Tighter safeguards proposed for high-risk clinical trials
pharmafile | July 26, 2006 | News story | Research and Development |Â Â Â
The expert group set up by the MHRA in the wake of the disastrous Northwick Park clinical trial has made its first recommendations on improving phase I trial safety.
The group's provisional conclusion was that pre-clinical testing, even though it followed current regulations, was at fault for not predicting a safe dose in the trial of TGN-1412, a new monoclonal antibody treatment.
Six men fell critically ill in March during a phase I trial for the drug, which was being developed to treat diseases such as rheumatoid arthritis and B-cell chronic lymphocytic leukaemia The trial was carried out by contract research organisation Parexel for the drug's manufacturers, the German biotech company TeGenero. TGN-1412 was TeGenero's first product to go to clinical trial, but as a result of the Northwick Park incident, the company has now filed for insolvency.
Chairman of the Expert Scientific Group Professor Gordon Duff said: "Clinical trials in general have an excellent safety record, but in the light of the TGN-1412 incident, there is a need to look at the future safety of clinical trials involving novel and potentially higher risk drugs."
The group interim report acknowledged there is always a risk – even if extremely small – with the first human exposure to a new medicine and it now suggests greater attention should be paid to first-in-man doses.
Its 22 recommendations include:
* In trials similar Northwick Park the first dose should be given to only one person and sufficient time left for adverse reactions to develop before further doses are administered
* Patients, rather than volunteers, could be involved in certain phase I trials, particularly for drugs that affect the immune system
* Specialist centres for phase I trials of higher risk drugs should be encouraged
* Pharma and biotech companies should look into providing open access to their unpublished pre-clinical studies and phase I trials
The report criticises organisations set up to conduct clinical trials for being increasingly separate from a medical environment and from universities and other educational centres.
"This is affecting their ability to train the next generation of relevant staff, especially pharmacologists," it said. "This should be addressed by better access to hands-on experience in the planning and conduct of clinical trials for relevant staff."
But fears the report would raise unnecessary barriers for UK research are not likely to be realised and the report's recommendations have been welcomed by the industry.
Chief executive of the BIA Aisling Burnand said: "We applaud the expert committee's recognition of the need to improve the safety of first-in-man trials for certain novel agents without stifling innovation or introducing undue delay, which would be against the interests of patients."
UK biotech and pharma industry associations the BIA and ABPI also set up their own joint committee of experts to provide input into Prof Duff's expert group.
The committee announced its findings a day before the expert group released its report and many of the recommendations match those of the second report, including using the concept of Minimal Anticipated Biological Effect Level (MABEL) to determine an initial trial dose.
The industry taskforce also recommended the conducting of clinical trials for novel agents that, as with TGN-1412, stimulate the immune system in a hospital with intensive care facilities and providing all investigators with appropriate training for such studies.
The ABPI/BIA taskforce based its recommendations on best practices in the industry and has submitted them to Prof Duff.
Health minister Andy Burnham said the expert group led by Prof Duff had made a great deal of progress in its first two months, adding: "It is important to recognise that this is an interim report, that a public consultation will take place on its proposal, and further opportunities for interested parties to give evidence will be available in the autumn."
The consultation closes on 14 September and will be followed by the full report in November.
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