Tough approval regime drives studies abroad

Ian Smith is from Lancashire but these days he spends more time in eastern Europe as he adapts his business to a gloomy view of the UK’s prospects as a place to test experimental medicines on patients.

“We’re the biggest recruiter in the UK, with 6,000 patients this year,” says Mr Smith, a former GP who founded Synexus, a company that tries out new medicines for pharmaceutical companies. “But we’re not going to open any more trial sites. It’s going downhill. We’ve just bought 10 sites in Germany, Ukraine and Austria.”

Such sentiments are common among commercial and academic medical researchers alike, despite efforts during the past decade by both the British government and the European Union to simplify, clarify and strengthen the framework for conducting clinical trials.

The UK has historically held a position that far outstrips the size of its economy or population. That reflects the long-standing presence of pharmaceutical companies, leading academic researchers and the high quality provided by the National Health Service. Yet many see its status ever more under threat, as developing countries in particular claim a growing share of clinical trials around the world.

One reason is the exhaustive approvals process required to begin any study in the UK, which makes recruitment into trials slow, costly and laborious. That defers results, delaying access to patients of new medicines and reducing the financial incentives for their development by eating into their remaining patent life before they are even authorised for use.

Regulators must scrutinise the benefits of any treatment under test to ensure they outweigh the risks. But ethical and research approvals are also required from both the NHS centrally and – in the latter case – from individual trusts around the country, each with its own procedures, timetables and potentially different conclusions.

Quintiles, a clinical res­earch organisation undertaking work for many drug companies, says that the average time taken from initial notification of a trial to a first visit to recruit patients in the UK was 173 days in 2007, up from 101 in 2006. In the US, the process takes a few weeks.

Adrienne Clarke, an executive at GlaxoSmithKline, is proud that the UK “arm” of a multi-country cardio-vascular drug trial recruited ahead of schedule recently. “We hit our targets,” she said. But she concedes that it also reflected low expectations: her objective was 300 patients, compared with 1,000 in Germany.

A second factor hindering trials in the UK is cost, which is higher than many other west European – let alone developing – countries. It also varies between NHS trusts, each of which charges different fees without much transparency or logic. Despite exhortations, they have no financial incentives to encourage research.

“One might charge you £300 just for a photocopy of a certificate while another will do it for free,” says Emma Radway-Bright, of the Association of the British Pharmaceutical Industry, the trade body. “The UK is expensive and there is a lot of variation.”

A third problem is recruitment of suitable participants. A growing number of poorer countries in eastern Europe, Asia and Latin America now offer low-cost networks of high-quality doctors – many trained in the UK – with a large pool of “treatment-naïve patients” keen to gain access to experimental new drugs. That makes finding volunteers willing to participate in trials rapid, speeding up trial results.

In the UK, by contrast, high standards of care and patients’ suspicions of trials makes recruitment slower. Companies are also discouraged by a growing reluctance of the NHS to approve and pay for innovative but expensive medicines, in turn reducing the knowledge of doctors traditionally seen as world-class “key opinion leaders”.

A senior executive at one multinational company describes how he was recently forced to pay not only for doctors’ time and the costs of his own experimental drug in a UK trial but also to buy the “gold standard” drug against which he was trying to compare it: a product approved by regulators and used abroad but not available on the NHS.

Kent Woods, head of the Medicines and Healthcare Products Regulatory Agency, cautions that any decline in the number of trials may reflect a slowdown in scientific innovation as well.

“Not all trials are of sufficient quality to get published or change practice,” he adds.

He argues that more sophisticated data are required to measure the true value of clinical studies and the numbers of patients enrolled.