Dr Damian O’Connell, Vice President for Clinical Research with Pfizer and Chair of Molecular Medicine Ireland spoke at the IPPOSI Strategic Forum on Clinical Research in November 2009 about the changes in the way the pharmaceutical industry funds clinical research and what Ireland has to do to become a core site for clinical trials. This is what he had to say.

 

Why Pharma is changing the way it funds clinical research

The drug development process, from pre-clinical testing through phase III clinical trials, can take anywhere from nine to 12 years, with phase II and III clinical trials consuming half that time. Given those numbers, it is no surprise that pharmaceutical and biotechnology companies are looking for ways to conduct trials more quickly and inexpensively. Enrollment rates in trials are too slow and they seem to be lengthening. Trials are getting bigger and sites are delivering fewer patients. Perhaps no more than 6% of eligible patients actually enter clinical trials. Many clinical trial sites recruit only one or two, or in some cases, no subjects. Over the last several years, Pfizer and other companies have responded by over-recruiting the number of sites they think are needed to make up for sites that will not deliver patients. But that increases per-patient costs, and also makes trial logistics much more complicated. With site-qualification visits and confidentiality agreements, and contracts and budgets, and regulatory documents and investigator meetings, and drug supply and monitoring the sites, as well as data cleaning and other things, the more sites involved the more complicated that becomes. With many studies continuing to demand ever-larger numbers of patients, the cost of running trials has swollen to nearly 30% of companies' drug development budgets. Any delays on the path to regulatory approval and launch can only add to this burden, yet 75% of clinical studies still do not stick to their timetable. These logistical problems, along with financial pressures, have spurred companies to a strategy to reduce the number of countries in which they conduct trials as an imperative to increase study execution speed and reduce costs while maintaining quality.

Metrics used by Pfizer to select core countries for clinical trials

Key clinical trial metrics that have been used by Pfizer to decide on which countries to place studies have included the following:

• Start up speed – median number of days from receipt of protocol package to letter   of regulatory approval or ethics approval.
• Cycle time – median number of days from regulatory approval to last subject first visit
• Recruitment reliability – number of actual subjects randomised as percentage of number planned per study.

Why Ireland is not a core country for Pfizer studies

Analysis of this performance data, with consideration of cost and risk factors, has led Pfizer to a new core county foot print of 34 countries representing an approximately 50% reduction in countries previously used in clinical trials. Unfortunately Ireland was not deemed core as it fell short in terms of performance around these key metrics. Why is this? Some thoughts as to key contributory factors:

• Fragmentation - research infrastructures are not connected and hard to find. The key opinion leaders and researchers are there and are performing at individual level with individual companies. This activity is not collated, communicated and connected to showcase Ireland’s capacity as a country level
• People - Ireland is “person dependent” – you need to know individuals in order to get connected to the right chain of knowledge – it is not a “system”. As described above industry has been evaluating cost cutting and productivity enhancement for several years – this means decisions to involve countries are no longer made on the basis of “who the medical director knew”. It is now in the hands of procurement departments, operational departments whose bonuses are based on performance of countries chosen. Ireland has not evolved from the person based influencing strategy
• Performance - not predictable – research approval processes – especially ethics, protracted negotiation process for trial cost negotiation as each facility has different costs for the same service, access to patient populations is quite diffused with lack of connectivity between the various points of care e.g. hospital, GP interface
• Cost of patients – the cost of the number of patients Ireland can contribute is too high to justify the effort. Coupled with the fact that Ireland has a limited patient population and also a limited market for the sale of products – the cumulative effect of the investment risk is not a positive one
• Compliance - For a number of companies there have been more findings (and of a more serious nature) in regulatory inspections in Irish sites compared to sites in the UK which colours views when it comes to allocating clinical research between sites in the UK and Ireland
• Personnel – the recent hiring freeze on research nurses has impacted on Pharma and the perception of recruitment difficulties is very hard to shake
• PR - Communication strategy for what Ireland has to offer is fragmented and does not have a strategic lead. Ireland is NOT the right country for EVERYTHING and an uncoordinated communication plan just adds to the perception of confusing, complicated and not joined up national thinking.

What makes a country competitive in clinical research?

Clinical Trial Research is not a commodity, but a sophisticated element of technology in a very competitive environment. Countries wishing to attract high-level clinical research must offer:

• Sophisticated healthcare environment
• Professional investigational environment - doctors need explicit incentives to conduct research (i.e. "good investigators are good doctors”)
• Institutions should have explicit objectives to engage in clinical research; they often charge overheads, so this is a revenue stream, but may be poorly organized
• Countries need to offer access to modern diagnostics and treatments, so that data generated will have relevance in a rapidly developing healthcare environment
• Comprehensive, integrated information systems are very valuable – they enable effective review/follow up of patients on new treatments with critical evaluation of new treatments.

So where does Ireland go?

The development of a functioning clinical research system is fundamental to the evolution of life sciences in Ireland. Healthcare practitioners play a vital role in identifying unmet medical needs and giving direction and support to life sciences research. The Strategy for Science, Technology & Innovation, 2006 – 2013 (SSTI), highlighted the relatively low levels of translational and/or clinical research underway in Ireland and stated that “the introduction of an R&D culture within mainstream health service has been relatively slow (and) there is a need to strengthen considerably the health services research and policy research capacity nationally”. The reality today is that the resource pressures faced by the hospital system means that research has tended to take ‘second place.’ If Ireland is to become a core site for clinical trials everyone must be committed to making Ireland a beacon for clinical research and we are currently far from that. A shared vision would help us focus on what each part of the chain needs to deliver whilst maintaining their independence. All parts of the chain must be working in the same direction - hospitals, universities, ethics committees and the IMB.