety, quality and efficacy of the finished product

ìAs a responsible industry, we were shocked and want to ensure a similar event never occurs again, and that is why we have developed these `points to consider' for first-in-human clinical studies,î said Dr David Chiswell, co-chairman of the industry taskforce. ìIn order to safeguard patient safety, we want to make the guidelines available to the research-based industry and - if either the UK or the European regulatory bodies find this useful - to help develop them into a more formal set of `points to consider'.

Earlier this month, TeGenero filed for insolvency saying the publicity surrounding the disastrous phase I trial made it impossible for it to attract investment to keep operating.