The UK “has slipped from one of the most attractive to one of the least attractive places to undertake clinical trials” due to an ever-growing regulatory burden, claims a recent article in the BMJ.

The build-up of bureaucracy, particularly in the wake of the European Union’s clinical trials directive, 2001/20/EC, is now “the biggest single threat to the UK clinical research base and warrants immediate action”, warn Paul Stewart, Morris Brown and colleagues in their paper for BMJ.com.

Stewart is Professor of Medicine at the University of Birmingham while Brown is Professor of Clinical Pharmacology at Birmingham University and Addenbrookes Hospital in Cambridge. Their observations are based on personal experience and “feedback from many clinical researchers”, Stewart et al say.

While earlier threats to clinical research in the UK – essentially a shortage of researchers and capacity – have been addressed through major investments by stakeholders such as the Medical Research Council and the Department of Health, “anyone taking up one of the new academic specialist registrar posts created to encourage clinical academic training is likely to spend the entire 12-month fellowship trying to obtain regulatory approval for any clinical research project”, the authors complain, adding that drug companies are having similar difficulties.

Although the declared aims of Directive 2001/20/EC were to simplify the administrative provisions for clinical trials and “establish a transparent procedure to harmonise trial conduct”, there is little harmony evident among regulatory bodies, Stewart et al write. “The application paperwork now requires up to 40 hours to complete, and there is uncertainty about what requires ethical approval (audit versus research, medical student research projects, etc), inconsistency and delays in review process, and inappropriate requirement by many committees for scientific peer review,” they maintain.

Nothing better illustrates “the legalistic red tape strangling clinical research” than the “hair-splitting between mistakes in the writing and execution of protocols, with academic consultants protected by NHS indemnity only for the execution because protocols are not written in NHS time”, the authors claim. Clinical research by university-contracted and National Health Service-funded staff is subject to local scrutiny, often including highly complex risk analysis.

“How can closely monitored research require such painstaking scrutiny when researchers holding honorary NHS contracts with just an annual joint appraisal process are deemed ‘safe’ to undertake much riskier clinical practice?,” Stewart et al ask.

MHRA approval

They also criticise the need for separate approval of all clinical trials in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA). “The application is difficult to complete, cannot be submitted online, and is sometimes lost by the MHRA,” the authors comment. This process adds long delays with no perceived benefits, particularly when the drug concerned is already licensed.

“No improvement in patient safety has been demonstrated as a consequence of the extra tier of bureaucracy for such studies”, Stewart et al assert. “On the contrary, the MHRA notably failed to prevent the TeGenero disaster at Northwick Park [where the exposure of six healthy volunteers to the experimental monoclonal antibody TGN1412 put them in intensive care] – or even acknowledge its failure.” The extension of the agency’s primary remit to oversee new investigative medical products “is now counterproductive”, the authors suggest.

While they acknowledge the efforts of the National Institute of Health Research (NIHR) to strip away layers of bureaucracy and duplication in the UK’s clinical research regulations, Stewart et al do not believe these initiatives go far enough.

Their recommendations for easing the study approval process include a “single and simple” web-based submission form for all research studies; automatic indemnity by the NIHR for all research protocols involving NHS patients; a national and consistent ethical review process; and confining the MHRA to its core remit of ensuring that medicines are safe and effective.

“In a risk-benefit arena that is now heavily stacked towards perceived risk, the instigators of over-regulation must bear responsibility for the real and emerging risks of a failure to deliver the potential life-saving benefits of clinical research promptly,” Stewart et al say.