Clinical Research - The climate for clinical research in the UK

The climate for clinical research in the UK

The Office for Life Sciences is the latest in a line of government initiatives intended to return the UK clinical trials sector to its former lead. But is it enough? Jenny Hone asks Geraldine Brown, Head of Clinical Research at AstraZeneca and Chair of the CREN, the Clinical Research Experts Network of the ABPI

Q: What proportion of the total number of patients in an AstraZeneca trial is recruited in the UK, and how does this compare with previous years?

This varies enormously. We do a lot of Phase I oncology work where we can contribute up to 50% of the small number of patients required. In larger Phase III trials it can be as low as 2%. My budget for global clinical trials is 30% less than it was two to three years ago, partly because of our current portfolio mix but it also indicative of a shift toward countries with a lower cost base and higher productivity.

Q: In what therapeutic areas does AstraZeneca consider the UK a core country for clinical trials and how has this changed?

Oncology and diabetes are key areas for the UK as we have a high success rate for our patient recruitment in both of these. We also work in other indications but our overall delivery performance and cost-effectiveness is lower than some other countries, and this is a constant challenge for the UK. In previous years we have conducted large-scale trials, with high numbers of patients, in respiratory and gastrointestinal but this has changed with our changing portfolio.

Q: Dr Pim Kon, VP and Medical Director for GlaxoSmithKline, was recently quoted as saying: “We are getting to the stage where it is going to be very difficult to defend conducting clinical trials in the UK.” Do you agree with this?

Yes, there is increasing competition from emerging markets where the quality of trials is high and the costs low. In AZ, we tend to use the UK for trials in therapeutic areas where we remain competitive in patient recruitment, and relatively reasonable on cost. It is in patients’ best interests to have a cohort of Investigators who have hands-on experience of managing the risk-benefit profile for specific UK patients. This experience cannot necessarily be replicated through Phase IV studies. However real world useage of medicines will become increasingly important to define the most appropriate use of a particular medicine, enable a more definitive safety profiling and facilitate the more appropriate value attached to medicines.

Q: The bureaucracy of ethical committee approval and the poor recruitment rate in the NHS are said to be proving a serious disincentive to conduct clinical trials in the UK. Indeed, Pfizer made the decision to stop performing in-house trials here earlier this year. As a UK company, how is AstraZeneca balancing these difficulties with the pressures to support the domestic market?

Unfortunately the drive pressure for cost-effective study delivery is gradually eroding the pressure to support the domestic market, and UK competitiveness in trial delivery is now one of the primary drivers in AZ for the selection of countries and allocation of patients in global clinical trials. For this reason, one of the most important factors in the UK’s ability to compete for patients vs other countries is how we deploy our biggest investment in trial delivery – our monitors and administrators.

The ability of sites to access an adequate number of patients and to deliver high quality data without need for excessive support from my team is a key selection criterion. To deal with this, the AZUK Clinical Research Group invests substantial time and resources training and coaching our teams to select the best sites and then managing those sites as efficiently and effectively as possible. Being able to access more clinical trial patients in fewer sites would be a major advantage.

This has paid off with AZUK having had almost 100% delivery vs target over the past couple of years, but at an unsustainably high cost in monitoring and administrative resource. I don’t view ethics and regulatory approvals as a major stumbling block in the UK, the biggest hold-up in study start-up is the time to obtain R&D approvals; with competitive recruitment now the norm, this can seriously affect our trial performance.

Q: Some critics have suggested the NHS does not have adequate structures in place to handle clinical trials along business efficient lines. Is this your view and if so what can be done to improve the situation?

There have been government-supported improvements over the past few years, with the introduction of the National Institute for Health Research (NIHR) and the associated improvements in systems, processes and staffing in the clinical trial networks. The UK is the envy of many countries in Europe for our standard clinical trial agreement, and now the research passport, IRAS (Integrated Research Application System), and the standard costing model are also helping to improve trial start-ups. What is needed is to embed this best practice across the entire NHS.

The remaining piece that also still needs to be achieved consistently is effective access to patients in settings where clinical trial professionals have the skills and time to conduct research to business standards, with clinical case loads reduced accordingly. While there is some understanding in the NHS that cost-effective delivery vs commitments is essential if we are to secure future work, this is not consistent and in my view pharma trials need to be prioritised if we are to compete globally.

