The recruitment of patients into clinical trials is a costly procedure that accounts for a sizeable portion of the overall study cost. But using a specialist recruitment and clinical research company can dramatically cut costs and shorten the time it takes to carry out studies. By Phil Taylor
One of the major problems in recruiting patients into clinical trials is the need to organise networks of part-time clinical investigators, mainly general practitioners and consultant specialists, who carry out clinical research on a part-time basis. This is costly and difficult to coordinate, with each investigator needing individual monitoring and contract arrangements.
Moreover, it is estimated that only 1% of GPs in the UK participate in clinical trial work, and this is reported to be declining due to increased control by the National Health Service and the increasing complexity of the clinical trial process.
An alternative being pioneered by companies such as Synexus of the UK is to replace this piecemeal approach with an organised system of dedicated sites that specialise in patient recruitment and clinical trial management.
Dr Ian Smith, Synexus’ medical director, believes the data speak for themselves, with savings for a typical Phase II or III study measured in terms of millions of dollars if this ‘super hub site’ model is adopted.
He told PharmaTimes that Synexus’ approach in sourcing, screening and managing patients in trials dramatically reduces the number of sites needed to run a study, can increase the number of patients that can be enrolled at each centre and shortens the overall duration.
For example, one clinical trial on lipid screening undertaken in part by Synexus provides an interesting price comparison. Synexus was able to carry out this 3,400 patient study in just 11 sites, versus 340 sites using a conventional clinical investigator network.
This resulted in a reduction in total study monitoring visits to 352 from 5,440, site set-up costs of $110,000 instead of $3.4 million, as well as savings on ongoing monitoring and auditing that cut the cost per patient – excluding the standard investigator fee – of $165 for the Synexus model and $2,676 for the network approach. The overall cost? Just $562,000, compared to $9.1 million.
Smith noted that the data are robust and seven- to 15-fold reductions in internal study costs are achievable, mainly from cutting set-up, monitoring, audit and data query expenses.
Speed and quality
But aside from cost, the other key benefits of the super hub site model is shorter studies, which can cut development times in half in some cases.
Recent data from the Tufts Centre for Drug Discovery and Development indicate that while overall R&D costs for medicines have gone up 5.8 times since the 1970s, the clinical portion of that has swelled by 8.6 times in the same period. Clinical costs now account for 40% - or $28 billion – of the $70 billion global annual expenditure on drug R&D.
But until very recently patient recruitment has not been on the minds of those with an overarching view on the costs of drug development process, and so the benefits of cutting clinical trial duration on development times has gone largely unnoticed. A recent study claimed that a week’s delay in a clinical trial could costs a pharmaceutical company anything between $600,000 and $8 million.
Meanwhile, on the issue and quality, data query rates and patient retention are better at Synexus sites and there tend to be fewer protocol violations than with conventional clinical investigators – as should be expected from staff who can give their whole attention to the trial, said Smith. Client companies indicate that drop-out rates are also lower, he noted.
All that aside, Synexus’ approach is not suitable for all studies. “The Synexus model typically works in chronic disease that is normally managed in primary care,” said Smith, although he noted that some elements of secondary care – such as specialist psychiatrists and neurologists for example – can be brought in if needed by a particular protocol.
“The key factor controlling what we can offer to clients is the identification of suitable patients,” he added. Synexus would not do cancer treatment studies, for instance, because the firm identifies patients via mail shots and advertising that are suitable for management in primary care settings, while cancer patients are almost always already being intensively managed in specialist centres.
The model also lends itself very well to prevention studies, one of the key growth areas in clinical trials in which patients who are not ill are monitored over time using surrogate markers. These include heart disease (e.g. measured via cholesterol-lowering), osteoporosis (bone mineral density), diabetes (blood glucose) and prostate cancer (prostate-specific antigen).
Recruitment into these studies cannot be carried out via doctors, and Synexus’ mailshot, advertising and existing patient database can tackle this problem. Moreover, disease prevention studies are on average 40% longer, so patient retention is critical and the company’s screening programme can limit drop-outs.
Another trend in clinical research that Synexus model addresses is the shift in geography in clinical testing into developing markets such as Central and Eastern Europe (CEE) and Asia, which have the enormous benefit of large numbers of treatment-naive patients who do not require earlier therapies to be washed out or who might otherwise be excluded from a trial.
The cost per patient also tends to be lower in emerging economies, and including patients from these areas also ties in with regulatory moves to encourage drug testing on ethnically-diverse populations. As a result, a recent report by Piribo estimated that, at present, the number of multicentre clinical trials being carried out in the CEE region is growing on average at an annual rate of 30%.
In addition to 12 sites in the UK, Synexus has pushed into Eastern Europe with a site in Poland, due to be followed by a second this autumn, and two further sites in Hungary and Bulgaria due to go live in the next few weeks. It also has a presence in Mumbai via a collaboration with India’s Institute of Clinical Research.
That said, it’s not all doom and gloom for countries in Western Europe and the USA, according to Smith, although clinical research in these countries is being affected by a shortage of treatment-naive patients, higher costs and poor delivery of data from clinical investigator sites.
What is happening is a segmentation of the market, with established markets becoming a focus for long-term safety and disease prevention studies, which are being driven by the twin demands of the pharmaceutical industry and regulators.
“If you are looking for men with a particular prostate-specific antigen level, you can do that study more easily in the UK than in India, because of access to medical procedures etc.”
“There are patient populations that are easier to find and manage in Western Europe than Eastern Europe,” said Smith.