Demand for patients to take part in clinical trials in oncology has become so intense that for some cancers half of all newly-diagnosed patients in the USA would have to enroll in studies in order to meet it, according to research presented last month.
The problems are many-fold. On the one hand, only a tiny proportion of cancer patients (less than 5%) participate in clinical trials, even though studies have suggested that their treatment outcomes can be better than those treated in regular clinical practice. On the other, the pharmaceutical and biotechnology has identified cancer as a key research priority in recent years, and discoveries in genomics and proteomics have revealed new drug targets that have led to a dramatic increase in the number of compounds in development.
As a result the cancer therapies market, currently worth around $32 billion, is forecast to grow to between $55 billion and $70 billion by 2010, according to consultancy firm Frost & Sullivan. The disease's high incidence rate and the lack of drugs and therapies that can either cure it or increase the life-expectancy period of patients is driving the discovery of novel agents – and demand for patients to test them.
Jennifer Tam-McDevitt and colleagues at the Geriatric Oncology Consortium in Baltimore, USA, has conducted a study of actively recruiting clinical trials in breast, lung and prostate cancers to gauge the shortfall in patient supply versus demand.
What she found could undermine the entire cancer drug development process in the USA, which currently includes 400 compounds in clinical testing.
Using the www.ClinicalTrials.gov database, maintained by National Institutes of Health, Tam-McDevitt identified 290 Phase I, I/II, II, and III trials in the three cancers, and calculated the number of patients needed to complete these trials is 151,311 (breast), 33,498 (lung), and 53,181 (prostate).
“These represent 19.4% to 71.6% of the American Cancer Society incidence estimates of the studied tumours,” she told the American Society of Clinical Oncology conference last month. That means that for breast cancer studies nearly 60% of all newly-diagnosed patients would have to be included in trials, with the figures for prostate and lung cancers being 20% and 15% of new cases, respectively.
Although not all trial participants are drawn from the incidence numbers, it is clear that given the current trial participation rate, demand has outpaced the supply.
“Many studies have anticipated enrollment period over several years [but] the number of trial participants needed to complete these studies is quite daunting.”
“Our results are likely under-estimates as not all studies currently enrolling patients may be included in this registry, and not all studies in the database specified the recruitment goal,” added Tam-McDevitt.
The medical community has the ethical responsibility to ensure sufficient patient enrollment for clinical trials, according to the study authors, who note that obstacles include the burden of regulation and paperwork, fear of litigation and costs.
A recent study of 14 high accruing sites uncovered average start-up costs of between
$5,600 and $8,600, which while affordable for specialist medical centres may be burdensome for smaller, community practices. This study also found that 44% of government and 37% of industry trials had not enrolled a single patient.
Another issue blocking recruitment in the USA is that patients costs associated with clinical trials are not necessarily reimbursable, usually because costs are higher compared to standard care, and there is a lot of variation between insurers, as well as the federal Medicaid and Medicare systems/Third-part payers, including pharmaceutical sponsors, sometimes do not reimburse the total cost of a patient’s treatment.
The USA’s decentralised system of cancer centres of excellence – often group around major cities - means that many thousands of patients in non-metropolitan areas may find it difficult to take part.
There can also be a perception among patients that taking part in clinical trials can place them at risk of receiving only a placebo, although this is almost never the case as cancer trials usually compare new drugs to placebo on top of standard treatment.
But the greater transparency in clinical trials – through sites such as clinicaltrials.gov and centerwatch.com - means that it is now easier for patients and their physicians to locate suitable studies.
In the meantime, unless ways to increase patient recruitment into studies can be found, a situation may arise where a national committee determines which trials are most important, and allocates patients accordingly, according to Tam-McDevitt.