A dearth of new expertise to evaluate the safety and efficacy of innovative compounds is jeopardising efforts to tighten up conditions for first-in-man trials, UK experts warn.
There is not enough hands-on experience in the National Health Service (NHS) or UK universities to keep pace with advances in pharmaceutical research, says Sir Gordon Duff, chairman of the Expert Scientific Group (ESG) that last December delivered its final report on Phase I trials following the disastrous volunteer study at Northwick Park Hospital.
Of the 20-odd specialist centres for Phase I trials in the UK, only two are associated with the NHS or universities, Sir Gordon told a conference organised by the Manchester Medicines Network this week. Moreover, there is a real danger the current ageing generation of clinical pharmacologists will simply not be replaced.
Among the 22 final recommendations in the Duff report was a call to widen real-life experience in the planning and conduct of clinical trials. Postgraduate training programmes could include secondment to commercial organisations or training periods in specialist centres within the NHS and universities, it suggested. Filling the skills gap with a new generation of clinical pharmacologists, toxicologists and related professionals required co-operation between higher-education funding bodies and institutions, the NHS and industry.
Vital skills being eroded
Other speakers at the conference were equally concerned that vital skills were being eroded. Manchester University – a beacon for medical and other research – does not have a professor of clinical pharmacology, pointed out Leon Aaarons, professor of pharmacometrics at the School of Pharmacy & Pharmaceutical Sciences. The discipline is “not sexy” but without it there will be more drug disasters, he commented.
Drug companies are also seriously worried, said Dr Richard Tiner, medical director of the Association of the British Pharmaceutical Industry (ABPI). Over the last 10 years the ABPI has funded 25 registrar clinical pharmacologist posts jointly with the Department of Health. Yet with the European Union’s Regulation on Paediatric Medicines now in force and opening up fresh channels for drug development, there are only three paediatric clinical pharmacologists working in the UK.
Dr Tiner had some progress to report on other ESG recommendations. Last week the Medicines and Healthcare products Regulatory Agency (MHRA) held its first meeting with industry and clinical pharmacologists on developing a national accreditation system for Phase I centres. And the Royal College of Physicians’ Faculty of Pharmaceutical Medicine is putting together a training programme for clinical investigators.
Volunteer recruitment falling away
Meanwhile, Dr Tiner added, volunteer recruitment is starting to fall off again, following an unexpected surge of interest prompted by media coverage of the Northwick Park incident. According to Sir Gordon, though, applications for first-in-man trials have not suffered much. An interim group was immediately set up at the Committee on Safety of Medicines to assess comparable Phase I candidates to TGN1412, and there are now only 10-12 applications outstanding, he told the conference.
Sir Gordon was reluctant to apportion blame for the violent adverse reactions to TGN1412. It is “easy to hit regulators with big sticks” but they have to take a very wide view, with accuracy, speed and decisiveness, he commented – all this when the rate of scientific development is accelerating.
While better access to information and more considered dosing could have avoided the problems at Northwick Park, TeGenero did all the relevant in vitro toxicological studies and carefully selected the animal model for species toxicity. The Phase I protocol was then vetted and approved by no fewer than three ethics committees and two experienced national regulators, he noted. As US historian Arthur Schlesinger once said, “Righteousness is easy in retrospect”. By Peter Mansell