LONDON. The volume of research conducted in Europe will be driven down dramatically, and thousands of lives will be lost, if a directive developed by the EU becomes law next year, warned leading UK research directors last week.
The guidance, which demands extra data collection, form-filling and inspections for even the most basic clinical trial, is diametrically opposed to what experts have been calling for - more simple and user-friendly trials.
The EU has made a "lethal error", said British Heart Foundation Professor of medicine and epidemiology at the University of Oxford, Rory Collins. "Bureaucrats who wouldn't know a clinical trial if it bit them have taken guidelines from the International Conference on Harmonisation (ICH) and bastardised them. If it becomes law it will have a most destructive effect on research and will mean that many people in Europe will die unnecessarily because it will be an obstacle to finding how to save lives."
His concerns were reiterated by Professor Richard Gray, director of the Clinical Trials Unit at the University of Birmingham, who at the European Society of Medical Oncologists in Hamburg last week criticised the current trend for clinical trials to become "fantastically complicated."
"The EU directive will cost lives because people will be put off performing small studies that may uncover a significant effect for certain patients," said Professor Gray.
Although the principles of the directive — to improve patient safety and confidentiality — are laudable, they have gone too far.
For example, researchers looking at chemotherapy will be expected to report every incidence of diarrhoea despite the fact that anti-cancer drugs are renowned for this side effect, according to Professor Gray.
"This kind of demand means that someone is going to be inundated with totally worthless reports. It doesn't mean that patient safety will be compromised without this directive, but we really need to concentrate on what is important and not get bogged down in irrelevant minutiae," he said.
The ICH, which is made up of specialists from the pharmaceutical industry and drug regulatory bodies in the US, Europe and Japan, developed their guidance on clinical trials to assist companies seeking the registration of new drug entities, or those which are not yet licensed.
However, the EU — without any expert assistance or advice — has extended the remit of the ICH guidance to all drugs, including those that have been licensed for many years.
"This means that if we want to know whether aspirin prevents heart attacks we will have to comply with extremely restrictive guidance which imposes endless obstacles to collecting evidence," said Professor Collins.
Clinical trials are already too complex, agree research leaders. Patients and medical staff are quite often deterred from taking part in trials because of the extra workload, tests and investigations involved. This means that trials take longer to perform. The knock-on effect is that the approval of new medicines is delayed, as is guidance on treatment options for doctors at the frontline.
"To get reliable answers clinical trials must get bigger and the only way to get them bigger is to make them streamlined so that they are easier for doctors and for patients to participate in — otherwise we will not get reliable results," said Professor Collins.
The demand for more tests and investigations actually stems from the pharmaceutical industry, which sponsors 50–75% of trials conducted in the UK.
Because they are investing large sums of money into the trials they want to gather as much information as possible about patients and their treatment, said Professor Gray. But there's a catch. Much of the information is superfluous and because of their complexity the trials can only attract a small number of patients, with the result that they are statistically weak and unable to deliver the answers to the questions they asked.
"Some trials currently demand a great deal of source data verification so that a clinical research associate is set the task of checking patients' date of birth, for example," said Professor Gray. "At the end of the day this makes no difference to the outcome of the trial and the exercise is a ritualistic waste of time.
"There is no need for clinical trials to be very special or confined to university hospitals. By focusing on what is important and answering a specific question in a real-life situation which fits in with clinical practice it is possible to run trials less expensively."
He points to two trials on the treatment for colon cancer to illustrate how things can go wrong.
The QUASAR trial looked at the treatment of both colon and rectal cancer, cost £1 million, involved 6,000 patients and provided definite answers on the most appropriate therapy. In contrast the Europe-wide PETACC study (Pan-European Trial for Adjuvant Treatment of Colon Cancer) only managed to recruit a total of 200 patients from the UK, cost substantially more than QUASAR and its findings were inconclusive.
Professor Gray admits that the entry criteria were slightly different in that only colon cancer patients were involved in PETACC. "Even so this trial should have been able to recruit 140 patients a month from the UK but it couldn't because the complicated trial procedure put many doctors off from entering their patients. Doctors are busy enough," he said.
If research organisations throughout Europe fail to act promptly to block the EU directive things will only get worse, not better, predicts Professor Collins.
"The directive is expected to become law in the middle of next year and if it goes through it will be a disaster," he said.
"What we need is for major research-funding organisations — like the Medical Research Council and the Imperial Cancer Research Fund — to take this problem seriously and to work on a Europe-wide basis in a coordinated way to block the current directive and to use people who know about the issues to draft a more appropriate document."