A multi-stakeholder scheme designed to show that the National Health Service in England is a viable environment for commercial clinical trials, one that can match the best in Europe in terms of quality, speed, efficiency and hitting recruitment targets, has delivered a median set-up time of 53 days for studies run under the programme.

That compares with an average 98 days for trials conducted outside the North West Exemplar Programme. It represents “a fantastic achievement in a globally competitive biopharmaceutical industry” that shows “the processes introduced by the NIHR are having tangible results”, said the National Institute for Health Research Clinical Research Network (NIHR CRN), the lead partner in the scheme.

There has been frustration in industry, government and academia about the ground-level impact of various efforts by the NIHR CRN and other stakeholders to streamline, harmonise and facilitate trials in the NHS – particularly at a time when established markets for clinical research are losing out to Central and Eastern Europe, Asia or Latin America.

The difficulty of translating intentions into actions was made clear at the end of last year, when it emerged that the volume of Phase II-IV trials approved in the UK had fallen from 728 in 2008 to 470 in 2009, the lowest level in the past decade.

The Phase 1 report from the North West Exemplar Programme provides some concrete evidence that, with close management and commitment on all sides, government investment in the NIHR CRN infrastructure can pay dividends. In addition to the significant improvements in set-up times, seven out of participating 20 studies recruited their first global patient through the scheme.

Launched in the summer of 2009, the NIHE CRN North West Exemplar Programme is one of the banner initiatives of the NIHR/NHS Biopharmaceutical Industry R&D Leadership Forum, which includes senior representatives from the NHS, the biopharmaceutical industry, the Department of Health and the NIHR CRN Coordinating Centre.

The programme is a joint initiative between the NIHR CRN, the NHS North West Strategic Health Authority and participating biopharmaceutical companies. The North West region was chosen, notes the Phase 1 report, because it has full geographical coverage of all the NIHR Clinical Research Networks as well as “a strong track record of delivering industry-sponsored research”.

Long set-up times

As the report observes, long set-up times and limited research capability “were making the UK less attractive as a location for clinical trials”. As a result, the country had slipped from second or third position in 2000 to eighth or ninth in 2008 on a measure of global clinical trial activity.

Accordingly, the NIHR NHS/Biopharmaceutical Industry R&D Leadership Forum decided a programme was needed “to demonstrate the step changes resulting from the NIHR infrastructure, leading to study set-up and delivery that was comparable with the best in Europe”.

The Forum “agreed that the infrastructure and processes put in place to deliver clinical research in the NHS were correct, but there was a need to demonstrate to global partners that study set up and recruitment could be consistently and reliably delivered”, the report adds.

The publication just released addresses the first phase of the Exemplar programme, which is about effective study set-up. Phase 2 concerns effective study delivery. It continues to monitor recruitment to Exemplar studies while implementing “contingency plans for any issues and barriers which may impact recruitment to time and target”.

The studies included in the scheme were the first 20 of those submitted to the NIHR Clinical Research Networks for feasibility and adoption that were ready to apply for NHS Permission (a standardised process used to approve NIHR CRN trials). This method of selection was designed to remove any potential bias towards less complex studies and to allow for close monitoring and data collection.

To be considered eligible for the Exemplar Programme, a study had to select at least one site in the North West, use the NIHR CRN Industry Costing Template as well as the unmodified model Clinical Trial Agreement, and agree to one of three
NIHR Comprehensive Local Research Networks (CLRN) in the North West acting as the Lead CLRN for the trial.

The headline performance outcomes from Phase 1 of the programme were as follows:

- The median time from R&D Form validation to NHS Permission at the first study site was 53 calendar days.

- The median time from validation of the Site-Specific Information (SSI) Form to NHS Permission at first and all North West sites was 31 days.

- The median time from R&D Form Validation to First Patient-First Visit was 88 calendar days.
- The Median Time from NHS Permission to First Patient-First Visit was 16 calendar days.

UK/European comparisons

None of the 20 Exemplar Programme studies have been conducted exclusively in the North West of England, and for some the region constituted only a very small proportion of the overall trial activity.

As a point of comparison, the median time from R&D Form to NHS Permission at all sites used was 87 calendars days; it was 50 days for SSI Form to NHS Permission. The corresponding figures for all North West sites were 77 days and 31 days respectively.

The median time of 53 calendar days from R&D Form to NHS Permission at First Site for the Exemplar studies compared with a median of 98 days for all commercial studies (106 in total) across the NHS in England between November 2008 and April 2010.

As the report notes, it is difficult to make direct comparisons between study set-up times in the UK and the rest of Europe, as most European countries regard ethics committee approval as a green light to start recruiting at any site, while in the UK NHS Permission is required from each participating site.

However, approval times provided by the Association of the British Pharmaceutical Industry (ABPI) for 2009, as well as data from two large pharmaceutical companies based on approval times for 2008/9, suggest that performance in the Exemplar programme is not only a distinct improvement in UK terms but brings the NHS into line with countries like France, Germany and Sweden – despite the need for additional NHS Permissions.

For example, the ABPI and industry figures for median set-up times in the UK are 77 calendar days (excludes time required for NHS Permissions) and 147 days (includes NHS Permission at all sites) respectively.

These sources give corresponding approval times of 56 (ABPI) and 105 (industry) calendar days for France, 56 and 77 for Germany, and 56 and 77 for Sweden. The quickest set-up times recorded were in the Czech Republic (42 and 98 days respectively) and Italy (49 and 77 days).

Key factors

According to the Phase 1 report, the key factors driving the improved set-up times seen in the North West Exemplar Programme were:

- The role of the Lead CLRN as a single point of contact for all study sites
- Rapid and appropriate escalation of issues and barriers
- Streamlining of internal processes within NHS Trusts
- Senior-level support from NHS chief executives.

A final report on the NIHR CRN North West Exemplar Programme will be published in
November 2010, including recommendations on how best practice can be adopted and
rolled out by key stakeholders across the NHS in England.