Time for D in R&D?

The article in this journal by Hackshaw et al. (JRSM 2008;101:299–304)¹ illustrates the difficulties faced by clinical trialists in the UK. There is now a comprehensive national legal and regulatory framework around clinical trials research that is necessarily complex, but can be negotiated with experience and time. Innovations such as the recent introduction of the Integrated Research Application System (IRAS) are bringing together the various pieces of regulatory paperwork into one enormous, but useable, document. The Medicines Regulations and the Mental Capacity Acts provide a clear framework for consent for medical research, and the Multi-site Research Ethics Committee (MREC) system has removed the need for multiple ethics applications. However, despite these improvements at a national level, UK clinical research too often struggles at a local level.

The finding published in JRSM that many NHS Trusts had failed to approve a low-risk trial (treating cancer patients with a statin) six months after they received the nationally approved paperwork illustrates how grave a failing there is at Trust Research and Development (R&D) level.¹ Researchers report a huge variation around the UK in the way that Trust R&D departments process clinical trial applications, with widely differing additional requirements for researchers to fulfill. As an example, some Trust R&D departments will give approval pending completion of ethical, contractual and MHRA applications, whereas others will not start to process an application until all other approvals are in place. Anecdotally, researchers find that larger hospitals – perhaps due to their greater exposure to the pharmaceutical industry – have slow and complex systems, whereas smaller hospitals tend to have rapid and efficient systems. There seems to be no ethical or legal reason why one NHS Trust should have different local requirements from another, other than the creation or interpretation of a set of rules by local bureaucrats with little understanding of medical research. Controls designed to maintain patient safety in the early phases of pharmaceutical industry trials are often misapplied to research by students and investigator-led clinical trials, even where the potential risk to patients is very small.

Many of the local rules are minor and can be complied with, so each could be seen as a ‘reasonable requirement’. When multiple NHS Trusts require different minor changes, however, this all adds up to a huge burden on the researcher, especially when added to the very slow processing of applications, which then have to be chased. All of this administrative activity has to take place at a stage when there is still a risk that approval will not be received and that the research will therefore not go ahead. This creates a catch-22 whereby funding approval is contingent upon gaining regulatory approval, but the bureaucratic hurdles can only be addressed by employing funded research staff. The cost of the six or so months of administrative time from the trial manager needs to be met, so someone has to take a financial risk. Universities and NHS Trusts are increasingly unwilling to accept this risk; in future, therefore, research funders will need to support the preparatory stage of a trial, making resources available as soon as funding is approved and accepting that funding cannot be contingent upon regulatory approval. Funding organizations will also need to accept that the employment of staff for a one-year lead-in phase will be the norm for all multicentre trials, even those which are low risk.

Pharmaceutical companies often have greater resources to administer a clinical trial than non-commercial researchers, but this is still a significant cost so there is a danger that the UK will become seen as an uncompetitive place in which to conduct clinical trials.² Both pharma-led and investigator-led clinical trials need to select research sites which have efficient and supportive research administration systems. At present, however, researchers do not have the information needed to make choices about which NHS Trusts to include as study centres. Time and effort will all too often have already been expended by the research team before it becomes apparent that negotiating the local administration system will be a struggle. At this point local clinicians have been engaged and it is difficult to withdraw.

In order to make choices between potential trial sites, researchers need information about the quality of the support available locally. The performance of the local R&D department should be available for each category of medical research, with overall performance being best measured by median time from application to approval. It would then be easy for researchers to decide how best to use their resources to achieve the maximum participation in the trial. This system would also allow NHS Trust Boards to decide how actively to engage in medical research and would increase research activity in those which set up a supportive environment for clinical trials. Some NHS Trusts have already decided that clinical research will be a significant future income stream and have set up systems which positively encourage and support researchers. Others seem to have decided, either actively or by default, that they do not wish to take part in clinical research. In these circumstances it is difficult to see why a Trust should continue to support an R&D department. Purveyors of excessive bureaucracy may therefore be regulating themselves out of a job.

The UK and Europe are increasingly being seen as difficult places in which to conduct clinical trials.² Many countries outside Europe have a strong central regulatory and ethical structure for the scrutiny of clinical trials, and once national approval is given there is significantly less local bureaucracy. Reducing Trust-level bureaucracy would reducing the administrative burden and greatly improve the UK's ability to conduct clinical trials.

Progress has been made, especially at a national level, but the UK NHS has not yet realized its potential to become a truly world-leading environment in which to perform clinical trials. The working practices and sets of data required for local R&D approval should be nationally defined, with local R&D departments prevented from creating additional requirements. The publication of performance data from NHS Trust R&D departments would allow researchers to make an informed selection of study centres and create a system that provides better value for the UK's clinical research funding.

Footnotes

DECLARATIONS —

Competing interests Both authors are involved in the management of multi-centre clinical trials

Funding None

Ethical approval Not applicable

Guarantor TJC

Contributorship Both authors contributed equally