Q: How effective has the UK Clinical Research Network (UKCRN) been, and has the NIHR CSP (Coordinated System for gaining NHS Permission) made a difference to approval times?

The UKCRN is welcome and is showing some promising metrics and improvements in start-up times and trial delivery. However, only with the right NHS incentives and targets in place will the UKCRN be able to deliver the overall speed and efficiency for the UK to be a major global player in clinical research.

The ongoing NIHR CSP process amendments are also very welcome, as they should help streamline and speed up approval times. One issue is that the CSP is currently used only for trials adopted by NIHR and full implementation across the NHS would be of major benefit to UK competitiveness.

Q: The UK is clearly facing increasing competition from emerging economies such as China, as well as Eastern European countries that are building up their expertise and capabilities and offering financial incentives. Would the UK benefit from a better reward structure for trial sites?

This is absolutely key. It is increasingly difficult to demonstrate the benefit of trial participation for site staff, given the effort now required to deliver trials for regulatory submissions. In the past, UK investigators were often contributing authors on publications arising from pharma research and could use trial payments for their own research, to pay staff or improve facilities. Most of these incentives have been eroded with increased globalisation of trials, R&D governance and centralised payments.

Q: What other areas still need to be improved if the UK is to re-establish itself as a world leader in clinical research and how can this be achieved?

We need a career structure for professional investigators who have the interest and desire to perform commercial clinical research. We also need access to patients that, in most cases, is supported but not restricted by the Primary Care Trusts (PCTs) and trusts that deliver their clinical care. Commercial clinical research organisations (CROs) achieve this but at a high cost. There is an opportunity within the NHS to operate on a not-for-profit basis and deliver similar patient recruitment targets. A key function of the NIHR networks could be to take ownership of trial performance, distributing trials across sites to minimise the number of competing trials per site, thus optimising numbers of patients recruited to individual trials and requiring fewer sites per trial. The biggest challenge to this concept is that NHS trusts, GP practices and PCTs are independent businesses and there is minimal scope to impose ways of working. Government-level targets and metrics, together with engagement of senior trust and PCT management, is key to the continued improvements we need to see.

Q: How will the actions of the Office for Life Sciences benefit companies like AstraZeneca and has the government gone far enough in putting “innovation at the heart of healthcare”?

The activities of the OLS are continuing to drive improvements in the clinical research environment in the UK. This is focused on addressing key areas of concern such as workstream 4.1g, Bureaucracy-Busting NIHR Research Support Services. This workstream is seeking to shorten R&D approval times and streamline the approval process. There are also innovative initiatives around improving the opportunities for translational research. From the outset there has been full consultation with industry; this is very welcome and should go some way to help return the UK to a competitive position in pharma research. The support and drive of the UK Government and the OLS are creating opportunities for the UK to be a major player in clinical trial delivery.

Q: To what extent does AstraZeneca rely on outsourcing for its trials work? Do you think the use of contract research organisations for conducting clinical studies will continue to increase, and how is the relationship between sponsor and CRO likely to develop in future?

In my view, there is every likelihood the use of CROs will continue to increase as companies seek to improve their operating models. Using CROs provides flexibility and access to operational expertise, while retaining discovery and early development in-house.

As market access considerations decrease, the justification for using in-house staff also diminishes. However, cost-effectiveness will always remain a major consideration in the decision to outsource work. The current AZ position is to retain a variety of delivery models including permanent staff in local affiliates, insourced staff and fully outsourcing the work.

Q: How can AstraZeneca help to improve clinical research in the UK?

AZ is currently fully engaged in supporting the range of development work in the UK, with staff participating in all the key fora, such as the Ministerial Industry Strategy Group (MISG), OLS workstream 4.1g, NIHR Roadmap, the ABPI Clinical Research Experts Network (CREN), commercial Clinical Operations Group (cCOG), and the Scottish Pharma Liason Group.

Q: What do you consider to be the long-term future of clinical research in this country?

I believe there will always be a need for UK participation in clinical trials for payer and regulatory data. However we will struggle to return to the leading position we once held unless we can change the mindset and delivery models of all partners in the clinical research arena.

Q: How do you see the relationship between AstraZeneca and the UK clinical research industry developing in the future?

I hope AZ will always maintain a strong presence in the UK and continue to champion and support best practice in trial delivery.