Clinical Research - The workings of the NIHR HTA programme

The workings of the NIHR HTA programme

The NIHR HTA programme is the largest national research programme for the NHS and is one of only a few research programmes to pro-actively monitor all the projects it funds. We look at how it supports its funded research teams

During the lifetime of a research project, from submission of a research proposal to delivery of the final report, many problems may arise. Recognised obstacles to completing successful trials include difficulties with ethical approval, patient recruitment, maintaining equipoise and running over budget or over schedule.

The 2005 KORAL study1 into osteo-arthritis of the knee highlights one of these obstacles. In this study placebo or ‘sham’ surgery was to be offered to patients with osteo-arthritis of the knee to compare its effects with arthroscopic lavage. The study was intended to confirm results of previous research that had found the surgery wasn’t beneficial in a selective group of patients2.

While the KORAL project recognised this design would be challenging to implement, two key issues arose relating to equipoise. One of these issues concerned the willingness of anaesthetists to anaesthetise patients in a trial involving ‘sham’ surgery, even though the surgery itself was of unproven benefit. The second related to the surgeons’ involvement. After initially expressing interest in the trial some surgeons became unwilling to participate, which may have been linked to falling rates of arthroscopic lavage noted following the publication of the first trial.

The KORAL study had been commissioned by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme, the largest single national research programme for the NHS. It commissions independent research information about the effectiveness, costs and broader impact of healthcare treatments and tests where clinical evidence gaps in the NHS have been identified. Because of the difficulties in completing successful trials, the HTA programme aims to assess all proposals for their feasibility, scientific merit and value for money prior to awarding funding. It also provides ongoing support to funded research to help ensure projects are successful and timely, and that trials are not overly complex, will be able to recruit a sufficient number of participants, and are sustainable.

According to the HTA programme, this pro-active monitoring of all its funded research projects is what sets it apart from most other research programmes – indeed, the programme’s suggested pilot study into the KORAL project recognised that a future trial was unfeasible.

Identifying study problems

Since it was established in 1993, the programme has invested more than £245 million in around 600 research projects. As the largest of the NIHR programmes, the HTA programme has a predicted annual budget of £88 million by 2011/12. The programme draws on the experience of approximately 200 experts who contribute to advisory panels and commissioning boards to identify the most relevant research and ensure its scientific quality. Many of these experts are either experienced NHS clinicians or experienced researchers. This enables them to highlight issues that may pose problems to the completion of a clinical trial.

Such problems can of course arise in all areas of primary research. For some studies important parameters need to be estimated before a trial can be initiated, and in this case researchers may be asked to perform a feasibility study to ensure the design is practicable. Such a study may, for example, assess the number of eligible patients, the willingness of clinicians to recruit participants, or the standard deviation of the outcome measure to enable a better estimation of sample size.

With recruitment being one of the most commonly reported issues – suffering anything from delays in the completion of a project to increasing costs or reducing the sample size, and hence statistical power of the trial – planning the recruitment methods and involving recruitment centres at an early stage are key aspects in planning a study’s duration. Clearly, a feasibility study can help to assess whether there are sufficient numbers of patients to confirm whether the main study would be viable. This is especially the case where a condition is relatively rare or if the research is likely to be of a sensitive nature. Such an approach can help identify any issues with the proposed recruitment protocol, for example, by highlighting the need for more recruitment centres to be involved and whether patients will be recruited within the anticipated timeline.

The demands of the trial or the information patients receive can also lead to them being reluctant to participate. Good patient involvement in the design and set up is a requirement of all HTA projects. Researchers may consult the public about their project design or collaborate with them and their organisations, and in doing so gain access to particular communities.

Ongoing support is also provided to the funded research teams, from project initiation meetings to discuss the potential issues that may arise during the lifetime of their project – where they receive advice from both the programme and other researchers – to at least one visit by the programme. Funded research teams are also asked to supply regular progress reports, so helping to ensure that difficulties are identified and the trials deliver scientifically sound research to a well-managed timeframe and budget.

To further support research groups the HTA programme, alongside the NIHR, has been working with Clinical Trials Units and NIHR Research Networks. The programme also provides priming funds to Clinical Trials Units planning to conduct HTA-funded research.

Lessons that have been learnt from HTA-funded projects and how difficulties have been overcome will be discussed by researchers at the HTA programme conference 2009, on 10 November at the Royal College of Physicians, London. To register visit www.hta2009.co.uk

References

1. Campbell M. Effectiveness and cost-effectiveness of arthroscopic lavage in the treatment of osteoarthritis of the knee (the KORAL study).
To view project details visit www.hta.ac.uk/project/1448
2. Moseley B, O’Malley K et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. NEJM 2002;347:81-88